Week 1 (Renal) Flashcards
Functions of the kidney
Maintain constant ECF volume and content: excrete metabolic waste, adjust urinary excretion of water and electrolytes
Endocrine organ: renin/angiotensin, prostaglandins, bradykinin, erythropoetin, 1,25-dihydroxy vitamin D
Determinants of GFR
Total GFR = single nephron GFR x nephron mass
snGFR = unit permeability of capillary wall x net pressure gradient (Starling forces) = Kf (ultrafiltration coefficient, which expresses intrinsic permeability of GBM to water) x Puf (mean ultrafiltration pressure across GBM)
snGFR = LpS x (Pgc - Pbs - OPgc)
snGFR = Kf x net filtration pressure
Lp = permeability; S = surface area
Autoregulation of GFR
Even when BP (and thus renal artery pressure) changes, GFR stays constant because it is autoregulated
However, angiotensin II is necessary for autoregulation so if you block ATII, GFR is not well autoregulated anymore
What is special about the glomerular capillary?
Very high hydraulic permeability
Very large surface area
Very high protein permselectivity
Causes of renal failure (loss of GFR)
Reduction in total number of glomeruli (normal or supernormal GFR): surgical removal of kidney or some kidney tissue (compensatory hypertrophy and remaining nephrons increase in size and snGFR increases; doesn’t happen after age 40 though), embolism or infarction of kidney tissue, drop out of individual glomeruli due to local glomerular disease (age), interstitial disease (tubular damage followed by glomerular dropout)
Reduction in snGFR (nephron number normal or decreased): reduced renal plasma flow (hemorrhagic/septic/anaphylactic shock), CHF, increased resistance of renal vasculature, impaired autoregulation, increased πgc (myeloma = high plasma protein, dehydration = hemoconcentration), decreased Pgc (ACEi = no constriction of eff art, BP decreased out of autoregulatory zone, NSAIDs inhibit prostaglandin = aff art constriction), increased Pbs (obstruction), decreased LpS (GBM thickened/not permeable due to disease, gentamicin decreases K, glomerular nephritis = inflammatory cells, fibrosis?)
Clinical estimation of GFR
GFR = UV/P
Ideal filtration marker should be: not protein bound in plasma, freely filtered at GBM, not secreted or reabsorbed, easy to measure, produced endogenously at steady state, not metabolized by any other organ in the body (only the kidney)
Inulin fits all of the above except is not created endogenously and need to infuse IV (not practical!)
Creatinine fits all of the above except 15% is secreted in proximal tubule, so tends to overestimate GFR (due to increased U); also levels depend on age, muscle mass, meat intake
Alternatives to using creatinine or inulin clearance to measure GFR
Cockroft Gault: uses age, weight, sex, FF
MDRD equation: uses sex, race, age, BUN, albumin, FF
Radiolabelled filtration markers: iothalamate, DTPA or EDTA
Cystatin-C
BUN
Blood urea nitrogen
BUN levels vary inversely with GFR (if BUN high, then GFR low)
Urea production not constant: increased with protein intake/bleeding; decreased by liver disease/malnutrition; increased in CHF (PCT Na and urease reabsorption increased due to low effective plasma volume)
Filtered and reabsorbed (with Na and H2O)
Urea reabosprtion is flow-dependent: more concentrated urine, the more urea is reabsorbed (if dehydrated, will reabsorb more = high BUN in dehydration)
How does the GBM determine which molecules can and cannot pass?
GBM behaves as size and charge discriminating membrane with pores of 4-4.5 nm radius
Water and small molecules (<1.8 nm) pass freely
Macromolecules (>5 nm) do not pass
Albumin (3.6 nm, polyanionic) passes in minute amounts due to negative charge
Barriers to protein passage across GBM: molecular size/shape, negative charge
Congenital nephrotic syndrome: Finnish type
Heavy proteinuria in utero
Death in first two years of life
Tx: kidney transplantation
Mutated gene responsible was isolated by positional cloning: NPHS1 (specifically expressed in kidney, mutations segregate with phenotype, encodes the protein nephrin)
Minimal change nephrotic syndrome (MCNS)
Commonest cause of nephrotic syndrome in children
May occur at any age
Relapsing and remitting course
Often responds dramatically to steroids
Minimal findings on light microscopy and IF
Fusion of podocytes on EM
Rarely causes CKD unless its pathology changes
Focal and segmental nephrosclerosis (FSGS)
May be specific or non-specific injury pattern
May be primary or secondary (obesity/HIV/drugs)
May be end-stage of MCNS
May cause massive proteinuria
May cause rapid kidney failure in young adults
May recur rapidly in kidney transplant
Putative role of circulating factor (suPAR)
Degrees of proteinuria
Normally <200 mg/day (mostly tubular)
Microalbuminuria (30-300 mg/day) is abnormal
Proteinuria >300 mg/day: transient (usually benign), orthostatic (often benign), fixed (marker of renal disease)
Heavy proteinuria (>3 g/day) “nephrotic range”
Nephrotic syndrome: edema, hypoalbuminemia, lipidemia, lipiduria, heavy proteinuria (>3g/day)
Some causes of nephrotic syndrome
Primary glomerulopathies: MCNS, FSGS, MN, MPGN, proliferative GN (IgA nephropathy)
Secondary glomerulopathies: diabetic nephropathy, SLE, plasma cell dyscrasias (myeloma, amyloid), virus infections (hepatitis, HIV), bacterial infections (strep, abscesses), other infections (malaria, amebiasis, syphilis), cancer (paraneoplastic syndrome)
What factors determine Puf (mean ultrafiltration pressure across GBM)?
Pgc: mean hydrostatic pressure in glomerular capillary (gc); 45mmHg, fairly constant along capillary; determined by balance of resistances of afferent arteriole and efferent arteriole
Pbs: mean hydrostatic pressure within tubule (Bowman’s space); constant at 10-12mmHg
πgc: mean oncotic pressure in glomerular capillary; rises along capillary as plasma is ultrafiltered and protein-free fluid is extracted (leaving more proteins and raising oncotic pressure!)
πbs: oncotic pressure within Bowman’s space; since GBM largely impremeable to protein, is close to 0 and can be ignored
When does creatinine clearance really badly overestimate GFR?
Chronic renal failure: GFR falls and secreted portion accounts for greater percent of urinary excretion
Heavy proteinuria: for unclear reasons, secretion increases and may lead to overestimation of GFR by 100%!
What happens to plasma creatinine when you remove a kidney and why?
1) When you remove a kidney, you cut the GFR in half
2) Creatinine filtration (GFR x Pcreat) and excretion (Ucreat x V) are cut in half too because GFR was cut in half
3) Production of creatinine remains the same (still same amount of muscle breakdown), so you’re in positive creatinine balance and plasma cretinine levels rise
4) As Pcreat rises, the creatinine filtration must also rise (since it’s GFR x Pcreat), and does so until creatinine excretion equals production
5) When Pcreat is doubled, the product of GFR x Pcreat is back to normal and new steady state is produced
Note: you’ll always be able to excrete 1500 mg/day because the plasma and thus urine concentration will just be higher!
How are GFR and serum creatinine related?
At near-normal levels of renal function, large changes in GFR produce only small changes in serum creatinine
When renal disease is advanced, small changes in GFR will produce large changes in serum creatinine
BUN:creatinine ratio
10 is normal BUN:creatinine ratio
Increased BUN ratio: increased urea production (excess dietary protein, GI bleeding, hemolytic anemia, steroid therapy = protein anabolism), increased urea reabsorption (CHF, dehydration), decreased creatinine production (muscle wasting)
Decreased BUN ratio (less used clinically): decreased urea production (low dietary protein, severe liver disease), increased urea excretion (overhydration), increased creatinine production (muscle breakdown = rhabdomyolysis)
Glomerular permselectivity
Size: 5.5 A is too big
Shape: linear, flexible molecules traverse GBM more easily than globular, rigid molecules
Charge: sialic acid is a mucoprotein in the basement membrane that has anionic residues (negative charge) to repel molecules with negative charge; albumin is 3.6 A but cannot pass due to negative charge
Podocin is anionic protein on sides of epithelial foot process and probably helps maintain separation of adjacent foot processes
Nephrin is located at slit diaphragm
In certain glomerular diseases, sialic acid content reduced so more negatively charged molecules can pass (some degree of size discrimination always remains though)
Consequences of loss of charge of GBM
1) Proteinuria
2) Fusion of epithelial foot processes
3) Retention of immunoglobulin aggregates (immune complexes) in the mesangium –> can lead to continuous stimulus for mesangial matrix production which could result in glomerular sclerosis and destruction
Blood flow into and around the nephron
Renal artery –> afferent arteriole –> glomerulus –> efferent arteriole –> capillary that supplies rest of nephron?!
Hydrostatic and oncotic pressures in that capillary that runs next to the nephron affects reabsorption from the tubule!
Low BP –> constrict efferent arteriole –> increased pressure in glomerular capillary but decreased pressure in efferent arteriole/capillary –> high oncotic pressure and low hydrostatic in capillary –> more fluid pulled out of PCT and into capillary –> reabsorb more water to increase BP (this shows that when BP down, you keep GFR up by constricting efferent arteriole AND you maintain body fluid by reabsorbing more water by the same mechanism!)
Three layers of glomerular capillary
Capillary lumen
1) Endothelial cells
2) Glomerular basement membrane (GBM)
3) Podocyte foot processes (part of visceral epithelial cells)
Filtrate in Bowman’s space?
Total body volume and distribution
Total body volume (TBV) = 60% of total body weight (TBW)
TBV = 60% intracellular and 40% extracellular (1/3 intravascular and 2/3 interstitial)
Of your total body weight, 60% is is total body volume, 40% is intracellular fluid and 20% is extracellular fluid (60-40-20 rule)
Ions and osmolality in different compartments
All compartments have same osmolality (because water follows solute to maintain osmotic equilibrium)
Intracellular: K+, PO4
Extracellular: Na+, Cl-
Effective plasma osmolality
Estimated to 2[Na+]
Posm = 280-290
Effective vs. ineffective solutes
Effective solutes contribute to osmolality and osmotic pressures; increase in number of solutes causes free water to move into their compartment; ex: Na+, K+, glucose
Ineffective solutes contribute to osmolality but not to osmotic pressures; can cross vascular walls and cell membranes so water never has to move to follow; ex: urea
Osmoregulation vs. volume regulation
Osmoregulation: maintains plasma osmolality (serum [Na+] and cell volume), uses osmoreceptors in hypothalamus to stimulate thirst and ADH, cause urine osmolality and water intake/excretion to change
Volume regulation: maintains effective circulating volume (effective tissue perfusion), uses sensors in carotid sinus (SNS, some ADH), afferent arteriole (RAAS, glomerular perfusion, GFR), and atria/ventricles when severe CHF (ANP when atria stretch/vol exapnds to get RID of water), cause urinary Na+ excretion and thirst
Remember, volume more important than osmolality!
Infusion of isotonic “normal saline”
Use volume regulation!
No osmolality change
Increased effective circulating volume (ECV)
Suppression of SNS, ADH, RAAS
Increased ANP to promote Na+ and water excretion
Free water ingestion
Use osmoregulation
Plasma osmolality decreased
Suppress ADH to excrete water
Urine osmolality decreases (more dilute)
Salt ingestion (potato chips with no water!)
Use both osmoregulation and volume regulation
Plasma osmolality increased so water shifts extracellularly (into blood vessels/plasma) to increase effective circulating volume (ECV)
Increased ADH, thirst to enhance free water reabsorption and intake which decreases water excretion and increases urine osmolality
Then, RAAS suppressed and ANP increases to cause water excretion
Sweating in a marathon runner
Uses both osmoregulation and volume regulation
Sweat is hypotonic so plasma osmolality increases and ECV decreases
Increased ADH, thirst, RAAS
Decreased ANP
Drink fluid equivalent to sweat composition so no electrolyte/volume disturbances! If drink water, will retain free water and become hyponatremic. If drink nothing, will continue to be hypernatremic.
Edema
Palpable swelling due to the expansion of interstitial fluid volume
Common clinical conditions associated with edema: CHF, cirrhosis, nephrotic syndrome
Why don’t you usually get edema?
Albumin in the blood maintains oncotic pressure
Lymphatics take away extra fluid
Edema formation
Alteration in more than one of Starling’s forces:
1) increased capillary hydraulic pressure
2) Increased capillary permeability
3) Increased interstitial oncotic pressure
4) Decreased plasma oncotic pressure
Lymphatic obstruction
Renal Na+ and water retention
Congestive heart failure causing edema
Poor CO –> decreased ECV –> decreased tissue perfusion
Increased RAAS, SNS, ADH –> Na+ and water retention –> increased plasma volume
Early in CHF, this enhances cardiac contractility and CO but as disease progresses, continuing accumulation of plasma volume reaches a point where cardiac contractility cannot be improved to improve CO so Na+ and water retention causes volume expansion and edema
Nephrotic syndrome
Edema, hypoalbuminemia, heavy proteinuria (>3g/day), hyperlipidemia/hyperlipiduria
Hypoalbuminemia due to urinary loss (and maybe altered albumin metabolism) –> decreased capillary oncotic pressure –> arterial underfilling
Also have renal Na+ retention due to underlying renal disease (independent of hypoalbuminemia)
Increased RAAS, SNS, ADH
Increased capillary permeability (Lp)
Altered reflection coefficient of proteins (s)
Administration of albumin improves renal Na+ excretion and edema (transiently since you’re still losing albumin due to renal disease!) because increases oncotic pressure of plasma so allows you to get rid of water!
Arguments against arterial underfilling due to hypoalbuminemia as sole cause of Na+ retention and edema formation in nephrosis
Gradual decrease in plasma albumin would mean gradual decrease in interstitial albumin (why…?) so oncotic pressure gradient would be minimal
People with no albumin don’t have edema!
Correction of renal disease improves Na+ excretion and corrects edema before hypoalbuminemia is corrected!
Ascites and hepatorenal syndrome
Happens in patients with cirrhosis
Portal hypertension (due to postsinusoidal obstruction from hepatic fibrosis) causes portosystemic shunt that reduces hepatic metabolism of vasoactive peptides (prostaglandins, substance P, VIP, glucagon all cause vasodilation!) which causes vasodilation of splanchnic bed and systemic circulation (also increased NO increased because reduced clearance of bacterial products and this also contributes)
Fall in systemic ECV and reduced systemic vascular resistance –> Increased RAAS, SNS, ADH to retain water –> heart decompensates and CO decreases –> ascites and edema
Also with SNS, overdo the vasoconstriction in kidneys, brain, liver, adrenals after water IS retained and this causes kidneys to shut down due to severe vasoconstriction (not disease of the kidney, it’s just that blood isn’t going there!) = decreased GFR = hepatorenal syndrome
Note: portal HTN causes splanchnic vasodilation but splanchnic vasodilation makes portal HTN worse because of blood pooling!
Definition of hepatorenal syndrome (HRS)
Clinical condition that occurs in patient with chronic liver disease, advanced hepatic failure, and portal HTN characterized by impaired renal function and marked abnormalities in arterial circulation and activity of endogenous vasoactive systems.
In kidney there is marked vasoconstriction that results in low GFR.
In extrarenal circulation there is predominance of arterial vasodilation that results in reduction of total systemic vascular resistance and arterial hypotension.
Diagnostic criteria for HRS
Cirrhosis with ascites
Serum creatinine >1.5 mg/dl
No improvement of serum Cr after > 2 days with diuretic withdrawal and volume expansion with albumin
Absence of shock
No current or recent nephrotoxic drugs
Absence of parenchymal kidney disease as indicated by proteinuria >500mg/day, microhematuria >50 RBC/hpf, and/or abnormal renal UTZ
Note: if patient improves with infusion of albumin, it is NOT HRS
Subtypes of HRS
Type I HRS: > doubling of initial serum creatinine to >2.5 mg/dl or 50% reduction in creatinine clearance to <20 ml/min within 2 weeks; may occur spontaneously but frequently has precipitating factor (severe bacterial infection (SBP), GI hemorrhage, major surgical procedure, or acute hepatitis imposed on cirrhosis); shorter survival of 2 weeks
Type II HRS: moderate and stable reduction in GFR; renal failure does not have rapidly progressive course; dominant clinical feature is severe ascites with poor or no response to diuretics; longer survival of 6 months
Management for HRS
Prevention: infuse albumin at dx of SBP; prophylaxis for SBP; use TNF inhibitor pentoxifylline in those with alcoholic hepatitis; avoid nephrotoxic agents/NSAIDs/ overdiuresis/large vol paracentesis
Use albumin to improve intravascular oncotic pressure and mobilize interstitial fluid into central blood volume
TIPS: divert portal blood flow to hepatic vein to systemic circulation; improve variceal bleed; improve renal perfusion; complications are bleeding, infection, hepatic encephalopathy and renal failure (due to dyes?)
Vasoconstrictors: analogues of vasopressin with decreased antidiuretic properties; terlipressin (not in US), octreotide (inhibits glucagon) + midodrine, NE + albumin; sometimes low dose vasopressin
Molecular adsorbent recycling system (MARS): combination of kidney and liver dialysis that has an albumin circuit so can remove albumin-bound toxins and water-soluble toxins (however not yet widely available or approved for tx of chronic liver disease)
Liver transplantation!!
Note: renal vasodilators do not work well!
Hyponatremia
[Na+] <136 mEq/L
Most common electrolyte disorder
Independent predictor of death amont ICU and geriatric patients, hear failure acute STEMI, cirrhosis (so need to pay attention to [Na] even though pt might not have symptoms!)
Pseudohyponatremia
Has nothing to do with total body water or salt imbalance
Falsely high volume: severe hyperlipidemia, hyperparaproteinemia (multiple myeloma, Waldenstrom’s macroglobulinemia)
Extracellular dilution due to extracellular free water shift: hyperglycemia (just give insulin to put glucose in cells!), hypertonic mannitol
Mis-measurement because lots of glucose/mannitol/sorbitol/glycine in blood brings water in but can’t measure those things so looks like hyponatremia
This doesn’t happen anymore!
True hyponatremia
Hypoosmolar state
Hypovolemic: sweat/renal/GI/pulmonary blood loss, third spacing (acute inflammatory state causes increased vascular permeability so intravascular vol shifts out into interstitial space), diuretics (HCTZ), mineralocorticoid insufficiency (cannot reabsorb Na+, cerebral salt wasting
Euvolemic: SIADH, hypothyroidism, cortisol insufficiency, psychogenic polydipsia, tea and toast/beer potomania, reset osmostat, pregnancy, nephrogenic SIAD
Hypervolemic: cirrhosis, nephrotic syndrome, CHF, renal failure
How do you get either hyper- or hypovolemic hyponatremia?
Initially you have low ECV (due to salt and water loss in hypovolemia or due to volume redistribution or vasodilation in hypervolemia), so increase ADH and thirst and drink a ton then get hyponatremic!
Must be able to secrete ADH and must have free water to drink in order to get hypovolemic hyponatremia
Note: looks like just the starting point that is different between hyper- and hypovolemic…mechanism is the same otherwise?
Causes of euvolemic hyponatremia
Hypothyroidism: not understood but maybe because CO down, renal plasma flow down so ADH upregulated to retain more water
Cortisol insufficiency: increased CRH which is co-expressed with ADH (just innocent bystander!)
Psychogenic polydipsia: dilution, kidneys can’t get rid of it quickly enough
SIADH: malignancies, drugs affecting CNS (antipsychotics, antidepressants, antiepileptics), CNS problems, pulmonary diseases, N/V, pain, hypoglycemia, NSAIDs, cyclophosphamide
Tea and toast syndrome/beer potomania: don’t eat enough so don’t have enough solute to make urine so can’t get rid of water (kidneys need solute in order to get rid of water)
Pregnancy: drink lots because higher thirst and threshold for ADH release is lower
Nephrogenic SIAD: gain of function mutation of ADH receptor so act like ADH always around!
Urine osmolality and urine Na+ findings in hyponatremia
Hypovolemia sweat/renal/GI/pulm/blood loss, third spacing: high urine osmolality, UNa <20
Hypovolemia mineralocorticoid insufficiency, cerebral salt wasting, diuretics: high urine osmolality, UNa >20
Euvolemia SIADH/SIAD, hypothyroid, cortisol insufficiency: high urine osmolality, UNa >40 (pts not retaining salt here!)
Euvolemia psychogenic polydipsia, tea and toast/beer potomania, reset osmostat, pregnancy: low urine osmolality, UNa varies
Hypervolemia cirrhosis, nephrotic syndrome, CHF: high urine osmolality, UNa <20 (trying to hold onto Na+)
Hypervolemia renal failure: urine osmolality similar to serum osmolality (cannot concentrate or dilute well), UNa >20 (cannot reabsorb Na+)
Clinical manifestations of hyponatremia
Moderate: lethargy, headache, N/V, muscle cramps, restlessness, disorientation, depressed reflexes
Severe: seizures, coma, permanent brain damage, respiratory arrest, brain stem herniation, death
Risks: severity and rate of change, Na>125 usually asymptomatic or minimally symptomatic
Osmotic demyelination syndrome (ODS)
When you rapidly increase serum [Na] and brain cells shrink and demyelinate
1-2 days: generalized encephalopathy
2-3 days: behavioral changes, cranial nerve palsies, progressive weakness culminating in quadriplegia with locked-in syndrome, possible death
Increased risk: malnourished patients, alcoholics, hypokalemic patients, burn victims, elderly women on thiazides, young menstruant women
Do not call this central pontine myelinolysis (CPM) because happens other places too!
Correction of symptomatic hyponatremia
5% increase in [Na+] should substantially reduce cerebral edema
Even seizures can be corrected by increase in [Na+] of 3-5 mmol/L
Acute symptomatic: correct at 1-2 mEq/L/hr for 2-3 hours or until neurological symptoms resolve
Chronic: 1/2 mEq/L/hr
Never exceed 8-10 mEq/L/day (use lower range for high risk patients)
Therapeutic options for hyponatremia
Water restriction in pts that are stable, euvolemic or hypervolemic (don’t want to water restrict someone who is dry!)
Salt supplement with isotonic normal saline in hypovolemic patients; use hypertonic saline in severely symptomatic patients w/severe hyponatremia or SIADH; use salt tablets if euvolemic or if SIADH of malignancy (sad to tell them to water restrict, but good to tell them to eat salty food!)
Increase renal water excretion in patients who aren’t eating make them eat, use vaptans to block vasopressin receptor 2, use furosemide to make dilute urine
Can get hyponatremic encephalopathy if not well oxygenated so make sure patient is oxygenated
What conditions can you use AVP (vaptans) for?
Euvolemic SIADH, hypothyroidism, cortisol insufficiency
Hypervolemic CHF, nephrotic syndrome, cirrhosis
In any of these conditions, if ADH is secreted too much, use vaptans
Vaptan: V2R antagonist (blocks action of ADH), aka “aquaretics” because get rid of water and not salt
Specific treatments for different kinds of hyponatremia
Hypovolemic: treat underlying disorder, give normal saline, discontinue HCTZ if applicable
Euvolemic SIADH, hypothyroid, cortisol insufficiency: treat underlying disorder, water restrict, salt suppress if severe
Euvolemic psychogenic polydipsia: water restriction
Euvolemic tea and toast/beer potomania: increase protein intake, consider urea
Euvolemic reset osmostat or pregnancy: leave them alone
Nephrogenic SIAD: same as SIADH except vaptans (won’t help bc this is gain of function mutation)
Hypervolemic: treat underlying disorder, water restriction, vaptans, salt supp if severe hyponatremia and vaptans not available
Potential pitralls in causing overcorrection of hyponatremia
Miscalculations
Failure to follow serum Na closely (if don’t catch disturbance until the next day it is too late)
Unrecognized sources of Na+ (other MD giving Na+, giving K+ causes Na+ to come out of cells and go into vasculature as if giving Na+!)
Excess free water loss (monitor urine output!): polyuria post pituitary infarction, GC replacement in pts with cortisol insufficiency, pts with central DI not taking ddAVP, excessive GI or skin hypotonic fluid loss, recovery from acute respiratory failure, withdrawal of thiazides during correction of hyponatremia, water deprivation in primary polydipsia, volume expansion with IV fluids
Problem with treating SIADH with normal saline infusion
Patient with SIADH has Uosm of 600
Give 1L of 300mM salt but kidneys want to concentrate urine (so much ADH around)
Kidney takes 300mosmol salt and 500ml water to create 600mosm urine! Then have 500ml free water left to reabsorb!
In the end it’s like you’re giving 500ml free water and making the problem worse!
Make sure osm of fluid is higher than osmolality of urine or else this will happen!
How does K+ administration cause Na+ to shift out of cells in intravascularly?
K+ into cells and Na+ out
K+ into cells and H+ out, but H+ does not contribute to osm because buffered, so water follows K+ into cells, decreasing intravascular volume
K+ and Cl- into cells, and again water follows K+ into cells, decreasing intravascular volume
If patient hyponatremic and hypokalemic, don’t give 200 Na+, give 150 Na+ and 50 K+
Types of polyuria
Water diuresis: nephrogenic DI, central DI, psychogenic polydipsia, pregnancy (vasopressinase in placenta degrades ADH!)
Solute diuresis: urea, glucose TPN, contrast dye, myoglobin, hemoglobin, mannitol, IV fluids
When do you get hypernatremia?
One of these 3 problems and inadequate free water replacement or thirst defect:
1) Excessive administration of Na+: NG feeding without adequate free water, normal saline replacement for hypotonic fluid loss, alkalinization of IV fluids (1 amp bicarb contains 45mEq Na!)
2) Free water loss: burn patient/GI/sweat loss of hypotonic fluid, nursing home/debilitate patient, DI + problem with free water access/thirst center, osmotic diuresis (TPN, glucose, urea, mannitol, diuretics, contrast dye)
3) Intracellular free water shift: rhabdomyolysis, seizures
Treatment for hypernatremia
If impending cardiovascular collapse use normal saline
If past +/- ongoing salt loss, use D5 1/4 NS, or D5 1/2 NS
If need excess glucose, use D10W
If water deprived nursing home/debilitated patient, use D5W, D5 1/4 NS (NEVER free water alone!)
Categories of kidney injury
Acute kidney injury: sudden decrease in GFR over hours or days
Rapidly progressive renal failure: renal fxn declines weeks to months
Chronic kidney disease: renal fxn declines >3 months
How to diagnose acute kidney injury
Presents as increase in serum BUN and creatinine and/or reduction in urine volume
Ongoing research of biomarkers but not ready for day to day clinical practice yet (most likely will be urine tests like KIM-1, NGAL)
Summary: most commonly diagnosed by change in BUN and/or serum creatinine (look at time course of change and if baseline creatinine not known, use clinical judgment); change in urine volume important mostly for defining prognosis but sometimes may be first manifestation of disease
Azotemia vs. uremia
Azotemia: increase in circulating concentrations of waste products/nitrogenous substances (viz. urea nitrogen, creatinine)
Uremia: syndrome of signs and symptoms associated with renal dysfunction
Every patient with uremia has azotemia, but most patients with azotemia are not uremic
RIFLE criteria minimum thresholds for acute kidney injury diagnosis
Risk of renal injury: creatinine 1.5x baseline, urine output <0.5 ml/kg/h for >6 hr
Injury to kidney: creatinine 2x baseline, urine output <0.5 mg/kg/h for >12 hr
Failure of kidney function: creatinine 3x baseline or >4mg/dl with increase >0.5 mg/dl, urine output <0.3 ml/kg/h for >24 hr or anuria for >12 hr
Loss of kidney function: persistent renal failure for >4 weeks
End-stage disease: persistent renal failure for >3 months
Other definitions: risk involves increase serum creatinine of 0.3-0.5 mg/dl over baseline
AKI is first 3 categories (“RIF”)
How do we diagnose kidney disease if we don’t know baseline serum creatinine?
Duration of renal dysfunction: pre-existing lab data, inpatient or outpatient
Anemia implies chronic kidney disease (no erythropoietin!): normocytic, normochromic anemia in the absence of any other cause of anemia
Kidney size: small kidneys specific for chronic kidney disease, normal sized kidneys can occur with either acute kidney injury or chronic kidney disease
Radiologic evidence for renal osteodystrophy or significant PTH elevation implies CKD
Greater the tolerance of azotemia, longer the time the patient has had kidney disease
What can interfere with creatinine secretion?
Drugs: trimethoprim, cimetidine inhibit the secretion of creatinine
Urine volume in AKI diagnosis
Urine volume <0.5 ml/kg/h considered to be reduced
Severity of AKI can be determined by presence/absence of oliguria (urine output <400 ml/day) or anuria (urine output <100 ml/day)
Prognosis of oliguric AKI (chance of recovery or death) is substantially worse than of non-oliguric AKI
Note: if urine volume less than 500, won’t be able to stay in fluid balance and will build up fluids
3 types of causes of AKI
Pre-renal: GFR falls due to inadequate renal perfusion (kidneys perceive low volume so produce less urine to maintain intravascular volume)
Intrinsic renal/renal parenchymal: involving glomeruli, tubules, interstitum, or blood vessels in renal parenchyma
Post-renal: mechanical obstruction to normal flow of urine from kidneys to ureters to bladder and finally through urethra
Pre-renal acute kidney injury
Hallmark is true or perceived decrease in perfusion to the kidneys
Causes include:
Hypovolemia: volume loss (GI, renal, skin), blood loss (GI, MVA)
Cardiac causes: acute cardiogenic shock, CHF
Liver disease: could be excessive diuretic use, GI bleeding causing vol depletion, hepato-renal syndrome, acute tubular necrosis
Nephrotic syndrome: ineffective intra-arterial volume and not a direct result of underlying disease
Renovascular: renal venous thrombosis
Intrinsic/parenchymal renal AKI
SIte of injury is glomerulus, tubulointerstitum, or intra-renal vasculature
Glomerulus: acute glomerulunephritis
Tubulointerstitial: acute tubular necrosis (ATN), acute tubulointerstitial nephritis, intra-tubular crystal deposition
Vascular: vasogenic, microangiopathic hemolytic anemia (MAHA), cholesterol emboli
Acute tubular necrosis (ATN)
Most common renal parenchymal disease that leads to AKI
Ischemic ATN: causes that lead to pre-renal disease cause ischemic ATN if severe enough or go on for long enough
Toxic ATN: caused by radiocontrast dye, aminoglycosides, amphotericin B, cis-platinum, endogenous myoglobin (after crush injury) and hemoglobin (after intravascular hemolysis)
On histology, see loss of brush border, some mitotic figures as cells divide and try to restore themselves
After ischemia and reperfusion, lose brush border, lose polarity, then cells undergo apoptosis and necrosis and obstruct lumen and cause backleak of tubular fluid
Acute interstitial nephritis
Form of parenchymal AKI caused by allergic reaction to administered medication (usually for 5 days or longer)
Most commonly caused by beta lactam antibiotics (penicillins, cephalosporins), PPIs, NSAIDs, H2 blockers
Renal dysfunction may be associated with fever or other systemic symptoms (rash, etc)
See eosinophiluria (>5%)
Intratubular obstruction
Parenchymal AKI caused by precipitation of some sort of crystals
Immunoglobulins/light chains in patients with multiple myeloma
Calcium in patients with hypercalcemia
Uric acid in people with tumor-lysis syndrome
Drug crystals in patients receiving acyclovir, indinavir, sulphadiazine
Oxalate in people who have consumed ethylene glycol or vitamin C
Vasogenic/Functional AKI
Can be classified as pre-renal or parenchymal
Functional disorder (reversed by stopping medication) due to change in vascular tone
Medication-induced AKI: NSAIDs cause inhibition of prostaglandins which leads to constriction of afferent arteriole which decreases GFR; ACEi and ARBs inhibit ATII which leads to dilation of efferent arteriole which also decreases GFR
Also cyclosporine/FK506 and hypercalcemia constrict afferent arteriole?
Post-renal AKI
Obstruction to urine flow leading to backup of fluid in bladder or in kidney
Obstruction must be bilateral, or unilateral in setting of underlying chronic kidney disease or single functioning kidney
Do US to see if buildup of urine
Key tests in virtually all cases of AKI
Urine analysis incuding microscopy
Urine electrolytes
Renal ultrasonography
Renal biopsy if suspect acute glomerulonephritis (rare to do this now though)
Urine analysis in AKI
Specific gravity tells you how concentrated the urine is
Dipstick measures albumin, blood, leukocytes/nitrate
Microscopy shows you cells (RBCs, WBCs), casts, crystals
Active urine sediment
Implies acute glomerulonephritis
Active urine sediment: glomerular hematuria (dysmorphic RBCs, RBC casts), generally associated with proteinuria
Only way to get red cells in urine is via glomerulus so must be problem with glomerulus causing AKI
WBC casts in the setting of AKI
In setting of AKI and sterile pyuria, implies tubulointerstitial nephritis
WBCs present if there is some sort of inflammation
Most common cause is acute pyelonephritis (bacteria), but drugs too??
Urine sediment in pre-renal AKI
Remember, usually no intrinsic damage to kidney yet
Generally benign
May see hyaline casts (but not sensitive or specific for any type of AKI)
Urine sediment in ATN
Epithelial cell casts
Muddy brown casts
This is rare, and occurs when tubule itself is undergoing necrosis
Interpretation of urine chemistry in pre-renal (incl HRS) vs. intrinsic renal
Pre-renal (incl HRS): urine vol decreased, sp gr >1.02, Uosm >500, FENa <1%, FEurea <35%, FEuric acid <7%, urine sediment has hyaline casts
Intrinsic renal: variable urine volume, sp gr 1.01, Uosm <350, FENa >2%, FEurea >35%, FEuric acid >15%, other urine sediment
Fractional excretion of sodium
FENa is percentage of filtered sodium that is excreted
In health (normal GFR): <1-2%
Pre-renal: <1%
Intrinsic renal >2%
FENa = [(UNa/PNa)/(UCr/PCr)] x 100 = [(UNa/UCr)/(PNa/PCr)] x 100
Considerations: urine volume (oliguric/non-oliguric) because normal FENa = pre-renal FENa!, false + FENa, diuretics (use FEurea instead because diuretics tell you not to reabsorb Na+)
Role for kidney biopsy
For overwhelming majority of clinical settings, decision making about distinction of acute vs. chronic, and potential causes is made on clinical grounds
Rarely used to diagnose AKI
Renal biopsy imperative in presence of urine sediment
Know someone has glomerulonephritis but want to know how to treat it?
Clinical course of AKI
Specifically ATN:
Initiation: don’t get BUN/creatinine increase until after time of injury; creatinine, eGFR poorly related to actual renal function
Maintenance
Recovery: may be polyuric
Time course generally lasts 3-10 days, may be up to 12 weeks
Principles of management of AKI
Correct underlying disease if possible: improve renal perfusion (give fluids or improve cardiac function) if pre-renal, relieve obstruction if post-renal, give steroids +/- cytotoxics for glomerulonephritis
If ATN or underlying causes not treatable, treatment is supportive: monitor fluids to prevent volume overload, manage metabolic complications, avoid nephrotoxics, know when to dialyze!
Agents to prevent or ameliorate course of parenchymal AKI have not been effective
What urinalysis reveals
Unremarkable: pre-renal AKI
RBCs in urine, dysmorphic: glomerulonephritis
Granular casts, epithelial casts, cellular debris: ATN
WBCs/WBC casts: pyelonephritis, interstitial nephritis (if WBCs are eosinophils) or glomerulonephritis
Eosinophiluria: allergic interstitial nephritis or cholesterol emboli
Muddy brown casts: acute tubular necrosis (ATN)
When do dialyze in AKI?
Absolute indications for dialysis: CHF despite diuretics, unable to medically manage hyperkalemia and metabolic acidosis, pericarditis, encephalopathy, signs/symptoms (severe volume overload where you need intubation or O2, etc..?)
AEIOU: acidosis, electrolytes (hyperkalemia), ingestion/intoxication, overload of fluid, uremia
Dialyze BEFORE any of these complications develop though (waiting for appearance of these is unacceptable!)
Prognosis of AKI
Occurrence of AKI increases death risk in patients with multi-organ failure in the ICU, in-hospital mortality may approach 80%
In patients who survive, renal function recovers in most, but even if serum creatinine normalizes, there is underlying scarring and GFR does not normalize
Also patients who survive are at higher risk for subsequent development of chronic kidney disease and end-stage renal disease
Prevention is always better but not always possible
What are the most common kinds of AKI?
Pre-renal azotemia and ATN comprise up to 80% of all causes of AKI
Need to distinguish between pre-renal azotemia and ATN!
Glomerular components from outermost in
Parietal epithelial cells of Bowman’s capsule (protect us from outside world!)
Bowman’s space (this is outside environment!)
Visceral epithelial cells (contain podocytes/foot processes that partially cover BM and spaces btwn are bridged by slit diaphragms)
Basement membrane (is outside of either endothelial cells of capillary or mesangial cells)
Endothelial cells (fenestrated)
Capillary lumen
Note: mesangial cells are inthe middle, contacting either BM or endothelial cells at all times
Mesangium
Support the capillaries and endothelial cells
Like stroma (support), modified smooth muscle cells/pericytes
Consists of matrix and mesangial cells
Mesangium contiguous with media of arterioles
Mesangial matrix material is similar to basement membrane material (both stain silver!)
Mesangial cells have contractile function, phagocytic, proliferate, secrete biologic mediators, produce mesangial matrix
What cells do the endothelial cells contact?
In the glomerulus, endothelium is only partially surrounded by mesangium
Where mesangium is absent, the endothelium is surrounded by glomerular basement membrane
So, endothelium supported by either mesangium or basement membrane
Subepithelial vs. subendothelial immune deposits
Subepithelial deposits: between epithelial cells (which have podocytes) and BM; usually have less inflammation; are father out toward Bowman’s capsule
Subendothelial deposits: between endothelial cell (fenestrated, right by capillary lumen) and BM; usually have more inflammation; closer in toward capillary lumen
Glomerular basement membrane (GBM)
Collagen Type IV (forms a network to which other proteins attach: laminin, proteoglycans, fibronectin)
6 different collagen IV alpha chains which combine in various forms to produce collagen Type IV triple helices (building blocks of GBM)
Slit diaphragm
Composed primarily of nephrin a transmembrane protein whose extracellular portion extends between the foot processes but intracellular portion connects to podocin, CD2AP, and actin cytoskeleton
This whole thing is one unit and comprises part of the cytoskeleton
Terminology for glomerular disease
Focal: involving <50% of glomeruli
Diffuse: involving >50% of glomeruli
Segmental: involving a portion of a glomerulus
Global: involving most of a glomerulus
Histologic alterations of glomeruli
Hypercellularity (used to be called proliferation)
BM thickening or duplication
Sclerosis: closure of capillary loops, solidification
Hyalinosis: insudates of plasma proteins that become trapped in areas of scarring; glassy, pink eosinophilic stuff
Crescents: cellular proliferation in Bowman’s space (macrophages, neutrophils, epithelial cells, fibrin); usually due to BM rupture; seen in severe glomerular injury
Pathogenesis of glomerular injury
1) In situ antibody antigen reactions (antibody against intrinsic glomerular antigen or against planted antigen (that got into glomerulus from elsewhere)): Type II hypersensitivity reaction
2) Deposition of circulating antibody antigen complexes: Type III hypersensitivity reaction
3) Cytotoxic antibodies
4) Cell mediated immunity
5) Soluble mediators (complement, cytokines, etc)
Detection of immune complex deposits
Use immunofluorescence to detect and characterize (IgG, IgA, IgM, C3, etc)
Use EM for precise localization of deposits (subepithelial vs. subendothelial)
How long do circulating immune complexes cause problems for?
If process of forming ICs is transient then deposits are phagocytized and/or degraded; inflammatory changes resulting from deposits resolve –> patient gets better
If process is continuous, disease is chronic and get progressive glomerulonephritis –> dialysis, death or transplantation
5 major clinical syndromes of glomerular disease
Nephrotic syndrome
Acute nephritic syndrome
Rapidly progressive glomerulonephritis (RPGN)
Asymptomatic hematuria and proteinuria
Chronic renal failure
Nephritic vs. nephrotic syndrome
Nephritic: inflammatory process (variable combo of neutrophils, lymphocytes and macrophages in capillary loops); hematuria (capillary wall injury), RBC casts, azotemia, oliguria, hypertension, mild proteinuria (<3.5g/day)
Nephrotic: edema, hypoalbuminemia, hyperlipidemia/hyperlipiduria, massive proteinuria (>3.5g/day)
Note: in nephrotic syndrome, the holes in the podocytes allow proteins to go through and leak out, but don’t allow cells to go through, so no RBCs in nephrotic syndrome!
Membranous nephropathy
Nephrotic syndrome
Most common cause of nephrotic syndrome in adult caucasians
Antibody reaction to antigens located on epithelial cells (Type II): Ags may be intrinsic to epithelium (phospholipase A2 receptor on visceral epithelial cell = primary/idiopathic) or planted on epithelial cell after crossing BM (bacterial or viral antigens (syphilis, schistosomiasis, malaria, Hep B, rarely Hep C), malignancy (lung, colon, breast, melanoma), rheumatic disease (lupus, scleroderma), inorganic salt (gold), some drugs (captopril, penicillamine))
Subepithelial deposits, then with progression get segmental and global sclerosis
LM: thickened GBM (epithelial cells respond to injury by making more BM); see “stubble” because BM spikes are dark and deposits are light
IF: granular deposits of IgG and complement along BM
EM: “spike and dome” appearance of new BM with spikes (podocytes) forming between subepithelial deposits
Prognosis: variable course, proteinuria in 60%, progressive renal disease in 40%, renal failure in 2-20 years
Minimal change nephropathy
Nephrotic syndrome
Most common cause of proteinuria in children, but can occur at any age
Lipoproteins in urine, follows viral infection, associated with Hodgkin’s lymphoma
LM: normal glomeruli
EM: foot process effacement
IF: negative
Tx: steroids (don’t need to take biopsy to treat)
Focal segmental glomerulosclerosis (FSGS)
Nephrotic syndrome
More common in AA and hispanic, risk is obesity
Hematuria and hypertension usually seen
Can be primary (idiopathic) or secondary as a component of glomerular ablation nephropathy (nephron loss leading to hyperfiltration of remaining glomeruli) or congenital (mutation in nephrin or podocin), or secondary to other glomerular diseases; soluble mediator in serum has been identified
FSGS recurs after transplantation in 10-20%, can recur within 24-48 hours, recurrence rate higher in patients who had aggressive disease in native kidney
IF: negative, no ICs
EM: negative, no ICs
Prognosis: 50% of patients in renal failure in 10 years
Tx: prevent recurrence after transplantation with aggressive plasmapheresis (get rid of soluble mediator)
Membranoproliferative glomerulonephritis (MPGN) Type I
AKA mesangiocapillary GN
Usually nephrotic but can present as mixed nephrotic and nephritic
Pathogenesis: ICs from serum sickness, deposits can trigger/fix complement, recruit inflammatory cells
Mesangial proliferation (reaction to deposits) and capillary wall abnormalities –> large glomeruli, “lobular accentuation” of glomerular tuft, hypercellular
Thickening of capillary walls due to massive subendothelial deposits
Double contoured (“tram-track”) capillary walls due to migration of mesangium into capillary wall in reponse to subendothelial deposits
Can be primary (idiopathic): IgG and complement deposits; more common in children
Can be secondary due to infections (infected shunts, Hep B, Hep C) or lupus: IgG and any combination of IgA, IgM, and complement; more common in adults
IF: granular deposits along loops and in mesangium
Prognosis: 30-40% progres to chronic renal failure
Membranoproliferative glomerulonephritis (MPGN) Type II
AKA dense deposit disease (DDD)
Similar presentation to idiopathic (Type I) MPGN: nephrotic or mixed
In children and young adults; not associated with hepatitis or bacterial infections or lupus; not associated with circulating ICs
Pathogenesis: activation of alternate complement pathway; mutations in complement components, Abs which interfere with various complement components resulting in inappropriate activation, anti-complement factor H or B; in children usually mutation in complement and in adults usually autoantibody
BM thickened by ribbon-like deposits; complement present in irregular granular and linear distribution, variable mesangial cell proliferation and inflammatory cell component
Difference from Type I is that get intramembranous very dense IC deposits in BM
Decreased serum C3 but normal C1 and C4
Acute proliferative glomerulonephritis
Nephritic syndrome
IC deposits trapped in glomerulus (bind/fix complement, leukocytic infiltration, proliferation of mesangial, endothelial and epithelial cells) that can be caused by exogenous antigens (post-infectious/poststreptococcal) or endogenous antigens (lupus)
Poststreptococcal GN is one type
Can also get it from staphylococcus, Hep B, plasmodium (malaria), treponema (syphilis)
Poststreptococcal glomerulonephritis
Nephritic syndrome
Type of acute proliferative glomerulonephritis
Group A (Strep pyogenes) beta hemolytic strep (strains 12, 4, 1)
1-4 weeks following skin or pharyngeal infection (latent period correlates with time required for production of antibodies against strep organism)
Diffuse global GN and glomeruli full of neutrophils (swollen endothelium, occasionally segmental fibrinoid necrosis, rarely see crescents)
IgG and complement on capillary walls and in mesangium; starry sky pattern (less uniform than in membranous nephropathy); subepithelial lumpy-bumpy pattern plus some subendothelial and mesangial deposits on EM
Prognosis: most children recover but 15-50% of adults develop end stage renal disease; deposits resolve within a few months, no scarring in most cases, biopsy not performed if diagnosis certain
IgA nephropathy (Berger’s Disease)
Nephritic syndrome
Most common primary glomerular disease worldwide; more common in Asian and hispanic but uncommon in AA
Often follows URI or GI infection; most present with hematuria or proteinuria; 10% present with nephrotic syndrome
Related to Henoch Schonlein purpura
Pathogenesis: IgA Ab/Ag complexes trapped in mesangium; abnormal IgA production and clearance (increased IgA production in bone marrow); only 50% have increased serum levels of IgA; increased incidence in twins; increased incidence with celiac disease and liver disease (liver can’t clear IgA Ab/Ag complexes from intestines); abnormal glycosylation may reduce plasma clearance of IgA
LM: mesangial proliferation, segmental sclerosis, crescents
IF: mesangial deposits
EM: deposits, mesangial matrix (both under BM but in mesangial cell, so not called subendothelial)
Prognosis: 25-30% develop renal failure over 20 years; rarely aggressive
Henoch Schonlein purpura
Systemic IgA syndrome due to IgA deposition in multiple organs
Skin: purpuric rash
GI: abdominal pain, bloody diarrhea
Joints: arthritis
Kidney: IgA nephropathy
Note: cannot diagnose Henoch Schonlein purpura by kidney biopsy–need to look at entire patient and see IgA vasculitis elsewhere
Alport syndrome (hereditary glomerulonephritis)
Nephritic syndrome
Mutation in Type IV collagen causes glomerulonephritis, deafness and eye problems
Variable inheritence; mutations in alpha 3, 4, 5 chains of collagen Type IV; X-linked, AR or AD inheritance
Variability in collagen deletion leads to variability in clinical presentation/severity
LM: variable and nonspecific; progressive glomerular sclerosis
IF: negative
EM: alternately thick and thin BMs; thick areas have irregular lamination of lamina densa (“basket weave” pattern)
Thin basement membrane nephropathy
Nephritic syndrome
Some siblings of Alport’s patients have this (in others it is sporadic); females in families with X-linked disease
Non-progressive microscopic hematuria only
Rapidly progressive glomerulonephritis (RPGN)
Nephritic syndrome
A clinical syndrome (rapidly deteriorating renal function over days to weeks) and if untreated have irreversible loss of renal function
Various causes/disease associations: Goodpasture’s syndrome, Wegener’s granulomatosis, microscopic polyangitis
LM and IF: all (>50%) glomeruli have crescents (severe glomerular injury almost always due to ruptured capillary loop BMs, contain fibrin in Bowman’s space, macrophages, epithelial cells, and plasma proteins like C3b; may see platelets walling off ruptured BM)
Note: if disease is not rapidly progressive (so not classified as RPGN) then just presents with nephritic syndrome
3 groups of crescentic GN
1) Anti-GBM disease (10-15%): Goodpasture’s syndrome (linear IgG deposits on capillary walls by IF but not EM, tx with plasmapheresis to remove pathogenic Ab)
2) Circulating immune complex mediated disease (45%): IgA (Henoch Schonlein purpura), MPGN, lupus, postinfectious, rarely membranous nephropathy; plasmapheresis does not help
3) Pauci-immune (45%): nothing seen on IF; most patients have +ANCA (microscopic polyangitis = pANCA/anti-MPO; Wegener’s granulomatosis = cANCA/anti-proteinase 3)
Why is it that when you have extensive loss of nephrons, you progress to ESRD?
1) Focal segmental glomerulosclerosis (FSGS): as nephrons die, the surviving ones have to work harder and become damaged; compensatory hypertrophy, increased blood flow/filtration/transcapillary pressure, injury to endothelial and epithelial cells, protein accumulation in mesangium –> triggers proliferative and inflammatory mediators which cause injury to epithelium –> proteinuria; segmental scarring and eventually global scarring –> decreased GFR –> vicious cycle
2) Tubular atrophy and interstitial fibrosis: glomerular scarring causes scarring of tubules because efferent arteriole cannot supply blood to tubulointerstitum so causes ischemia and inflammation and scarring –> inflammation induces fibrosis and that entraps next tubule over –> tubule scarring causes sclerosis of the upstream glomeruli –> severe proteinuria and vicious cycle
What 3 conditions is low C3 associated with?
1) Post-infectious GN
2) Lupus
3) Membranoproliferative glomerulonephritis (MPGN)
Note: lots of things that cause GN do not have low C3, but if you DO find low C3, must be one of these
Treatment for AFR due to ATN caused by myoglobinuria
Alkalinize urine to solubilize myoglobin
Mannitol and saline to enhance excretion of myoglobin
Keep patient hydrated to flush out myoglobin
Obtain urine electrolytes prior to treatment to provide insight into diagnosis
Diuretics and dye studies (nephrotoxicity) contraindicated
Hemolytic uremic syndrome
Triad:
1) Microangiopathic hemolytic anemia
2) Thrombocytopenia (low platelets)
3) AKI (uremia)
Things that increase/decrease BUN:creatinine ratio
Muscle wasting and cachexia: decreased creatinine production –> increases ratio
Rhabdomyolysis: spills creatinine into the blood –> decreases ratio
Dehydration: induces urea reabsorption –> increases ratio
High dietary protein: increases BUN –> increases ratio
GI bleeding: increases urea production as RBCs are broken down in the intestine –> increases ratio
Liver disease –> decreased urea production because no urea cycle –> decreases ratio
Kidney injury caused by NSAIDs and ACEIs
NSAIDs: block effect of prostaglandins, constricting afferent arteriole to decrease GFR; acute interstitial nephritis (AIN), nephrotic syndrome, renal papillary necrosis
ACEIs: block effect of angiotensin II, dilating efferent arteriole to decrease GFR; acute interstitial nephritis (AIN), membranous glomerulonephropathy, immune complex glomerulonephritis, acute tubular necrosis
If taking both ACEI then NSAID, can develop pre-renal azotemia because very low GFR!
