Acute Renal Failure Ebadur Rahman FRCP Edin FASN

Acute Renal Failure Ebadur Rahman FRCP (Edin), FASN, Specialty Certificate in Nephrology (UK) MRCP (UK), DIM (UK), DNeph (UK), Mmed. Sci. Nephrology (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/d. L GFR <10 m. L/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 m. L/d Azotemia: Incr Cr, BUN Uremia : symptomatic azotemia

KDIGO AKI Staging Stage Serum creatinine 1 ≥ 1. 5 -1. 9 times baseline (7 days) OR 26. 5 µmol/L increase (48 hrs) 2 ≥ 2. 0 -2. 9 times baseline ≥ 3. 0 times baseline OR 3 increase in creatinine to ≥ 354 µmol/L OR Renal replacement therapy Urine output < 0. 5 ml/kg/hr for -12 hrs 6 < 0. 5 ml/kg/hr for ≥ 12 hrs < 0. 3 ml/kg/hr for ≥ 24 hrs OR Anuria for ≥ 12 hrs KDIGO AKI Guideline. Kidney inter. , Suppl. 2012; 2: 1– 138

ATN Prerenal Cr increases at 0. 3 -0. 5 /day U Na, Fe. Na increases slower than 0. 3 /day UNa<20 Fe. Na<1% Normal UNa>40 Fe. Na >2% epi cells, granular casts Cr won’t Cr improves improve much with IVF 10 -15: 1 >20: 1 UA Response to volume BUN/Cr

Fe. Na = (urine Na x plasma Cr) (plasma Na x urine Cr)

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

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

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 e. GFR 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 – Urine electrolytes and Urine Cr to calculate Fe. Na – 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 m. Eq/L) or a rapidly increasing serum potassium ●Signs of uremia, such as pericarditis, or an otherwise unexplained decline in mental status ●Severe metabolic acidosis (p. H <7. 1)

$Indications for dialysis therapy —IN AKI include: Fluid overload that is refractory to diuretics.$

Indications for dialysis therapy —IN AKI include: Fluid overload that is refractory to diuretics. Hyperkalemia (serum potassium concentration >6. 5 m. Eq/L) or rapidly rising potassium levels, refractory to medical therapy. Metabolic acidosis (p. H <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 22 yo 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. Glomerulonephritis C. Dehydration D. AIN from NSAIDs

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 1. 2. 3. 4. Tubular (ATN) Interstitial (AIN) Glomerular (Glomerulonephritis) Vascular

You evaluate a 57 yo man w/ oliguria and rapidly increasing BUN, Cr. A. B. C. D. ATN Acute glomerulonephritis Acute interstitial nephritis Nephrotic Syndrome

Muddy brown granular casts

ATN • Renal tubular epithelial cell casts (below)

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

56 yo woman with previously normal renal function now has BUN=24, Cr 1. 8. Which drug is responsible? A. B. C. Ibuprofen Paracetamol Prednisolone

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 32 yo woman with HTN, oliguria, and rapidly increasing Cr, BUN. A. ATN B. Acute glomerulonephritis C. Acute interstitial nephritis D. Nephrotic Syndrome

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?

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

A 21 y 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+++ A. Nephrotic Syn B. Systemic Vasculitis C. Acute Glomerulonephritis D. Hemolytic-Uremic Syn E. 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. 1 had negative cardiac cath 4 days ago, now Cr=2. 2 and A. Renal Artery Stenosis B. 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 35 yo woman with previously normal renal function now with BUN=60, Cr=3. 5. • her K=7. 8 Cxray –puledema • What do you do next

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? A. Send her for Stat CT with IV contrast B. Send her for Stat CT without IV contrast C. Just give her heparin D. Begin IV hydration E. Begin pre-procedure Mannitol F. 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. 9 NS) 1 -1. 5 mg/kg/hour x 12 hours prior to procedure and 6 -12 hours after 2. (N-acetylcysteine)