1. Acute Renal Failure (ARF) Acute Kidney Injury (AKI) Mitra Basiratnia Ped Nephrologist SUMS

2. AKI Formerly referred to as acute renal failure Abrupt reduction in kidney function measured by decline in GFR Results in disturbances –Impaired nitrogenous waste excretion –Loss of H2O & electrolyte regulation –Loss of acid-base regulation Contributing factor in morbidity & mortality of critically ill

3. The pRifle Criteria End-stage kidney disease Persistant AKI = complete loss of renal function > 4 weeks Increased creatinine × 3 or GFR decrease >75% or creatinine > 4 mg/dL (acute rise >0.5 mg/dL) UO < 0.3 ml/kg/hr × 24 hours or anuria × 12 hours Increased creatinine × 2 or GFR decrease > 50% UO <0.5 ml/kg/hr × 16 hours Increased creatinine × 1.5 or GFR decrease > 25% UO<0.5 ml/kg/hr × 8 hours Bellomo et al. Crit Care 2004;8:R204-R212. Oliguria  Specificity  Sensitivity Risk Injury Failure Loss End- stage

4. Azotemia is a consistent feature of acute renal failure (ARF), oliguria is not. anuria ::: urine output < 0.5 ml/kg/h Oliguria ::: urine output< 1 ml/kg/h

5. acute renal failure: common clinical features azotemia hypervolemia electrolytes abnormalities:  K+  phosphate  Na+  calcium metabolic acidosis hypertension oliguria - anuria

6. acute renal failure: classification Prerenal (hypoperfusion) Renal (intrinsic) Postrenal (obstructive)

7. prerenal decreased perfusion without cellular injury renal tubular and glomerular functions are intact reversible if underlying cause is corrected

8. prerenal common etiologies: –dehydration –hypovolemia –hemodynamic factors that can compromise renal perfusion (CHF, shock) Sustained prerenal azotemia is the main factor that predisposes patients to ischemia- induced acute tubular necrosis (ATN)

9. postrenal obstruction of urinary tract important to rule out quickly: –potential for recovery of renal function is often inversely related to the duration of the obstruction

10. renal classified according primary site of injury: –tubular –interstitium –vessels –glomerulus

11. Clinical Approach to AKI: Pre-, Intra-, and Post-Renal History Volume status Ultrasound Urinalysis US shows Hydronephrosis Post-Rena l Urinalysis Normal Urinalysis Abnormal Tubulointerstial Disorders Glomerular and Vascular Disorders Pre-renal

12. Nephrologists Clinical Approach to AKI History Volume Status Ultrasound Urinalysis Hydronephrosis Post-Renal Prostate disease BPH Cancer Pelvic malignancy Stones Stricture Retroperitoneal fibrosis Normal Urinalysis Pre-Renal Low ECF Volume GI losses Hemorrhage Diuretics Osmotic diuresis Altered renal blood flow or hemodynamics Sepsis Heart failure Cirrhosis/Hepatorenal syndrome Hypercalcemia Medications NSAIDs/Cox-2 inhibitors ACE inhibitors Angiotensin II receptor blockers Vascular disease Vascular Disorders Tubulointerstitial Disorders Glomerular Disorders Tubular obstruction Crystals Calcium oxalate (Ethylene glycol, orlistat) Indinivir Acyclovir Methotrexate Tumor lysis syndrome Myeloma cast nephropathy Acute tubular necrosis Ischemic Nephrotoxic Contrast-induced Rhabdomyolysis Acute interstitial nephritis Medication-induced Autoimmune Sjogren syndrome Sarcoidosis Infection-related Arterial Renal artery stenosis Renal artery thromboembolism Fibromuscular dysplasia Takayasu arteritis Medium vessel Polyarteritis nodosa Kawasaki disease Small vessel Glomerulonephritis Thrombotic microangiopathies Cholesterol emboli Renal vein Renal vein thrombosis Abdominal compartment syndrome Renal parenchymal disorders Abnormal urinalysis

13. acute renal failure: diagnosis History and Physical examination Blood tests : CBC, BUN/creatinine, electrolytes, uric acid, CK Urine analysis Renal Indices Renal ultrasound (useful for obstructive forms) Doppler (to assess renal blood flow) Nuclear Medicine Scans DMSA: anatomy DTPA and MAG3: renal function, urinary excretion and upper tract outflow

14. Presentation: Children History: –AGE, hemorrhage, sepsis, decreased oral intake –Bloody diarrhea w/ oliguria (<500ml/1.73m2/day) or anuria – HUS –Pharyngitis or impetigo – PIGN –Hemoptysis and renal impairment – Pulm-Renal Syndrome (Wegner’s, Goodpasture’s) –Trauma/crush injury – rhabdomyolysis –Exposure to nephrotoxins – aminoglycosides, amphotericin-B, chemotherapy Rx PxEx: –Tachycardia, dry MM, sunken eyes/fontanel, orthostatic BP, decreased skin turgor –Edema – nephrotic syndrome, heart failure, liver failure –Skin findings – purpura, petechiae, malar rash, maculopapular – HSP/SLE, AIN

15. Reabsorption of water and sodium: - intact in pre-renal failure - impaired in tubulo-interstitial disease and ATN Since urinary indices depend on urine sodium concentration, they should be interpreted cautiously if the patient has received diuretic therapy renal indices

16. Fractional Excretion of Na (FENa) FENa: [ urine Na/serum Na] x 100 % [urine creatinine/serum creatinine] renal indices

17. prerenal azotemia: –Urine sediment: hyaline and fine granular casts –Urinary to plasma creatinine ratio: high –Urinary Na: low –FENa: low Increased urine output in response to hydration

18. renal azotemia: –Urine sediment: brown granular casts and tubular epithelial cells –Urinary to plasma creatinine ratio: low –Urinary Na: high –FENa: high

19. Urine Sediment Monomorphic RBCs Dysmorphic RBCs Hyaline castRBC cast

20. Urine Sediment RTE cast Fatty castATN WBC cast

21. urine and serum laboratory values

22. hemoglobinuria + myoglobinuria hemoglobinuria: transfusion reactions, HUS myoglobinuria: crush injuries, rhabdomyolisis urine (+) blood but (-) red blood cells  CPK  K+ treatment aggressive hydration + urine alkalinization mannitol / furosemide

23. acute renal failure: management treat the underlying disease strictly monitor intake and output (weight, urine output, insensible losses, IVF) monitor serum electrolytes adjust medication dosages according to GFR avoid highly nephrotoxic drugs attempt to convert oliguric to non-oliguric renal failure (furosemide )

24. acute renal failure: 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 (below) If patient is euvolemic: restrict to insensible losses (30-35 ml/100kcal/24 hours) + other losses (urine, chest tubes, etc)

25. sodium most patients have dilutional hyponatremia which should be treated with fluid restriction Na< 120mEq/L or symptomatic: hypertonic saline

26. potassium Oliguric renal failure is often complicated by hyperkalemia, increasing the risk in cardiac arrhythmias K>6 resin K>7 emergency treatment Treatment of hyperkalemia:.calcium gluconate ( 1cc/kg IV ) over 3-5 min sodium bicarbonate (1-2 mEq/kg) over 5-10 min insulin + hypertonic dextrose: 0.1 U/kg with 1 cc/kg 50% glucose over 1 hour sodium polystyrene (Kayexalate): 1 gm/kg. Can be repeated qh. (Hypernatremia and hypertension are potential complications) dialysis

27. nutrition provide adequate caloric intake limit protein intake to control increases in BUN minimize potassium and phosphorus intake limit fluid intake If adequate caloric intake can not be achieved due to fluid limitations, some form of dialysis should be considered

28. Management Anemia Hb<7 Acidosis PH<7.15 HCO3<8 Neurologic Hypertension

29. Indication for dialysis Volume overload Refractory electrolyte imbalance & acidosis BUN> 100-150 or lower if rapidly rising Pericarditis Uremic encephalopathy