Acute Renal Failure

It is no exaggeration to say that the composition of blood is determined, not by what the mouth takes in, but
Dr.Kannan Murugesan M.D Dean & Professor of Medicine RAK College of Medical Sciences

by what the kidneys keep !!!

Acute Renal Failure (ARF)

Definition
Sudden, but usually reversible loss of renal function. Reduction in urine volume Retention of nitrogenous waste products in the blood Inability of kidneys to regulate fluid, electrolytes and acid-base homeostasis

Acute Renal Failure

Definitions
Azotemia - the accumulation of nitrogenous wastes Uremia - symptomatic renal failure Oliguria - urine output < 400 mL/24 hours Anuria - urine output < 100 mL/24 hours

Manifestations of ARF
Azotemia progressing to uremia Hyperkalemia Metabolic acidosis Volume overload & decreased GFR Accumulation and toxicity of medications excreted by the kidney

Relationship Between GFR and Serum Creatinine in ARF

120 80 40 0 6 Serum Creatinine (mg/dL) 4 2 0 0 7 14 Days 21 28 GFR (mL/min)

Classification of Acute Renal Failure

Acute Renal Failure

Pathogenesis of Prerenal Azotemia

Volume Depletion Congestive Heart Failure Liver Failure Sepsis
+ +

Prerenal ARF

Intrinsic ARF

Postrenal ARF

Angiotensin II

Renal Vasoconstriction -

itric oxide Prostaglandins

Adrenergic nerves
+

Vasopressin Acute Tubular ecrosis Acute Interstitial ephritis Acute G Acute Vascular Syndromes Intratubular Obstruction

Decreased GFR

Pre renal Failure

Volume Depletion Decreased effective blood volume
congestive heart failure cirrhosis nephrotic syndrome sepsis

Pre renal Failure: Clinical Presentation

History volume loss (e.g., diarrhea, acute blood loss) heart disease liver disease evidence of infection diuretic use thirst orthostatic symptoms

Renal vasoconstriction
hepatorenal syndrome hypercalcemia nonsteroidal anti-inflammatory drugs

Pre renal Failure: Clinical Presentation

Physical Examination
Orthostatic changes in blood pressure Skin turgor Dryness of mucous membranes and axillae Neck veins Cardiopulmonary exam Peripheral edema
> 20:1

Pre renal Failure: Laboratory indices

BUN:Creatinine ratio Urine indices
Oliguria
usually < 500 mL/24 hours; but may be non-oliguric

Elevated urine concentration

UOsm > 700 mmol/L specific gravity > 1.020

Evidence of high renal sodium resorption

UNa < 20 mmol/L FENa < 0.01

Inactive urine sediment

Treatment of Pre renal Failure

Correction of volume deficits Discontinuation of antagonizing medications NSAIDs/COX-2 inhibitors Diuretics Optimization of cardiac function

Post renal Acute Failure

Urinary tract obstruction
level of obstruction
upper tract (ureters) lower tract (bladder outlet or urethra)

degree of obstruction
partial complete

Etiologies of Post renal Acute Failure

Upper tract obstruction Intrinsic
nephrolithiasis papillary necrosis blood clot

Postrenal Acute Renal Failure: Clinical Presentation

History
Symptoms of bladder outlet obstruction urinary frequency urgency intermittency hesitancy nocturia incomplete voiding

Lower tract obstruction

benign prostatic hypertrophy prostate cancer urethral stricture bladder stones blood clot

Extrinsic
retroperitoneal or pelvic malignancy abdominal aortic aneurysm

Postrenal Acute Renal Failure: Clinical Presentation

History
Changes in urine volume
anuria polyuria fluctuating urine volume

Postrenal Acute Renal Failure: Clinical Presentation

Physical Examination Suprapubic mass Prostatic enlargement Pelvic masses Adenopathy

Flank pain Hematuria History of pelvic malignancy

Postrenal Acute Renal Failure: Evaluation

Diagnostic studies
BUN: Creatinine ratio > 20:1 Unremarkable urine sediment Variable urine chemistries

Postrenal Acute Renal Failure: Laboratory Evaluation

Diagnostic studies
Post-void residual bladder volume
> 100 mL consistent with voiding dysfunction

Radiologic studies
Ultrasound CT scan Nuclear medicine Retrograde pyelography

Treatment of Postrenal Acute Renal Failure

Relief of obstruction
Lower tract obstruction
bladder catheter

Intrinsic Acute Renal Failure

Acute tubular necrosis (ATN) Acute interstitial nephritis (AIN) Acute glomerulonephritis (AGN) Acute vascular syndromes Intratubular obstruction

Upper tract obstruction

ureteral stents percutaneous nephrostomies

Recovery of renal function dependent upon duration of obstruction Risk of post-obstructive diuresis

Acute Tubular ecrosis

Ischemic
prolonged prerenal azotemia hypotension hypovolemic shock cardiopulmonary arrest cardiopulmonary bypass

Pathophysiology of Acute Tubular ecrosis

Mechanisms of decreased renal function
Vasoconstriction Tubular obstruction by sloughed debris Backleak of glomerular filtrate across denuded tubular basement membrane

Nephrotoxic
drug-induced
radiocontrast agents aminoglycosides amphotericin B cisplatinum acetaminophen

pigment nephropathy
hemoglobin myoglobin

Sepsis

Phases of Ischemic AT

Pathophysiology of AT
Ischemia

Endothelial Injury

Tubular Injury Disruption of Cytoskeleton

GFR

Inflammation Activation of Vasoconstrictors Impaired Vasodilation Increased Leukocyte Adhesion

Loss of Cell Polarity

Apoptosis & Necrosis

Desquamation of Cells

Time

Capillary Obstruction & Continued Ischemia

Tubular Obstruction & Backleak

Pathophysiology of ATN:
Tubular Epithelial Cell Injury and Repair
Ischemia/ Reperfusion Necrosis Apoptosis

Acute Tubular ecrosis: Clinical Presentation

History
Acute illness Exposure to nephrotoxins Episodes of hypotension

Normal Epithelium Differentiation & Reestablishment of polarity

Loss of polarity

Cell death

Physical examination
Hemodynamic status Volume status Features of associated illness

Proliferation

Sloughing of viable and dead cells with luminal obstruction Adhesion molecules Na+/K+-ATPase

Laboratory data
BUN:Creatinine ratio < 10:1 Evidence of toxin exposure

Migration , Dedifferentiation of Viable Cells

Acute Tubular ecrosis: Laboratory Indices

Urine indices Urine volume may be oliguric or non-oliguric Isosthenuric urine concentration UOsm 300 mmol/L specific gravity 1.010 Evidence of renal sodium wasting UNa > 40 mmol/L FENa > 0.02 Urine sediment tubular epithelial cells granular casts

Acute Tubular ecrosis: Treatment

Supportive therapy No specific pharmacologic treatments Acute dialysis for:
volume overload metabolic acidosis hyperkalemia uremic syndrome
pericarditis encephalopathy

azotemia

Prognosis of Acute Tubular ecrosis

Mortality dependent upon comorbid conditions overall mortality ~ 50% Recovery of renal function seen in ~ 90% of patients who survive - although not necessarily back to prior baseline renal function

Acute Interstitial ephritis

Acute renal failure due to lymphocytic infiltration of the interstitium Classic triad of fever rash eosinophilia

Acute Interstitial ephritis

Drug-induced
penicillins cephalosporins sulfonamides rifampin phenytoin furosemide NSAIDs

Acute Interstitial ephritis: Clinical Presentation

History preceding illness or drug exposure Physical examination fever

Infection-related
bacterial viral rickettsial Tuberculosis

Systemic diseases
SLE sarcoidosis Sjgrens syndrome

rash Laboratory Findings eosinophilia / eosinophiluria

Malignancy Idiopathic

Acute Interstitial ephritis:

Urine findings
non-nephrotic protinuria hematuria pyuria WBC casts eosinophiluria

Acute Interstitial ephritis: Treatment

Discontinue offending drug Treat underlying infection Treat systemic illness Glucocorticoid therapy may be used in patients who fail to respond to more conservative therapy

Acute Glomerulonephritis
Nephritic presentation proteinuria may be in nephrotic range (> 3 g/day) hematuria RBC casts Diagnosis usually requires renal biopsy

Cast

Hyaline Cast

Red Cell Cast

Granular cast

WBC (Pus cell) Cast

Acute Glomerulonephritis

Acute Glomerulonephritis
Etiologies
Post streptococcal glomerulonephritis Post infectious glomerulonephritis Endocarditis -associated glomerulonephritis Systemic vasculitis Thrombotic microangiopathy
hemolytic-uremic syndrome thrombotic thrombocytopenic purpura

Acute Vascular Syndromes

Renal artery thromboembolism Renal artery dissection Renal vein thrombosis

Atheroembolic disease

Intratubular Obstruction
Intratubular crystal deposition
tumor lysis syndrome
acute urate nephropathy

Acute Renal Failure: Diagnostic Evaluation

Evaluate for prerenal causes
clinical exam
blood pressure orthostasis skin turgor mucosal membrane hydration

ethylene glycol toxicity

calcium oxylate deposition

Intratubular protein deposition

multiple myeloma
-Bence-Jones protein deposition

central venous pressures and cardiac output intake/output record urine sediment urine sodium
UNa < 20 mmol/L FENa < 0.01

therapeutic trial of volume replacement

Acute Renal Failure: Diagnostic Evaluation

Evaluate for postrenal causes bladder catheterization renal ultrasound

Diagnostic Evaluation of ARF

Form of ARF Prerenal Postrenal Intrinsic AT <10:1 >40 > 2% Muddy brown casts; tubular epithelial cells WBCs WBC casts, RBCs, eosinophils RBCs, RBC casts Normal or RBCs BU :Cr >20:1 >20:1 U a (mEq/L) <20 >20 FE
a

Urine Sediment ormal Normal or RBCs

< 1% variable

AI

<20:1

>20

>1%

AG Vascular

variable variable

<40 >20

<1% variable

Dietary restrictions
Be careful;
Proteins: avoid non-veg items as far as possible Potassium: avoid fruits and coconut Cholesterol: avoid oily & fried items Fluid restriction: depending on individuals urine output

Time is ticking
away!

Acute Renal Failure: Management

Prerenal ARF
volume repletion inotropic support discontinue diuretics

Acute Renal Failure: Management

Intrinsic ARF
General supportive care fluid management diuretics bicarbonate supplementation potassium phosphate drug dosing nutrition

Postrenal ARF
bladder catheterization percutaneous nephrostomy or ureteral stents fluid management during post-obstructive diuresis

Dialysis
Definition: Passage of molecules in solution by diffusion across a semi-permeable membrane

Acute Renal Failure: Management

Indications for dialysis
volume overload metabolic acidosis hyperkalemia uremic syndrome
pericarditis encephalopathy

azotemia

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