Nephrology Flashcards
what is a normal 24-hour urine protein?
less than 150 mg
how much protein w/i 24 hours indicates significant GLOMERULAR pathology?
more than 2 g/day (or 40-50 mg/kg/d)
how much protein w/i 24 hours indicates significant INTERSTITIAL pathology?
less than 1 g/day
the only exceptions in which there can be pathology and a NORMAL URINE SEDIMENT with MINIMAL proteinuria (2)
- medullary cystic disease
2. obstructive uropathy
will urinary light chains in myeloma be picked up on a urine dipstick?
NO
causes of false-positive urine albumin on urine dipstick: (6)
- very alkaline urine with a pH > 8
- fever
- heart failure (HF)
- urinary tract infection (UTI)
- hematuria
- very concentrated urine
common in people during a febrile illness, after strenuous exercise, and in pts w/ HF and COPD
transient proteinuria
first step in a pt w/ transient proteinuria
recheck UA (if negative; benign)
proteinuria reverts to near-normal when pt is SUPINE
BENIGN ORTHOSTATIC PROTEINURIA
what equates to 24-hour urinary protein?
spot protein:creatinine ratio
proteinuria ranges using spot ratio:
- normal
- microalbuminuria
- overt proteinuria, usually d/t interstitial disease
- nephrotic range
- less than 0.15 (150 mg)
- 0.03 - 0.3 (30 - 300 mg)
- 0.3 - 1 (300 mg - 1 g)
- 3 - 3.5 (3 - 3.5 g)
EARLIEST indicator of diabetic and hypertensive nephropathy
microalbuminuria
indicate probable glomerulonephritis/nephritic syndrome
RBC casts, or “dysmorphic” RBCs
FEW RBCs on microscopic analysis, BUT urine dipstick is POSITIVE for blood
HEMOglobinuria or MYOglobinuria (rhabdomyolysis)
hematuria associated w/ proteinuria, especially if dysmorphic cells and/or RBC casts are present in the urine, is ALWAYS d/t
glomerular bleeding
MCC of ISOLATED GLOMERULAR HEMATURIA (normal renal function, NO proteinuria)
- IgA nephropathy
- thin basement membrane disease
- early Alport syndrome
can cause transient hematuria
strenuous exercise
pts w/ sickle cell TRAIT may also have
hematuria
isolated microscopic or gross hematuria is more likely what in origin?
urologic
in older pts, complete GU imaging must be done to exclude what?
renal cell or GU tract carcinomas
what GU imaging must be done to r/o renal cell or GU tract carcinomas?
US, MRI, or CT
w/ EOSINOPHILURIA, think of
drug-induced interstitial nephritis
w/ COARSE GRANULAR casts, or “MUDDY BROWN” casts, think
acute tubular injury
w/ OVAL FAT BODIES (“maltese crosses” under polarized light) may be seen in
nephrotic syndrome
what suggests rhabdomyolysis-induced renal failure?
unusually rapid rise in serum creatinine (more than 1.5 mg/dL over 24H)
in the elderly, what will be normal despite reduced renal function?
creatinine
serum creatinine (sCr) is artificially INCREASED by these medications (4)
- cimetidine
- probenecid
- tenofovir
- trimethoprim
interfere w/ the test for creatinine and may falsely elevate results
- acetone
- cefoxitin
indicates either PRERENAL AZOTEMIA (low flow and increased absorption), or increased protein breakdown
elevated (> 20:1) BUN:Cr ratio
is a nonglycosylated protein that better reflects GFR than sCr
cystatin C
a measure of overall renal function
glomerular filtration rate (GFR)
what is used to estimate GFR?
creatinine clearance
formula to calculate GFR
GFR = U(Cr)V/P(Cr)
= (total urine creatinine/24H)/sCr
name the 2 main creatinine-based GFR formulas used to calculate GFR in pts w/ IMPAIRED renal function
- modification of diet in renal disease (MDRD)
2. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
what is required to calculate the MDRD?
- sCr
- race
- sex
- age
is MORE accurate than MDRD at NEAR-normal kidney function (eGFR > 60mL/min/1.73m2)
CKD-EPI
is another acceptable way to estimate GFR
Cockcroft-Gault formula
the equation of choice in the general population, especially at higher levels of GFR
CKD-EPI
when should you not calculate GFR?
during AKI
when will estimates of GFR be inaccurate?
- extreme age
- extreme weight
- pts w/ amputations
- cirrhosis
- pregnancy
how do you calculate GFR in pts w/ extreme age, extreme weight, pts w/ amputations, cirrhosis, pregnancy?
- 24H urine
- measure serum cystatin C
the fractional excretion of sodium (FeNa+) is the ratio of?
excreted Na+:total filtered load of Na+
when is calculating the FeNa+ most useful?
evaluating oliguric AKI to differentiate PRERENAL AZOTEMIA from acute tubular necrosis (ATN)
FeNa+ for prerenal azotemia
less than 1%
FeNa+ for acute tubular necrosis (ATN)
more than 2%
other causes of AKI w/ FeNa+ less than 1% (6)
- contrast-induced ATN
- cardiorenal syndrome
- hepatorenal syndrome
- nonoliguric ATN
- pigment nephropathy (hemoglobinuria, myoglobinuria)
- acute glomerulonephritis
formula to calculate FeNa+(%)
(sCr x uNa)/(sNa x uCr) x 100
since diuretics may increase FeNa+, what can be used instead?
FeUrea
the fractional excretion of urea (FeUrea) is the ratio of?
excreted urea:total filtered load of urea
formula to calculate FeUrea
(sCr x U(urea))/(BUN x U(Cr)) x 100
what FeUrea is suggestive of prerenal state?
less than 35%
- is used to diagnose unexplained causes of AKI, nephrotic syndrome, and GN
- routinely utilized to evaluate increases in sCr to distinguish between medication toxicity, ATN, viral infections, and acute rejection
renal biopsy
primary acid-base disorders are either what or what in origin?
respiratory or metabolic
primary respiratory disorders:
- change in what?
- compensated how?
- PaCO2
- kidney SLOWLY dumping/holding on to HCO3- in the OPPOSITE direction
primary metabolic disorders:
- change in what?
- compensated how?
- HCO3-
- respiratory rate IMMEDIATELY increases or decreases
- Henderson-Hasselbalch equation
- and its easier derivation of
- pH = pK + log(HCO3- / [0.03 x PaCO2])
- H+ = 24 x (PaCO2 / HCO3-)
Henderson-Hasselbalch equation tells us the body only has 2 ways to control serum pH, which are?
- regulate RR and TV, thus control PaCO2
2. regulate kidney’s absorption of HCO3-
what determines pH?
the RATIO of PaCO2 to HCO3-, NOT the absolute values
significant alkalemia of any etiology can cause what?
diffuse paresthesias/numbness and muscle spasms, usually associated w/ acute hyperventilation (acute resp. alkalosis)
diffuse paresthesias/numbness and muscle spasms are usually associated w/ acute hyperventilation (acute resp. alkalosis), but can also be caused by?
- rapid overload w/ IV HCO3-
- citrate (massive blood transfusion)
why are pts with metabolic acidosis and hypocalcemia protected from the hypocalcemia?
since acidosis decreases the fraction of BOUND Ca2+ and INCREASES the IONIZED Ca2+
correction of acidosis prior to correction of hypocalcemia can cause what?
removes protective effect of acidosis, and precipitate seizures
serum anion gap (AG) equation
AG = (Na+ - HCO3-) - Cl-
AG is a determination of?
unmeasured anions
name the anions in the blood
- HCO3-
- Cl-
- phosphate (phos)
- sulfate
- albumin
- organic acids
name the cations in the blood
- Na+
- K+
- Ca++
- Mg++
remember that any increase in unmeasured anions always is 1:1 w/ the increase of
H+
HIGH AG ALWAYS INDICATES
METABOLIC ACIDOSIS
under NORMAL conditions, what anion is the main contributor to the AG?
albumin
what is the correction for hypoalbuminemia to calculate AG?
about 2.5 mEq/L for each 1G/dL decrease in albumin
does ethanol itself cause elevated AG?
no, but alcoholic ketoacidosis does
when is the urine anion gap (UAG) used?
to evaluate the etiology of NAGMA to differentiate between GI loss of HCO3- and RTA
formula for UAG
UAG = Na+ + K+ - Cl-
normal value of UAG
close to 0
positive UAG value suggests
low urinary NH4+ (e.g. RTA TYPE 4)
neGUTive UAG value suggests
HIGH urinary NH4+ (e.g. DIARRHEA)
in the setting of metabolic acidosis d/t EXTRA-renal HCO3- losses, why is the urinary NH4+ high?
renal H+ is excreted in the form of NH4+
serum osmolality is mainly determined by concentrations of?
Na+, glucose, and urea
osmolal gap (OG) helps determine what?
whether unmeasured osmotically active substances (osmoles) are circulating in the blood (possibly causing acidosis)
formula for Osm(calc)
Osm(calc) = 2[Na+] + (BUN/2.8) + (glucose/18)
simplified equation: Osm(calc) = 2[Na+] + (BUN/3) + (glucose/20)
formula for OG
OG = Osm(meas) - Osm(calc)
what is the normal OG?
less than 10
important causes of high OG
- METHANOL
- ETHYLENE GLYCOL
- PROPYLENE GLYCOL
- CKD (d/t retention of small solutes)
- lactic acidosis and ketoacidosis (ALSO d/t retention of small solutes and not from the actual lactic acid or ketoacids themselves)
is NOT associated with acidosis (AG is normal), but osmolal gap is increased
ISOPROPYL alcohol
nontoxic causes of increased OG and normal AG (3)
- mannitol
- sorbitol
- glycerol
what is the main use of OG?
w/u of pt w/ possible acid alcohol ingestion (e.g. ethylene glycol, methanol, or propylene glycol)
when should possible acid alcohol ingestion especially be considered?
if OG is more than 25 mOsm/kg
ethylene glycol is a common primary ingredient in?
ANTIFREEZE
methanol is a common ingredient in?
- PAINT THINNERS
- DEICING solutions (e.g. windshield washer fluids)
rarely, an inadvertent contaminant of “MOONSHINE;” a by-product of grain fermentation
methanol
propylene glycol is a SOLVENT used in?
IV lorazepam
what quickly happens w/ ethylene glycol, methanol, and propylene glycol, and what is the effect on the OG and AG?
initial substrates cause high OG and HAGMA, but are quickly converted to their TOXIC metabolites, which do not cause OG, but cause HAGMA
ethanol, ISOPROPYL ALCOHOL, or ACETONE ingestion will give what OG and AG?
- HIGH OG withOUT acidosis
- normal chemistry
- normal AG
toxic metabolites of ethylene glycol
mainly glycolic acid and oxalic acid
toxic metabolite of methanol
formic acid
toxic metabolites of propylene glycol
- pyruvic acid (normal)
- lactic acid (normal)
- acetic acid
- propionaldehyde
metabolite of isopropyl alcohol
acetone (less toxic)
signs of possible acid alcohol ingestions
- stupor
- coma
- hypotension
AG and OG in the obtunded patient:
- methanol and ethylene glycol
- ketoacidosis and lactic acidosis
- chronic kidney disease
- high AG
- very high OG
AG and OG in the obtunded patient:
- ketoacidosis and lactic acidosis
- chronic kidney disease
- high AG
- high OG
AG and OG in the obtunded patient:
- salicylate poisoning
- methanol or ethylene glycol ingestion after substrates have been converted to acid metabolites
- high AG
- normal OG
AG and OG in the obtunded patient:
- isopropyl alcohol, acetone, or ethanol ingestion
- normal AG
- high OG
AG and OG in the obtunded patient:
- think carbon monoxide poisoning; BEFORE lactic acidosis develops
- normal AG
- normal OG
- commensurate increase in Cl- w/ the decrease in HCO3-
- also called “hyperchloremic” acidosis
NAGMA
why is the Cl- retained in NAGMA?
to maintain electrical neutrality
3 main causes of NAGMA
- usual: LOSS of HCO3- d/t DIARRHEA or PROXIMAL RTA
- increased organic acids (NH4+, e.g. pts on TPN)
- inability of kidney to excrete endogenous acids (renal failure or DISTAL RTA)
NAGMA plus HYPERkalemia, think of?
RTA type 4 (hypOaldosteronism)
NAGMA plus HYPOkalemia is caused by
- GI loss (sometimes)
- RTA types 1 (distal) and 2 (proximal)
is a common solvent in glues and paints and can cause NAGMA
toluene
treat NAGMA with?
sodium bicarbonate replacement
in HAGMA, is there an equivalent increase in Cl-?
no
net charge in the serum is always?
neutral
because the net charge in the serum is always neutral, in HAGMA there must be what?
increase in UNmeasured anions
what tests should immediately be performed in a pt w/ unexplained HAGMA?
- fundoscopic exam
- toxicology screen
- serum glucose; urine and serum ketones
- lactic acid level
- serum osm w/ calculation of OG
- UA to assess for calcium oxalate crystals
common causes of HAGMA
- severe CKD: decreased acid (especially NH4) excretion (MCC)
- uremia: sulfate, phosphate, urate
- diabetic ketoacidosis, alcoholic ketoacidosis, starvation ketoacidosis
- lactic acidosis: drugs, toxins, circulatory compromise
- poisonings: salicylates, methanol, ethylene glycol, propylene glycol
common causes of NAGMA
- renal tubular acidosis
- diarrhea
- carbonic anhydrase inhibitors
- hyperalimentation w/ TPN
check for what in ketosis?
- B-hydroxybutyrate
- urine ketones
treatment for DKA
- insulin
- IVF
- electrolyte replacement
classic findings of AKA (alcoholic ketoacidosis)
- HAGMA
- hypophosphatemia
- hypoglycemia
treatment for AKA
dextrose
how does uremia cause HAGMA?
causes an accumulation of anions: SULFATE, PHOSPHATE, URATE
what is lactic acidosis type A?
d/t muscle hypOperfusion during shock, cardiac failure, or sepsis
what is lactic acidosis type B?
- findings of systemic hypoperfusion are lacking
- DRUG-induced mitochondrial dysfunction (zidovudine, metformin, propofol)
- tumor-induced LA
- alcoholism
- high doses of propofol for more than 48 hours
- renal failure
- rhabdomyolysis
- hyperlipidemia
- J-point elevation on EKG
- various arrhythmias
propofol-related infusion syndrome (type B lactic acidosis)
- can occur in pts w/ short bowel syndrome
- present w/ typical neurologic sxs (from slurred speech to obtundation)
D-lactic acidosis
- key clue is MIXED RESPIRATORY ALKALOSIS and HAGMA
- initially causes respiratory alkalosis, THEN additionally the HAGMA
- suspect in elderly pts taking pain meds for arthritis
salicylate overdose
- key clue is CALCIUM OXALATE crystals in urine
- metabolizes to glycolic acid and oxalic acid resulting in HAGMA
ethylene glycol
- key clue is visual sxs described as “walking through a sandstorm”
- metabolizes to formaldehyde and formic acid resulting in HAGMA
- nausea, vomiting, abdominal pain
methanol
standard of care for ethylene glycol poisoning and methanol poisoning
fomepizole and dialysis
- is used as a solvent for IV LORAZEPAM
- caused by continuous infusion or large IV doses of lorazepam
- HAGMA w/ OG
propylene glycol
treatment for HAGMA
treat underlying cause
treatment for propofol-related infusion syndrome
- d/c propofol
- if AKI and severe acidosis; HD
treatment for salicylate poisoning
aggressive sodium bicarbonate therapy (protects CNS)
when should DKA be treated with bicarbonate?
pH less than 7.0
when should lactic acidosis be treated with bicarbonate?
pH less than 7.1
pyroglutamic acidosis is caused by?
chronic acetaminophen use
commonly results from VOLUME CONTRACTION caused by diuretics or vomiting/gastric suctioning
metabolic alkalosis
metabolic alkalosis always involves what 2 phases?
- generation phase = initial H+ loss or HCO3- gain)
- maintenance phase = failure of kidney to excrete HCO3- to correct the alkalosis
vomiting and NG suction leads to
HCl loss via GASTRIC secretions
primary hyperaldosteronism leads to
RENAL acid loss
diuretic-induced “contraction” alkalosis leads to
RENAL loss of bicarb-free FLUID –> reduction in ECF volume around fixed quantity of EC bicarbonate
metabolic alkalosis is MAINTAINED by
volume depletion, which leads to decreased distal Cl- delivery and high aldosterone levels
aldosterone enhances distal sodium reabsorption by activating what?
distal tubular Na+/H+ and Na+/K+ pumps
what is the expected urine pH in the setting of metabolic alkalosis?
LOW; “paradoxical aciduria”
what happens to K+ levels in metabolic alkalosis?
K+ shifts from extracellular space to intracellular space in exchange for H+
what are the 2 types of metabolic alkalosis?
- chloride responsive
- chloride resistant
what is elevated in metabolic alkalosis even though there is volume depletion and why?
- U(Na+) and FeNa+
- bc bicarbonaturia takes Na+ as accompanying cation
what is the expected urine Cl- in metabolic alkalosis in the setting of volume depletion and why?
- U(Cl-) less than 10 meq/L
- bc NaCl is desperately reabsorbed to maintain intravascular volume
if urine Cl- is greater than 10 meq/L think of (8)
- Cushing syndrome
- Bartter syndrome
- Gitelman syndrome
- primary hyperaldosteronism
- Liddle syndrome
- licorice ingestion
- severe hypokalemia
- increased intake of HCO3- (i.e. milk-alkali syndrome)
treatment for chloride-responsive alkalosis (urinary Cl- < 10 meq/L)
RESTORATION OF VOLUME and POTASSIUM CORRECTION
both interrupt aldosterone production, which is causing H+ and K+ in the distal tubule
treatment for SEVERE metabolic alkalosis (> 7.55)
HCl through central venous catheter in ICU
chloride resistant WITH HTN
- exogenous steroids
- endogenous steroids
(- primary hyperaldosteronism)
(- Cushing syndrome)
(- 11-OH deficiency)
(- Liddle syndrome)
chloride resistant withOUT HTN
- Bartter syndrome
- Gitelman syndrome
- surreptitious syndrome
list the 4 steps to interpreting acid-base disorders
- pH: determine is acidemic or alkalemic
- calculate AG
3a. calculate expected HCO3-
3b. expected HCO3- - measured HCO3-
4a. calculate expected pCO2
4b. compare expected pCO2 to actual pCO2 from the blood gas
what is the body’s main extracellular buffer?
bicarb
what happens to HCO3- as anions go up?
go down proportionally: about 1:1 ratio, but sometimes 1.6:1
if the MEASURED BICARBONATE is LESS, then what is expected?
NAGMA
if the MEASURED BICARBONATE is MORE, then what is expected?
METABOLIC ALKALOSIS
if the AG is elevated, then the expected bicarb =
[25 - (change in AG)]
in metabolic acidosis, the expected pCO2 =
15 + actual HCO3- from the chemistry
in metabolic alkalosis, the expected pCO2 increases by
0.7 mmHg for every 1 meq/L increase in HCO3-
if pCO2 is HIGHER than expected, then
respiratory ACIDOSIS
if pCO2 is LOWER than expected, then
respiratory ALKALOSIS
if HCO3- is less than 9, or greater than 40, then what happens to expected pCO2?
may be unreliable
in chronic respiratory acidosis, the serum bicarb does NOT increase above what?
38 meq/L
pCO2 greater than 55 usually suggests what?
an additional primary respiratory acidosis
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
acute hyperventilation episode
- acute respiratory alkalosis
- 7.56/20/90/22
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
acute asthma/PE/chest trauma
- acute respiratory alkalosis d/t hypoxia
- 7.56/20/50/24
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
CNS problem, chronic hyperventilation
- chronic respiratory alkalosis w/ metabolic compensation
- 7.44/25/90/16
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
COPD w/ chronic bronchitis
- chronic respiratory alkalosis w/ metabolic compensation w/ hypoxia
- 7.43/30/60/20
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
pt in transition to respiratory failure
- normal except hypoxia
- 7.40/40/50/24
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
sedative overdose
- acute respiratory acidosis
- 7.24/60/80/26
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
respiratory failure from hypoxia
- acute respiratory acidosis w/ hypoxia
- 7.16/70/50/25
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
emphysematous COPD
- respiratory acidosis w/ metabolic compensation
- 7.37/60/60/34
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
bicarbonate overdose
- metabolic alkalosis w/ respiratory compensation
- 7.44/60/90/39
expected ABGs with certain conditions:
(assuming consistent HCO3- and Cl-)
sepsis, ASA overdose, renal failure
- metabolic acidosis w/ respiratory compensation
- 7.36/28/90/15
what is normal serum osmolality?
282 +/- 2 mOsm/kg H2O
what is the common term for arginine vasopressin (AVP)?
antidiuretic hormone (ADH)
what are the most important mechanisms that regulate ADH levels?
- osmoreceptors in the hypothalamus
2. volume (stretch) receptors in the LA
what is the STRONGEST stimulant for ADH release?
significant VOLUME LOSS resulting in hypotension
what is CRITICAL in determining treatment for a pt w/ a sodium abnormality?
volume status
in general, if a pt is EDEMATOUS, what is the volume status?
volume OVERLOAD
if the pt has clinical signs of VOLUME LOSS, what is the volume status?
volume DEFICIT
if the pt is neither edematous, nor showing signs of volume loss, what is the volume status?
euvolemic
what are the clinical clues to hypovolemia?
- tachycardia
- narrowed pulse pressure
- orthostatic hypotension
- resting tachycardia w/ hypotension
- low central venous pressure
what is the MC electrolyte abnormality?
hyponatremia
how is hyponatremia further classified?
- ISOOSMOLAR
- HYPEROSMOLAR
- HYPOOSMOLAR
what is the 1st step after discovering hyponatremia?
determine serum osmolality
artifactual decrease in serum Na+ associated w/ older lab instruments
isoosmolar hyponatremia
both GLUCOSE and MANNITOL cause an osmotic shift of water OUT of cells, which dilutes plasma Na+
hyperosmolar hyponatremia
by far, the largest low-Na+ subgroup
hypoosmolar hyponatremia
low osmolality causes water movement into cells, leading to
INTRACELLULAR SWELLING
what can occur when Na+ falls ACUTELY (usually < 120)?
- neuromuscular excitability
- seizures
- coma
how is the hypoosmolar subgroup of hyponatremia further subdivided?
VOLUME status: low, high, and normal
serum sodium concentration is a ratio of total body sodium to water, which means the pt has more water relative to total body sodium; what are the 3 ways this can happen?
- loss of sodium
- true water excess
- total body sodium excess exceeded by water excess
what is the FIRST thing to do in a pt w/ hypotonic hyponatremia?
assess volume status (done clinically)
in a pt w/ hypotonic hyponatremia, what does volume status essentially reflect?
total body sodium content
why do LOW-VOLUME pts have hypotonic hyponatremia?
lose both water and Na+, but more Na+ than water
what are causes of hypotonic hypovolemic hyponatremia?
- diuretics
- GI losses (vomiting and diarrhea)
- third spacing of fluid
- adrenal insufficiency (Addison disease)
how does primary adrenal insufficiency cause hypotonic hypovolemic hyponatremia?
- cortisol and aldosterone deficiency
- low aldosterone = renal Na+ wasting, decreased K+ and H+ excretion resulting in hypovolemia (sometimes w/ hypotension), hyperkalemia, and metabolic acidosis
- low cortisol = stimulates ADH production
why do HIGH-VOLUME pts (w/ dependent EDEMA and JVD) have hypotonic hyponatremia?
retain water and Na+, but more water than Na+
what are causes of hypotonic hypervolemic hyponatremia?
- heart failure
- cirrhosis
- nephrotic syndrome
- kidney failure: acute or chronic
treatment for hypotonic hypervolemic hyponatremia
WATER and Na+ restriction
treatment for hypotonic hypervolemic hyponatremia if water and Na+ restriction are not enough
LITHIUM or DEMECLOCYCLINE = induce tubular resistance to ADH
what can worsen hypotonic hypervolemic hyponatremia by impairing urinary-diluting ability?
THIAZIDE diuretics
what type of diuretic can be very effective in the treatment of high-volume hyponatremia?
loop diuretics
what high-volume pt has a low GFR even w/ a normal creatinine and rapid diuresis can easily precipitate AKI?
cirrhotic pt
what are causes of hypotonic euvolemic hyponatremia?
- SIADH
- drugs that mimic ADH or release ADH
- psychogenic polydipsia
- hypothyroidism
- isolated glucocorticoid deficiency
causes of SIADH
- CNS disease (e.g. meningitis)
- lung disease (e.g. pneumonia)
- neoplasms (especially small cell lung cancer)
- drugs
MC drugs associated w/ SIADH
- NSAIDs
- SSRIs
- carbamazepine and oxcarbazepine
- psychotropic drugs: haloperidol, amitriptyline
- IV cyclophosphamide
- vincristine/vinblastine
- cisplatin
- chlorpropamide (now rarely used)
- ecstasy (methylenedioxymethamphetamine)
diagnosis for SIADH
compare urine and serum osmolalities (serum osm will be low, urine osm inappropriately high (> 250 mOsm/L))
serum and urine osms in psychogenic polydipsia
- serum osm = low
- urine osm = low (kidney is excreting free water by making dilute urine)
what is the mechanism for ADH release in moderate-to-severe hypothyroidism?
decreased cardiac output –> stimulates carotid baroreceptors
what should be r/o in all pts w/ hyponatremia before making a dx of SIADH, and why?
- hypothyroidism
- glucocorticoid deficiency
- both can cause low serum osmolalities and high urine osmolalities
what drug class can cause euvolemic low osmolality hyponatremia via ADH-related and non-ADH-related mechanisms?
thiazides
how can cause euvolemic low osmolality hyponatremia?
- inducing mild volume depletion –> stimulates ADH release
- impairs urinary dilution in early DISTAL tubule
what pt population is highly susceptible to thiazides impairing urinary dilution?
elderly pts
how is ASYMPTOMATIC hyponatremia treated?
based on etiology
treatment for normal serum osmolality hyponatremia
artifact, no treatment required
treatment for high serum osmolality hyponatremia
treat underlying cause (e.g. DKA)
treatment for low serum osmolality HYPOvolemic hyponatremia
normal saline to replenish deficit (watch for over-rapid correction!)
treatment for low serum osmolality HYPERvolemic hyponatremia
fluid restriction (about 800 cc/day) +/- loop diuretics
treatment for low serum osmolality euvolemic hyponatremia
treat SIADH w/ fluid restriction (about 800 cc/day)
treatment for refractory SIADH
ADH receptor antagonist (-vaptan; conivaptan, tolvaptan)
when are conivaptan, or tolvaptan used to treat SIADH?
severe, chronic hyponatremia (Na+ < 120 mg/dL)
what are the SEVERE symptoms of hyponatremia?
- lethargy
- confusion
- coma
- seizures
what is the treatment of hyponatremia if symptoms are SEVERE, and when should it be used?
- 100mL bolus of 3% saline (to quickly raise Na+ by 2-3 meq/L)
- if the pt is NOT hypovolemic
what correction rate should NEVER be exceeded when correcting for hyponatremia, and why?
- 9 MEQ/L OVER 24 HOURS
- risk of osmotic demyelination syndrome
treatment for severe symptoms of hyponatremia if symptoms persist after the initial bolus
2 more boluses of 3% saline in 10-minute intervals
treatment for MODERATE symptoms (confusion, lethargy) of hyponatremia and suspected SIADH
3% saline at initial rate of 0.5-1 mL/kg lean body weight/hour
in what pt is osmotic demyelination syndrome more likely to occur in?
pt w/ chronic, severe hyponatremia (Na+ < 115 meq/L for > 2 days) whose sodium is corrected rapidly (> 10 meq/L over 24 hours)
what are the symptoms of osmotic demyelination syndrome?
- speech and swallowing difficulties
- weakness, or paralysis
- cognitive deficits
- coma
- can cause severe and sometimes symptomatic hyponatremia
- reported in marathon runners
exercise-induced hyponatremia
severe hypernatremia is fairly rare but ALWAYS represents what?
WATER DEFICIT
unlike hyponatremia, hypernatremic pts are ALWAYS
HYPEROSMOLAR
what is the 1st step in a pt w/ hypernatremia?
determining volume status
treatment for severe hypovolemic hypernatremia
NORMAL SALINE first to correct volume deficit, then hypotonic fluids to further replace the water deficit
calculation for free water deficit
Vol(water) = total body water x ([Na+(serum) - 140]/140)
Vol(water) = 0.6 x body weight x ([Na+(serum) - 140]/140)
correction rate for hypernatremia
0.5 meq/L/hr or 10-12 meq/L/day
what can occur from too rapid a correction of any severe hyperosmolar state, such as hypernatremia, nonketotic hyperglycemic coma, and severe uremia?
cellular swelling
what can cellular swelling cause?
- cerebral edema
- seizures
- coma
causes of high-volume hypernatremia
- salt water drowning
- large amounts of sodium bicarbonate or hypertonic saline during ACLS
treatment for high-volume hypernatremia
loop diuretics and free water
causes of normal-volume hypernatremia
- diabetes insipidus (DI)
- reduced access to water (become hypernatremic) before developing volume depletion
what’s the Na+ level of a typical DI pt?
NORMAL or BORDERLINE-HIGH (bc they’re constantly drinking water)
primary complaint of a DI pt
polyuria and polydipsia
- pt w/ high Na+ and high urine volume
- h/o recent neurosurgery, head trauma, brain cancer/metastases
central DI
causes of nephrogenic DI
- can be hereditary (mutations in vasopressin 2 receptor or aquaporin 2 genes)
- hypercalcemia (serum Ca2+ > 11 mg/dL)
- chronic hypokalemia ( serum K+ < 3 meq/L)
- intrinsic renal disease (especially SJOGREN syndrome)
- drugs (especially LITHIUM)
what test not only diagnoses DI, but also differentiates between central and nephrogenic types?
water restriction test
in CENTRAL DI, even w/ water restriction, what happens to the ADH level and urine osmolality?
- ADH stays LOW
- urine is dilute
in a normal pt, what happens to the ADH level and urine concentration when the plasma osmolality increases to 295?
- ADH level is high
- urine is maximally concentrated (> 700 mOsm/L)
treatment for MILD cases of central DI
thiazides and salt restriction
treatment for PARTIAL central DI when desmopressin might be too potent or limited in supply
- chlorpropamide
- carbamazepine
treatment for resistant central DI
oral or intranasal desmopressin (synthetic vasopressin analog)
in NEPHROGENIC DI, what happens to the ADH level and urine osmolality w/ water restriction?
- ADH is appropriately high
- urine is DILUTE
treatment for nephrogenic DI
thiazide diuretics or amiloride
treatment for hereditary forms of nephrogenic DI
NSAIDs
URINE OSMOLALITY range
50-1,200 mOsm/L
what must be known in order to make sense of the urine osmolality?
URINE OUTPUT (L/d)
multiply osmolality by output (1 kg = 1 L)
what is a normal urine osmolality?
about 500
after glomerular filtration, the filtrate flows through which sections of tubules?
- proximal tubule
- loop of Henle
(- thin descending segment)
(- thin ascending segment)
(- thick ascending segment) - early distal tubule
- late distal tubule and cortical collecting duct
- medullary collecting duct
what is filtered in the proximal tubule?
65% of filtered Na+, Cl-, and water is reabsorbed
is water permeable in the proximal tubule?
yes, very permeable; is reabsorbed in 1:1 fashion w/ Na+ (filtrate volume is reduced along tubule)
name the transport channels in the proximal tubule
- counter-transport of Na+ (into interstitium) and H+ (into filtrate); via secondary active transport
- counter-transport of Na+ (into interstitium) and K+ (into filtrate); via ATPase active transport
- cotransport of Na+, Cl-, K+, glucose, amino acids (into interstitium)
- paracellular absorption of Ca2+, and other solutes
how is the Na+/H+ counter-transport channel in the PT stimulated and what drugs inhibit it?
- stimulated by angiotensin II
- CARBONIC ANHYDRASE INHIBITORS and THIAZIDES (slightly)
how much HCO3- is reabsorbed in PT?
90% of filtered HCO3- is reabsorbed indirectly by Na+/H+ counter-transport pump
for each H+ secreted, what is reabsorbed in the PT and how?
- one Na+ and one HCO3-
- H+ is counter-transported into filtrate –> combines w/ filtered HCO3- to form H2CO3 (carbonic acid) –> CA converts H2CO3 to H2O and CO2 –> CO2 is absorbed into tubular cells –> gets converted back to HCO3- –> HCO3- reabsorbed into interstitium
what also affects Na+/H+ counter-transporter?
POTASSIUM CONCENTRATION
how does hypOkalemia affect serum acid-base level?
stimulates H+ secretion –> stimulates bicarb reabsorption –> alkalosis
how does hypERkalemia affect serum acid-base level?
inibhits H+ secretion –> inhibits bicarb reabsorption –> acidosis
what are the clinical effects of proximal tubule damage?
- failure to REABSORB water
- failure to SECRETE ACID and REABSORB BICARBONATE = proximal (type 2) NAGMA
- failure to reabsorb solutes (Na+, Cl-, K+, glucose, aa) = Fanconi syndrome +/- hypokalemia
in the THIN descending segment, how much H2O moves from the filtrate into the interstitium? and, where is the maximum concentration of fluid?
- 20%
- base of the loop
WHY is the renal medulla very hypERtonic?
- in THIN ascending segment NaCl passively diffuses into interstitium
- in THICK ascending segment solutes ACTIVELY transported into interstitium
cotransport of Na+, 2 Cl-, and K+ (into interstitium) is INHIBITED by
LOOP diuretics
name the 4 loop diuretics
- furosemide
- bumetanide
- torsemide
- ethacrynic acid
at what GFR do loop diuretics REMAIN EFFECTIVE?
low GFR = CrCl < 20 (just have to increase dose and/or give IV)
which 2 loop diuretics are associated w/ permanent ototoxicity at high IV bolus doses?
- furosemide
- ethacrynic acid
what are the 2 mechanisms in which loop diuretics cause diuresis?
- prevent Na+ reabsorption in THICK ascending segment
2. prevent development of interstitial osmotic gradient in the THIN descending segment
when are LOOP DIURETICS used to treat hypercalcemia?
use is considered QUESTIONABLE, UNLESS becomes VOLUME OVERLOAD
cotransport of Na+ and Cl- (into interstitium) in the EARLY distal tubule is inhibited by
thiazide diuretics
name the 4 thiazide diuretics
- chlorothiazide
- hydrochlorothiazide
- chlorthalidone
- metolazone
why are thiazide diuretics less effective at an extremely low GFR?
have to be secreted INTO filtrate
how do thiazides cause hypOkalemia?
slightly inhibit carbonic anhydrase in proximal tubule –> increased delivery of Na+ to early distal tubule –> upregulation of Na/K ATPase counter-transport channel
which diuretics INCREASE CALCIUM REABSORPTION?
thiazides
can help in reducing urinary calcium in pts w/ kidney stones
thiazides
allow for further solute and water reabsorption and are controlled by ALDOSTERONE and ADH
LATE DISTAL tubule and CORTICAL COLLECTING DUCT
2 cell types in the LATE DISTAL tubule and CORTICAL COLLECTING DUCT that reabsorb solutes
- principal cells
2. intercalated cells
what gets counter-transported in the principal cells?
Na+ (into interstitium) and K+ (into filtrate)
what stimulates principal cells in the LATE DISTAL tubule and CORTICAL COLLECTING DUCT?
- aldosterone
- hyperkalemia
what inhibits principal cells in the LATE DISTAL tubule and CORTICAL COLLECTING DUCT?
potassium-sparing diuretics (amiloride, triamterene, spironolactone, eplerenone)
what gets secreted in the intercalated cells?
H+ (into filtrate)
what controls water reabsorption in the LATE DISTAL tubule and CORTICAL COLLECTING DUCT?
ADH which stimulates AQUAPORINS
name 2 diseases that affect the last distal tubules and cortical collecting ducts
- distal (type 1 RTA)
- distal (type 4 RTA)
- impairment of H+-ATPase active transport pump in intercalated cells –> inability to secrete acid (and reabsorb bicarb)
- urine pH is always > 5.3
distal (type 1 RTA) NAGMA
- tubular aldosterone resistance –> impairment of Na+/K+ ATPase counter-transporter
- HYPERKALEMIA
- can also occur in DM
distal (type 4 RTA) NAGMA
where is the remaining 10% of Na+ and water absorbed?
medullary collecting duct
in the absence of ADH, which segments of the nephron are relatively impermeable to water?
LATE DISTAL tubule and CORTICAL COLLECTING DUCT
- name 2 ADH-receptor antagonists
- sometimes used to treat hypOnatremia
- conivaptan (IV only)
- tolvaptan (PO)
- problem in H+-ATPase
- failure to acidify urine
- HYPOkalemia
- hypercalciuria +/- nephrocalcinosis
distal (type 1) RTA
MCC of distal (type 1) RTA
- genetic (presents in childhood)
- autoimmune (Sjogren’s, SLE, RA)
- hereditary hypercalciuria
- drugs (amphotericin B, lithium)
treatment for distal (type 1) RTA
- NaHCO3
- K+ replacement
- tx underlying cause
- problem w/ cells in PROXIMAL tubule –> BICARBONATE WASTING
- also, problems w/ cotransport of Na+ w/ glucose, aa, Cl-, and K+
proximal (type 2) RTA
MCC of proximal (type 2) RTA
- monoclonal gammopathies (MM) w/ buildup of light chains that damage tubule cells
- CA inhibitors
treatment for proximal (type 2) RTA
- bicarbonate (very large doses)
- K+ replacement
- vitamin D supplementation
- HYPORENINEMIC HYPOALDOSTERONISM (or ALDOSTERONE RESISTANCE) in the principal cells of the late distal tubule and cortical collecting duct
- nonfunctioning Na+/K+ ATPase counter-transport
- associated w/ HYPERkalemia
type 4 (distal) RTA
causes of hyporeninemic hypoaldosteronism (3)
- diabetic nephropathy
- obstructive uropathy
- chronic interstitial nephritis
common drugs that can lead to hyperkalemic metabolic acidosis SIMILAR to type 4 (distal) RTA
- spironolactone
- ACEIs/ARBs
- NSAIDs (exacerbates a concurrent hyporeninemic state)
treatment for type 4 (distal) RTA
- dietary potassium restriction
- or bicarbonate administration
- furosemide if 1st 2 don’t work
- HYPERCALCIURIA
- +/- NEPHROCALCINOSIS
- high urine pH
- HYPOKALEMIA
type 1 (distal) RTA
- BICARBONATE WASTING
- FANCONI’S
- urine pH and serum K+ are variable
- think MYELOMA
type 2 (proximal) RTA
- ALDOSTERONE DEFICIENCY or RESISTANCE
- mild acidosis
- HYPERkalemia
- think causes of hyporeninemic hypoaldosteronism (interstitial disease, diabetes, NSAIDs, ACEIs)
type 4 (distal) RTA
which chemistry profile is associated w/ the following clinical scenario?
- DKA
A) Na+ 140 K+ 2.6 Cl- 113 HCO3- 17 urine pH 7.9 urine K+ 50 urine Na+ 100
B) Na+ 140 K+ 5.5 Cl- 117 HCO3- 13 urine pH 6 urine K+ 50 urine Na+ 100
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
D) Na+ 140 K+ 4 Cl- 105 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
E) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 10 urine Na+ 10
D) Na+ 140 K+ 4 Cl- 105 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
which chemistry profile is associated w/ the following clinical scenario?
- pt w/ DM and CKD
A) Na+ 140 K+ 2.6 Cl- 113 HCO3- 17 urine pH 7.9 urine K+ 50 urine Na+ 100
B) Na+ 140 K+ 5.5 Cl- 117 HCO3- 13 urine pH 6 urine K+ 50 urine Na+ 100
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
D) Na+ 140 K+ 4 Cl- 105 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
E) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 10 urine Na+ 10
B) Na+ 140 K+ 5.5 Cl- 117 HCO3- 13 urine pH 6 urine K+ 50 urine Na+ 100
which chemistry profile is associated w/ the following clinical scenario?
- pt w/ myeloma
A) Na+ 140 K+ 2.6 Cl- 113 HCO3- 17 urine pH 7.9 urine K+ 50 urine Na+ 100
B) Na+ 140 K+ 5.5 Cl- 117 HCO3- 13 urine pH 6 urine K+ 50 urine Na+ 100
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
D) Na+ 140 K+ 4 Cl- 105 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
E) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 10 urine Na+ 10
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
which chemistry profile is associated w/ the following clinical scenario?
- woman w/ nephrolithiasis
A) Na+ 140 K+ 2.6 Cl- 113 HCO3- 17 urine pH 7.9 urine K+ 50 urine Na+ 100
B) Na+ 140 K+ 5.5 Cl- 117 HCO3- 13 urine pH 6 urine K+ 50 urine Na+ 100
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
D) Na+ 140 K+ 4 Cl- 105 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
E) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 10 urine Na+ 10
A) Na+ 140 K+ 2.6 Cl- 113 HCO3- 17 urine pH 7.9 urine K+ 50 urine Na+ 100
which chemistry profile is associated w/ the following clinical scenario?
- pt w/ heavy metal poisoning
A) Na+ 140 K+ 2.6 Cl- 113 HCO3- 17 urine pH 7.9 urine K+ 50 urine Na+ 100
B) Na+ 140 K+ 5.5 Cl- 117 HCO3- 13 urine pH 6 urine K+ 50 urine Na+ 100
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
D) Na+ 140 K+ 4 Cl- 105 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
E) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 10 urine Na+ 10
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
which chemistry profile is associated w/ the following clinical scenario?
- pt w/ chronic diarrhea
A) Na+ 140 K+ 2.6 Cl- 113 HCO3- 17 urine pH 7.9 urine K+ 50 urine Na+ 100
B) Na+ 140 K+ 5.5 Cl- 117 HCO3- 13 urine pH 6 urine K+ 50 urine Na+ 100
C) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
D) Na+ 140 K+ 4 Cl- 105 HCO3- 15 urine pH 6 urine K+ 50 urine Na+ 100
E) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 10 urine Na+ 10
E) Na+ 140 K+ 4 Cl- 115 HCO3- 15 urine pH 6 urine K+ 10 urine Na+ 10
any situation that causes aldosterone to be released (or mimics aldosterone), will have what effect on K+?
LOWERS it
situations that cause aldosterone release (4)
- increased renin d/t decreased effective arterial blood volume
- volume depletion (GI losses, diuretics)
- decreased renal perfusion (HF, renovascular dz, NSAIDs) - increased renin d/t inappropriate release
- renin-secreting renal tumors - increased aldosterone d/t inappropriate release
- B/L adrenal hyperplasia
- aldosterone-secreting adrenal adenoma - increased excretion of hormone w/ aldosterone-like effects
- Cushing syndrome
any situation that INHIBITS aldosterone release or action, will have what effect on K+?
INCREASES it
situations that cause aldosterone release (4)
- K+-sparing diuretics (spironolactone blocks aldosterone receptor; amiloride blocks the channel its action depends on)
- dysfunctional kidneys that do not release renin (chronic interstitial nephritis, DM, exacerbated by NSAIDs)
- ACEIs, ARBs, renin inhibition
- only primary adrenal disease (Addison’s) [NOT secondary adrenal insufficiency]
- heparins (both UFH and LMWH) (directly toxic to zona glomerulosa)
what increase K+ uptake causing hypOkalemia?
- alkalosis
- beta-agonists
- insulin
what decrease K+ uptake causing hypERkalemia?
- acidosis
- alpha-agonists
what electrolyte abnormality can cause alkalosis?
hypOkalemia
what electrolyte abnormality can cause acidosis?
hypERkalemia
conditions leading to increased cell turnover associated w/ hypERkalemia (3)
- tumor lysis syndrome
- rhabdomyolysis
- acute leukemia
medication that interferes w/ K+ secretion in principal cells (late distal tubule and cortical collecting duct) causing hypERkalemia
trimethoprim in TMP/SMX
RTA associated w/ hypOkalemia for unclear reasons
type 1 (distal) RTA
block absorption of solutes and water causing hypOkalemia
loop and thiazide diuretics
drugs associated w/ renal K+ wasting causing hypOkalemia
- cisplatin
- penicillins
genetic syndromes associated w/ hypOkalemia (3)
- Liddle’s
- Barter’s
- Gitelman’s
presentation of hypERkalemia (signs/symptoms)
- significant weakness or paralysis
- conduction abnormalities
- arrhythmias
if a pt is weak d/t hypERkalemia, will there be EKG changes?
yes, but the opposite is not necessarily true
name the sequence of EKG changes w/ progressive hypERkalemia
- peaked T wave and short QT interval, then
- progressive lengthening of PR and QRS intervals, then
- loss of P wave, and QRS widening into sine wave, then
- ventricular fibrillation or cardiac standstill
treatment for acute hypERkalemia w/ EKG changes
- IV calcium gluconate (or CaCl if pt has central line)
- insulin w/ glucose
- NaHCO3 (if acidosis is present)
- albuterol nebulization/injection
- loop diuretics (in pts who make urine)
- dialysis
when calcium gluconate not be given for the treatment of hypERkalemia?
pts on digoxin
sodium polystyrene sulfonate (SPS; Kayexalate) in sorbitol (MC preparation) has been associated w/?
colon necrosis
especially w/i a week after surgery and pts w/ ileus
when should hypERkalemia be treatment even w/o symptoms or EKG changes?
6.5 or more
what hypERkalemia treatment can cause edema and may precipitate cardiac decompensation?
NaHCO3
signs and symptoms of severe hypOkalemia
- U waves
- decreased tendon reflexes
- rhabdomyolysis
at what net loss of K+ will serum K+ decrease?
200-300 meq
what comorbid electrolyte deficiency can cause renal K+ wasting?
magnesium
caused by disease in the adrenal gland
primary hyperaldosteronism
caused by disease in the kidneys or a restricted blood flow in the renal arteries
secondary hyperaldosteronism
mechanism of secondary hyperaldosteronism
decreased renal blood flow –> increased renin –> increased angiotensin II –> increased aldosterone
what should be considered in a pt w/ hypokalemia w/o an obvious cause, HTN, and metabolic alkalosis?
hyperaldosteronism
- HTN
- hypOkalemic metabolic alkalosis
- primary Na+ retention
- rare genetic mutation activating the epithelial Na+ channel in principal cells of the late distal tubule and cortical collecting duct
- decreased renin and aldosterone levels
Liddle syndrome
name 2 syndromes that are d/t rare genetic or sporadic defects that cause abnormal solute transport in the THICK ASCENDING segment and EARLY DISTAL TUBULE
- Bartter syndrome
2. Gitelman syndrome
- 4 types
- typically AR
- clinically, pts look like they’re taking a loop diuretic
- onset = infants/children
- type 4 is associated w/ deafness
- HYPERcalciuria/nephrocalcinosis
- hypOkalemic, METABOLIC ALKALOSIS
Bartter syndrome
- defect in Na+/Cl- cotransporter in early distal tubule
- clinically, pts look like they’re taking a thiazide diuretic
- some pts have SEVERE MAGNESIUM WASTING
- onset = early adults
- present w/ sxs of muscle weakness, cramps, and spasms d/t hypomagnesemia
- HYPOcalciuria
- hypOkalemic, METABOLIC ALKALOSIS
Gitelman syndrome
clinical approach to hypOkalemia
- hypokalemia and NAGMA WITHOUT HTN
- hypokalemia and metabolic alkalosis AND HTN
- hypokalemia and metabolic alkalosis WITHOUT HTN
causes of hypokalemia and NAGMA WITHOUT HTN (3)
- diarrhea
- type 1 (distal) RTA
- type 2 (proximal) RTA
causes of hypokalemia and metabolic alkalosis AND HTN (5)
- diuretics (MC)
- hyperaldosteronism (primary or secondary)
- Cushing syndrome
- Liddle syndrome
- adrenal hydroxylase deficiencies
causes of hypokalemia and metabolic alkalosis WITHOUT HTN (2)
- Bartter syndrome
- Gitelman syndrome
hypERcalcemia found incidentally in an asymptomatic pt is usually d/t
- THIAZIDE diuretics or
- PRIMARY HYPERPARATHYROIDISM (especially if h/o NECK IRRADIATION)
most common causes of hypOcalcemia (5)
- vitamin D deficiency
- CKD
- severe pancreatitis
- rhabdomyolysis
- hypermagnesemia
less common causes of hypOcalcemia (4)
- hungry bone syndrome following parathyroidectomy
- hypoparathyroidism
- pseudohypoparathyroidism
- citrate
both increased and decreased magnesium can cause
hypOcalcemia
how does increased calcium affect magnesium?
hypOmagnesemia
hypOmagnesemia has what effect on K+?
hypOkalemia
causes of hypOmagnesemia (VERY COMMON electrolyte abnormality) (9)
- GI disease
- kidney losses (especially tubular disease)
- medications that affect the tubules
- PPIs
- hungry bone syndrome
- alcohol abuse
- post-surgical state
- foscarnet (d/t chelation)
- hypERcalcemia
clinical manifestations of hypOmagnesemia
- muscle weakness, spasms, tetany
- wide QRS
- peaked T waves
depleted magnesium STORES, even w/ a NORMAL serum LEVEL are associated w/ what?
REFRACTORY cardiac arrhythmias
how many meq of Mg++ are in 1G?
8.12 meq
causes of hypERmagnesemia (RARE)
- Mg-containing laxatives, antacids, enemas in pts w/ renal failure (CONTRAINDICATED)
- over-infusion during eclampsia tx
- less common: TLS, milk-alkali syndrome, lithium overdose, Epsom salts ingestion
when do sxs from hypERmagnesemia occur?
> 4-6 meq/L
clinical manifestations of hypERmagnesemia
nausea initially –> sedation –> muscle WEAKNESS –> loss of DTRs –> paralysis (including heart/respiratory mm)
treatment for hypERmagnesemia
- IVF and Ca2+
- HD in renal failure
ACUTE increases of phosphate causing hypERphosphatemia (3)
- ATN (especially if d/t rhabdo)
- IV solutions
- rapid cell turnover (tumor lysis or acute leukemia)
CHRONIC increases of phosphate causing hypERphosphatemia (2)
- CKD
- hypOparathyroidism
causes of hypOphosphatemia
- think ALCOHOLISM and ALCOHOLIC KETOACIDOSIS
- REFEEDING syndrome
clinical manifestations of severe hypOphosphatemia (if PO4 < 1 mg/dL)
- rhabdomyolysis
- cardiomyopathy
- respiratory insufficiency (diaphragm function failure)
- irritability and hyperventilation –> profound muscle weakness –> seizures –> coma –> death
volume contraction: vomiting
choose the correct answer
a. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 10 urine calc osm 700
b. Na+ low-NL Cl- 115 HCO3- 15 urine Cl- 10 urine calc osm 700
c. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 100 urine calc osm 700
d. Na+ low-NL Cl- NL HCO3- NL urine Cl- 100 urine calc osm 300 (but high volume)
a. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 10 urine calc osm 700
volume contraction: diarrhea
choose the correct answer
a. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 10 urine calc osm 700
b. Na+ low-NL Cl- 115 HCO3- 15 urine Cl- 10 urine calc osm 700
c. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 100 urine calc osm 700
d. Na+ low-NL Cl- NL HCO3- NL urine Cl- 100 urine calc osm 300 (but high volume)
b. Na+ low-NL Cl- 115 HCO3- 15 urine Cl- 10 urine calc osm 700
volume contraction: thiazides
choose the correct answer
a. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 10 urine calc osm 700
b. Na+ low-NL Cl- 115 HCO3- 15 urine Cl- 10 urine calc osm 700
c. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 100 urine calc osm 700
d. Na+ low-NL Cl- NL HCO3- NL urine Cl- 100 urine calc osm 300 (but high volume)
c. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 100 urine calc osm 700
volume contraction: osmotic diuretics
choose the correct answer
a. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 10 urine calc osm 700
b. Na+ low-NL Cl- 115 HCO3- 15 urine Cl- 10 urine calc osm 700
c. Na+ low-NL Cl- 95 HCO3- 35 urine Cl- 100 urine calc osm 700
d. Na+ low-NL Cl- NL HCO3- NL urine Cl- 100 urine calc osm 300 (but high volume)
d. Na+ low-NL Cl- NL HCO3- NL urine Cl- 100 urine calc osm 300 (but high volume)
volume contraction
VOMITING causes metabolic ALKALOSIS and:
- low serum Cl-
- hypOkalemia d/t aldosterone
volume contraction
DIARRHEA causes metabolic ACIDOSIS (NAGMA) and:
- appropriately high serum Cl-
- Cl- is reabsorbed to make up for HCO3- loss
THIAZIDE diuretics also cause metabolic ALKALOSIS w/ low serum Cl-, but has what effect on urinary Cl-?
HIGH
when do DIABETES INSIPIDUS pts become hypERnatremic?
only pts who are unable to drink
usually have a NORMAL intravascular volume and Na+ concentration
how is HTN diagnosed?
2 or more readings taken on 2 or more visits
what is stage ONE HTN?
SBP 140-159, or DBP 90-99
what is stage TWO HTN?
SBP 160 or more, or DBP 100 or more
in any stage of HTN, which sex and race has a higher morbidity and mortality?
- MEN
- BLACKS
when should you f/u or w/u?
- DBP < 85
recheck in 2-3 years
when should you f/u or w/u?
- 85-90
recheck in 1 year
when should you f/u or w/u?
- 90-104
recheck w/i 2 months
when should you f/u or w/u?
- 105-114
w/u w/i 2 weeks
when should you f/u or w/u?
- > 115
w/u immediately
standard evaluation for newly diagnosed HTN
- major cardiovascular disease risk factors
- IDENTIFIABLE CAUSES of HTN
list the IDENTIFIABLE CAUSES of HTN (8)
- pheochromocytoma
- renovascular HTN
- coarctation of aorta
- polycystic kidneys
- renal parenchymal disease
- hyperparathyroidism
- granulomatous disease
- hyperaldosteronism
- labile HTN
- medullary thyroid cancer
- primary hyperparathyroidism (MEN2)
pheochromocytoma
- HTN
- continuous abdominal bruit
renovascular HTN (renal artery stenosis or fibromuscular dysplasia)
- HTN
- decreased BP in LEs or absent/delayed femoral pulses
coarctation of aorta
- HTN
- abdominal or flank masses
polycystic kidneys
- HTN
- elevated creatinine or abnormal UA
renal parenchymal disease
- HTN
- hypercalcemia
- hyperparathyroidism
- granulomatous disease
- HTN
- hypokalemia
hyperaldosteronism
what are the indications for evaluation of secondary HTN?
- abnormal initial lab tests (hypERcalcemia/hypOkalemia)
- abrupt onset
- onset at age < 30 yoa or > 55 yoa
- malignant HTN
- refractory HTN (BP > target despite 3 meds, one being a diuretic)
MCC of secondary HTN
renovascular HTN (renal artery stenosis or fibromuscular dysplasia)
- treatment for HTN w/
- edema w/ HF or CKD
loop diuretic
- treatment for HTN w/
- systolic dysfunction and low EF or problems w/ hypokalemia
spironolactone
what dose of HCTZ provides the greatest antihypertensive effect?
12.5 mg
which antihypertensive medication can cause severe hypOnatremia in pts w/ poor solute intake; especially the elderly?
thiazide diuretics
how does angiotensin II increase BP?
- DIRECT VASOCONSTRICTION
- potentiation of the SYMPATHETIC NERVOUS SYSTEM
- increasing Na+ reabsorption in the proximal tubule
- stimulation of ALDOSTERONE PRODUCTION by the ADRENAL GLAND
name the 10 ACEIs
- captopril
- enalapril
- benazepril
- fosinopril
- lisinopril
- quinapril
- moexipril
- ramipril
- perindopril
- trandolapril
MOA of ACEIs
inhibit angiotensin-converting enzyme
MOA of ARBs
block angiotensin receptors, which blocks angiotensin II effect
what effect do ACEIs/ARBs have on the glomerulus?
DILATION OF EFFERENT arteriole –> decreased glomerular capillary pressure
what decreases progression of both DIABETIC and HYPERTENSIVE nephropathies, and other types of CKD?
decreased glomerular pressure
name the 7 ARBs
- candesartan
- eprosartan
- irbesartan
- losartan
- olmesartan
- telmisartan
- valsartan
what are the absolute INDICATIONS for ACEIs/ARBs? (4)
- systolic dysfunction
- h/o STEMI
- anterior NSTEMI
- CKD (especially w/ proteinuria)
complications of ACEIs
- increase in serum K+ by 0.5 meq/L
- renal function decline
when do you stop ACEI or ARB?
- creatinine increases to > 30% over baseline
- and/or serum K+ is uncontrollable
ACEIs + what combination is particularly noteworthy for complications?
HF and sudden initiation of NSAIDs
up to 20% of pts have to stop ACEIs because of
COUGH
what is a possible FATAL adverse effect of ACEIs?
angioedema
ACEIs/ARBs are absolutely CI in _____ bc they are?
- pregnancy
- TERATOGENIC
ACEIs/ARBs should be avoided in which pts?
hyperkalemic pts
ACEIs/ARBs should be used w/ caution in which pts?
- B/L RAS
- HF
- ADPKD
- hypertensive nephrosclerosis
what is ALISKIREN?
renin inhibitor; acts similarly to ACEIs/ARBs
aliskiren plus an ACEI or ARB in type 2 diabetics showed an increased risk in?
- stroke
- hyperkalemia
- low BP
- renal insufficiency
what are the 2 types of CCBs?
- dihydropyridines
- non-dihydropyridines
name the dihydropyridine CCBs (6)
- amlodipine
- clevidipine
- felodipine
- isradipine
- nicardipine
- nisoldipine
name the non-dihydropyridine CCBs (2)
- verapamil
- diltiazem
CCBs are used to treat what?
- HTN
- angina
- arrhythmias
what are the complications of CCBs?
significant EDEMA (especially w/ dihydropyridines), and CONSTIPATION (especially w/ non-dihydropyridines)
several studies have shown adverse associations (e.g. increased risk of death post-MI) w/?
short-acting CCBs (but not long-acting ones)
may increase proteinuria in pts w/ DM and CKD
dihydropyridines (but not verapamil or diltiazem)
are NOT recommended as 1st line treatment for HTN
BBs
some indications for BBs
- post-MI
- stable HF
- AF (rate control)
- angina
try to AVOID BBs in pts w/
- reactive airway disease
- frequent hypoglycemic episodes
- hyperlipidemia
- PVD
HTN treatment:
- general NONblack population
- +/- DM
- THIAZIDE
- CCB
- ACEI/ARB
HTN treatment:
- BLACK population
- +/- DM
- THIAZIDE
- CCB
in HEART FAILURE, treat HTN w/
- thiazide-type diuretic
bottom line for HTN treatment
- use any drug or drug combination w/ fewest side effects to get BP < 140/90 (< 150/90 if > 60 yoa)
which antihypertensive is NOT recommended as monotherapy d/t increased risk of STROKE and HEART DISEASE?
BB
monotherapy w/ a thiazide, ACEI/ARB, or long-acting CCB is fine for pts w/?
MILD HTN
blacks do better w/ which antihypertensives?
thiazide or long-acting CCB
young pts do best w/ which antihypertensives?
ACEI
pts who are NOT controlled w/ monotherapy usually do better w/?
LOW-DOSE 2nd DRUG
when should pts INITIALLY be treated w/ 2 drugs?
BP > 160/100
what are the lifestyle guidelines for preventing and controlling HTN?
- smoking cessation
- lose weight/DASH diet
- regular aerobic activity
- moderate alcohol and Na+ intake
- sufficient K+, Mg++, and Ca++ intake
- reduce saturated and cholesterol intake
JNC 8 goals of treatment are based on
- AGE
- DM
- CKD
BP goals of treatment
- general population < 60 yoa
< 140/90
BP goals of treatment
- general population > 60 yoa
< 150/90
BP goals of treatment
- all ages, NO CKD, diabetes
< 140/90
BP goals of treatment
- all ages, CKD, with/without DM
< 140/90
elderly persons generally have what type of HTN?
ISOLATED SYSTOLIC
should pts > 80 yoa w/ isolated systolic HTN be treated?
YES
if pharmacologic treatment for high BP in pts > 60 yoa leads to BP < 140 and is well tolerated, does it need to be adjusted?
no
what is malignant HTN?
HTN w/:
- papilledema, retinal hemorrhages, exudates
- nephrosclerosis (AKI, proteinuria, hematuria)
what is hypertensive encephalopathy?
severe HTN w/ signs of cerebral edema
presents as HA, N/V, confusion, coma, and/or seizures
treatment goal for hypertensive crisis
decrease DBP to 100-105 mmHg w/i 2-6 hours w/o dropping BP by > 25%
when treating a hypertensive crisis, TOO RAPID of drop in BP can result in
- ischemic stroke
- MI
MCC of secondary HTN
renovascular disease causing secondary hyperaldosteronism
2 main causes of renovascular HTN
- atherosclerotic RAS (often BILATERAL, mainly MEN > 50, especially diabetics)
- fibromuscular dysplasia (also often BILATERAL, mainly WOMEN < 40)
strongly suggestive of renovascular HTN (especially w/ other risk factors; > 55 yoa, diabetic)
- continuous abdominal bruit
- hypOkalemia
which pts should be worked up for renovascular HTN?
- have a moderate-to-high risk for disease
- are candidates for intervention (surgery, or angioplasty w/ stent placement)
if POTASSIUM levels are NORMAL, screen pts for secondary HTN w/?
- imaging studies
- CTA
- MRA
- duplex Doppler US
which pts w/ secondary HTN d/t renovascular disease are almost always candidates for intervention?
FIBROMUSCULAR DYSPLASIA, bc they can frequently be CURED
when atherosclerotic renal artery stenosis be considered for intervention?
ONLY if ONE of the following criteria is met:
- uncontrolled BP despite 3 or more meds
- recurrent “flash” pulmonary edema
- renal salvage (progressive decline in renal function)
should elderly pts be screened for secondary HTN?
definitely DO NOT SCREEN if mild HTN and normal serum K+
pts w/ possible secondary HTN, if the serum K+ is:
NORMAL, what is the next step?
go straight to imaging:
- CTA
- MRA
- duplex Doppler US
pts w/ possible secondary HTN, if the serum K+ is:
LOW, what is the next step?
screen for primary hyperaldosteronism:
- PAC:PRA (plasma aldosterone concentration to plasma renin activity) ratio
pts w/ possible secondary HTN, who are NOT candidates for intervention:
what is the next step?
do NOT screen
what is the GOLD STANDARD for renovascular HTN?
ARTERIOGRAPHY
pt not on diuretics, hypOkalemia of unknown etiology, and HTN, suspect?
primary or secondary hyperaldosteronism
what are the 2 main causes of primary hyperaldosteronism?
- adrenal adenomas (70%; Conn syndrome)
2. idiopathic B/L adrenal hyperplasia (25%)
screening and diagnosis of primary hyperaldosteronism
PAC:PRA (plasma aldosterone concentration to plasma renin activity) ratio
next step after diagnosing primary hyperaldosteronism w/ PAC:PRA ratio
CT scan of adrenals to characterize the gland
PAC:PRA ratio indicating primary hyperaldosteronism
> 20
in a suspected primary hyperaldosteronism pt, how can you assess whether you can suppress aldosterone?
recheck aldosterone level after either fluid or salt loading
initial treatment of primary hyperaldosteronism
- salt and water restriction
- K+ sparing diuretics (spironolactone, triamterene, amiloride)
- +/- thiazide diuretic
- cause of secondary HTN
- VERY RARE
- 90% occur in adrenal MEDULLA
- 90% U/L
- 90% BENIGN
- 90% SPORADIC
pheochromocytoma
paroxysmal signs and symptoms of pheochromocytoma
- palpitations
- dizziness
- HTN
how many pts w/ pheochromocytoma have SUSTAINED HTN?
1/2-2/3
diagnosis of pheochromocytoma if low-pretest probability
24-hour urine for fractionated metanephrines and catecholamines
diagnosis of pheochromocytoma in higher risk pts (family h/o pheo, MEN2, NF)
screen w/ fractionated metanephrines on RANDOM PLASMA sample
next step in diagnosis for pheochromocytoma if biochemical tests are suggestive
CT or MRI w/ contrast
test to diagnose pheochromocytoma if imaging is negative and you still suspect pheo
metaiodobenzylguanidine scintigraphy (norepinephrine analog that concentrates in adrenal pheo)
what should BP always be in pregnancy?
< 120/80
what are the 4 categories of HTN in pregnancy?
- chronic HTN
- preeclampsia
- gestational HTN
- chronic HTN w/ superimposed preeclampsia
define chronic HTN in pregnancy
preexisting HTN or HTN BEFORE 20th WEEK of gestation
define preeclampsia in pregnancy
HTN + proteinuria AFTER 20th WEEK of gestation in woman w/o h/o HTN
define gestational HTN in pregnancy
HTN AFTER 20th WEEK of gestation WITHOUT proteinuria in woman w/o h/o HTN
define chronic HTN w/ superimposed preeclampsia in pregnancy
worsening HTN + NEW ONSET proteinuria AFTER 20th WEEK of gestation WITH h/o controlled, chronic HTN
define eclampsia
grand mal seizures in a woman w/ preeclampsia or gestational HTN
what are the defining features of preeclampsia?
proteinuria and HTN, not symptoms
what an indication of preeclampsia severity?
signs and symptoms
what are the signs and symptoms of preeclampsia?
- HA
- vision changes
- seizures
- low platelets
- stroke
- intracerebral hemorrhage
- pulmonary edema
- hepatic and/or renal failure
- placental abruption
what is HELLP syndrome?
severe form of preeclampsia
- Hemolytic anemia
- Elevated Liver enzymes
- Low Platelets
what are the risk factors for preeclampsia?
- DM
- chronic HTN
- multiple gestations (twins, triplets)
- h/o preeclampsia
what medication should be given in pregnant women w/ moderate-to-high risk for preeclampsia?
- reduces preeclampsia risk by 24%
- reduces premature birth risk by 14%
- reduces intrauterine growth restriction risk by 20%
aspirin 81mg PO daily
BP goal for SEVERE HTN in pregnancy regardless of category
< 160/110
recommendations to start BP treatment for preeclampsia
- if symptoms are present
2. asymptomatic w/ SBP 150 or more, or DBP 95 or more
target BP in preeclampsia
130-150/80-100
what BP medications need to be d/c’d for chronic hypertensives thinking about getting pregnant
- ACEIs/ARBs
- thiazides
BP meds of choice in pregnancy
- a-methyldopa
- labetalol
- nifedipine
parenteral antihypertensives of choice in malignant HTN in pregnancy
- labetalol (preferred)
- hydralazine
- nicardipine (2nd line)
antihypertensives C/I in pregnancy
- ACEIs/ARBs
- renin inhibitors
- nitroprusside (cyanide poisoning in the baby)
what are the 1ST LINE PO agents used to treat:
- CHRONIC, asymptomatic preeclampsia
- GESTATIONAL HTN
- and CHRONIC HTN in pregnancy
- LABETALOL
- A-METHYLDOPA
- XR-NIFEDIPINE
what are the 2ND LINE PO agents used to treat:
- CHRONIC, asymptomatic preeclampsia
- GESTATIONAL HTN
- and CHRONIC HTN in pregnancy
- DILTIAZEM
- VERAPAMIL
- THIAZIDES (watch for s/s of volume contraction; including oligohydramnios)
other important secondary causes of HTN that must be excluded
- OCPs
- coarctation of the aorta
- treatment of obesity
- decreasing alcohol intake to 2 drinks or less/day
- correcting CALCIUM or POTASSIUM deficiency
AKI can be
- non-oliguric
- oliguric
- anuric
definition of AKI
- increase in serum Cr by 0.3 mg/dL
- 1.5-fold over baseline w/i 48 hours
- or oliguria (UO < 0.5 mL/kg/hour) for at least 6 hours
define ANURIA
UO < 50 mL/DAY
PRErenal AKI is caused by
UNDERPERFUSION, either from:
- true volume loss
- or decreased effective arterial blood volume
POSTrenal AKI is caused by
OBSTRUCTION w/i urinary system
INTRINSIC AKI is caused by
problem w/:
- glomeruli
- tubules
- interstitium
prerenal AKI is ALWAYS d/t a real or “effective”
DECREASE in renal BLOOD FLOW:
- severe intravascular volume loss from volume depletion, blood loss, hypOtension, or diuretics
- RAS or FMD
- systolic dysfunction (CRS)
- NSAIDs or posttransplant immunosuppression drugs
- hepatorenal syndrome
- abdominal compartment syndrome
NSAIDs can cause AKI by causing CONSTRICTION of the
AFFERENT arteriole decreasing GFR
evidence of portal HTN (ascites, esophageal varices, splenomegaly, leukopenia, thrombocytopenia, anemia) and jaundice w/ AKI, think
hepatorenal syndrome
what are the diagnostic criteria to diagnose hepatorenal syndrome?
- cirrhosis w/ ascites and evidence of portal HTN
- serum Cr > 1.5 mg/dL progressing over days/weeks
- lack of improvement in renal function after w/d of diuretics and volume expansion w/ albumin for at least 2 days
- no evidence of parenchymal kidney disease
- no other apparent cause of AKI
organ dysfunction caused by intraabdominal HTN that can cause AKI
abdominal compartment syndrome
how do you calculate abdominal perfusion pressure (APP)?
MAP - IAP = AAP
mean arterial pressure - intraabdominal pressure = abdominal perfusion pressure
prerenal AKI: labs
- BUN:Cr ratio
typically > 20
prerenal AKI: labs
- urine osmolality
> 400, and often > 700
prerenal AKI: labs
- URINE Na+
< 20 (indicating normal tubular function and avid reabsorption of Na+ to increase glomerular pressure)
prerenal AKI: labs
- urine sediment
usually normal; can show granular or hyaline casts
prerenal AKI: labs
- FeNa+
< 1%
what is more accurate than FeNa+ if pt is on diuretics?
FeUrea or FeUric Acid
postrenal AKI results from
either EXTERNAL COMPRESSION or intraluminal/intratubular OBSTRUCTION
causes of intratubular OBSTRUCTION
- uric acid precipitation
- oxalate depositions
- hypercalcemia w/ intrarenal deposits
- MM w/ light chains
- certain drugs that crystallize in the urine (METHOTREXATE, INDINAVIR, ACYCLOVIR, GANCICLOVIR, and SULFA ABX)
usual causes of postrenal AKI
- prostatic hypertrophy
- stones
in postrenal AKI, does knowing the amount of urine produced give an indication about the degree of obstruction?
NO
anuria almost never occurs with urinary obstruction unless it is?
which is commonly associated w/?
- complete
- shock
postrenal AKI: labs
- UA
typically “bland” (no abnormalities)
PAPILLARY NECROSIS occurs in (3)
- pyogenic kidneys w/ postrenal obstruction
- chronic analgesic abuse
- SCD
if you suspect stones, diagnosis for urinary obstruction
US or CT scan
3 main categories of intrinsic renal AKI
- acute tubular necrosis (ATN)
- interstitial disease
- glomerular disease
MCC of intrinsic renal AKI
acute tubular necrosis (ATN)
acute tubular necrosis (ATN) causes
- ISCHEMIA
- NEPHROTOXIN
what are the 2 causes of nephrotoxic ATN?
- ENDOgenous
- EXOgenous
what are the causes of ENDOgenous nephrotoxic ATN?
- free myoglobin (rhabdomyolysis)
- free hemoglobin (intravascular hemolysis)
what are the causes of EXOgenous nephrotoxic ATN?
- contrast-related
- drugs
- osmotic nephropathy
- acute phosphate nephropathy
- use of bowel purgatives containing sodium phosphate
what is acute phosphate nephropathy?
AKI occurring after the use of bowel purgatives containing SODIUM PHOSPHATE
CLUE leading to diagnosis of acute phosphate nephropathy
hyperphosphatemia out of proportion to degree of kidney injury
what are the 2 renal problems caused by contrast-related AKI?
- immediate contrast-induced ATN (improves and has no skin findings)
- cholesterol atheroemboli
contrast-related AKI occurring days after procedure
cholesterol atheroembolic kidney disease
- blue toes
- livedo reticularis
- stepwise progression
- eosinophilia
- eosinophiluria
- low complements
cholesterol atheroembolic kidney disease
“STEPWISE PROGRESSION” of renal failure
cholesterol atheroembolic kidney disease
cholesterol emboli in retinal arterioles that appear as orange-white dots interrupting circulation
Hollenhorst plaques
treatment for AKI d/t cholesterol emboli
SUPPORTIVE only
ATN: labs
- BUN:Cr ratio
10-15:1
ATN: labs
- urine osmolality
< 350 (tubules cannot concentrate urine)
ATN: labs
- URINE Na+
> 40 (but, can be dilute if water reabsorption is significantly affected)
ATN: labs
- FeNa+
> 2%
can be LOW in CONTRAST-induced nephropathy
ATN: labs
- urine sediment
- MUDDY BROWN, “DIRTY” GRANULAR CASTS (nonspecific, but very sensitive)
- epithelial cell casts
initial management of ATN
- treat precipitating cause
- treat any hypERkalemia
OLIGURIC ATN usually resolves in
1-4 weeks
is oliguria required for the diagnosis of ATN?
NO
if oliguric, pts w/ ATN are more prone to?
becoming hypERkalemic, and volume-overloaded
causes of rhabdomyolysis
- crush injuries (compartment syndromes)
- coma
- traumatic immobilization
- prolonged surgeries
- strenuous exercise
- generalized seizures
- heat stroke
- severe volume contraction
- drugs
- infections (usually viral, esp influenza A and B)
- endocrinopathies (DKA, hypothyroidism, hyperthyroidism, pheochromocytoma)
- electrolyte abnormalities (severe hypOkalemia, hypOphosphatemia)
lab abnormalities in rhabdomyolysis
- INCREASED CPK (> 100,000 IU/L)
- nonspecific increases in AST and ALT
- elevated Cr
- hypERkalemia
- hypERphosphatemia
- increased UA
- hypOcalcemia
UA shows what in rhabdomyolysis
- MUDDY BROWN CASTS
- POSITIVE BLOOD
- NO RBCs
2 mechanisms causing hypOcalcemia in rhabdomyolysis
- decreased production of 1,25-(OH)2-D d/t renal injury
2. hypERphosphatemia d/t renal injury and tissue breakdown
what electrolyte can become significantly increased during recovery?
CALCIUM
what electrolyte abnormality, in ATN d/t rhabdomyolysis, should only be treated if severe or pt is symptomatic?
hypOcalcemia
treatment for rhabdomyolysis
- isotonic fluid resuscitation, or
- forced diuresis w/ ALKALINIZATION OF URINE
how does hemoglobinuria d/t severe intravascular hemolysis cause ATN?
Hb causing mechanical obstruction of tubules
interstitial kidney disease is caused by
inflammation and/or fibrosis of interstitium
acute interstitial nephritis (AIN) is caused by
drugs
proteinuria in tubular and interstitial diseases
low-grade (< 1-1.5 g/day)
acute (or allergic) interstitial nephritis (AIN) is most often a _____
drug-induced HYPERSENSITIVITY reaction
acute (or allergic) interstitial nephritis (AIN) can present w/
- fever
- eosinophilia
- rash
(only 10% present w all 3)
MC drugs that cause acute (or allergic) interstitial nephritis (AIN)
- NSAIDs
- abx
- PPIs
- cimetidine
- thiazides
- allopurinol
MC abx causing acute (or allergic) interstitial nephritis (AIN)
- beta-lactams
- TMP/SMX
- rifampin
- ciprofloxacin
now identified as a MAJOR cause of interstitial nephritis
PPIs
- typically ingested for MONTHS before symptoms occur
- rash, fever, and eosinophilia are frequently absent
NSAID-induced AIN
NSAID-induced AIN typically causes what range proteinuria?
NEPHROTIC-RANGE PROTEINURIA
NSAID-induced AIN results in glomerular changes consistent w/?
MINIMAL CHANGE DISEASE
what are other causes, besides drugs, of acute (or allergic) interstitial nephritis AIN?
- sarcoidosis
- SLE
- Sjogren’s
- transplant rejection
- infection
acute (or allergic) interstitial nephritis: labs
- urine sediment
- few red cells
- white cells +/- WBC casts
- mild protein (< 1 g/day)
- urinary eosinophils w/ Hansel stain
acute (or allergic) interstitial nephritis: labs
- FeNa+
usually > 1%
treatment for acute (or allergic) interstitial nephritis
discontinuing offending drug and observing
causes of chronic interstitial nephritis
- drugs
- HTN
- heavy metals (esp lead and cadmium)
- obstruction
- infections
- sarcoidosis
- Sjogren’s disease
- SCD
- MM
what drug combination can lead to chronic interstitial nephritis?
acetaminophen + ASA, esp if further combined w/ caffeine or codeine
- pt w/ h/o frequent pain
- low urine SG
- minimal proteinuria
- sterile pyuria
- elevated Cr
analgesic-abuse nephropathy (chronic interstitial nephritis)
in analgesic-abuse nephropathy (chronic interstitial nephritis), a noncontrast CT of the kidneys may show what?
papillary necrosis
possible sources of lead poisoning leading to chronic interstitial nephritis
- OCCUPATIONAL exposure
- drinking “MOONSHINE”
- HERBAL MEDICATIONS
- LEAD-GLAZED PLATES or COOKWARE
- smoking MARIJUANA
- nephropathy develops after YEARS
- presents as azotemia
- tiny bit of proteinuria
- hyperuricemia
- bland urine sediment
- may have crystalline arthropathy (“SATURNINE GOUT”)
chronic interstitial nephritis 2/2 LEAD poisoning
what ingredient found in Chinese herbs for weight-loss can cause an unusual kind of renal interstitial fibrosis?
ARISTOLOCHIC ACID
what 2 patterns are glomerular diseases divided into?
- nephritic
2. nephrotic
- acute, subacute, or chronic
- potentially reversible
- INFLAMMATORY process
- presents w/ hematuria, proteinuria (usually < 2 g/day), +/- RBC casts
nephrItic glomerular disease
nephrItic glomerular disease can be further subdivided into 2 categories
- focal and mild
(active sediment w/o HTN or edema) - diffuse and severe
(active sediment w/ heavy proteinuria, renal failure, HTN, and edema)
- noninflammatory process
- presents w/ proteinuria and edema, +/- urine oval fat bodies
- often WITHOUT red cells and casts in urine sediment
nephrOtic glomerular disease
3 classic features of nephrOtic syndrome
- HYPERCHOLESTEROLEMIA
- HTN
- HYPOALBUMINEMIA
either nephritic or nephrotic glomerular disease can occur in which 2 diseases?
- SLE
- MPGN (membranoproliferative glomerulonephritis)
what are the pulmonary-renal syndromes (AGN)?
- Goodpasture’s
- granulomatosis w/ polyangiitis
- microscopic polyangiitis
- Churg-Strauss
- Henoch-Schonlein purpura
- cryoglobulinemia
what are the basement membrane syndromes (AGN)?
- anti-GBM disease (Goodpasture’s)
- Alport’s
- thin basement membrane disease
what are the infectious disease syndromes (AGN)?
- post-infectious GN
- endocarditis
- HIV
- HBV
- HCV
- syphilis
- malaria
definitive diagnosis of AGN (except for diabetic nephropathy) is made w/
renal biopsy
what differentiates microscopic hematuria coming from the kidney vs lower urinary tract?
lower urinary tract = ISOLATED microscopic hematuria
glomerular origin = hematuria WITH proteinuria, dysmorphic red cells, and/or RBC casts
urine sediment finding DEFINITIVE for GN
RED CELL CASTS
- VARIABLE PROTEINURIA
- “ACTIVE” urine sediment (proteinuria, red cells > 10/hpf, white cells, red cell/white cell/granular casts
nephritic GN
casts ALWAYS originate in tubules
- very specific finding
- seen ONLY in GN
red cell casts
casts ALWAYS originate in tubules
- typically seen in pyelonephritis, or AIN
white cell casts
casts ALWAYS originate in tubules
- can be nonspecific
- characteristic of ATN
granular casts
casts ALWAYS originate in tubules
- indicate advanced renal disease
waxy casts
casts ALWAYS originate in tubules
- in pts w/ a lot of proteinuria
- characterized by “Maltese crosses” under polarized light
- can suspend in urine as droplets
fatty casts (or oval fat bodies)
casts ALWAYS originate in tubules
- do not indicate disease; seen w/ CONCENTRATED urine
hyaline casts
- typically heavy proteinuria
- urine fat visible as OVAL fat bodies
- fatty/waxy casts
- renal tubular cells w/ lipid droplets
- urine sediment usually normal besides the fat
nephrotic GN
what is nephrotic-range proteinuria?
> 3.5 g/d (or 40-50 mg/kg/d)
- HYPOALBUMINEMIA (w/ secondary EDEMA)
- HYPOGAMMAGLOBULINEMIA (w/ risk of infections w/ encapsulated organisms)
- loss of ANTITHROMBIN III (hypercoagulable state; at risk for PULMONARY EMBOLISM and RENAL VEIN thrombosis)
- HYPERLIPIDEMIA
- severe PERIPHERAL EDEMA
- PLEURAL EFFUSIONS
- ASCITES
nephrotic syndrome
strategy to classify the glomerular diseases (3 steps)
- is the urine NEPHRITIC or NEPHROTIC?
- if nephritic, are the complements LOW or NORMAL?
- does the pt present w/ a SYSTEMIC d/o by H&P, or is the presentation primarily a KIDNEY d/o?
name the GN’s
- nephrOtic
- presentation: kidney ONLY
- minimal change disease
- FSGS
- membranous
name the GN’s
- nephrOtic
- presentation: systemic
- DM
- AL amyloidosis
- AA amyloidosis
name the GN’s
- nephrItic
- NORMAL complement
- presentation: kidney ONLY
- IgA
- Alport
name the GN’s
- nephrItic
- NORMAL complement
- presentation: systemic
- Goodpasture’s
- vasculitides
- TTP/HUS
name the GN’s
- nephrItic
- LOW complement
- presentation: kidney ONLY
- PIGN
- MPGN
name the GN’s
- nephrItic
- LOW complement
- presentation: systemic
- SLE
- endocarditis
- cryoglobulinemia
name the GN
- any nephrItic GN can become _____
- complement: VARIABLE
- presentation: VARIABLE
- RPGN
C3 is ALWAYS low for how long in PIGN?
6-8 weeks
FIRST test to order for a NEPHRITIC picture
COMPLEMENT levels
PIGN is usually caused by
- group A beta-hemolytic streptococcal infections
- also associated w/ staph
- gross hematuria
- and/or edema
- sxs occur 1-6 WEEKS after initial illness (average; throat infection = 10 days, skin infection = 2-4 weeks)
PIGN
what is the diagnostic key in differentiating between PIGN from IgA nephropathy?
“LATENCY PERIOD”
what are the ANTISTREPTOCOCCAL ANTIBODIES that aid in dx?
- antistreptolysin O (ASO) titer
- antideoxyribonuclease B (anti-DNase B) titer
- antihyaluronidase titer
how long does antistreptolysin O (ASO) titer stay elevated?
SEVERAL WEEKS
how long does antideoxyribonuclease B (anti-DNase B) titer stay elevated?
several months
how long do complement levels remain LOW in PIGN?
6-8 weeks
PIGN renal biopsy shows what
immune deposits (IgG, IgM, complement) in subendothelial and subepithelial regions (“HUMPS”), and neutrophil invasion of glomerulus
treatment for PIGN
- abx for underlying infection
- supportive care
diagnosis for MPGN
biopsy diagnosis
- can be idiopathic w/ isolated kidney disease, but more commonly associated w/ SYSTEMIC diseases
- 50% of time LOW complement levels
- usually nephrItic, but nephrOtic is not uncommon
MPGN
LOW C3 and C4 are more common in which form of MPGN?
immune complex-mediated MPGN
- chronic hepatitis C or B w/ or w/o cryoglobulinemia, shunt nephritis, abscess
- AI disease (SLE, Sjogren’s)
- monoclonal gammopathy
immune complex-mediated MPGN
- d/t dysregulation of alternative complement pathway
- d/t mutation in complement factors H, I, and B, or
- Abs against factors H, I, and B
complement-mediated MPGN
LOW C3 and NORMAL C4 is more common in which form of MPGN?
complement-mediated MPGN
LOW C3 in PIGN returns to normal after how long?
2-3 months
C3 remains low in MPGN for how long?
INDEFINITELY
if you initially suspected PIGN, but C3 stays low > 3 months, what should you suspect instead and what should be done?
- MPGN
- renal biopsy!
treatment for MPGN
treat underlying cause
name the 6 classes of lupus nephritis
class I: normal/minimal mesangial class II: mesangial class III: focal proliferative class IV: diffuse proliferative class V: membranous class VI: end-stage/sclerosis
which lupus pts are candidates for renal bx?
ALL lupus pts w/ active urine sediment REGARDLESS of GFR
treatment for lupus nephritis
- mycophenolate mofetil, or
- cyclophosphamide
- WORLDWIDE, MC GN
- more common in Asians and males
IgA nephropathy, aka Berger disease
“mesangial proliferative GN”
what are the 4 different ways IgA nephropathy can present?
- gross hematuria coincident w/ or immediately following a URI
- microscopic hematuria w/ proteinuria and progressive disease
- nephrotic syndrome
- RPGN
when does the hematuria seen in IgA nephropathy occur?
either during viral illness, or just after exercise
what is an important distinguishing feature between IgA nephropathy and PIGN?
NO LATENT PERIOD
serum complement levels in IgA nephropathy
usually normal
renal bx and immunofluorescence staining findings in IgA nephropathy
- bx shows IgA and complement deposits in the mesangium
- immunofluorescence staining shows IgA and complement deposits in the glomerular capillaries
(- light microscopy shows isolated proliferation in mesangium (w/ CRESCENT formation if dz is severe))
what is “secondary IgA nephropathy?”
when other illnesses cause IgA deposition in the mesangium, but aren’t actually IgA nephropathy
what are the determining factors for the prognosis of IgA nephropathy?
- serum Cr
- BP
- amount of proteinuria
treatment for IgA nephropathy, if:
normal renal function
observe
treatment for IgA nephropathy, if:
proteinuria (> 0.5 g/d) and progressive disease
ACEI/ARB
treatment for IgA nephropathy, if:
persistent proteinuria (> 1 g/d) despite ACEI/ARB x 6 mos
corticosteroids
- hereditary (usually X-linked) syndrome
- chronic GN +/- NERVE DEAFNESS
- congenital EYE PROBLEMS
Alport’s
hallmark finding on EM for Alport’s
split lamina densa (part of GBM)
acute GN w/ evidence of anti-GBM Abs WITH PULMONARY HEMORRHAGE (70% of pts)
GOODPASTURE’S
Goodpasture’s presentation
- active urine sediment
- hemoptysis
- dyspnea
diagnosis for anti-GBM disease
anti-GBM Abs, or renal bx if serum Abs are negative
renal bx finding for anti-GBM disease
anti-GBM IgG deposits in LINEAR fashion along GBM
treatment for Goodpasture’s
- plasmapheresis (to remove Abs)
- immunomodulation (steroids + cyclophosphamide)
what are the main vasculitides that commonly involve an acute GN?
- granulomatosis w/ polyangiitis
- microscopic polyangiitis
- eosinophilic granulomatosis w/ polyangiitis (Churg-Strauss)
- Henoch-Schonlein purpura (HSP)
kidney or skin findings in HSP
identical to IgA nephropathy
- most aggressive syndrome of AGN
- refers to any form of AGN that progresses RAPIDLY (DAYS to WEEKS)
- hallmark histopathologic finding of glomerular CRESCENTS (EXTRACAPILLARY PROLIFERATION) inside Bowman’s capsule
rapidly progressive GN
RPGN should always be considered, when?
severe and progressive renal failure of recent onset w/ NEPHRITIC urine
urine sediment findings in RPGN
- PROTEIN
- RED CELLS
- sometimes RBC CASTS
3 major pathogenic causes of RPGN
type 1 = anti-GBM Abs (Goodpasture’s)
type 2 = immune complex deposition
(IgA deposits = IgA nephropathy; ANA = lupus; cryoglobulins = cryoglobulinemia; Abs against infection = eg streptococci)
type 3 = no evidence of immune deposits (“PAUCI-IMMUNE”)
evaluation of RPGN
- RAPID HISTOPATHOLOGIC DIAGNOSIS
- measure ANCA titers
- pulmonary hemorrhage
- LINEAR staining of IgG along GBM on renal bx
- high titer of serum anti-GBM Abs
GOODPASTURE SYNDROME
- ENT manifestations (sinusitis, epistaxis)
- pulmonary infiltrates/hemoptysis
- negative immunofluorescence on kidney bx
- positive c-ANCA
GRANULOMATOSIS W/ POLYANGIITIS
- pt w/ h/o ASTHMA/ATOPY w/ peripheral eosinophilia
- positive p-ANCA
eosinophilic granulomatosis w/ polyangiitis
- no systemic features
- negative immunofluorescence on kidney bx
- positive ANCA
PAUCI-IMMUNE GN (aka renal limited-ANCA vasculitis)
empiric treatment for RPGN
high-dose methylprednisolone, then prednisone + cyclophosphamide +/- plasmapheresis (if pulmonary hemorrhage)
treatment for RPGN once renal bx results are available
treat underlying cause
MCC of primary nephrotic syndrome
minimal change disease
MCD is most commonly idiopathic, but has been associated w/
- drugs (NSAIDs, rarely others)
- lymphoma (both Hodgkin’s and NHL)
presentation of MCD
ANASARCA, or severe peripheral EDEMA (develops over weeks), and WITHOUT HTN
MCD renal bx findings
- LM shows NO CHANGE
- EM shows FUSION OF EPITHELIAL FOOT PROCESSES (but can be seen in any nephrotic syndrome)
initial treatment for MCD
steroids
treatment for MCD if steroid-resistant
- cyclophosphamide
- cyclosporine
- MCC of idiopathic nephrotic syndrome in blacks
- MC glomerular process causing ESRD in the US
- consider if there’s a h/o HIV/AIDS, HEROIN use, obesity, SCD, chronic vesicoureteral reflux
focal segmental glomerulosclerosis (FSGS)
- diffuse FOOT PROCESS FUSION
- additional sclerosis limited to SEGMENTS of the glomeruli
- hypertensive on presentation
- 50% have reduced renal function at dx
focal segmental glomerulosclerosis (FSGS)
- have slowly progressive renal failure
- those NOT responding to tx REQUIRE DIALYSIS w/i about 5-10 years
focal segmental glomerulosclerosis (FSGS)
initial treatment for focal segmental glomerulosclerosis (FSGS)
ACEIs/ARBs and high-dose steroids
secondary causes of membranous nephropathy (MN)
- chronic INFECTIONS (esp. chronic HBV)
- several DRUGS (NSAIDs, penicillamine, and gold)
- underlying SOLID TUMORS
- AI thyroiditis and SLE (consider in young female)
- gradually worsening nephrotic syndrome
- 50% of pts have red cells in urinary sediment (w/o RBC casts)
- most have normal BP and renal function at dx
membranous nephropathy (MN)
renal biopsy results in membranous nephropathy (MN)
- immunofluorescence shows GBM subepithelial IgG and C3 deposits
- EM shows shows GBM subepithelial deposits w/ loss of overlying foot processes
test to distinguish between idiopathic and secondary membranous nephropathy (MN)
Abs to M-type phospholipase A2 receptor (anti-PLA2R)
positive in primary
treatment for secondary membranous nephropathy (MN)
- discontinue offending drugs
- treat underlying disease
when do you aggressively treat membranous nephropathy (MN)?
persistent high-grade proteinuria (> 4 g/d) despite at least 6 months w/ an ACEI/ARB and HTN control
has the highest prevalence of renal vein thrombosis compared w/ other causes of nephrotic syndrome
membranous nephropathy (MN)
pt w/ known membranous nephropathy (MN) has flank pain, hematuria, high LDH, think of
RENAL INFARCTION 2/2 renal vein thrombosis
MC systemic cause of nephrotic syndrome in adults
diabetic nephropathy
diabetic nephropathy may be associated w/
hyporeninemic hypoaldosteronism and type 4 RTA
in diabetic nephropathy, what PRECEDES NEPHROPATHY?
RETINOPATHY
renal biopsy results in diabetic nephropathy
- expansion of mesangium
- thickening of GBM
- sclerosis of glomeruli (KIMMELSTIEL-WILSON lesion)
how many phases does diabetic nephropathy occur in, and what are they?
- 2
- phase 1 = silent or preclinical phase
- phase 2 = clinical phase
what is the 1st measurable change in renal function in phase 1 of diabetic nephropathy?
MICROALBUMINURIA (30-300 mg/24H)
next step in diabetics tested yearly for albuminuria
treat w/ ACEI/ARB EVEN IF NORMOTENSIVE
clinical phase of diabetic nephropathy is associated w/
- proteinuria (> 300 mg/d, and often nephrotic range)
- HTN
- progressive loss of kidney function
what slows progression of diabetic nephropathy?
- BP control < 140/90 w/ ACEI/ARB
- and glycemia control (HbA1c < 7)
in what 2 scenarios should a pt with DM undergo a renal bx to exclude other possible causes of nephrotic syndrome?
- NO eye disease
- dysmorphic red cells on urine sediment
as renal function decreases, insulin requirements
decrease (2/2 decreased metabolism by kidneys)
MM can cause which of the following problems w/ renal involvement?
- cast nephropathy (myeloma kidney)
- hypercalcemia
- primary “AL” amyloidosis
- monoclonal Ig deposition disease (MIDD)
- secondary “AA” amyloidosis
MC form of renal involvement d/t MM
cast nephropathy (myeloma kidney)
- immunoglobulins (Bence Jones proteins) precipitate in tubules leading to acute renal failure
- NEGATIVE DIPSTICK protein, but POSITIVE PROTEINURIA
cast nephropathy (myeloma kidney)
electrolyte imbalance in MM that can acute renal failure
hypercalcemia
- multisystem disease
- nephrotic syndrome and renal failure
- (Congo-red stain shows deposits w/ apple-green birefringence)
primary “AL” amyloidosis associated w/ MM
- monoclonal immunoglobulin light chains or heavy chains are deposited in GBM
- can resemble diabetic nephropathy w/ nodular glomerulosclerosis
monoclonal Ig deposition disease (MIDD)
- seen in chronic inflammatory states (RA and familial Mediterranean fever (FMF))
- also caused by recurrent skin/soft tissue infections
- carpal tunnel syndrome
- new-onset HF assoc. w/ nephrotic syndrome
secondary “AA” amyloidosis
controlling what is vital in ANY glomerular disease
glomerular pressure
best in decreasing intraglomerular pressure
ACEIs or ARBs
treatments used in MOST nephrotic syndromes, EXCEPT those caused by AMYLOID and DIABETES
glucocorticoids +/- cytotoxics
hypocomplementemia NEVER occurs in
the nephrotic syndromes (MCD, FSGS, MG, diabetic nephropathy, amyloid nephropathy)
RBC casts are NOT seen in
the nephrotic syndromes (MCD, FSGS, MG, diabetic nephropathy, amyloid nephropathy)
urine sediment in renal disease:
bland UA; occasionally granular and/or hyaline casts
prerenal failure
urine sediment in renal disease:
frequently bland, may have blood; WBC casts if d/t infection; sterile pyuria if d/t papillary necrosis; NEVER red cells casts
postrenal failure
urine sediment in renal disease:
dirty brown granular casts
intrinsic renal: ATN
DILATION of AFFERENT arteriole and maintenance of glomerular perfusion pressure require
prostaglandins (PG)
mechanism of NSAIDs causing hyperkalemia
block PG-mediated renin release from JGA –> low aldosterone –> decreased renal K+ excretion
what types of kidney problems are chronic injection drug users at risk for?
- acute bacterial endocarditis –> progressive GN by IMMUNE COMPLEX DEPOSITION
- septic EMBOLI (renal infarction and hematuria)
- chronically progressive FOCAL SCLEROSIS
- HIV-associated nephropathy caused by FSGS
possible reasons for AKI in cancer
- direct infiltration
- obstruction
- glomerular disease
- chemotherapy drug toxicity
- hypercalcemia
possible reasons for AKI in cancer:
- direct infiltration causes
- lymphoma
- leukemia
- myeloma
possible reasons for AKI in cancer:
- obstruction
- pelvic/abdominal tumors
- intratubular uric acid obstruction d/t TLS
- methotrexate crystallization
possible reasons for AKI in cancer:
- glomerular disease
- MCD = Hodgkin disease
- secondary MGN = solid tumors
- amyloidosis = MM
possible reasons for AKI in cancer:
- chemotherapy drug toxicity
- mitomycin C-induced HEMOLYTIC UREMIC SYNDROME
- cisplatin-induced tubular injury
- bevacizumab-induced thrombotic microangiopathy
- ifosfamide causing ATN
electrolyte abnormality causing AKI in cancer
hypercalcemia
prophylactic treatment for TLS (acute urate nephropathy)
- aggressive IV hydration (hypotonic or isotonic saline)
- ALLOPURINOL, or RASBURICASE
rasburicase is CI in which pts?
G6PD deficiency
definition of CKD
- kidney damage > 3 mos, w/ or w/o decreased GFR, w/ either pathological abnormalities or markers of kidney damage
- GFR < 60 mL/min/1.73m2 > 3 mos, w/ or w/o kidney damage
CKD stages
- stage 1 = normal GFR
- stage 2 = 60-89 mL/min/1.73m2 body surface area
- stage 3 = 30-59
- stage 4 = 15-29
- stage 5 = < 15 or on dialysis
pts w/ CKD have an increased risk of
heart disease
1 cause of death in pts w/ CKD
heart disease
serum phosphorus levels remain normal until what stage?
about CKD stage 3
mechanism of chronic kidney disease-mineral bone disorders (CKD-MBD)
- phosphorus retention –> stimulates PTH release
- hypocalcemia-induced PTH release
1. calcium-phosphorus complex deposits in vasculature and tissues
2. decreased active vitamin D production
is associated w/ increased risk of death and heart disease, even in pts w/o CKD; but especially in those w/ CKD stages 3-5
hyperphosphatemia
what are the 2 types of phosphate binders?
- CALCIUM-BASED (CaCO3; Ca acetate)
- NONCALCIUM-BASED (sevelamer; lanthanum)
CKD stage 3 or more causes what?
- increased PO4
- normal/low-normal Ca2++
- increased iPTH
- low 1,25-(OH)2-D
ideal management to control PO4 in CKD
diet and binder
controlling PO4 in CKD leads to what?
- normalization of PO4
- increased Ca2++
- decreased iPTH
if PTH is not adequately corrected with diet and PO4 binder, next step?
add 1,25-(OH)2-D (calcitriol)
pts w/ CKD can have what 3 types of bone d/o’s?
- osteitis fibrosa cystica
- adynamic bone disease
- osteomalacia
secondary hyperparathyroidism labs
- high PO4
- low 1,25-(OH)2-D
- very high iPTH
- normal/low-normal Ca2++
treatment for secondary hyperparathyroidism 2/2 CKD
- follow iPTH
- phosphate binder
- 1,25-(OH)2-D, or paricalcitol/doxercalciferol
- +/- cinacalcet
how do you choose which phosphate binder to use?
based on serum Ca++ level
what is the goal when using phosphate binders?
normalize phosphorus WITHOUT creating adynamic bone
adynamic bone disease labs
- high/normal PO4
- low 1,25-(OH)2-D
- LOW iPTH
- normal/high Ca2++
cause for adynamic bone disease
oversuppression of PTH by phosphate binders and concomitant use of vitamin D analogs
- associated w/ GFR < 15 mL/min
- anorexia
- N/V
- pericardial and pleural effusions
- hemorrhagic pericarditis
- platelet dysfunction and bleeding
- pruritis
- sensory neuropathies
- central nervous system dysfunction (confusion, difficulty concentrating, encephalopathy, coma)
uremia
what endocrine problems can be caused in CKD?
- decreased glucose intolerance
- decreased gonadal hormone production (w/ impotence or amenorrhea/infertility)
- low T3 w/ normal TSH
anemia of chronic kidney disease is a diagnosis of
exclusion
first r/o iron deficiency; responds dramatically to recombinant erythropoietin
NORMOCHROMIC-NORMOCYTIC ANEMIA in CKD
what should be checked before starting ESAs?
iron stores:
- Fe sat > 20%
- ferritin > 100
target Hb when treating w/ ESAs
- no specific target
- NO IMPROVEMENT in outcome and INCREASED MORBIDITY and MORTALITY if Hb is CORRECTED TO NORMAL (> 13)
progression of CKD is slowed by which meds?
ACEIs or ARBs
progression of CKD is also slowed down by management of which comorbidities?
- metabolic acidosis
- hyperlipidemia
- stop smoking
AVOID NEPHROTOXINS in CKD, especially
- contrast dye
- NSAIDs
- aminoglycosides
treatment for gout in CKD
colchicine or NSAIDs +/- allopurinol
CONTRAINDICATED in treatment for gout in CKD
probenecid
when do you start dialysis?
when CKD pt has ADVANCING UREMIA: ANY uremic sxs in pt w/ CrCl < 15 mL/min
MCC of DEATH in dialysis pts
- CARDIOVASCULAR disease
- next is infection
one of the key factors in reducing morbidity and mortality in dialysis pts
maintaining ADEQUATE NUTRITION
what is the main complication for CAPD?
PERITONITIS
peritonitis in CAPD is usually caused by which bugs?
gram-positive skin flora (S. epidermidis or S aureus), followed by gram-negative organisms
can be completely removed during dialysis, and therefore need to be re-dosed after treatment
AMINOGLYCOSIDES
which abx have some clearance during dialysis and need to be re-dosed afterwards and may require supplemental doses?
- most beta-lactams
- daptomycin
- metronidazole
- ciprofloxacin
- levofloxacin
in CKD STAGES 4 AND 5, which contrast type should be AVOIDED?
GADOLINIUM
GADOLINIUM can cause this this in pts w/ advanced CKD (all forms, regardless of whether on dialysis or what type of dialysis)
NEPHROGENIC SYSTEMIC FIBROSIS (NSF)
- presents as a thickening of skin w/ symmetrical plaques, papules, or nodules
- STARTS DISTALLY
- disease course is progressive, sometimes fulminant
NEPHROGENIC SYSTEMIC FIBROSIS (NSF)
is NOT associated w/ nephrogenic systemic fibrosis (NSF)
livedo reticularis
diagnosis for nephrogenic systemic fibrosis (NSF)
deep punch bx of involved skin
