Acute Renal Failure

Yuli Hermansyah

Acute Renal Failure:

still a problem
Prerenal causes: 20%

Intrinsic causes:
75% Tubular necrosis Ischemia: 50% Toxins: 35%

Postrenal causes: 5%

Sutomo Teaching Hospital (1999) :

Renal transplantation

- 159 cases of ARF : 57.23% as a complication of other diseases - Internal Ward : 47.17%, - Surgical Ward : 27.67% - Internal Ward : 1. Septicemia : 20.25% 2. Urinary Tract Infection : 16.85% 3. Leptospirosis : 15.73 % - Obstruction + ARF : 15.09%

ESRD

Who is at risk of ARF?

..Introduction

Defined as .

characterized by an abrupt decline in glomerular filtration rate (GFR) usually associated with azotemia and a fall in urine output (oliguri/anuria)
(Lameire, 2004)

A clinical syndrome

(Belomo,2004)

Natural History of ARF

48% ICU pts require dialysis 58% inpt mortality among patients who develop ARF in the ICU
(Crit Care Med 24(2);192-198, 1996)

36 % mortality among all inpts with ARF 20% of survivors received dialysis
(JASN 9(4):692-698, 1998)

Dr. Soetomo Hospital 159 cases 47,17% found in Internal Ward

27,67% found in Surgery Ward

(Pranawa, 1999)
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Prerenal ARF

Acute Prerenal Failure

Most common cause of ARF Physiologic response to renal hypoperfusion Caused by true hypovolemia reduction in effective circulating volume BP falls vasodilatation of preglomerular arterioles ( mediated by arachidonic acid & nitric oxide)
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Etiologies of ARF
ARF

Pre-Renal

Intra-Renal

Post-Renal

Vascular Glomerular Tubular Interstitial

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Tubuloglomerular feedback mechanism stabilizes GFR & Fluid, mediated by complex communication between macula densa & glomerular microvascular Acute volume depletion glomerular feedback mitigates the prerenal reduction in GFR Prerenal azotemia corrected if the extrarenal factors causing the renal hypoperfusion reversed

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Acute Tubular Necrosis

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Acute Tubular Necrosis

Global spectrum in snake bites, crushing injury in earthquake, enviromental & therapeutic nephrotoxic agents

In ICU, 35-50% due to sepsis 20-25% post-surgery ATN

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.....Acute Tubular Necrosis

Risk in Pre-exixting renal impairment Hypertension, Diabetes Mellitus Cardiac disease Peripheral vascular disease Advanced age

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Pathophysiology of ATN
Ischemia

Endothelial Injury

Tubular Injury Disruption of Cytoskeleton Inflammation

Loss of Cell Polarity

Apoptosis & Necrosis

Activation of Vasoconstrictors Impaired Vasodilation Increased Leukocyte Adhesion

Desquamation of Cells Capillary Obstruction & Continued Ischemia Tubular Obstruction & Backleak 14

Post Renal ARF

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..Post renal ARF

Hydrolic pressure in proximal tubulus Vasodilation of afferent arteriol

Intraglomerular pressure
Glomerular Filtration Rate

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Postrenal ARF
Obstruction of the passage of urine The most common cause secondary bladder outlet obstruction due to BPH Intraluminal Obst bilateral renal calculi, bladder Ca, fungus Extraluminal Obst retroperitoneal fibrosis, colorectal tumor Important to rule out quickly potential for recovery renal function inversely related with duration of obstruction

Average time : 72h permanent nephron damage.

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Pathophysiology of Renal Failure in Obstructive Uropathy

Early Phase
Increased intratubular pressure Initial increase followed by decrease in renal plasma flow

Late Phase
Normal intratubular pressure Marked decrease in renal plasma flow
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Postrenal Acute Renal Failure

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Postrenal Acute Renal Failure

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ARF in Leptospirosis
Emerging infectious disease of human

Important cause in certain tropical countries Evade local defenses, produce bacteremia Renal involvement occurs almost invariably in leptospirosis

Primary lesion

Tubulointerstitiel nephritis with local / diffuse mononuclear cell infiltration in association with proximal & distal tubular cell degeneration

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ARF in Sepsis
Sepsis arterial vasodilatation activation of sympathetic syst activation the renin -angiotensin-aldosteron axis activation non-osmotic release of vasopressin may lead to ARF
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Mechanisms leading to acute renal failure in sepsis

Infectious agents, severe trauma
Activation of leukocytes Monocytes Polymorphs Release of reactive oxygen species and protease Activation of the coagulation cascade Activation of the complement cascade

Release of cytokines : tumor necrosis factor, interleukins 1, 8 Activation of inducible nitric oxide synthetase (NOS) Endothelial cell production of vasoconstrictor and proinflammatory factors Endothelin Thromboxane A2 Leukotrienes Platelet-activating factor Intrarenal vasoconstriction

Microvascular thrombosis Upregulation of leukocyte adhesion molecules Endothelial injury Capilary leak Parenchymal ischemia

DIC

Increased nitric oxide production

Systemic vasodilatation

Prerenal azotemia

Acute tubular necrosis

Cardiac dysfunction Liver dysfunction 23 Pulmonary dysfunction

Contrast Induced Nephropathy

CIN Predisposing Factors Renal Medullary Hypoxia Altered Renal Hemodynamics Reactive Oxygen Species Prostaglandins/Endothelin/NO synthesis/inhibition
1. Heyman et al., Pathophysiology of Radiocontrast Nephropathy: A Role for Medullary Hypoxia. Investigative Radiology. 34(11):685, November 1999.

2. Bakris et al., Radiocontrast medium-induced declines in renal function: a role for oxygen free radicals. Am J. Physiol. 1990 258:F115-120

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Contrast Induced Nephropathy

Contrast agent causes vasoconstriction and is also a direct tubular toxin Low osmolar and isosmolar agents have lower toxicity

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PATHOPHYSIOLOGY OF CONTRAST NEPHROPATHY

Contrast Media

PGE2 ANP Adenosine

Endothelin Vasopressin PGI2

Systemic Hypoxemia Blood Viscosity

Osmotic Load to Distal Tubule

Blood Flow

O2 Delivery

O2 Consumption

Direct Cellular Toxicity

Renal Medullary Hypoxia

Contrast Media Nephrotoxicity

From Rudnick et al, Am J of Kidney Disease, 1994

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Clinical Features of Acute Renal Failure

Patients may have clinical findings related to the underlying causes of ARF. Such signs and symptoms may result from fluid retention, abnormal serum electrolytes, acidosis, uremia, decreased excretion of drugs or, rarely, changes in hormone production.
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Beers and Berkow (1999). Merck Manual of Diagnosis and Therapy. CD ROM

Management of acute renal failure

Prevention Conservative treatment Renal replacement therapy

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Prevention of acute renal failure (1)

Applicable to medical setting Identif of high risk patients for pharm agent induced nephrotoxicity Minimimalization of use of potential nephrotoxin, especially in high risk patient Aggressive surveillance for nephrotoxin induced renal dysfunction Use of volume expansion , diuretics, and renal vasodilators in selected clinical setting

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Prevention of acute renal failure (2)

Applicable to surgical/trauma/ICU setting
Aggressive resuscitation of traumated patients Preoperative optimalization of cardiovascular hemodynamics in selected cases Elevation of systemic oxygen delivery in selected critically ill patients Minimalization of use and length of use of invasive lines and indwelling catheters to avoid nosocomial sepsis
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Conservative treatment of acute renal failure

Exclude reversible/treatable causes of ARF Obtain and maintain euvolemic state Attempt to establish an urine output if patient remains oliguric Provide adequate nutrition Minimize use of invasive lines and procedures Monitor drug usage carefully, and appropriately modify drug dosage and/or dosing interval Monitor and treat for clinical and biochem complic
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Indication of renal replacement therapy in ARF

Persistent hyperkalemia

Fluid overload
Ongoing marked acidemia

Symptoms of uremia
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Thank you

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