Acute Kidney Injury. I. David Weiner, M.D. Division of Nephrology, Hypertension and Transplantation University of Florida and NF/SGVHS

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1 Acute Kidney Injury I. David Weiner, M.D. Division of Nephrology, Hypertension and Transplantation University of Florida and NF/SGVHS

2 Concentration (Initial = 100) The good, the bad and the ugly The good: Very effective at removing toxins Renal Clearance of Compounds in the Plasma 80.0 Clint Eastwood Lee Van Cleef Eli Wallach Time (Minutes)

3 The good, the bad and the ugly Clint Eastwood Lee Van Cleef Eli Wallach The good: Very effective at removing toxins The bad: Very high metabolic rate and O 2 consumption Very sensitive to toxins or decreased O 2 delivery The ugly: Kidney damage dramatically increases mortality ~40% of people with acute kidney injury requiring dialysis die

4 What can we do for the person with AKI? Give medications to speed renal recovery None available Identify and treat the cause of the AKI Treat complications

5 What causes AKI? Blood doesn t get to the kidney Pre-renal azotemia

6 What causes AKI? Blood doesn t get to the kidney Pre-renal azotemia Glomeruli and tubules cannot function Intrinsic or parenchymal

7 What causes AKI? Blood doesn t get to the kidney Pre-renal azotemia Glomeruli and tubules cannot function Intrinsic Urine cannot get out Obstructive uropathy

8 Case 1 48 year old with history of alcohol abuse has been vomiting blood and having diarrhea for the past 4 days PEx BP 72/48, HR 132 Dry mucous membranes JVP 1 cm H 2 O Labs BUN, 157 mg/dl (~10, nl) Creatinine, 7.2 mg/dl egfr, 8 ml/min/m 2

9 Pre-renal azotemia - blood doesn t get to the kidneys No blood Decreased intravascular volume Bleeding Vomiting Diarrhea Excessive diuresis

10 What causes blood not to get to the kidneys? No pump Myocardial dysfunction

11 What causes blood not to get to the kidneys? Hormones that maintain renal perfusion during low flow conditions are blocked Examples Renal artery stenosis Mild intravascular volume depletion Hormones Ang II ACE-I or ARB Prostaglandins NSAIDs and COX-2 inhibitors

12 What causes blood not to get to the kidneys? Excessive renal artery constriction during certain diseases Sepsis Hepatorenal syndrome

13 What causes AKI? Blood cannot get to the kidney - Pre-renal No blood No pump Blood goes somewhere else

14 Detection trick the kidneys are very smart! If not enough blood gets to kidneys, the kidneys think we are volume depleted Decide to make less urine (<600 ml/d) Activate urine concentration Urea reabsorption Less urinary urea excretion Blood urea nitrogen (BUN) increased out of proportion to changes in GFR Elevated BUN:Creatinine Ratio Normal, 10:1 Pre-renal azotemia, ~20:1 BUN 157 mg/dl, Cr, 7.2 mg/dl BUN/Cr = 21.8

15 Case #2 28 year old involved in motorcycle accident. In ER has BP 90/40 with HR 128. He undergoes CT scan with intravenous contrast and then is taken to the OR for exploratory laparotomy. During surgery he requires norepinephrine infusion to maintain his BP. 12 hrs later he has urine output of 10 ml/hr. Three days later his BP is normal, but he has BUN 74 and creatinine 7.6.

16 What causes AKI? Blood cannot get to the kidney Pre-renal Glomeruli and tubules cannot function Intrinsic or parenchymal

17 Parenchymal AKI Acute Glomerulonephritis Glomeruli Acute Interstitial Interstitium Nephritis Acute Tubular Tubules Necrosis

18 Parenchymal AKI Acute Glomerulonephritis Acute Interstitial Nephritis Immunecomplex Deposition Cell-mediated Acute Tubular Necrosis Antibody to glomerular Basement membrane SLE Chronic Infection (Endocarditis, HCV, Osteomyelitis) Anti-neutrophil cytoplasmic antibody (ANCA) Antibody Cross-reactivity (Lungs)

19 Immunofluorescence of renal biopsy Lumpy-bumpy Immune-complex deposition Pauci-immune ANCA-associated systemic vasculitis Linear Anti-GBM disease Goodpasture s disease, if pulmonary involvement

20 Parenchymal AKI Acute Glomerulonephritis Acute Interstitial Nephritis Acute Tubular Necrosis Decreased O 2 delivery Nephrotoxin Exposure Hypotension and/or vasoconstrictive agents Surgery Exogenous (Medications, X-ray contrast) Endogenous (Myoglobin)

21 Parenchymal AKI Acute Glomerulonephritis Acute Interstitial Nephritis Acute Tubular Necrosis Allergic Non-allergic Skin rash Proteinuria Medications Eosinophiluria NSAIDs

22 Trick BUN:Creatinine ratio is normal, ~10:1

23 Case #3 74 year old gentleman with a 30+ year history of DM, with complications including retinopathy, neuropathy and enteropathy. Chief complaint: I haven t passed water for three days. PEx: VS: BP 147/84, HR 84 Grapefruit-sized mass in lower abdomen, non-tender Labs: BUN 141, creatinine 12.8 Bladder ( foley ) catheter is placed and drains 1200 cc of urine.

24 What causes AKI? Blood cannot get to the kidney Pre-renal Glomeruli and tubules cannot function Parenchymal Urine cannot get out Obstructive uropathy

25 Obstructive uropathy Bladder cannot empty Urethral obstruction, e.g., BPH Bladder cannot squeeze Neurogenic bladder Urine cannot get from kidneys to bladder Ureteral obstruction, e.g., pelvic malignancy, kidney stones Renal tubular obstruction

26 What caused the AKI? Diagnostic hints from selected laboratory test

27 Urinalysis Dysmorphic RBC suggests glomerulonephritis

28 Urinalysis Renal tubular epithelial cells suggest ATN

29 Urinalysis Urine eosinophils suggest acute tubulointerstitial nephritis

30 Renal ultrasound Normal Hydronephrosis Liver Kidney

31 Renal ultrasound Normal Small, echogenic Liver Kidney

32 Most common causes of AKI Pre-renal azotemia Acute tubular necrosis Both are caused by hypotension Both present with oliguria (low urine output, < 600 ml/d)

33 Differentiating pre-renal azotemia and ATN Intravascular volume depletion ( prerenal azotemia ) Tubules sense intravascular volume depletion Maximally reabsorb Na+ and water Reabsorb >99% of filtered Na + Excrete < 1% of filtered Na + Acute Tubular Necrosis Tubule cells that reabsorb Na + are damaged Cannot reabsorb 99% of filtered Na + Excrete > 1% of filtered Na +

34 Fractional excretion of sodium (FE Na ) Calculates percentage of filtered sodium (GFR x [Na+]) not reabsorbed and excreted in urine FE Na = (U Na / P Na ) / (U Cr / P Cr ) Pre-renal azotemia, < 1% ATN, >1% Only needed if the patient is oliguric Yes, you need to know this formula

35 Coming attractions Biomarkers Kidney-specific proteins present in renal cells and not in the urine Released by damaged cells

36 Acute Kidney Injury What caused it?

37 Acute Kidney Injury What caused it? Treat complications.

38 Indications for emergent dialysis Patient will die in new few hours if you don t, i.e., refractory, life-threatening Hyperkalemia Pulmonary edema Specific drug overdoses Lithium, ethylene glycol, methanol Most medications Highly protein bound or high volume distribution Not removed quickly by dialysis

39 Evaluation of Acute Kidney Injury (AKI) What caused it? What should be done about it? Treat underlying cause Treat complications