Exam 2 (AKI, CKD) Flashcards
Criteria for CKD
If either of the following is present for >3 months
-Markers of kidney damage (one or more)
Albuminuria, urine sediment, electrolyte or other
disorders, H/O transplant, other
-Decreased GFR (<60mL/min)
What is the easiest way to know if a patient has CKD?
By monitoring decreased GFR using MDRD.
Can also assess protein in urine because that typically doesnt happen in AKI
Stages of CKD
1- Normal, GFR>90mL/min
2-Mildly decreased, GFR 60-89
3- Mild to moderate decrease, GFR 45-59
Moderate to severely decreased, GFR 30-44
4- Severe decreased GFR, GFR 15-29
5- Kidney Failure, GFR <15 or dialysisWhat are the common causes of ESRD?
Diabetes and HTN are the main causes
Can also be because of glomerulonephritis
CKD susceptibility risk factors
Diabetes, HTN, Older age (>55), family history, racial or ethnic minority
Progression factors of CKD
higher levels of proteinuria Higher BP Poor glycemic control Smoking Hyperlipidemia Drugs Obesity
CKD complications
CVD
Anemia
Altered bone and mineral metabolism
Pathophysiology of CKD
Loss of nephron mass-damage due to one or more of the progression factors
Glomerular capillary HTN- mediated by AT II
Proteinuria- Both a marker of damage and can lead to further damage as proteins are toxic to tubular cells
If a patient had a recent infection, symptoms with urination, a skin rash, or arthritis, what might be the potential problem?
Post-step glomerulonephritis
UTI
Lupus
If a patient has chronic disease such as CHF, cirrhosis, diabetes, HTN, what might be the potential problem?
Prerenal CKD or CKD
If a patient has a family history, what might be the potential problem?
Polycystic kidney disease
What lab values should you measure for CKD patients?
Estimated GFR (at least annually)
BP
Urine examination (at least annually)
-Albumin:Cr ratio (UACR) in early morning urine
sample(Albuminuria if >30)
-Examination for casts, sediment, etc.
Imaging studies
What is progression of CKD defined as?
A drop in GFR more than 5mL/min/year
What are common CKD complications?
Anemia, HTN, Vit D deficiency, acidosis, hyperphosphatemia, hyperparathyroidism
What are interventions of CKD that can delay progression?
ACE-Is, ARBs, BP control, blood glucose control
How do ACE-Is and ARBs delay the progression of CKD?
They lower systemic blood pressure, thus lowering glomerular capillary blood pressure and protein filtration rate. They also reduce AT II mediated cell proliferation and fibrosis.
This is accomplished in very low doses.
What is the evidence of ACE-Is and ARBs in delaying progression of CKD?
Should be used if UAE >30mg/day with diabetes
Should be used in all CKD pts with UAE >300mg/day
Patiromer (Veltassa)
Non-absorbed cation exchange polymer (K+ binder, exchanges for Na)
Used in patients with chronic hyperkalemia associated with ACE/ARB use
8.4g QD- Space out from other oral medications by 3 hours
May cause constipation or diarrhea
Sodium Zirconium Cyclosilicate (Lokelma)
Used in patients with chronic hyperkalemia associated with ACE/ARB use.
Use this or Patiromer (Not both)
10mg TID- space out from other medications by at least 2 hours
May cause edema
What do we do if Cr increases more than expected when a patient is on an ACE or an ARB?
If increased 30-50%, reduce dose
If increased >50%, D/C
This is a dose related effect
Can ACE and ARBs be used together?
No
Too high of a risk for hypotension, hyperkalemia, and decrease in kidney function.
This combination could cause an AKI on top of a patients CKD.
ACE-Is and Aldosterone blockers in CKD
Avoid combination except in CHF patients because of the high risk of hyperkalemia
Diuretics in CKD
Generally necessary in most CKD patients to help control fluid volume and BP
Most CKD patients have hypernatremia so diuretics reduce the Na levels.
Diuretics work synergistically with ACEe/ARBs by activating RAAS and promoting fluid retention
When do you use which diuretic in CKD
Thiazides if CrCl >30ml/min
Loops for CrCl <30ml/min
Cautious use of K-sparing diuretics especially if pt is on an ACE/ARB or has CrCl <30ml/min
Overdoing diuresis can lead to decreased GFR
What electrolytes do you monitor for with diuretic use?
Hypokalemia- loop and thiazide Hyperkalemia- K sparing Hypomagnesemia- Loop Hypocalcemia-Loop Hypercalcemia- Thiazide
What are additional antihypertensive options for CKD?
Beta-blockers- Not helpful or harmful in CKD but proven CVD benefits. Must counsel patient if diabetic. Do not use or adjust dosage of atenolol (renally cleared) Non-DHP CCBs (Verapamil, Dilt)- reduces proteinuria Avoid DHPs (nifedipine, Amlodipine) unless out of options and avoid aliskiren because of hyperkalemia.
What constitutes uremia?
Having baseline symptoms chronically
Nutrition considerations for CKD
Eat low K and Phos foods
Keep salt intake <2g/day
Low sugar, low carb, normal BMI
What is the general approach of HTN and CKD?
Goal is to prevent ESRD and CVD
Most patients will be on 2 or more antihypertensives
Monitor BP and level of proteinuria
Side effects are more likely in CKD pts
What did the SPRINT trial teach us?
CKD is worsened if BP gets too low.
Because of this trial we now have a goal BB for CKD+HTN pts <130/80 (ACC guidelines)
If urine albumin is >300 in a HTN/CKD pt, what do you do?
Maximize ACE-Is when protein is in urine.
Give ACE-Is across the board if protein in urine.
May have to use additional HTN medications if blood pressure is not <130/80
Hemoglobin A1C
Measures long-term diabetes control.
Keeping A1c <7% slows the development of complications
Macrovascular complications-CAD, stroke
Microvascular complications- Nephropathy, retinopathy, neuropathy
Medications in diabetes
Insulin- renally cleared (be cautious with dosing)
Oral agents:
sulfonylureas- cleared by kidney (Glipizide is only one w/o active metabolites so it is preffered)
Metformin- if drug and metabolites accumulate it causes lactic acidosis
Diabetic nephropathy
Generally occurs with 10 years of poorly controlled diabetes.
Has persistent albuminuria
20-40% of diabetic patients develop CKD
Pathophysiology of diabetic nephropathy
Mesangial cell hypertrophy (reduced GFR) Advanced glycation end products (leads to sclerosis and fibrosis of glomerulus) Oxidative stress Damaged glomerular filtration barrier Tubulointerstitial injury RAAS
Screening of diabetic nephropathy
Urine albumin excretion tested annually
If >30, repeat 2 more times within 3-6 months
Positive test if 2/3rds are positive
SCr annually (calculate GFR)
Treatment of diabetic nephropathy
Intensive glucose control to slow progression of albuminuria (A1C <7%)
Control BP <130/80 with ACE
Control albuminuria- ACE or ARB
Smoking cessation
Protein restriction (0.6-0.8g/kg/day)
DM alone is not an indication for ACE/ARB, must also have CKD
Tight glucose control in CKD
Blood sugar goals
Pre-prandial 80-140mg/dL
Post-prandial <180mg/dL
A1C goal <7%
GLP-1 agonists and SGLT2 inhibitors in CKD
Both classes reduce CV events
Incidence of CVD in CKD patients
> 50% of dialysis pts have coronary calcifications
CHF is the leading CV condition you will see (HTN+volume overload)
40% increase of stroke
Pts should be on high-intensity statin and ASA
Cardiac monitoring for CKD
BNP
-BNP is not accurate when GFR <60mL/min
Troponins
-Not accurate when GFR <60mL/min
What is the significance of proteinuria?
Results from injury to glomerular filtration (marker of kidney disease)
Marker of systemic injury (increased CV risk)
Dyslipidemia in CKD
All CKD patients >50 should receive a high-dose intensity statin
Avoid statins in dialysis patients
The increased risk of proteinuria with statins is dose related so rosuvastatin must be limited to 10mg/day in stages 4 and 5
What did the SHARP trial teach us?
Do not give statins in dialysis pts
Eze/simv combo did not reduce events
Polycystic kidney disease (PKD)
Genetic autoimmune disorder
Causes fluid filled cysts on both kidneys which cause a dramatic increase in size
2 forms- autosomal dominant and recessive (infants)
Symptoms of PKD
HTN Family history heart problems or strokes kidney stones constant or intermittent pain in back or side hematuria
Treatment of PKD
Manage pain
Treat infections
Treat HTN- goal <130/80
Prepare for ESRD (dialysis or transplant)
Tolvaptan has some data that shows that it may slow the increase in renal volume and decline in renal function
What are the methods of urine analysis?
Random (no warning or prep)
Clean catch, midstream (1st half discarded, second half collected and evaluated)
Bladder catherization- avoid if possible
Suprapubic needle aspiration- Needle directly into bladder to catch urine
24 hr urine collection- cumbersome and inaccurate
What are the definitions of polyuria, oliguria, and anuria?
Polyuria-excess urine production
Oliguria- Urine production <500mL/24 hours
Anuria- Urine production <50mL/24 horus
What do the following odors of urine mean? Sweet or fruity, foul, strong
Sweet or fruity- Glucose, ketones
Foul- infection
Strong- dehydration, foods
What drugs change the color of urine?
Nitrofurantoin- brown
Amitriptyline- Green/blue
Phenazopyridine- orange
Rifampin- Red
What is the purpose of the urinalysis?
To reveal diseases that may go unnoticed. Glomerulonephritis Hypertensive nephropathy Renal failure Infection Diabetes
Why do hypertensive patients get a urinalysis every year?
Because it takes 1/2 of the nephrons to be damaged in order to affect the creatinine.
How do infections affect the urine pH?
They increase it (more basic)
Specific gravity of urine
Normal range (1.002-1.035)
Measures urine density
Ability of the kidney to concentrate urine
High specific gravity=Dehydrated patient=Hypovolemia
High specific gravity=kidney stones
Protein in urine
Normal is negative or trace Primarily albumin Protein is filtered at the glomerulus and reabsorbed in the proximal tubule. If there is protein in the urine, there has been tubular damage. Microalbuminuria- 30-300mg/day Macroalbuminuria- >300mg/day
Glucose in urine
Normal is negative
Usually correlates with blood glucose >180mg/dl, because it “spills” into the urine.
Ketones in urine
Normal is negative
Spilled into the urine when the body cannot utilize glucose or lack of glucose intake.
Find in patients with life-threatening hyperglycemia (diabetic ketocacidosis)
Blood glucose 800-1000mgdL or starvation
Bilirubin in urine
Normal is negative
If present, a marker of liver disease
Blood in urine
Normal is negative
Called hematuria
Correlates clinically with an injury to the kidney (UTI, traumatic sample, injury, stones)
Can also be caused by mygoglobinuria from rhabdomyolysis
Nitrites in urine
Normal is negative
Bacteria in the urine is converted into nitrates, which then get converted into nitrites.
Presence of nitrites in urine signals the presence of gram negative organisms in the urine.
A negative result does not rule out a UTI, but a positive result indicates a UTI
Leukocyte esterase in urine
Normal is negative
Positive test detects the presence of lysed white blood cells in urine.
Indicates infection
Red blood cells in urine sediment
Normal 0-2/hpf Hematuria A marker of: Glomerular disease Tumors that affect urinary tract Kidney trauma Renal infarcts Infections Traumatic catheterizations Renal stones Nephrotoxins
White blood cells in urine sediment
Normal 0.-3/hpf
Termed pyuria
Marker of infection, glomerulonephritis, interstitial nephritis, inflammation, or rejection of transplant
Squamous epithelial cells in urine sediment
If present, likely contaminated with skin flora
Bacteria and yeast in urine sediment
Should not be present, if present look at nitrates, WBCs, etc.
Correlates clinically with s/s of a UTI
Can be caused by asymptomatic bacteruria, chronically catheterized patients, pregnancy, or be a contaminated specimen.
Culture and Sensitivity (C&S) is next step
Significant bacteruria >100,000 CFU of one organism needs to be addressed
Repeat if only yeast because contamination likely occurred.
Casts in urine sediment
Means any nephrons have been damaged
Collection of protein, cells, and debris
Formed in distal tubule and collecting duct
Important marker of kidney damage
Types of casts
Hyaline- most common, marker of kidney disease
Red cells- hematuria, glomerulonephritis (GN)
Granular- significant renal disease, “muddy brown”, ATN or GN
Epithelial- interstitial nephritis, ATN
Waxy- degenerated granular casts, marker of significant CKD
Crystals in urine sediment
Formed by precipitation of urine salts subjected to changes in pH or concentration
Calcium- kidney stones
Urate- hyperuricemia
Both could indicate post-renal obstruction
Some drugs (sulfonamides) may crystallize in the urine so you have to take with water.
UA markers of renal disease
Protein, blood/hematuria, casts (hyaline or granular)
UA markers of infection
Nitrites (gram neg), leukocyte esterase, pyuria/WBC, bacteria if above are found and symptomatic
What does mucous in UA indicate?
Contaminated specimen
Azotemia
Accumulation of nitrogenous wastes in blood (increased BUN)
Uremia
Constellation of symptoms associated with azotemia
Uremic symptoms drive treatment recommendations
Oliguria
Urine output <500ml/day
Signal high risk of morbidity and mortality
Anuria
Urine output <50ml/day
Signal high risk of morbidity and mortality
Nonoliguria
Urine output >500ml/day
Urine output is normal, but patient has AKI
What is the KDIGO definition of AKI?
Rapid (hours to days) deterioration of renal function.
This can be shown by:
-Increase in creatinine of >/=0.3mg/dl in <48 hours
OR
-Increase in creatinine to >/=1.5 times baseline which is presumed to have occurred in the prior 7 days
OR (less commonly used)
-Urine output <0.5mg/kg/hr for 6 hours. The urine output is more immediately affected by AKI than SCr.
What might future definitions of AKI include?
Tubular injury and kidney stress biomarkers
What is the difference between AKI and CKD?
AKI- abrupt onset, often reversible if treated early
CKD- the end result of irreparable damage to the kidneys. Develops slowly over the course of years. Technically defined as greater than 3 months of chronically decreased GFR. You have to lose 1/2 of your nephrons before CKD occurs.
Epidemiology of AKI
2-20% of hospitalized patients
(20-60%) ICU patients
Associated with significant morbidity and mortality
Mortality of 15-40% if acquired in hospital-prevention is key!
Why do so many ICU patients develop an AKI?
The body adapts to serious illness by bringing blood to the brain and heart.
Some patients in ICU are given pressors (Norepinephrine) to increase BP and they cause AKIs because they are very nephrotoxic. Sacrifice kidneys to save the patient.
What constitutes the syndrome of AKI?
Accumulation of nitrogenous waste products (Increased BUN and Cr)
Increased SCr
Derangement of extracellular fluid balance
Acid-base disturbance
Electrolyte and mineral disorders (hyperkalemia and hyperphosphatemia)
What are the symptoms of AKI?
Decreased urine output (70%) Edema (especially lower extremity) Mental status change (uremia) Heart failure N/V (uremia) Pruritus (uremia) Symptoms that correlate with any associated electrolyte disorders
What constitutes uremia?
Renal failure Mental status changes (lethargy, confusion) Muscle weakness Anorexia Dysgeusia (metallic taste) Pericarditis (can cause fatal arrhythmias) Neuropathy N/V Pruritis Dyspnea Pulmonary edema
What are the types of AKI?
Prerenal, intrarenal, postrenal
What are the types of intrarenal AKI?
Vascular, glomerular, tubular, interstitial
Prerenal azotemia
Caused by decreased blood flow to the kidney. This causes decreased filtration of toxins and increased SCr and BUN (azotemia)
The integrity of renal tissue is preserved initially so it may be reversible! It causes ischemic damage if not corrected.
Which patients are most likely to have prerenal azotemia?
Patients with dehydration and hypotension
What factors increase the susceptibility to renal hypoperfusion?
- Structural changes in arteries (old age >75)
- Chronic HTN or acute hypotension
- CKD
- Reduction in vasodilatory prostaglandins
- Failure to vasoconstrict the efferent arterioles (ACE/ARB)
- Renal artery stenosis
- Intravascular volume depletion (dehydration, CHF, liver disease)
Why are elderly patients (>75) more susceptible to renal hypoperfusion?
Elderly people have decreased renal blood flow and their SCr may not increase because they have lower muscle mass.
Which medications cause an impaired compensatory mechanism?
NSAIDs- suppress afferent arteriole vasodilation that body would desire to increase renal blood flow
ACE/ARBs- suppress the efferent vasoconstriction that body would desire to maintain adequate perfusion pressure inside the glomerulus
Signs/Symptoms of hypovolemia
Decreased blood pressure Increased HR Orthostasis Pallor, dry mucous membranes BUN:SCr ratio increased FENa
Main categories of prerenal AKI
decreased circulatory volume (hypovolemia) diminished cardiac output (HF) hypotension impaired compensatory regulation Systemic/renal vasoconstriction Renovascular obstruction
What causes decreased circulatory volume, and thus a prerenal AKI?
Dehydrated patient Renal losses- diuretics, diabetes Skin losses- sweating, burns Third spacing due to hypoalbuminuria- cirrhosis Hemorrhage
plasma BUN:Cr ratio
Normal ratio is 20:1
In pre-renal AKI- >20 usually. Rises faster than usual due to more reabsorption
If BUN and SCr are elevated, but the ratio is still close to 20, then this is indicative or a chronic renal disorder.
FENa
Fractional excretion of sodium
FENa=(Urine Na+plasma Cr)/(Plasma Na+ Urine Cr) x 100
FENa <1%= prerenal AKI ( body is trying to preserve Na in the face of volume depletion)
FENa>2%= acute tubular necrosis (body cannot preserve Na because tubules are damaged)
What kind of medication will elevate urine sodium and make FENa calculation innacurate?
Loop diuretics (furosemide)
Risk factors for ACE/ARB induced AKI
Reduced renal blood flow- CHF, bilateral renal artery stenosis
Volume depletion- dehydration, excessive diuresis
Hold ACE/ARBs if patient is volume depleted!
What should you do if SCr rises with ACE/ARB?
It is expected to rise up to 30%
It should stabilize, but if it doesn’t D/C medicine and correct underlying condition (rehydration)
Consider captopril if you still want an ACE but are unsure of renal effects. It has a very short 1/2 life.
Effects of ACEI-s on the kidneys
Protects the kidney by decreased pressure inside the glomerulus
- Reduces damage to glomerulus and reduces protein spillage in urine
- This is why ACE-is are drugs of choice for diabetics and those with hypertensive kidney disease
May decrease renal function by decreasing pressure inside glomerulus
-Decreases filtration of creatinine which raises SCr levels
Effects of NSAIDs on the kidneys
Inhibition of cyclo-oxygenase leads to vasoconstriction of afferent arterioles
This reduces GFR
This sets up patients who are already at risk of reduced GFR to go into renal failure- elderly, CHF, hypotensive, dehydration
What are the causes of systemic/ renal vasoconstriction that can cause a prerenal AKI?
pressors- vasopressors
General anesthesia
Afferent vasoconstriction- sepsis, cyclosporine, tacrolimus, radiocontrast dyes
Why do NSAIDs increase the risk of AKI?
afferent vasoconstriction
What is hepatorenal syndrome?
It is found in patients with liver failure because liver failure causes renal failure
Portal HTN causes ascites and renal vasoconstriction
Cyclosporine/Tacrolimus
Afferent constrictors
Used to prevent rejection of implanted organs
Can have acute and chronic toxicity
Renal function improves rapidly following dose reduction.
Prevention- closely monitor levels, use CCBs to manage HTN (dilate afferent arterioles)
Intrarenal AKI- vascular
Clot in renal artery
Can be caused by thromboembolic disease, angioplasty, severe CHF, AFIB, etc.)
Bilateral 15-30% of time
Symptoms- flank pain, tenderness
Tx- anticoagulant medications if unilateral, surgery if bilateral
Could also be caused by high cholesterol
Renal artery stenosis
Correlates with poor cardiac health
Consider RAS when there is an abrupt onset of HTN in a young pt or there is refractory HTN
Avoid ACE/ARB
Treat surgically via angioplasty
Acute tubular necrosis (ATN)
Intrarenal tubular AKI
Slow to resolve
Prolonged prerenal azotemia of any cause
Ischemic- due to lack of blood flow and O2 supply (sepsis, surgery)
Nephrotoxic- endogenous (body is creating)
Myoglobin, myeloma, uric acid
What exogenous nephrotoxins can cause ATN?
Aminoglycosides Amphotericin B Cisplatin and carboplatin Cyclosporine, tacrolimus Intratubular drug precipitation Rhabdo (statins, cocaine) Iodinated contract dyes
What do you typically see on a UA with ATN?
Granular casts (Muddy brown)
Aminoglycosides
Cause ATN by proximal tubule cell damage
Examples: gentamycin, tobramycin, amikacin
These abx are used in life-threatening situations and the tx plans are very individualized.
Generally see ATN after 5-10 days (SCr will rise)
What are the risk factors for aminoglycoside toxicity?
Large cumulative doses and multiple daily doses
Use of furosemide or other loops in conjunction
Pre-existing renal disease, elderly, sepsis, dehydration
Aminoglycoside considerations
Monitor SCr daily and d/c if it rises quickly
Consider inhaled formulation if resp infection
Recovery from ATN takes about 3 weeks, but some nephrons never recover
Amphotericin B
Broad spectrum antifungal agent that is used when nothing else is available
Causes ATN in the proximal and distal tubules
Afferent vasoconstriction and ischemic injury
If you have to run it- run it slowly over 24 hours because the amount of exposure is reduced.
Amphotericin B considerations
Use liposomal formulation if you can (costly)
Associated with substantial losses in Mg and K
Prevention- avoid cumulative exposure, avoid nephrotoxins, hydrate
Cisplatin and Carboplatin
ATN (proximal)
Elevations in SCr generally appear 10-12 days after initiation of therapy and recover by day 21
Prevent toxicity- reduce dose/frequency, use carboplatin over cisplatin, pre-hydrate with NS, Amifostine to help direct drugs to cancer cells
Intratubular precipitation
Tumor lysis syndrome- elevated uric acid levels often due to chemotherapy
Intratubular drug precipitations- sulfonamides, methotrexate, acyclovir, triamterene (take with H2O)
Rhabdo- statins, cocaine
Instrinsic AKI rhabodomyolysis
Mech- myoglobin from muscle breakdown precipitates in the tubules and obstructs them
Causes- trauma, toxins/drugs (statins), seizures, infections
Treatment- hydration and urine alkalization with sodium bicarb, Maintain UOP at 300ml/hr
You will be able to tell if the urine is clear of myoglobin by color (myoglobin makes urine red, purple, or dark brown)
Acute interstitial nephritis (AIN)
Allergic hypersensitivity response
fever, rash, eosinophilia are common
UA- may have eosinophils, hematuria, pyuria, and arthralgia
Can occur one day to several weeks after exposure
Often caused by drugs
Drugs that commonly cause AIN
Allopurinol Quinolones (cipro) Furosemide (and other loops) NSAIDs Penicillin Phenytoin Sulfa drugs Thiazides PPIs
Usually reversible if caught on time!
Chronic interstitial nephritis
Often caused by NSAIDs, lithium, cyclosporine/tacrolimus
Delayed, irreversible damage
Contrast-Induced nephropathy (CIN)
AKI occurring w/in 48 hours of exposure to IV contrast
Generally find hyaline and granular casts on UA
Risk factors for CIN
Pre-existing renal disease HTN CHF pre-procedural hypovolemia Nephrotoxic agents Intra-procedural hypotension Age >75
Metformin and CIN
Metformin itself is not nephrotoxic, but it has a metabolite that is cleared by the kidneys leading to lactic acidosis
D/C metformin prior to procedure and for 48 hours after
Prevention of CIN
Remove renal toxins
hydration- volume supplementation with NS 3-12 hrs before procedure (min 300-500ml)
choice and quality of contrasts (target low-osmolar and iso-osmolar dyes)
end-organ protection (statins?)
monitor
Maintain adequate BP
N-acetyl cysteine (NAC)
Cyto-protective agent against oxidative injury (free radical scavenger)
Vasodilator
NAC 600mg BID the day before and of contrast surgery
Best data in angioplasty
Statins and CIN
Give prophylaxis dose of statin prior to contrast
Post-procedure monitoring for contrast surgery
SCr for 48 hours
BP
No metformin or nephrotoxins
UOP- 150ml/hr for 6 hours
What type of kidney injury can piperacillin/tazobactam cause?
AIN
Glomerulonephrophathy
5% of AKI
Can cause acute and/or chronic kidney failure
Nephritic- 1-3.5g/24 hours of proteinuria
Nephrotic- >3.5g/24 hours of proteinuria
Types of glomerulonephropathy
Can be either: diffuse- all glomeruli focal-some not all segmental- part of individual glomerulus proliferative- overgrowth membranous- thickening of GBM sclerotic
Pathophysiology of glomerulonephropathy
Antibodies made to antigens in the glomerulus become trapped in glomerulus, leading to capillary damage
May progress to ESRD
Nephritic syndrome
Inflammatory syndrome that leads to glomerular capillary rupture- can be triggered by infection or autoimmune disorder
Abrupt onset of azotemia, oliguria, hematuria
RBC casts and granular casts are present
Nephrotic syndrome
Proteinuria >3.5g/day
Marked edema and hypoalbuminuria
-Kidney has loss of oncotic pressure and increased reabsorption of Na due to resistance to ANP
Hyperlipidemia
Hypercoaguable state (increased platelet aggregation)
Tx- limit fluid and Na intake, loop diuretics
Treatment of glomerulonephritis
Immunosuppressants- corticosteroids, cytotoxic agents (cyclophosphamide, chlorambucil, azathioprine, methotrexate)
-Cyclosporine, mycofenolate mofetil
Plasmapheresis
Glomerulopathies
Usually found in children, usually accompanied by AIN
For adults, you see with NSAID use
Abrupt nephrotic-range proteinuria, hypoalbuminemia, hyperlipidemia
Types of glomerulopathy
focal segmental- leads to ESRD
membranous- idiopathic
IgA mediated- most common, steroids + tight BP control for tx
rapidly progressive- steroids+cytotoxic agents
post-streptococcal- most common in children, often dont know you have
lupus nephritis-steroids+immunosuppressants together
postrenal obstruction AKI
Stones- cause anuria bladder obstruction neurogenic bladder crystallization of drugs Drugs that cause urinary retention (anticholinergics, antihistamines, phenazothiazines, narcotics)
General workup of an AKI pt
Find cause of AKI
UA
labwork
Management of AKI
Treat depending on etiology Hypovolemia- fluid resuscitation (NS) Hypotension- vasopressors, stop HTN meds AIN or ATN due to drugs- d/c and hydrate Treat infections Correct acid-base disturbances (metabolic acidosis- sodium bicarb) Correct electrolyte disturbances
Indications for dialysis
A- acidosis E- electrolytes (hyperkalemia) I- intoxications O- overload, fluid U- uremia
Hemoglobin
Most important for determining anemia
-oxygen carrying molecule
Men: 13-17.5g/dL
Women: 12-16g/dL
Hematocrit
Volume of RBCs per unit of blood volume
Men: 42-53%
Women: 36-46%
Mean Corpuscular Volume (MCV)
Average volume of each RBC
Normal range 80-100
Anemia classifications
Large RBC's= macrocytic= High MCV
-folic acid and vitamin B12 deficiency
Normal RBC=normocytic
-anemia of chronic disease
Small RBC=microcytic=low MCV
-iron deficiency anemiaErythropoietin
Hormone that initiates and stimulates the production of RBCs
It is the prime regulator of RBC production
Produced by the kidneys
ESAs
Erythropoietin stimulating agents
Darbepoetin, epoetin
Hypoxia- inducible factor (HIF)
Gene product that is found in the cells that produce erythropoietin
- Recognize oxygen availability
- Drugs can target this factor and make it stimulate erythropoietin production and iron absorption and transport.
Hepcidin
Central regulator of iron homeostasis
Synthesized in hepatocytes
-Inhibits intestinal iron uptake
-High iron levels stimulate production of hepcidin.
-Hepcidin is reduced in iron deficiency anemia
Cleared by kidneys so levels are elevated in CKD patients.
Pathophysiology of anemia in CKD
Decreased erythropoietin production (stages 4 and 5)
Blood loss from testing
Reduced life span of RBCs due to uremia
Iron, folate, or B12 deficiency
Increased risk of bleeding due to platelet dysfunction
Consequences of anemia with CKD
Reduced oxygen delivery to tissues
Compensated by increased cardiac output
LVH
Cardiac and renal damage
How often should hemoglobin be monitored with CKD?
W/O anemia- 2 times a year, every 3 months if on dialysis
W/ anemia- Every 3 months, monthly if on dialysis
Iron indices
Transferrin saturation (Tsat)-
- carrier protein for iron - indicator of iron immediately available to the bone marrow to incorporate into Hgb - can be affected by nutrition status - Normal is 20-50%
Serum Ferritin-
-indirect measure of storage iron
-Artificially elevated during infection or inflammation
Normal 12-200ng/ml (most >100)
General approaches to iron therapy
Iron is required as a building block for Hgb synthesis
Goal is to minimize blood transfusions, decrease need for/dose of ESA, and relieve symptoms
Iron targets
If CKD w/ anemia +/- ESA
Dialysis- IV iron
Non-dialysis- PO (1-3 months) or IV
-If ferritin <500 and/or TSAT <30%
Do not administer iron to intentionally keep the iron goals
Oral iron
Difficult to use for replacement therapy, better for management
Ferrous sulfate, ferrous gluconate, Slow Fe, ferrous fumarate, Niferex
Why is oral iron inadequate?
There is low intestinal absorption of iron even in healthy people. This occurs if ferritin >100.
Patients also have poor adherence and tolerance due to GI upset
IV iron products
Iron dextran Iron sucrose Sodium ferric gluconate Ferumoxytol Ferric pyrophosphate citrate Ferric carboxymaltose
IV iron dosing considerations
Give periodic doses when iron status is low
For continuous treatment, give smaller doses
Give larger doses to non-dialysis pts for convenience
Hold doses when TSAT >30% and ferritin >500
Goals of ESA treatment
Keep Hgb no greater than 11g/dL
Reduce the need for transfusions
Decrease LVH and mortality
Guidelines for ESA use in CKD
Non-dialysis- consider if Hgb <10mg/dL and patient likely to receive transfusion
-D/C when Hgb >10mg/dL
Dialysis- initiate ESA if Hgb <10mg/dL. D/C when Hgb>11
ESA MOA
stimulates erythropoietin by the same mechanism as endogenous erythropoietin
IV or SQ ESA?
SQ has lower bioavailability but longer 1/2 life
SQ is considered to give better response
Many dialysis pts get IV for convenience
Precautions with ESAs
Increased risk of CV events (use caution in pts with H/O stroke)
Risk of tumor progression- do not use in cancer pts
Pure red cell aplasia
HTN
seizures
Darbepoetin vs Epoetin
Darbepoetin has 2 additional N-linked chains and a much longer 1/2 life.
Much cheaper
Epoetin alpha
Indicated for anemia secondary to CKD (both on and not on dialysis)
1/2 life of 12 h (IV) and 24h (SQ)
contraindications-
uncontrolled HTN, history of stroke
Darbepoetin alpha
Indicated for anemia secondary to CKD (both on and not on dialysis)
1/2 life 21 hrs (IV) and 49 hrs (SQ)
contraindications-
uncontrolled HTN, history of stroke
Adjusting ESA therapy
Goal Hgb 10-11g/dL, monitor weekly until stable and then monthly
Increase dose by 25% if:
-Hgb <10 and has not increased by 1g after 4 weeks
Increase dose no more than once/month
If inadequate response after 12 weeks use lowest dose necessary to avoid transfusions
Decrease dose by 25% if
-Hgb increases by >1g in any 2 week period
Hold if Hgb >11
Monitoring anemia in CKD
Iron status evaluated every 1-3 months
Iron status has to be adequate in order to give ESA
ESA hyporesponsiveness
Initial-no increase in Hgb from baseline after 1st month of ESA tx
Acquired- previously stable, now requiring 2 increases in ESA doses
HIF stabilizing agent
Roxadustat oral therapy
New drug, will be approved soon
Has been shown to increase EPO levels
Where is calcium found in the body?
Intracellular
Extracellular (in the blood primarily bound to protein)
Bone (99% in mineral phase, 1% available to exchange with extracellular calcium)
What organs supply calcium to the body?
3 organs participate in supplying calcium to and removing from the blood.
- small intestine-where dietary calcium absorption occurs
- bone- reservoir of calcium. Bone reabsorption releases calcium from bone into blood.
- Kidney- almost all of the calcium that enters the glomerulus is reabsorbed back into the blood
Parathyroid organ effect on calcium
Increases blood concentration of calcium.
Normal range 10-65pg/ml
Secreted in response to low Ca, low vit D, and high phos
-Stimulates the production of the biologically active form of vitamin D in the kidney.
-Mobilizes Ca and Phos from bone
-Maximizes tubular reabsorption of calcium within the kidney and increases phosphate loss
Vitamin D effect on calcium
Normal range 30-60ng/ml
-Cholesterol derivative formed in the sun after exposure to sunlight (D3)
-Dietary sources (D2 and D3)
-Converted into active form by 1-alpha-hydroxylase in the kidney.
Calcitriol is the active form of vitamin D. It is responsible for the absorption of calcium and phos in the small intestine.
-Facilitates the flux of calcium out of the bone and inhibits PTH secretion (when give as med)
Calcitonin effect on calcium
Reduces blood calcium levels
- suppresses renal tubule reabsorption of calcium (enhanced excretion)
- inhibits bone reabsorption
In cases of hypocalcemia, what happens to PTH, Vit D, and calcitonin?
PTH- secretion stimulated
Vit D- production stimulated by increase in PTH
Calcitonin- Inhibited
In the case of hypocalcemia, what happens to the intestinal absorption of calcium?
It is enhanced due to Vit D
In the case of hypocalcemia, what happens to the release of calcium and phosphate from bone?
It is stimulated by PTH and Vit D
In the case of hypocalcemia, what happens to the excretion of calcium?
renal excretion is decreased due to enhanced reabsorption stimulated by PTH and Vit D
In the case of hypocalcemia, what happens to the renal excretion of phosphate?
Increased due to PTH
In the case of hypercalcemia, what happens to PTH, Vit D, and calcitonin?
PTH and Vit D are inhibited
Calcitonin secretion is stimulated
In the case if hypercalcemia, what happens to the intestinal absorption of calcium?
Decreased
In the case of hypercalcemia, what happens to the release of Ca and Phos from bone?
Decreased
In the case of hypercalcemia, what happens to the renal excretion of Ca?
Increased
In the case of hypercalcemia, what happens to the renal excretion of phosphate?
Decreased
Normal bone turnover
Bone is constantly metabolically active with an annual turnover of 10% of skeleton.
PTH is constantly being turned on and off
Too high PTH=too much bone resorption= high turnover in bone=weak bone
Too low PTH= not enough turnover in bone= lower bone mass and quality= weak bone
PTH levels need to remain w/in range
Secondary hyperparathyroidism (SHPT) and CKD
As kidney function decreases, two things happen
- ) Increased phosphate retention resulting in hyperphosphatemia. This results in hypocalcemia, stimulation of PTH, and reduced Vit D levels.
- ) Decreased production of calcitriol. This reduces calcium absorption by 90%.
Hyperphosphatemia and CKD
Phos begins to accumulate when the GFR <30ml/min
- Giving vitamin D to enhance calcium absorption in the small intestine also enhances phos absorption
- Elevated PTH should enhance phos elimination renally, but as kidney function decreases this does not occur. Because PTH also releases Ca and Phos from bone, it further increases levels.
Normal Phosphorous range
3.5-5.5mg/dL
SHPT and PTH
Parathyroid hyperplasia occurs due to continuous production of PTH
- This makes the parathyroid gland resistant to calcium and Vit D and thus it is unable to “turn itself off”
The kidneys inability to clear PTH in cases of CKD further increases PTH levels in the body.
It is difficult to stop PTH production!
Effect of excess PTH on the body
Increases rate of bone resorption which elevates serum calcium and phosphorous levels.
-There is an increased rate of bone formation so the new bone is immature and structurally weak
There is an excess of calcium-phosphorous product that leads to coronary artery calcification
Renal Osteodystrophy
A condition in CKD (usually starts in stage 3) that results from SHPT, hyperphosphatemia, hypocalcemia, and Vit D deficiency
What does renal osteodystrophy result in?
Skeletal conditions:
- Osteitis fibrosa- high turnover bone disease. Occurs when PTH levels go unchecked and are very high.
- Osteomalacia- low bone turnover caused by low calcification due to low Vit D
- Adynamic bone disease-low bone formation caused by low levels of PTH
Renal osteodystrophy calcifications
Caused by an increased calcium-phosphorous product (generally product >70). Goal is to get this product under 55!
These calcifications can occur anywhere throughout the body and are termed calciphylaxis
Calciphylaxis
Severe, painful lesions that do not heal. 1 year mortality in most cases.
Calcium supplements, calcium phosphate binders, vit D and warfarin all increase risk.
Warfarin increases risk because all of the proteins that inhibit calcification are Vit K dependent.
Tx- wound care and pain management. Sodium thiosulfate prevents from occurring, control underlying issues.
Vascular calcifications
Loss of arterial elasticity-> hypertension
Development of left ventricular hypertrophy
Decreased in coronary artery perfusion
Myocardial ischemia and failure! Mortality increases with PTH>495
Screening and goals of therapy for SHPT and CKD
Measure PTH, phosphorous, calcium in all CKD patients with GFR <60ml/min
BMD testing to assess fracture risk
Goals of therapy- control hyperphosphatemia, correct hypocalcemia, maintain adequate Vit D levels, consider calcimetic to directly control PTH production.
Treatment of SHPT
Dietary phosphorous restriction (800-100mg/day)
Minimize exposure to aluminum (alum decreases bone mineralization)
Phosphate binders
Vit D supplementations
Calcimetics
Dialysis
Parathyroidectomy
How do phosphate binders work?
Bind dietary phosphorous in the GI tract to limit absorption
Treats elevated serum phos levels
Treats elevated PTH levels even if phos is not elevated
Phosphate binders
Calcium acetate (PhosLo)
-calcium carbonate is less effective
Sevelamer (non calcium non alum phos binder)
Lanthanum (non calcium non alum phos binder)
Ferric citrate (Auryxia)
Sucrogerric oxyhydroxide (Velphoro)
Generally avoid aluminum and magnesium products (antacids, antidiarrheals)
When to use calcium phosphate binders
Calcium products 1st line in stage 3 and 4 CKD
-Goal phos 2.7-4.6
-Goal calcium <10.5
Stage 5 CKD- either calcium or non-calcium OK (can use together)
-D/C if calcium >9.5 or PTH <150
Be very diligent to avoid hypercalcemia!
Non-calcium binders
Lanthanum, sevelamer, ferric citrate, and sucroferric oxyhydroxide
Preferred if hypercalcemia is present
Preferred in dialysis patients with severe vascular calcifications (likely reduces mortality)
Preferred if pt has low PTH
Sevelamer preferred if LDL also needs lowering
Ferric sulfate preferred if iron replacement is needed
Vitamin D options
Ergocalciferol (D2) Cholecalciferol (D3) Calcitriol (Active Vit D) Doxercalciferol (liver activates) Paracalcitriol (active)
How to choose Vit D option
Ideally, give enough Vit D to suppress PTH but not cause hypercalcemia and hyperphosphatemia
-Doxercalciferol and paricalcitol produce less hypercalcemia
If not on dialysis, reserve Vit D to patients not responding to other tx
Monitor PTH, calcium, phosphate, and Ca x Ph
When to use Vit D in CKD
Stage 4- initiate ergocalciferol if serum vit D levels <30 and PTH elevated
-D/C if calcium >10.2
-Add/increase dose of phosphate binder if phosphorous levels >4.6. D/C Vit D if levels persist.
-Vit D therapy still used if PTH above target range, even if Vt D >30
Stage 5 =use calcitriol, paricalcitol, or doxercalciferol if PTH >300
Calcimimetics
Cinacalcet- typically stage 5 CKD
- amplifies the effect of calcium to the parathyroid gland, reducing the secretion of PTH
- suppresses PTH w/o causing hypercalcemia or hyperphosphatemia
- can cause hypocalcemia
Etelcalcitide- CKD+hemodialysis
- reduces secretion of PTH
- more potent that cinacalcet, more hypocalcemia
Goal treatment level of corrected calcium
Stage 3 and 4 CKD- Normal: 8.4-10.5
Stage 5 CKD- 8.4-9.5
Goal treatment levels of phosphorous
Stage 3 and 4 CKD- 2.7-4.6
Stage 5 CKD- 3.5-5.5
Goal treatment level of Ca x Phos (use corrected Ca)
Stage 3, 4, and 5 CKD- <55
Goal treatment level of PTH
Stage 3 CKD- 35-70
Stage 4 CKD- 70-110
Stage 5 CKD- 150-300
Frequency of labs for the different stages of CKD
Stage 3 CKD- annually
Stage 4 CKD- Q 3 months
Stage 5 CKD- Q month (except PTH- every 3 months)
Treatment of bone disease in CKD
High turnover disease (high PTH)
- CKD stage 3: PTH>70
- CKD stage 4: PTH >110
- CKD stage 5: PTH>300
Low turnover disease (low PTH)
- Allow PTH to return to appropriate range for stage of CKD to increase bone turnover
- Decrease or D/C calcium phosphate binder and/or vit D (can switch to non calcium phosphate binder)
Elemental iron content in ferrous sulfate 325mg
65mg
Elemental iron content in Slow Fe 160mg (ferrous sulfate)
50mg
Elemental iron content in ferrous fumarate 300mg
99mg
Elemental iron content in gluconate 325mg
36mg
Elemental iron content in Niferex 50mg
50mg
Elemental iron content in Niferex 150mg
150mg
What is the goal for iron replacement?
Goal is to replace 200mg elemental iron/day
Evidence is emerging that QOD therapy may work just as well (due to hepcidin upregulation when iron is given)
Oral iron supplements
Generally utilized in the early stages of CKD due to convenience. For maintenance.
Poor oral absorption (10%)
Absorption is decreased by food, acid-suppressing agents
Ascorbic acid enhances absorption
Side effects of oral iron
GI: abdominal cramping, constipation, nausea
Esophagitis, esophageal ulceration
Patient information for oral iron
Iron should be taken on an empty stomach but can be taken with food if the GI side effects are intolerable Stool discoloration (dark) Liquid discolorations may discolor teeth
Oral iron drug interactions
Acid suppressing agents reduce absorption
-H2RAs (ranitidine, famotidine)
-PPIs (omeprazole, pantoprazole, etc.)
Oral quinolones (chelation)
-Ciprofloxacin, moxifloxacin, levofloxacin
-Take quinolone 4 hours before or 8 hours after
iron product.
Oral tetracyclines (chelation)
-Doxycycline, etc.
-Give iron 4-6 hours before or 1 hour after
tetracycline product.
Calcium, aluminum, magnesium containing products
-Antacids- reduce absorption
IV iron products
Iron dextran, ferric gluconate, iron sucrose, ferumoxytol, ferric pyrophosphate citrate, ferric carboxymaltose
Iron dextran dose
25mg test dose with 1 hr observation then dose in ml
Give IV or IM
Ferric gluconate dose
Dialysis: 125mg per dose at each dialysis session for a total of 8 sessions
IV only
Iron sucrose dose
Dialysis: 100mg per dose at each dialysis session for a total of 10 sessions
Non-dialysis- 200mg per dose for a total of 5 doses in a 14 day period
IV only
Ferumoxytol dose
Dialysis and non-dialysis: 510mg dose then repeat 510mg 3-8 days only
IV only
Ferric pyrophosphate citrate dose
Add one amp to the dialysate solution
Ferric carboxymaltose dose
750mg per dose for a total of 2 doses separated by 7 days
Newer IV iron products
Ferric pyrophosphate citrate- use in hemodialysis only.
-Maintains hemoglobin w/o increasing iron stores
-Can cause HA, nausea, and hypotension but more
tolerable than most.
Ferric carboxymaltose
-Not for use in HD pts
-Causes HYPERtension, nausea, flushing
IV iron products adverse effects
Allergic rxn (iron dextran-BBW)
hypotension, dizziness, dyspnea, HA, back pain, syncope, rash, pruritis, nausea
-Can increase risk of bacterial infection
-Injection site reaction
-Iron overload (hemachromatosis)
Decreasing dose and rate can decrease hypotension and flushing.
IV iron monitoring
Monitor Hgb and iron indices (ferritin and transferrin concentration)
Iron overload
Only happens with IV iron because hepcidin will not allow oral iron to become overloaded.
No physiologic mech for iron excretion
HD patients are at the highest risk
Can cause liver failure!
Iron toxicity
Overwhelms iron binding proteins leading to free iron in blood, this leads to oxidative stress and CV disease.
ESA dosing
Epoetin alpha: 50-100units/kg given 3 times/week (IV or SQ). Dosing same for HD and non-HD pts
Darbepoetin- Dialysis- 0.45mcg/kg IV or SQ weekly OR 0.75mcg/kg IV q 2 weeks
non-dialysis- 0.45mcg/kg IV or SQ Q4 weeks
ESAs and Hypertension
Most common adverse event
ESAs expand blood volume, increase blood viscosity, and reverse hypoxic vasodilation
25-50% of patients need antihypertensive therapy
ESAs and BBW
CKD
- increases risk of CV events with a hemoglobin target >11g/dL
- Use the lowest procrit dose sufficient to reduce need for RBC transfusions
Perisurgery (Epoetin only)
-DVT prophylaxis is recommended.
Darbepoetin does not have the same BBW, but follows same rec
ESAs adverse reactions
Hypertension Arthralgias/HA Muscle spasms Dizziness Injection site reaction Fever Dyspnea (darbepoetin)
ESA administration
- ) Check expiration date
- ) Wash hands
- ) Remove cap and wipe with alcohol swab
- ) Remove needle cover and inject equal amount of air into vial that you are removing.
- ) Withdraw dose and check for and remove air bubbles in syringe
- ) Clean and pinch skin where injection is to occur (45 to 90 degree angle)
- ) Do not recap needle and expose properly
Darbepoetin pre-filled syringe administration
- ) Wash hands
- ) Remove needle cover
- ) Follow same subcutaneous injection instructions as normal)
- ) Activate needle guard
- ) Discard in appropriate container
ESA patient information
Do not shake
Protect from light
Store in refrigerator
If multi-dose vial (MDV), good for 21 days in fridge
Counsel on S/S of heart attack, stroke, and DVT/PE
Proper admin instructions
Calcium acetate (PhosLo) 667mg tabs
Calcium phosphate binder
2668mg TID with meals
Calcium acetate (PhosLo) 667mg tabs drug interactions
Oral quinolones (chelation)
-Ciprofloxacin, etc.
-Separate by 1-2 hours
Oral tetracyclines (chelation)
-Doxycycline
- separate by 1-2 hoursCalcium acetate (PhosLo) 667mg tabs patient counseling
Must take with meals
Do not take any other calcium supplements (antacids, tums)
Constipation is common
Calcium acetate (PhosLo) 667mg tabs monitoring
Serum calcium, PTH, Ca x Phos product
Sevelamer
Non-calcium phosphate binder
800-2400mg TID with meals
-Give dose with snacks as well
-carbonate reduces the risk of metabolic acidosis (sevelamer carbonate= Renvela)
Can be used in combination with calcium acetate
Give all other medications 1 hour before or 3 hours after
Sevelamer AE and monitoring
AE- GI upset (nausea, vomiting, dyspepsia, diarrhea)
Monitoring- Phos, PTH, provides additional LDL reduction
Lanthanum
Non- calcium phosphate binder
250mg-1000mg TID with meals
Have to chew tablets before swallowing!
Can be used in combo with calcium acetate
Give all other medications 2 hours before or after
AE- N/V, abdominal pain
Monitor Phos and PTH
Auryxia (ferric citrate)
Non-calcium phosphate binder
Dialysis patients only
2 tabs (420mg) TID with meals
Take tetracyclines 1 hour prior and quinolones 2 hours prior
AE- may increase iron levels, darken stools, diarrhea, nausea, constipation
Monitor Phos, PTH, ferritin, TSAT
Side benefit of increasing TSAT and serum ferritin and may reduce EPO and IV dose/need
Sucroferric oxyhydroxide (Velphoro)
Non-calcium phosphate binder 500mg (1 tab) TID with meals Chew before swallowing No significant drug interactions Monitor PTH, phos AE: darkening stools, diarrhea Dialysis only
Vitamin D agents adverse reactions, monitoring, and drug interactions
AE: hypercalcemia (all cause)
N/V, edema, HA (paricalcitol, doxercalciferol)
Monitor- PTH, calcium, phosphorous, Ca x Phos
Drug interactions- Paricalcitol increased by strong 3A4 inhibitors
Cinacalcet (Sensipar)
Typically used in stage 5 pts, but can be used it stage 3 and 4
30mg PO QD initially (max 180mg) with food (increases absorption)
AE: symptoms related to hypocalcemia (paresthesias, myalgias, muscle cramping, tetany, convulsions)
N/V, diarrhea
Can be used alone or in combo with Vit D and phosphate binders
Cinacalcet (Sensipar) monitoring parameters
Monitor PTH, calcium (one week after initiation and any dose change, then monthly)
Managing hypocalcemia in Cinacalcet and etelcalcitide
Do not start if serum calcium <8.4mg/dL
If serum calcium falls below 8.4 but greater than 7.5 or symptomatic then can consider adding or increasing dose of calcium phosphate binders or vit D
If serum calcium less than 7.5mg/dL or adding/increasing dose of calcium phosphate binders or vit D. If not possible or still symptomatic DC cinacalcet or etelcalcitide
Etelcalcitide (Parsabic)
5mg IV bolus x 3 weeks at the end of dialysis
AE: symptoms related to hypocalcemia
N/V, GI bleed
No drug interactions
Monitor corrected calcium prior to initiation and 1 week after dose initiation or adjustment, then monthly
Monitor PTH prior to initiation and then 4 weeks after dose initiation or adjustment
AKI and medication considerations
Use the C-G formula but understand that it is not super accurate in AKI
Use drug reference
Adjust all medication that have >30% excretion in urine
Edema is common and changes volume of distribution
Use therapeutic drug monitoring when possible!
Loading doses are often necessary when a rapid drug effect is desired
Do not does drugs based on prerenal SCr because they are often underdosed
CKD and drug alterations
Bioavailability Distribution volume Protein binding Metabolic activity Drug excretion
Drug bioavailability (CKD drug alterations)
Altered in CKD by
- changes in gastrointestinal transit time (generally does not affect extent of absorption)
- Increased gastric pH (usually due to ammonia buildup or phosphate binder/PPI/H2RA use). This reduces the absorption of drugs that need an acidic environment.
- Edema of the GI tract decreases absorption
- Decreased intestinal first pass metab increases bioavailability
- Vomiting and diarrhea (uremic symptoms many pts have)
Drug distribution in CKD
Volume of distribution is typically increased This is due to: -decreased protein binding -increased tissue binding -increased edema
Loading doses indicated in many cases
Protein binding in CKD
Protein binding of many acidic drugs (warfarin, phenytoin, metolazone) and some basic drugs (diazepam) decreased
This is due to:
-changes in protein binding sites
-Uremia
-Decreased albumin
CKD pts are spilling protein in their urine so both the amount of protein available and the ability of protein to bind decreases.
This results in more “free drug” and increases drug toxicity.
Measure unbound concentrations if possible. (ex-phenytoin)
CKD and drug metabolism
CKD alters other elimination pathways, notably CYP450 system.
The second phase of metabolism (conjugation rxns) are also slowed
The kidney is a site of drug metabolism and well as the liver
Metabolites in CKD
Many drugs have metabolites with pharmacologic or toxic activity
Allopurinol- Oxipurinol, responsible for suppression of xanthine oxidase
Meperidine-Normeperidine, responsible for CNS stimulation and seizures
Morphine- Morphine-6-glucuronide, prolongs analgesia
Drug excretion in CKD
If more than 30% of a drug is excreted unchanged in the urine, it should be renally dosed.
Dosing depends on type of kidney disease
Dosing adjustments in CKD
Reduce dose
- tends to maintain more constant drug levels
- Lower peak, higher trough
- Higher risk of toxicities if dosing interval is inadequate for elimination
Lengthen dosing interval
- Lower risk of toxicity but higher risk of subtherapeutic drug concentrations
- Better regimen for drugs with peak-related efficacy
Can do both
Antihypertensives- Diuretics drug dosing
Loops preferred over thiazides with CrCl <30ml/min
Be very cautious with K sparing diuretics due to risk of hyperkalemia
Overdosing a diuretic can lead to acute renal failure, especially in CKD
Antihypertensives- ACE/ARB drug dosing
> 50% risk in SCr after initiating ACE/ARB D/C med
Fosinopril is least likely to accumulate in CKD
Hyperkalemia common
Antihypertensives- beta blockers dosing
Hydrophilic beta blockers (atenolol, bisoprolol, acebutolol, nadolol) are eliminated renally.
-Reduce dose by 50% if CrCl <30mL/min
Lipophilic beta blockers (metoprolol, carvedilol, labetalol, propranolol) do not need adjustment
Misc cardiac meds dose adjustment
CCBs, clonidine, hydralazine, alpha blockers do not need dose adjustment
Digoxin- reduce drug by 50% if CrCl <50mL/min. Watch levels closely
Hypoglycemic agents dose adjustment
Avoid metformin if CrCl <30mL/min
-cautious in patients >80, CHF, or cirrhosis
Choose glyburide over glipizide in patients with CKD
Most oral meds need renally dosed
All insulins will accumulate
Time-dependent killing antibiotic
Maintaining a drug level above the minimum level needed to kill an organism
Vanc, beta lactams
Concentration- dependent killing antibiotic
Try to obtain high peaks of drug to maximize killing, let that level drop to almost nothing
Quinolones, aminoglycosides
Dosing penicillins
Most need to be renally dosed
Can cause seizures, thrombocytopenia
Dosing quinolones (cipro, levaquin, avelox)
Avelox is the only one that does not need to be renally dosed.
Cause QTc prolongation and increased CNS manifestations
Dosing bactrim
Trimethoprim interferes with the tubular secretion of creatinine so can elevated SCr
Needs to be renally dosed
Vancomycin dosing
Pharmacokinetic dosing formulas needed for patients with CKD
Nitrofurantoin dosing
Toxic metabolites that accumulates in renal failure
causes peripheral neuropathy
Avoid if CrCl <60mL/min
Aminoglycosides dosing
Avoid in CKD patients if possible
If no other options, must carefully calculate doses and follow levels closely
Analgesics drug dosing
Most opioid narcotics have metabolites that accumulate in CKD
-Meperidine
Morphine
Tramadol
Methadone and fentanyl are the safest agents
Toxicities associated with analgesics in CKD
Increased sedation Seizures Resp depression Coma Death
Be very cautious if using ER product
Warfarin in CKD
Decreased protein binding is offset by increased metabolism
Uremia increases risk of bleeding due to platelet aggregation
Dabigatran (Pradaxa) dosing
75mg BID if crcl 15-30ml/min (AFIB)
Rivaroxaban (Xarelto) dosing
15mg QD (stroke prevention in AFIB) if CrCl 15-50 avoid
Apixaban (Eliquis) dosing
2.5mg BID if SCr >1.5ng/dL and either >80 or <60 pounds (AFIB)
or
SCr <1.5 and both of above
Edoxaban dosing
do not use if CrCl >95mL/min
30mg QD if CrCl 15-30
Betrixaban dosing
80mg once then 40mg qd if CrCl 15-30
Low molecular weight heparins and arixtra dosing
Do not use if CrCl <30ml/min
Misc drugs that accumulate in CKD
Gabapentin-sedation
H2 blockers- CrCl must be above 50
Metoclopramide- seizures, risk of extrapyramidal symptoms
Phenergan- sedation
What is dialysis
A procedure that replaces the functions of the kidney
- removes excess fluid
- removes water-soluble waste (primarily BUN)
- maintenance of electrolyte homeostasis (primarily K)
How is dialysis performed
Perfusing blood and a physiologic solution (dialysate) on opposite sides of a semipermeable membrane. Dialysate puts bicarb into blood.
- Fluid and solutes move into dialysate fluid and is then discarded
- Drugs may also be removed
Ultrafiltration
Pressure of water through a membrane under a pressure gradient (hydrostatic or oncotic)
- Primary method of removal of excess body water
- Ultrafiltrate describes the excess fluid removed
Diffusion
Movements of substances through a semi-permeable membrane across a concentration gradient
Major process involved in IHD and PD
Rate of diffusion depends on magnitude of concentration gradient, solute characteristics, membrane characteristics, and loo/fluid flow rates
Convection
Movement of solutes through a membrane by the force of water. Also called solvent drag.
Particularly useful for middle-sized particles.
Types of dialysis
Hemodialysis
-Intermittent hemodialysis (IHD)
Continuous renal replacement therapy (CRRT)
Peritoneal dialysis
Intermittent hemodialysis
Typically 3 days/week for 3-5 hours each
Home machines exist but are rare
Continuous renal replacement dialysis (CRRT)
Indicated for hospital patients in AKI that cannot tolerate intermittent HD.
Often seen in ICU pts because you can use even in low blood flow
May utilize dialysate or replacement fluids
Dialysate allows for diffusion
Replacement fluids allow ultrafiltration and convection
Types of CRRT
Slow continuous ultrafiltration (SCUF)- no fluid
Continuous Veno-Venous Hemofiltration (CVVH)- replacement fluid only
Continuous Veno-Venous Hemodialysis (CVVHD)- Dialysate only
Continuous Veno-Venous Hemodiafiltration-both
Peritoneal Dialysis
A process in which a patient instills sterile fluid into his/her abdomen via a surgically implanted catheter
Peritoneal membrane serves as the dialysis filter
Old fluid is drained from the abdomen prior to adding new fluid
Hemodialysis vascular access
- ) Arteriovenous fistula
- created surgically by joining artery and vein usually in arm or wrist
- Vein will bulge out - ) AV graft
- synthetic, internal - ) Venous catheters
- External access directly to large veins, capped off between uses
Success Fistula> graft>catheter
Dialysis filters
Housed within the dialyzer
Provides a semi permeable barrier between blood and dialysate fluid
3 types:
conventional/standard
High-efficiency- larger SA to remove water and small molecules
High-flux- most common, greater ability to remove large molecules
2 main goals of hemodialysis
1.) Maintain euvolemia, goal is to return to “dry weight” after dialysis session
- ) Effective removal of solutes
- primarily urea
- also ensure electrolyte balance
Common complications in IHD
Hypotension- can use midodrine prior to dialysis
Muscle cramps
Filter thrombosis- use citrate or heparin in dialysis
Infection- treat
Medications commonly administered in dialysis
Anticoagulants Anemia management- ESAs, iron IV Vit D Midodrine Catheter lock solutions Antu-pruritics Antibiotics
Peritoneal Dialysis (PD)
Continuous ambulatory PD (CAPD)- done manually Automated PD (APD)- more common, generally runs while someone sleeps Combo
PD fluid
Sterile fluid designed to use osmotic pressure to remove fluids and solutes
Volume is adjusted per patient size, typically 1.5-3L
Osmotically active ingredient- Dextrose 1.5-4.25%, the higher the dextrose concentrations the more efficient removal of water
The more often the fluid is exchanged, the greater the solute clearance
Complications of PD
Mechanical problems Hyperglycemia Fluid overload Chemical peritonitis Malnutrition Fibrin formation in dialysate Infections
Intraperitoneal administration of drugs
For a local effect- abx, heparin
For a systemic effect- may replace injections or infusions
Examples- abx, calcitriol, insulin, epoetin alfa
Drug dosing in dialysis
For specific situations:
Must determine dialyzer clearance and calculate the patients estimated drug clearance.
Must add these numbers together to get total clearance.
Drug characteristics for dialysis
Lower Vd= greater clearance Lower Mol wt= greater clearance Lower protein binding= greater clearance HD flow rate=faster=better clearance Longer sessions=greater clearance
