CLINICAL PHARMACY IN NEPHROLOGY

2. CLINICAL PHARMACY IN NEPHROLOGY ACUTE RENAL FAILURE

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

6. 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

8. Acute Renal FailureDiagnosis • 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

9. 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

10. Acute Renal Failure Diagnosis (cont’d) • Urinary Indices; • FE Na = (U/P) Na X (P/U)CrX 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

12. 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 FENa (<1%) • high BUN/creat ratio, normal urinary sediment • Treat by correction of predisposing factors

16. 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

17. Acute Tubular Necrosis (ATN) -- 2 • Diagnose by history,  FENa (>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.

19. Contrast nephropathy • 12-24 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.

20. 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 .

22. 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

23. 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)

24. 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.)

25. 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)

26. 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

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

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

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

30. 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

32. Dialysis Indications • Refractory hyperkalemia • Metabolic acidosis • Volume overload • Mental status changes