Acute renal failure (arf)

Acute renal failure

1. Acute Kidney Injury (AKI) CHAIRPERSON – DR. SANJEEV KUMAR SPEAKER - DR. ASHISH KUMAR

2. DEFINITION AKI is a sudden and usually reversible decrease in the glomerular filtration rate (GFR) occurring over a period of hours to days. The term “ Acute Kidney Injury” now replaces the term ARF; the term Acute Renal Failure should now be restricted to patients who have AKI and “ need renal replacement therapy”.

3. ‘ ACUTE KIDNEY INJURY’ Abrupt reduction [<48 hrs] in kidney function, defined as an absolute increase in S creatinine of ≥0.3 mg/ dL A percentage increase in S creatinine of ≥ 50% [1.5 fold from baseline] or a reduction in urine output-- documented oliguria of < 0.5 ml/kg/hr, for more than six hours.

4. Hilton, R. BMJ 2006;333:786-790 CAUSES OF ACUTE KIDNEY INJURY AKI

5. Pre-renal causes of AKI Volume depletion Renal losses (diuretics, polyuria ) GI losses (vomiting, diarrhea) Cutaneous losses (burns, Stevens-Johnson syndrome) Hemorrhage Pancreatitis Decreased cardiac output   Heart failure Pulmonary embolus Acute myocardial infarction Severe valvular heart disease

6. Post-renal causes of AKI Ureteric obstruction Stone disease, Tumor, Fibrosis, Ligation during pelvic surgery Bladder neck obstruction Benign prostatic hypertrophy [BPH] Cancer of the prostate Neurogenic bladder Drugs( Tricyclic antidepressants, ganglion blockers, Bladder tumor, Stone disease, hemorrhage/clot) Urethral obstruction (strictures, tumor)

7. R enal Causes of AKI Large Vascular Small vascular and Glomerular Interstitial nephritis Acute tubular necrosis

8. Renal Causes of AKI Large Vascular Renovasc disease + ACEI Renal artery thrombosis/dissection Cholersterol emboli (recent Cardiac cath /aortic surgery) Renal vein Thrombosis ( hypercoagulable , Nephrotic )

9. Acute Glomerulonephritis (GN) / Small vascular Anti– glomerular basement membrane (GBM) disease ( Goodpasture syndrome) Anti– neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-associated GN) (Wegener granulomatosis , microscopic polyangiitis ) Immune complex GN (lupus, postinfectious , cryoglobulinemia , primary membranoproliferative glomerulonephritis ) IgA nephropathy HUS/TTP Malignant hypertension

10. Tubular Ischemic Toxic Heme pigment ( rhabdomyolysis , intravascular hemolysis ) Crystals (tumor lysis syndrome, seizures, ethylene glycol poisoning, megadose vitamin C, acyclovir, indinavir , methotrexate ) Drugs ( aminoglycosides , lithium, amphotericin B, pentamidine , cisplatin , ifosfamide , radiocontrast agents)

11. Interstitial Drugs ( penicillins , cephalosporins , NSAIDs, proton-pump inhibitors, allopurinol , rifampin , indinavir , mesalamine , sulfonamides) Infection ( pyelonephritis , viral nephritis) Systemic disease ( Sjogren syndrome, sarcoid , lupus, lymphoma, leukemia )

12. Pre-renal AKI History -- blood or volume loss -- cardiac failure, arrhythmia, ( cardiogenic shock) -- sepsis Physical exam – focus on volume status Vital signs – current and preceding the development of AKI Neck veins, lungs, heart, mucous membranes and edema

13. Pre-renal AKI There is no intrinsic kidney damage in pre-renal AKI ; rising BUN and creat occur because the kidneys are inadequately perfused . Therefore, normal renal physiologic responses occur, manifested in urine electrolytes that reflect intact renal tubular function.

14. Pre-renal AKI Intact renal tubular function in the setting of impaired renal perfusion results in avid tubular reabsorption of sodium. Therefore, low urine Na (<20 mEq /L) and low fractional excretion of Na (<1%) and of urea (<35%) in pre-renal ARF.

15. Pre-renal AKI Laboratory studies BUN:creatinine ratio – elevated in pre-renal; >20:1 Urine sediment : hyaline and fine granular casts Urine Specific gravity : high Urine dipstick : negative (no blood or protein) Urinary to plasma creatinine ratio : high Urinary Na : low FENa : low

16. Sustained prerenal azotemia is the main factor that predisposes patients to ischemia- induced acute tubular necrosis (ATN) Prerenal azotemia and ischemic tubular necrosis represent a continuum. Azotemia progresses to necrosis when blood flow is sufficiently compromised to result in the death of tubular cells. Most cases of ischemic AKI are reversible if the underlying cause is corrected.

17. Renal or Intrinsic AKI In all types of intrinsic AKI, BUN:creat ratio preserved (10-20:1) The history, P/E, and especially urine analysis will help to differentiate

18. Renal or Intrinsic ARF – Vascular Type Large vessels – must be bilateral Renal vein thrombosis Renal artery stenosis Small vessels Vasculitis Atheroembolic Malignant hypertension Thrombotic microangiopathies (HUS/TTP)

19. Renal or Intrinsic AKI – Glomerular History – systemic or primary kidney P/E – BP (usually hypertensive) -- edema BUN:creatinine ratio: preserved Urine analysis : + protein, blood RBCs,+ Often require kidney biopsy RBC Casts

20. Renal or Intrinsic AKI – Interstitial History – exposure to medications usually 7- 14 days earlier -- penicillins , cephalosporins , dilantin P/E – maculopapular erythematous skin rash -- 1/3 have fever, arthralgias BUN:creatinine ratio: 10-20:1 Urine analysis: + protein, blood WBCs, WBC casts, eosinophils

21. Renal or Intrinsic ATN – Acute Tubular Necrosis The most common type of hospital-acquired ARF May be 1) ischemic or 2) nephrotoxic in etiology Most common ATN is ischemic, most often due to a prolonged pre-renal state (prolonged reduced renal perfusion)

22. Renal or Intrinsic ATN – Acute Tubular Necrosis History – prolonged pre-renal state -- exposure to nephrotoxin aminoglycoside antibiotics ethylene glycol pigments ( myoglobin , hemoglobin) P/E – assess volume status (to exclude pre-renal AKI)

23. Renal or Intrinsic ATN – Acute Tubular Necrosis BUN:creatinine ratio: preserved (10-20:1) Urine analysis : negative protein, blood -- granular casts (dirty brown casts) -- renal tubular epithelial cells Urine chemistries – U rinary Na : high ( >40 meq /L) FENa : high ( >2%) Urinary to plasma creatinine ratio: low

24. Contrast-Induced AKI Prevalence Less than 1% in patients with normal renal function Increases significantly with renal insufficiency Risk factors Renal insufficiency Diabetes mellitus Multiple myeloma High osmolar (ionic) contrast media Contrast medium volume

25. Contrast-induced AKI Clinical Characteristics Onset - 24 to 48 hrs after exposure Duration - 5 to 7 days Non- oliguric (majority) Dialysis - rarely needed Urinary sediment - variable FENa : Low

26. Contrast-induced AKI Prophylatic Strategies Use I.V. contrast only when necessary Hydration Minimize contrast volume Low- osmolar (nonionic) contrast media

27. Post-Renal AKI Elevated pressure in urinary conduits results in renal parenchymal destruction if unrelieved important to rule out quickly : potential for recovery of renal function is often inversely related to the duration of the obstruction

28. Post-Renal AKI History – symptoms (frequency, hesitancy, etc) -- carcinoma, DM, stones, medications P/E – distended bladder, prostatic enlargement, pelvic masses , lymph nodes Laboratory studies-- elevated BUN:creat ratio -- unremarkable urine sediment -- variable urine chemistries Renal ultrasound – hydronephrosis Treatment is to relieve the obstruction Bladder catheterization Nephrostomy tubes

29. AKI: URINE VOLUME Anuria (< 100 ml/24h) Acute bilateral arterial or venous occlusion Bilateral cortical necrosis Acute necrotizing glomerulonephritis Obstruction (complete) ATN (very rare) Oliguria (100-500 ml/24h) Pre-renal azotemia ATN Non- Oliguria (> 500 ml/24h) ATN Obstruction (partial)

30. INVESTIGATIONS Biochemistry Blood urea, creatinine , electrolytes, Blood gas analysis. Urine osmolality /sodium/ creatinine

31. Serum Creatinine as a marker for AKI and GFR Normal S.Creatinine is 0.6-1.2mg/dl and is the most commonly used parameter to assess renal function. Unfortunately the correlation between S.Creatinine concentration and GFR may be confounded by several factors.

32. There is abrupt drop in GFR but the S.Cr. does not start going up for 24 or 36 hours after the acute insult . 40 80 GFR (mL/min) 7 14 21 28 4 Days 2 6 Serum Creatinine (mg/dL) Relationship between GFR and serum creatinine in AKI

33. Creatinine is not an ideal marker 1. Creatinine excretion is dependent on renal factors independent of function: Certain medications such as cimetidine and trimethoprim interfere with proximal tubular creatinine secretion and may cause rise in S. creatinine without fall in GFR.

34. 2 . S.Creatinine is dependent on nonrenal factors independent of renal function S.Creatinine is dependent on muscle mass, infection, volume of distribution, age, gender, race, body habitus , diet, presence of amputations. Eg . S. Creatinine of 1.2mg/dl in a 40kg elderly signifies severe reduction of GFR while the same value in a 100kg represents a normal renal function 3. Creatinine production and excretion must be in a steady state before creatinine may be used in any formula for the estimation of GFR.

35. Fractional Excretion of Na Since urinary indices depend on urine sodium concentration, they should be interpreted cautiously if the patient has received diuretic Spot urine Na may be affected (raised) by diuretic use and baseline impaired kidney function (CKD where maximum urine Na reabsorption is impaired) Fractional excretion of Na accounts for this by including creatinine : FxExNa = urine [Na] ÷ plasma [Na] X 100 urine creatinine ÷ plasma creatinine

36. RENAL INDICES Renal Failure Index (RFI) RFI = urine [Na] urine creatinine /serum creatinine

37. URINE AND SERUM LABORATORY VALUES Pre-renal

38. URINE ANALYSIS Dipstick for blood, protein – Suggests a renal inflammatory process Microscopy may show cells, casts, crystals

39. RBCs in Urine Present in glomerulonephritis , vasculitis , HUS TTP scleroderma crisis

40. URINARY CASTS Hyaline – prerenal ARF Granular –ATN (muddy brown ) Red blood cell casts – glomerulonephritis,vasculitis malignant hypertension WBC casts- AIN, pyelonephritis ,leukemic or lymphomatous infiltrates

41. Red Blood Cell Cast Two examples of red blood cell casts, typical of glomerular bleeding.

42. White Blood Cell Cast

43. Pigmented Granular Casts Pigmented granular (“muddy brown”) casts are characteristic of acute tubular necrosis

44. Crystals Urate crystals – acute urate nephropathy Oxalate crystals –ethylene glycol ingestion /acyclovir/ indinavir Eosinophiluria  > 5 % of WBC s AIN , atherothrombotic disease

45. Haematology Full blood count, blood film : Eosinophilia may be present in acute interstitial nephritis, cholesterol embolization , or vasculitis (CSS) Thrombocytopenia and red cell fragments suggest thrombotic microangiopathy –TTP, HUS Coagulation studies Disseminated intravascular coagulation associated with sepsis

46. Immunology Antinuclear antibody (ANA) , Anti-double stranded (ds) antibody - ANA positive in SLE and other autoimmune disorders;DNA antibodies anti-ds DNA antibodies more specific for SLE C3 & C4 complement concentrations- Low in SLE, acute post infectious glomerulonephritis, Cryoglobulinemia ASO and anti-DNAse B titres High after streptococcal infection

47. Immunology... ANCA p-ANCA - Anti PR3 antibodies c-ANCA - Anti MPO antibodies Associated with systemic vasculitis - Wegener’s granulomatosis ; Microscopic polyangiitis . AntiGBM antibodies Present in Goodpasture’s disease

48. Serology Hepatitis B and C, HIV serology

49. Radiology Renal ultrasonography : For renal size, symmetry, evidence of obstruction Pyelography : localization MRA/ Doppler US : arterial /venous obstruction

50. NEW MARKER Cystatin C –protein Produced by nucleated cells Filtered and completely reabsorbed Changes in serum levels occur sooner

51. NOVEL BIOMARKERS 1. IL- 18 2.KIM-1 3.Gro α /KC 4.NGAL-neutrophil gelatinase associated lipocalin 5.NHE-3 - Sodium–hydrogen antiporter 3

52. Complications

53. Complications

54. Complications

55. Other Complications Hyperuricemia Infection- pneumonia, sepsis Git - nausea, vomiting, malnutrition, git bleeding CNS- asterixis , mental changes, seizures Uremic syndrome

56. AKI : PREVENTION R ecognize patients at risk (postoperative states, cardiac surgery, septic shock) Prevent progression from prerenal to renal Preserve renal perfusion ( i sovolemia , cardiac output, normal blood pressure) Avoid nephrotoxins ( aminoglycosides , NSAIDS, amphotericin )

57. GENERAL PROTOCOL FOR MANAGEMENT OF AKI T reat the underlying disease S trictly monitor intake and output (weight, urine output, insensible losses, IVF) M onitor serum electrolytes A djust medication dosages according to GFR A void highly nephrotoxic drugs A ttempt to convert oliguric to non- oliguric renal failure ( furosemide )

58. FLUID THERAPY If patient is fluid overloaded fluid restriction (insensible losses) attempt furosemide 1-2 mg/kg Renal replacement therapy If patient is dehydrated: restore intravascular volume first then treat as euvolemic If patient is euvolemic : restrict to insensible losses (30-35 ml/100kcal/24 hours) + other losses (urine, chest tubes, etc)

59. SODIUM M ost patients have dilutional hyponatremia which should be treated with fluid restriction S evere hyponatremia (Na< 125 mEq /L) : dialysis or hemofiltration

60. POTASSIUM Oliguric renal failure is often complicated by hyperkalemia , increasing the risk of cardiac arrhythmias Treatment of hyperkalemia : sodium bicarbonate (1-2 mEq /kg) insulin + hypertonic dextrose sodium polystyrene : 1 gm/kg . ( Hypernatremia and hypertension are potential complications) dialysis

61. MANAGEMENT OF AKI Metabolic acidosis – soda bicarb ., if < 15 meq Hyperphosphatemia – PO4 binders – sevalamer Hypocalcemia –calcium carbonate Nutrition –restriction of dietary protein < 0.8 g/kg /d calories – 25-30 kcal /kg/d enteral nutrition preferred

62. Criteria for Initiation of RRT Anuria Oliguria Pulmonary edema Hyperkalemia >6.5mmol/L Severe acidemia <7.2 Uremic encephalopathy Uremic pericarditis

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