Acute Renal Failure Ebadur Rahman FRCP (Edin),FASN, Specialty Certificate in Nephrology (UK) MRCP (UK), DIM (UK), DNeph (UK), MmedSciNephrology (UK). Consultant & clinical tutor Department of Nephrology PSMMC

Acute Renal Failure 30 different definition Rapid decline in the GFR over days to weeks. Cr increases by >0.5 mg/dL GFR <10mL/min, or <25% of normal

KDIGO AKI Definition Acute kidney injury/impairment (AKI) is defined as any of the following: Increase in SCr by >0.3 mg/dl (>26.4 µmol/L) within 48 hours, or Increase in SCr by >1.5-fold above baseline which is known or presumed to have occurred within 7 days, or Urine volume <0.5 ml/kg/h for 6 hours. KDIGO AKI GL. Kidney inter., Suppl. 2012; 2: 1–138

Definitions Anuria: No UOP Oliguria: UOP<400-500 mL/d Azotemia: Incr Cr, BUN Uremia : symptomatic azotemia

KDIGO AKI Staging Stage Serum creatinine Urine output 1 ≥ 1.5-1.9 times baseline (7 days) OR 26.5 µmol/L increase (48 hrs) < 0.5 ml/kg/hr for 6-12 hrs 2 ≥ 2.0-2.9 times baseline < 0.5 ml/kg/hr for ≥12hrs 3 ≥ 3.0 times baseline increase in creatinine to ≥ 354 µmol/L Renal replacement therapy < 0.3 ml/kg/hr for ≥24hrs Anuria for ≥ 12hrs KDIGO AKI Guideline. Kidney inter., Suppl. 2012; 2: 1–138

ATN Prerenal Cr increases at 0.3-0.5 /day increases slower than 0.3 /day U Na, FeNa UNa>40 FeNa >2% UNa<20 FeNa<1% UA epi cells, granular casts Normal Response to volume Cr won’t improve much Cr improves with IVF BUN/Cr 10-15:1 >20:1

FeNa = (urine Na x plasma Cr) (plasma Na x urine Cr)

More FeNa FeNa 1%-2% 1. Prerenal-sometimes 2. ATN-sometimes 3. AIN-higher FeNa due to tubular damage FeNa >2% ATN Damaged tubules can't reabsorb Na

Calculating FeNa after pt has gotten Lasix... 1. Fractional Excretion of Lithium (endogenous) 2. Fractional Excretion of Uric Acid 3. Fractional Excretion of Urea

Causes of ARF in hospitalized pts 45% ATN Ischemia, Nephrotoxins 21% Prerenal CHF, volume depletion, sepsis 10% Urinary obstruction 4% Glomerulonephritis or vasculitis 2% AIN 1% Atheroemboli

Presentation of Kidney Disease Normal Renal Function (hematuria/Proteinurea) Asymptomatic, only incidental finding on routine checkup AKI Abnormal radiological imaging of kidney Various stages of impairment of CKD (1-5)

Acute Kidney Injury and Sepsis AKI occurs in 19% culture positive in moderate sepsis 23% culture positive in severe sepsis 51% culture positive in septic shock 70% mortality in sepsis and AKI combined Rangel-Frausto et al. JAMA 1995;273:117-123 Schrier & Wang NEJM 2004;351:159-69

ARF: Signs Hyperkalemia HTN Pulmonary edema Ascites Asterixis Encephalopathy

Diagnostic approach History Physical examination Assessment of renal function by eGFR Careful examination of urine Radiological imaging of Kidney Serological Testing Tissue Diagnosis by Renal Biopsy

ARF: Focused History Vomiting? Diarrhea? Hx of heart disease, liver disease, previous renal disease, kidney stones, BPH? Any edema, change in urination? Any new medications? Any recent radiology studies? Rashes?

Physical Exam Volume Status Mucus membranes, orthostatics Cardiovascular JVD, rubs Pulmonary Decreased breath sounds Rales Rash (Allergic interstitial nephritis) Large prostate Extremities (Skin turgor, Edema)

W/U for ARF Chem Urine Kidney U/S - r/o hydronephrosis Urine electrolytes and Urine Cr to calculate FeNa Urine eosinophils Urine sediment: casts, cells, protein Uosm Kidney U/S - r/o hydronephrosis

Immediate therapy  — The management of life-threatening Common complications of AKI include the following: ●Fluid overload ●Hyperkalemia (serum potassium >5.5 mEq/L) or a rapidly increasing serum potassium ●Signs of uremia, such as pericarditis, or an otherwise unexplained decline in mental status ●Severe metabolic acidosis (pH <7.1)

Indications for dialysis therapy —IN AKI include: Fluid overload that is refractory to diuretics. Hyperkalemia (serum potassium concentration >6.5 mEq/L) or rapidly rising potassium levels, refractory to medical therapy. Metabolic acidosis (pH <7.1) in patients in whom the administration of bicarbonate is not indicated, such as those with volume overload (who would not tolerate the obligate sodium load), or those with lactic acidosis or ketoacidosis, in whom bicarbonate administration has not been shown to be effective. Signs of uremia such as pericarditis, neuropathy, or an otherwise unexplained decline in mental status.

A. ATN B. Glomerulo-nephritis C. Dehydration D. AIN from NSAIDs A 22yo male with sickle cell anemia and abdominal pain who has been vomiting nonstop for 2 days. BUN=45, Cr=2.2. previous u& e normal. A. ATN B. Glomerulo-nephritis C. Dehydration D. AIN from NSAIDs hyaline cast, normal finding, Prerenal.

Prerenal ARF Hyaline casts can be seen in normal pts NOT an abnormal finding UA in prerenal ARF is normal Prerenal: causes 21% of ARF in hosp. pts Reversible Prevent ATN with volume replacement Fluid boluses or continuous IVF Monitor Uop

Prerenal causes Intravascular volume depletion Hemorrhage Vomiting, diarrhea “Third spacing” Diuretics Reduced Cardiac output Cardiogenic shock, CHF, tamponade, huge PE.... Systemic vasodilation Sepsis Anaphylaxis, Antihypertensive drugs Renal vasoconstriction Hepatorenal syndrome

Intrinsic ARF Tubular (ATN) Interstitial (AIN) Glomerular (Glomerulonephritis) Vascular

You evaluate a 57yo man w/ oliguria and rapidly increasing BUN, Cr. ATN Acute glomerulonephritis Acute interstitial nephritis Nephrotic Syndrome muddy brown granular casts

Muddy brown granular casts

ATN Renal tubular epithelial cell casts (below) epithelial cell cast (cells are larger than WBCs; have nuclei)

ATN Broad casts (form in dilated, damaged tubules)

ATN Causes 1. Hypotension Relative low BP May occur immediately after low BP episode or up to 7 days later! 2. Post-op Ischemia Post-aortic clamping, post-CABG 3. Crystal precipitation 4. Myoglobinuria (Rhabdo) 5. Contrast Dye ARF usually 1-2 days after test 6. Aminoglycosides (10-26%)

ATN—What to do Remove any offending agent IVF Try Lasix if euvolemic pt is anuric Dialysis Most pts return to baseline Cr in 7-21 days

56yo woman with previously normal renal function now has BUN=24, Cr 1 56yo woman with previously normal renal function now has BUN=24, Cr 1.8. Which drug is responsible? Ibuprofen Paracetamol Prednisolone WBC cast which drug? gentamicin for SBE, motrin for RA, ASA for CAD,

WBC Casts Cells in the cast have nuclei (unlike RBC casts) Acute Interstitial Nephritis

Acute Interstitial Nephritis 70% Drug hypersensitivity 30% Antibiotics: PCNs (Methicillin), Cephalosporins, Cipro Sulfa drugs NSAIDs Allopurinol... 15% Infection Strep, Legionella, CMV, other bact/viruses 8% Idiopathic 6% Autoimmune Dz (Sarcoid, Tubulointerstitial nephritis/Uveitis)

AIN from Drugs Renal damage is NOT dose-dependent May take wks after initial exposure to drug Up to 18 mos to get AIN from NSAIDS! But only 3-5 d to develop AIN after second exposure to drug Fever (27%) Serum Eosinophilia (23%) Maculopapular rash (15%) Bland sediment or WBCs, RBCs, non-nephrotic proteinuria WBC Casts are pathognomonic! Urine eosinophils on Wright’s or Hansel’s Stain Also see urine eos in RPGN, renal atheroemboli...

AIN Management Remove offending agent Most patients recover full kidney function in 1 year

You evaluate a 32yo woman with HTN, oliguria, and rapidly increasing Cr, BUN. ATN Acute glomerulonephritis Acute interstitial nephritis Nephrotic Syndrome RBC casts

Acute Glomerulonephritis RBC casts: cells have no nuclei Casts in urine: think INTRINSIC renal dz If she had a sore throat 10 days ago, think Postinfectious Proliferative Glomerulonephritis

What are these? Another pic of RBC casts; just look different

Glomerular Hematuria (dysmorphic RBCs) RBC casts Lipiduria (increased glomerular permeability) Proteinuria (may be in nephrotic range) Fever, rash, arthralgias, pulmonary sx Elevated ESR, low complement levels

Acute Glomerulonephritis Hemolytic-Uremic Syn Rhabdomyolysis A 21y woman with Breast Cancer s/p chemo in the ER has weakness, fever, rash. WBC=15.4, Hct 24, Cr 2.9, LDH 600, CK=600. UA=3+ prot, 3+blood, 20 RBC.blood film schistocytes+++ Nephrotic Syn Systemic Vasculitis Acute Glomerulonephritis Hemolytic-Uremic Syn Rhabdomyolysis

TTP Order blood smear to r/o TTP TTP associated with malignancy, chemo TTP may mimic Glomerulonephritis on UA (RBCs, WBCs) Thrombocytopenia, anemia not consistent with nephrotic or nephritic syndrome Need CK in the thousands to cause ARF

Microvascular ARF TTP/HUS HELLP syndrome Plasma exchange

Macrovascular ARF Aortic Aneurysm Renal artery dissection or thrombosis Renal vein thrombus Atheroembolic disease New onset or accelerated HTN? Abdominal bruits, reduced femoral pulses? Vascular disease? Embolic source?

Your 70 yo male inpatient with baseline Cr=1 Your 70 yo male inpatient with baseline Cr=1.1 had negative cardiac cath 4 days ago, now Cr=2.2 and Renal Artery Stenosis Contrast-Induced Nephropathy C. Abdominal Aortic Aneurysm D. Cholesterol Atheroemboli

Renal Atheroembolic disaese 1% of Cardiac caths: atheromatous debris scraped from the aortic wall will embolize Retinal Cerebral Skin (Livedo Reticularis, Purple toes) Renal (ARF) Gut (Mesenteric ischemia) Unlike in Contrast-Induced Nephropathy, Cr will NOT improve with IVF Diagnosis of exclusion: will NOT show up on MRI or Renal U/S; WILL show up on renal bx Tx: supportive

You’re called to the ER to see... A 35yo woman with previously normal renal function now with BUN=60, Cr=3.5. her K=7.8 Cxray –puledema What do you do next

Send her for Stat CT with IV contrast A pt with chronic lung disease has acute pleuritic pain and desats to 92%RA. You want to r/o PE but her Cr=1.4. Can you get a CT with IV contrast? Send her for Stat CT with IV contrast Send her for Stat CT without IV contrast C. Just give her heparin Begin IV hydration Begin pre-procedure Mannitol Get a VQ scan instead

Contrast-Induced Nephrotoxicity Cr increases by 25% post-procedure Contrast causes renal vasoconstriction renal hypoxia Iodine itself may be renally toxic If Cr>1.4, use pre-procedure prophylaxis

Pre-Procedure Prophylaxis 1. IVF ( 0.9NS) 1-1.5 mg/kg/hour x12 hours prior to procedure and 6-12 hours after (N-acetylcysteine)