CLINICAL PHARMACY IN NEPHROLOGY ACUTE RENAL FAILURE

Background Common in Hospitalized patients Associated with high Morbidity and Mortality Often Multifactorial Identifiable risk factors.

Acute Renal Failure Sudden decrease in function (hours-days) Often multifactorial Pre-renal and intrinsic renal causes 70% oliguric UOP < 400 ml Non-oliguric (up to 65%) Associated with high mortality and morbidity

Acute Renal Failure Diagnosis Laboratory Evaluation: –Scr, More reliable marker of GFR Falsely elevated with Septra, Cimetidine small change reflects large change in GFR –BUN, generally follows Scr increase Elevation may be independent of GFR –Steroids, GIB, Catabolic state, hypovolemia –BUN/Cr helpful in classifying cause of ARF ratio> 20:1 suggests prerenal cause ratio 10-15:1 suggests intrinsic renal cause

Acute Renal Failure Diagnosis (cont’d) Urinalysis –Unremarkable in pre and post renal causes –Differentiates ATN vs. AIN. vs. AGN Muddy brown casts in ATN WBC casts in AIN –Hansel stain for Eosinophils

Acute Renal Failure Diagnosis (cont’d) Urinary Indices; –FE Na = (U/P) Na X (P/U) Cr X 100 FENa < 1% C/W Pre-renal state –May be low in selected intrinsic cause »Contrast nephropathy »Acute GN »Myoglobin induced ATN FENa> 1% C/W intrinsic cause of ARF

Prerenal Azotemia Nearly as common as ATN (think of as early part of the disease spectrum) Diagnose by history and physical exam –N/V, Diarrhea, Diuretic use,... low FE Na (<1%) high BUN/creat ratio, normal urinary sediment Treat by correction of predisposing factors

Acute Renal Failure Etiologies Acute Tubular Necrosis –Most common cause of intrinsic cause of ARF –Often multifactorial –Non-oliguria carries better prognosis –Ischemic ATN: Hypotension, sepsis, prolonged pre-renal state –Nephrotoxic ATN: Contrast, Antibiotics, Heme proteins

Acute Tubular Necrosis (ATN) -- 2 Diagnose by history,  FE Na (>2%) sediment with coarse granular casts, RTE cells Treatment is supportive care. –Maintenance of euvolemia (with judicious use of diuretics, IVF, as necessary) –Avoidance of hypotension –Avoidance of nephrotoxic medications (including NSAIDs and ACE-I) when possible –Dialysis, if necessary 80% will recover, if initial insult can be reversed.

Contrast nephropathy hours post exposure, peaks in 3-5 days Non-oliguric, FE Na <1% !! RX/Prevention: 1/2 NS 1 cc/kg/hr 12 hours pre/post Mucomyst 600 BID pre/post (4 doses) Risk Factors: CRF, Hypovolemia.

Rhabdomyolytic ARF Diagnose with  serum CPK (usu. > 10,000), urine dipstick (+) for blood, without RBCs on microscopy, pigmented granular casts Common after trauma (“crush injuries”), seizures, burns, limb ischemia occasionally after IABP or cardiopulmonary bypass Treatment is largely supportive care. Alkalinization of urine.

Acute Glomerulonephritis Rare in the hospitalized patient Most common types: acute post-infectious GN, “crescentic” RPGN Diagnose by history, hematuria, RBC casts, proteinuria (usually non-nephrotic range), low serum complement in post-infectious GN), RPGN often associated with anti- GBM or ANCA Usually will need to perform renal biopsy

Acute Glomerulonephritis (2) If diagnosis is post-infectious, disease is usually self-limited, and supportive care is usually all that is necessary. For RPGN, may need immunosuppressive therapy with steroids ± Cytoxan, plasmapheresis (if assoc. with anti-GBM)

Atheroembolic ARF Associated with emboli of fragments of atherosclerotic plaque from aorta and other large arteries Diagnose by history, physical findings (evidence of other embolic phenomena--CVA, ischemic digits, “blue toe” syndrome, etc), low serum C3 and C4, peripheral eosinophilia, eosinophiluria, rarely WBC casts Commonly occur after intravascular procedures or cannulation (cardiac cath, CABG, AAA repair, etc.)

Acute Interstitial Nephritis –Usually drug induced methicillin, rifampin, NSAIDS –Develops 3-7 days after exposure –Fever, Rash, and eosinophilia common –U/A reveals WBC, WBC casts, + Hansel stain –Often resolves spontaneously –Steroids may be beneficial ( if Scr>2.5 mg/dl)

Acute Renal Failure Etiologies Post-Renal –Bladder outlet obstruction BPH, intrapelvic pathology –Crystalluria Acyclovir, Indanivir, Uric Acid –Papillary tip necrosis DM with pyelonephritis Analgesic abuse Sickle cell disease

Prevention What works? Maintenance of euvolemia Avoidance of nephrotoxins when possible –NSAIDs, aminoglycoside, Amphotericin, IV contrast BP control--avoidance of excessive hypo- or hypertension

Prevention What doesn’t work? Empiric use of: –Diuretics (i.e., Furosemide, Mannitol) –Dopamine (or Dopamine agonists such as Fenoldopam) –Calcium-channel blockers

Acute Renal Failure Treatment Water and sodium restriction Protein restriction Potassium and phosphate restriction Adjust medication dosages Avoidance of further insults –BP support –Nephrotoxins

Hyperkalemia Highly Arrhythmogenic –Usually with progressive EKG changes Peaked T waves ---> Widened QRS--> Sinus wave –K> 5.5 meq/L needs evaluation/intervention –Usually in setting of Decrease GFR but: medication also a common cause –ACEI –NSAIDS –Septra, Heparin

Dialysis Indications Refractory hyperkalemia Metabolic acidosis Volume overload Mental status changes