Acute Renal Failure

1. Acute Renal Failure Anthony R Mato, MD

2. Basic Facts • Renal failure over the course of hours to days. • The result will be failure to excrete nitrogenous waste and electrolyte imbalance. • Hard to define: in 26 studies, no two used the same definition!!!

3. Classic laboratory definition • Cr increase of .5 mg / dl. • Increase in more than 50% over baseline Cr. • Decreased in calculated Cr Clearance by more than 50%. • Any decrease in renal function that requires dialysis.

4. Pre-Renal: Decreased renal perfusion without cellular injury. 70% of community acquired cases. 40% of hospital acquired cases. 1 cause of Intra-Renal failure. Intra-Renal: ATN: Ischemic, toxic insult to the renal tubule. Tubular AIN: Inflammation and edema. GN:Injury to the filtering mechanism. Post-Renal: obstruction the urinary outflow tract.   Basic Differential Diagnosis

5. Prerenal Failure • Often rapidly reversible if we can identify this early. • The elderly at high risk because of their predisposition to hypovolemia and renal atherosclerotic disease. • This is by definition rapidly reversible upon the restoration of renal blood flow and glomerular perfusion pressure. • THE KIDNEYS ARE NORMAL. • This will accompany any disease that involves hypovolemia, low cardiac output, systemic dilation, or selective intrarenal vasoconstriction.

6. Differential Diagnosis • Hypovolemia • GI loss: Nausea, vomiting, diarrhea • Renal loss: diuresis, hypo adrenalism, osmotic diuresis (DM) • Sequestration: pancreatitis, peritonitis,trauma, low albumin. • Hemorrhage, burns, dehydration.

7. Differential Diagnosis • Renal vasoconstriction: hyper Ca, norepi, epi, cyclosporine, tacrolimus, ampho B. • Systemic vasodilation: sepsis, medications, anesthesia, anaphylaxis. • Cirrhosis with ascites • Hepato-renal syndrome • Impairment of autoregulation: NSAIDs, ACE, ARBs. • Hyperviscosity syndromes: MM, WM, PCV

8. Differential Diagnosis • Low CO • Myocardial diseases • Valvular heart disease • Pericardial disease • Tamponande • Pulmonart HTNPE • Pos pressure mechanical ventillation

9. Reduced arterial stretch and activated baro-receptors  • Neuro-humoral responses activated to maintain blood volume and pressure  • Sympathetic nervous system • AT II system • AVP system • They will act together to maintain flow to the heart and the brain at the expense of other non-essential vascular beds. • Renal afferent vaso-dilation is triggered via : PGE2 (afferent), Local myogenic reflex, ATII(efferent) • We have maximum dilation at SBP of 80 mm Hg. PHYSIOLOGY OF HYPOVOLEMIA

10. Intrinsic Renal Disease • Anatomic organization seems to work best. ARF DOES NOT EQUAL ATN. • 30% of cases of intrinsic renal failure will not show any evidence of ATN on UA. • Glomerulus • Vessels • Interstitum • Tubules

11. THE DIFFERENTIAL DIAGNOSIS

12. Differential Diagnosis

13. Tubules : ATN • Ischemic Injuries to the renal tubule: • Takes 1-2 weeks to recover from after perfusion has been normalized. • In the extreme form this can lead to bilateral renal cortical necrosis • Three phases: • Initiation phase • Tubuloglomerular feedback: afferent arteriole constriction triggered by an increase in the salt delivery sensed by the macula densa. • Recovery phase: tubular epithelial cell repair and regeneration. This may be associated with a marked diuretic phase.

14. ATN: Ischemic • Hypovolemia • Low cardiac output • Renal vasoconstriction • Systemic dilation • Hemorrhage

15. Exogenous Radiocontrast CSP TAC Amino glycosides Chemotherapy Ethylene glycol Tylenol Endogenous Myoglobin Hemoglobin Uric acid Oxylate Light chains ATN : Toxic

16. ATN : Toxic facts • ATN : Exacerbated in the elderly, CRI, hypovolemia, and exposure to multiple toxins. • Intrarenal vaso-constriction: radiocontrast, cyclosporin, tacrolimus. Initially they will look prerenal. • Contrast – toxicity is worst in patients with CRI, DM, MM, CHF, hypovolemia. This is dose related. • Direct toxicity to epithelial cells: frequent offenders are : acyclovir, foscarnet, aminoglycosides (30% of patients with therapeutic levels will have ARF), Ampho B (causes vasoconstriction as well as direct toxicity). • Cisplatin (mitochondrial injury). • Myoglobin and hemoglobin will both increase epithelial cell oxidative stress. They also inhibit NO  vasoconstriciton. • Light chains : can form intratubular casts and are directly toxic. UA crystal deposition.

17. Allergic : AIN Allergic reaction in the tubules. IT IS PARAMOUNT TO IDENTIFY THE OFFENDING AGENT AND REMOVE IT. There may be some role for steroids in the case of AIN.

18. AIN : Allergic • Beta lactams / Cephalosporins • Sulfinamides • TMP • NSAIDs • Diuretics • Captopril • Autoimmune diseases • Infiltrative diseases • Infections: Legionella / Hanta virus

19. Others • Infection: Pyelonephritis, CMV, Candida • Infiltration: lymphoma, leukemia, sarcoid • Intratubular deposition and obstruction

20. Post Renal Causes If we can identify this early, this can be readily reversible. This accounts for fewer than 5% of cases of ARF.

21. BPH #1 Prostatitis Prostate / Cervical cancer Retroperitoneal fibrosis / disorders Extraluminal malignancy Neurogenic bladder / anticholinergic drug use: functional obstruction Bilateral renal calculi Myeloma light chains Papillary necrosis Urethritis with spasm Inadvertent surgical ligature Intraluminal Thrombosis Intraluminal (collecting system) crystal disease Uric acid Calcium oxylate Acyclovir Sulfonamide MTX Differential Diagnosis

22. Ricky’s Story 50 year old man presents to the ED with a 1 day history of RUQ pain, N/V. He also reports fever and chills and decreased urine output. PMH is a sore throat a week ago, tx w/ an antibiotic. He is on ibuprofen only. T = 102, HR 123, BP 80/60. In general, he is an ill-appearing. Abd: + tenderness RUQ; no peritoneal signs; remainder of exam is WNL.

23. Ricky’s Story Labs: • WBC 20 w/ • 16% bands • Hgb 14 • Plts 300 • Na 140 • K 4.1 • Cl 111 • HCO3 22 • BUN 35 • Cr 1.6 (baseline is 0.7) 

24. H and P : Prerenal • Thirst, orthostatic dizziness, hypovolemia on exam, tachycarida, decreased JVP, poor skin turgor, dry mucous membranes, reduced axillary sweating. • Start of new medications: NSAIDs, ACE, ARBs. Stigmata of chronic liver disease. Advanced CHF. Signs of sepsis.

25. H and P: Intrinsic Renal • Recent history or hypovolemia / septic shock. Careful review of clinical data, pharmacy, nursing, and radiology records for evidence of toxin exposure. History of myeloma. Recent rhabdo. • Flank pain (worry for arterial occlusion) : SC nodules, livedo reticularia, hollenhorst plaques, digital ischemia with palpable pulses. Fevers, arthralgias, pruritis erythemetous rash: AIN.

26. H and P : Post renal • Presence of suprapubic and flank pain. Pain radiating to the groin. History of nocturia, frequency, hesitancy. • History of anticholinergic medication use.  

27. What is your differential?

28. What additional workup do you want to diagnose the etiology of his ARF / abdominal pain?

29. Urinalysis • Dip: pH, SG, glucose, protein, nitrite, leuk esterase, bili, heme. • Micro: RBCs, WBCs, casts, crystals, bacteria. • Normal: 0-2 RBCs, 0-4 WBC, occasional hyaline cast.

30. Urinalysis: Prerenal / Post-renal • Sediment is acellular and may contain hyaline casts • This is protein that is normally part of the urine (Tamm-Horsfall Protein). • Post renal : Sediment is classically acellular and “bland”. • May also see pyuria and hematuria. No casts.

31. Renal : ATN • Muddy brown casts • (contain tubular-epithelial cells). • They are usually associated with microscopic hematuria and mild tubular proteinuria (< 1 g / d) from impaired re-absorption. • CASTS ARE ABSENT IN 30% OF THE CASES OF ATN.

32. Renal : GN • Red blood cell casts are the classic finding. • Dysmorphic RBCs. • These indicate glomerular injury. • These are rarely seen in acute ATN. • May also see proteinuria: > 1 g / day.

34. Renal : AIN • White cell / granular casts. • KEEP IN MIND THAT BROAD GRANULAR CASTS REFELCT CHRONIC RENAL DISEASE (fibrosis). • Eosinophiluria (> 5%) is a classic finding (Hansel’s Stain) – especially in antibiotic associated AIN.

35. Common UA Patterns • Rhabdo: dip is pos for heme, neg for RBCs • MM: dip is neg for protein, + for light chains on UPEP • EG: look for calcium oxylate crystals, elevated AG, elevated osm gap. • TLS: uric acid crystals (can also be a normal variant of concentrated urine)

36. URINE BLING

37. Results • Tbili : 2.0 • Alk: 269 • ALT : 44 • AST : 44 • UA : SG 1.02, trace ketones • Micro : No cells, No casts, No crystals • Urine Na: 10 • Urine Cr: 80

38. Renal Failure Indices • Fractional excretion of Na: this will relate the clearance of Na to that of Cr. • In the case of prerenal disease Na is actively reabsorbed to restore intravascular volume. • This is not the case in renal injury (absorptive mechanisms are broken). In either case Cr is NOT reabsorbed. So we have the makings of a comparative ratio. The cut off is 1%. U Na / P Na __________ x 100% = .14% (Prerenal) U Cr / P Cr

39. Keep in mind… • Keep in mind that when pre renal patients are receiving diuretics or have bicarbonaturia all bets are off. • Also salt wasting states such as CRI and adrenal insufficiency will also alter results. • In 15% if patients with ATN FeNa can be < 1 % : reflecting patchy injury with partially preserved function. • In GN, acute urinary post renal obstruction, and vascular diseases the FeNa will often be < 1%. • Urine sodium, specific gravity, urine osm, BUN : Cr ratio are less sensitive and of limited value in differentiating this differential.

40. Additional Labs • Peak Cr: • In prerenal disease : may fluctuate with hemodynamics. Rise will be rapid. This is true for contrast (5 days to peak and 7 to normal) • Atheroembolization (later peak and return to baseline), and ischemia (later peak and return to baseline). • Rise will be delayed in toxin exposure. • Rhabdo: elevated K, Phos, hypocalcemia with elevations in CK and UA. • TLS: elevated UA, K, Phos, low Ca, elevated Cr and elevated LDH (intracellular enzyme). • Elevated anion gap + elevated osm gap : suggests ethylene glycol / methanol exposure. • Anemia may suggest hemolysis, MM, or TTP. • Eosinophillia may suggest AIN, atheroembolic disease, PAN.

41. Back to Ricky • An abdominal CT with contrast shows acute cholecystitis. He is given an intravenous dose of ampicillin and gentamycin, along with normal saline. • The next morning you note LE edema and bibasilar crackles. His blood pressure has improved to 110/70 and fever has resolved. His overnight urine output was 150cc. • Na 137, K 6.7, Cl 100, H2CO3 15, BUN 37, Cr 2.7

42. Why is he hyperkalemic?What is the management?Does need dialysis?

43. Hyperkalemia • Plasma Potassium > 5.0 • Pseudohyperkalemia • Prolonged tourniquet use • Hemolysis • Leukostasis / Thrombocytosis

44. Physiology • A large meal has enough potassium to kill us. How will the body handle this load initially. • Buffering system will stimulate liver / muscle N-K ATPase • Insulin • Epinephrine • Aldosterone

45. The Kidney to the Rescue • Kidney handles it in a unique way. • It virtually reabsorbs 100% of the K in the proximal tubule (70%) and the loop of henle (30%). • Solvent Drag • Single Effect / Paracellular pathway • We reabsorb almost all of the K before we reach the distal segments.

46. The Principal Cell • BL membrane we have a Na/ K ATPase • On the apical side we have amilloride Na channels and other channels that allow the movement for K. • Tight junctions - the potential across the apical membrane is – 30. The BM is at - 70mv. • The common denominator: intracellular K will raise electrochemical gradient for K inside of the cell will cause an increase in K secretion into the urine.

47. The Key Players 1. K concentration 2. Aldosterone 3. Flow 4. Distal Na 5. ADH 6. Acid base status of the blood

48. Differential Diagnosis • Increased intake : rare except in iatrogenesis • Cellular release • TLS, Rhabdomyolysis, exercise, trauma • Metabolic acidosis • Insulin deficiency • Hyperkalemic periodic paralysis • Digoxin toxicity, beta blockers • Adrenal insufficiency • Succinylcholine

49. Differential Diagnosis • Impaired excretion • Renal failure • Primary hypoaldosteronism • Secondary hypoakdosteronism • ACE, NSAIDs, Heparin, Type 4 RTA • Aldo resistance • K sparing diuretics, bactrim, pentamidine, sickle cell disease, multiple myeloma. • Gordon’s syndrome (enhanced Cl reabsorption, less K secretion, HTN) • Ureter Diversion to Jejunum.

50. Symptoms / Signs • Flaccid paralysis • Arrhythmia • Peaked T waves • PR / QRS prolongation • AV conduction delay • Loss of P waves • Sine wave • V fib