Acute Renal Failure By Abhishek Jaguessar

ARF is an

ABRUPT & RAPID decline in the GFR, not necessarily

accompanied by a decrement in urine output or by compromise in tubular function, but associated with a

PROGRESSIVE & DETECTABLE increment in serum

creatinine over hours to days, but sometimes weeks.
Dr. Mortimer Levy, 2003

AZOTEMIA is the state where excess

urea and other nitrogenous wastes is found in the blood, whereas UREMIA is the symptomatic condition that results from excess urea and other nitrogenous wastes in the blood and is associated with other electrolyte and endocrine abnormalities of renal dysfunction.

Clinical Description of Acute Renal Failure

NON-OLIGURIC > 400 mL urine output in 24 h NON-

OLIGURIC < 400 mL urine output in 24 h

ANURIC < 100 mL urine output in 24 h

Determinants of GFR
GFR = LPA x ((P - (T) (( (T)
LPA = ultrafiltration coefficient (hydraulic permeability & glomerular membrane surface area) (P = PGC PPT (hydrostatic pressure difference between the glomerular capillary & Bowmans space)

GFR

(T = TGC TPT (oncotic pressure difference between the glomerular capillary & Bowmans space)

Pathophysiology of ARF
GFR = LPA x [(PGC PPT ) (TGC TPT )]
LPA Glomerular disease & drugs via unknown mechanism but associated with mesangial cell contraction q Renal arterial pressure o Afferent-arteriolar resistance Afferentq Efferent-arteriolar resistance Efferento Intratubular pressure from tubular or extraextra-renal urinary system obstruction o System plasma oncotic pressure q Renal plasma flow

PGC

PBC
TGC

Intrarenal vasoconstriction is the major mechanism of q GFR in ARF, and stressed renal microvasculature is more sensitive to further hypotensive insults.

Assessing the Severity of ARF

A Creatinine rise from 190 to 240 QM results in a GFR decline from ~ 52 ml/min to ~ 47 ml/min, a drop of 10 %

A Creatinine rise from 90 to 120 QM results in a GFR decline from ~ 135 ml/min to ~ 95 ml/min, a drop of 30 %

Similar decrements in serum Creatinine at lower values result in more significant changes in GFR than the same decrement at higher values.

Distinguishing ARF from CRF

Helpful clues
Previous creatinine values Hb anemia suggests chronic problem Renal ultrasound small, echogenic kidneys suggest a chronic problem X-rays renal osteodystrophy suggests chronic problem Renal biopsy

Exceptions to the small kidneys = CRF rule: early DM, amyloid, HIV nephropathy, PCKD

What causes it?

The ARF Paradigm

1. Pre-renal

2. Intrinsic Renal

3. Post-renal

1. Pre-renal

Pre-renal ARF
q Renal Perfusion

2. Intrinsic Renal

3. Post-renal

Volume Depletion
Renal losses: diuretics, osmotic diuresis, etc ExtraExtra-renal losses: vomiting, diarrhea, skin

q Arterial Volume
Cardiogenic (CHF, ACS, arrhythmias, shock) Septic shock Hepatorenal syndrome Adrenal insufficiency

Renal Vasoconstricn
Radiocontrast Prostaglandin inhibition Calcinurin inhibitors ACE inhibitors Amphotericin B

When autoregulatory mechanisms are maximized, any small renal insult will subsequently precipitate acute renal failure.

Intrinsic Renal ARF

2. Intrinsic Renal

1. Pre-renal

3. Post-renal

1 2 3

Glomerular

Tubulointerstitial

Vascular

Though in all cases of intrinsic renal failure the kidney is the site of pathology, determining the nature of the problem is critical since TREATMENT & PROGNOSIS vary considerably.

Glomerular

NEPHROTIC

NEPHRITIC

Diabetes Minimal Change

Amyloidosis Membranous IgA Nephropathy MPGN I & II RPGN

FSGS

Rapidly Progressive Glomerulonephritis

AntiAnti-GMB Diseases
Goodpastures Syndrome AntiAnti-GBM nephritis

Immune Complex
SLE IgA Cryoglobulinemia Infectious (hepatitis B/C, postpost-streptococcal, endocarditis)

Pauci-immune/ANCA PauciWegeners Granulomatosis Microscopic Polyangiitis

Tubular
2 Acute Tubular Necrosis (ATN) Tubulointerstitial
~ 45 % ARF in hospitalized patients is from ATN

Ischemic ATN

Interstitial
Acute Interstitial Nephritis (AIN)
~ 30 % AIN associated with systemic Sx of fevers, arthralgias, maculopapular erythematous rash & eosinophilia
Drugs: Drugs: penicillins, cephalosporins, NSAIDs, sufonamide analogues Infections: Infections: renal parenchymal or systemic Immunologic disorders: SLE, Sjorgrens, disorders: mixed cryoglobulinemia Idiopathic: Idiopathic: 10 20 % of Bx-proven AIN Bx-

Most common Often following prolonged hypoperfusion

Nephrotoxic ATN
Drugs: Drugs: aminoglycosides, amphotericin B, chemotherapeutic agents Endogenous toxins: hemoglobin, myoglobin, toxins: light chains

Obstructive Nephropathy
Heme pigments Myeloma proteins Drug crystals

Vascular

Microvascular
Malignant hypertension Scleroderma crisis Cholesterol emboli syndrome Vasculitis Microangiopathy (HUS/TTP) PrePre-eclampsia/eclampsia Hyperviscosity syndrome

Macrovascular
Renal artery stenosis Renal vein thrombosis Renal infarction Tumor

Macrovascular causes of ARF must affect both kidneys in the absence of a solitary kidney or significantly diseased contralateral kidney.

1. Pre-renal

Post-renal ARF
Obstruction
Urethral
Clots Tumor Prostate Endometrial

2. Intrinsic Renal

3. Post-renal

Ureteral
Crystals Stones Clots Tumor Papillary necrosis

Retroperitoneal
Fibosis

Neurogenic bladder

PostPost-renal causes of ARF must result from bilateral kidney/ureteral obstruction, or obstruction in the lower urinary tract, in the absence of a solitary kidney or significantly diseased contralateral kidney.

1. Pre-renal

q Renal Perfusion
2. Intrinsic Renal

Glomerular Tubular Interstitial Vascular

3. Post-renal

Obstruction

How do we diagnose it?

History & Physical Will Guide DDx

Primer on Kidney Diseases 3rd Ed. pg 248.

Basic Initial Investigations

Foley catheter maybe Ultrasound to evaluate kidneys + GU tract Urinalysis Urine culture 24h urine collection for CrCl and proteinuria Basic electrolytes, Ca/PO4 + acid/base status Consideration for dialysis Other investigations guided by DDx immunologic pot pourri

The Value of Urinalysis

Urinalysis
PrePre-renal Intrinsic renal
Glomerular ATN AIN Proteinuria, hematuria, RBC casts Low specific gravity, muddy brown casts, tubular epithelial cells Mild proteinuria, hematuria, WBC, WBC casts, eosinophils Normal or hematuria, WBC, occasional granular casts High specific gravity, normal or hyaline casts

PostPost-renal

PrePre-renal vs. ATN

Favours PrePre-renal
Creatinine:Urea ratio UNa Uosm FENa U specific gravity Urinalysis > 20:1 < 20 > 500 mO/kg <1% > 1.018
Normal or hyaline casts

Favours ATN
<10<10-15:1 > 40 ~ isotonic >2% < 1.010
Tubular cells & muddy brown granular casts

Fractional Excretion of Substance X

FEX = the proportion of the filtered mass of X that is excreted X FEX = mass excreted mass filtered FEX = UX x V GFR x PX FEX = UX x V PCr UCr x V PX FEX = UX x PCr = U/P X U/P PX x UCr U/P Cr

When Should Biopsy be Considered

ASYMPTOMATIC HEMATURIA (red cell casts or dysmorphic RBCs) PROTEINURIA NEPHRITIC SYNDROME (HTN, hematuria, C3/4, proteinuria) RAPIDLY PROGRESS GLOMERULONEPHRITIS NEPHROTIC SYNDROME (proteinuria, edema, dyslipidemia, hypoalbuminemia) except in children ACUTE RENAL FAILURE (not known to be pre-renal or postprepostrenal)

Indications for Dialysis

HYPERKALEMIA not amenable to medical therapy ACIDOSIS not amenable to medical therapy UREMIA resulting in pericarditis, neuropathy or encephalopathy Critical VOLUME OVERLOAD not responsive to diuresis (dialyzable drug intoxication)