Acute Renal Failure

Dr Hussain Azhar Medical IV CHK

Topic Outline
Definition and Classification

Epidemiology
Pathophysiology and Etiology

Prerenal ARF Intrinisic ARF Postrenal ARF Pharmacologic Management of ARF RRT in ARF

Definition

Figure 1 Conceptual model of AKI

Murugan, R. & Kellum, J. A. (2011) Acute kidney injury: whats the prognosis? Nat. Rev. Nephrol. doi:10.1038/nrneph.2011.13

Figure 2 RIFLE criteria for diagnosing AKI

Permission obtained from BioMed Central Bellomo, R. et al. Crit. Care 8, R204R212 (2004) Murugan, R. & Kellum, J. A. (2011) Acute kidney injury: whats the prognosis? Nat. Rev. Nephrol. doi:10.1038/nrneph.2011.13

Formulae for Renal Function Assessment

MDRD
eGFR= 186 x Screat X Age X 1.21 [if black] X o.74 [if female] Undersetimates GFR in healthy people (when GFR >60 ml/min)

Cockcroft-Gault formula
(140-Age) X Mass (In KG) X [o.85 if female]/72 X Serum Creat The non-steady-state conditions that prevail in ARF preclude estimation of GFR using standard formulae

Shortcomings
The assignement of corresponding changes in serum creat and

changes in urine output to the same strata is not based on evidence. The criteria that results in the least favorable rifle strata to be used. The patient would progress from "risk" on day one to "injury" on day two and "failure" on day three, even though the actual GFR has been <10 mL/min over the entire period. It is impossible to calculate the change in serum creatinine in patients who present with ARF but without a baseline measurement of the serum creat. The authors of the RIFLE criteria suggest back-calculating an estimated baseline creat using the four-variable MDRD equation, assuming a baseline GFR of 75 mL/min per 1.73 m2 .

Diagnostic criteria for AKI

Abrupt (within 48 hours) absolute increase in the serum

creatinine concentration of 0.3 mg/dL (26.4 micromol/L) from baseline.

Or a percentage increase in the serum creatinine concentration

of 50 percent.
Or oliguria of less than 0.5 mL/kg per hour for more than six

The diagnostic criteria could be applied only after volume status had been optimized Urinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criteria

hours.

Table 1 Classification and staging systems for AKI

Ricci, Z. et al. (2011) Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria Nat. Rev. Nephrol. doi:10.1038/nrneph.2011.14

EPIDEMIOLOGY, CLINICAL FEATURES, AND DIAGNOSTIC STUDIES FOR MAJOR CAUSES OF ACUTE RENAL FAILURE
Etiology Epidemiology Clinical Features Serum Studies
High BUN/CR ratio (20) is suggestive but not diagnostic

Urine Studies

Prerenal ARF

Most common cause of community-acquired ARF; history of poor fluid intake, treatment with NSAIDs/ACE inhibitors/ ARBs, worsening heart failure

Volume depletion (absolute/ postural hypotension, low jugular venous pressure, dry mucus membranes) or decreased effective circulatory volume (e.g., heart failure or liver disease)

Hyaline casts FENa <1% UNa <10 mmol/L SG >1.018

Etiology

Epidemiology

Clinical Features
New cardiac murmur (postinfectious) Skin rash/ulcers, arthralgias (lupus) Sinusitis (antiGBM disease) Lung hemorrhage (anti- GBM, ANCA, lupus)

Serum Studies
ANA, ANCA, anti-GBM antibody, hepatitis serologies , cryoglobul ins, blood cultures, ASO, complem ents (positive tests depend on etiology)

Urine Studies

Diseases of small vessels and glomeruli Glomerulone phritis/ vasculitis

Associated with recent infection (postinfectious or endocarditis), systemic lupus erythematosus, liver disease (hepatitis B or C) Anti-GBM disease: Typically men in their 20s40s ANCA disease: Two peaks: 20s30s and 50s60s

Hematuria with red cell casts/ dysmorphic red blood cells Granular casts Proteinuria (usually <1 g/d)

Etiology Hemolyticuremic syndrome/ thrombotic thrombocyt openic

Epidemiology Recent GI infection (E. coli) or use of calcineurin inhibitors (FK506 and cyclosporine)

Clinical Features Fever, neurologic abnormalities

Serum Studies Schistocytes on peripheral blood smear, elevated LDH, anemia, thrombocyto penia

Urine Studies Hematuria Mild proteinuria Red cell casts (rare)

Etiology

Epidemiolog y

Clinical Features

Serum Urine Studies Studies

Malignant Severe/ hypertensi uncontrolled on hypertension

Evidence of damage to other organs: headache, papilledema, heart failure with LVH by echocardiograp hy/ ECG Typically resolves with blood pressure control

Hematuria with red cell casts/ proteinuria

Acute tubular necrosis

Etiology Epidemiolog y Recent hemorrhage or severe hypotension Clinical Features Serum Urine Studies Studies Muddy brown granular or tubular epithelial cell casts FENa >1% UNa >20 mmol/L SG <1.015 Ischemia

Acute tubular necrosis

Etiology Epidemiology Clinical Features Serum Studies Urine Studies

Exogenous toxins

Recent exposure to radiocontrast, often in association with volume depletion, diabetes or CKD

Muddy brown granular or Tubular epithelial cell casts Urinalysis may be normal FENa often <1% UNa often <20 mmol/L

Acute tubular necrosis

Etiology Epide miolog y Clinical Features Serum Studies Urine Studies

Endogenou Rhabdo Post ictal state s toxins myolysi (seizures), evidence of s trauma or prolonged immobilization

Increase d myoglobi n, and/or creatine kinase

U/A positive for heme but no hematuria

Acute tubular necrosis

Etiology Epidemiology Clinical Features Serum Studies Urine Studies

Endogenou Hemolysis: s toxins recent blood transfusion

Fever, other evidence of transfusion reaction

Pink plasma, increase d LDH

Pink, hemepositive urine without hematuria

Acute tubular necrosis

Etiology Epidemiology Clinical Features Serum Studies Urine Studies

Exogenous toxins

Recent exposure to nephrotoxic antibiotics or chemotherapy, often in association with sepsis, or volume depletion

Muddy brown granular or tubular epithelial cell casts FENa >1% UNa >20 mmol/L SG <1.015

Acute tubular necrosis

Etiology Epidemio Clinical logy Features Serum Studies Urine Studies

Endogenou Tumor s toxins lysis: recent chemothe rapy

Hyperuricemia, increased LDH

Urate crystals

Acute tubular necrosis

Etiology Epidemi ology Multiple myeloma Clinical Features Individuals >60 years of age, ongoing constitutional symptoms (fatigue, malaise) Serum Studies Urine Studies Endogeno us toxins Circulating Dipstickmonoclonal negative spike, anemia proteinuria, monoclonal spike on electrophor esis

Diseases Of The Tubulointerstitium

Etiology Epidemiol Clinical ogy Features Serum Studies Urine Studies

Allergic interstitial Nephritis

Recent Fever, rash, medication arthralgias exposure

Eosinophilia

White cell casts, Eosinophiluria

Acute bilateral pyelonephri tis

Fever, flank pain and tenderness

Positive blood cultures

Leukocytes, proteinuria, positive urine culture

Postrenal ARF
Etiology Epidemiology Clinical Features Serum Studies Urine Studies Usually normal; hematuria if due to stones Postrenal ARF History of renal Palpable bladder, stones or flank or prostatic abdominal pain disease

Diseases Of Large Renal Vessels

Etiolog y Athero embolic disease Epidemiology Clinical Features Serum Studies Eosinophilia Hypocomple mentemia Urine Studies Vascular disease; classically occurs within daysweeks of manipulation of the aorta or other large vessels, often in the setting of anticoagulation Retinal plaques, palpable purpura, livedo reticularis Eosinophiluria

Epidemiology of ARF

 The observed incidence, etiology, and outcomes of ARF are

highly dependent upon the populations studied and the definition of ARF employed.
The absence of centralized registries to track the incidence and

outcomes of patients with ARF has hindered our understanding of its epidemiology.

The changing epidemiology of acute renal failure

Nature Clinical Practice Nephrology (2006) 2,364-377

Non -ICU

ICU

Figure 3 Incidence of various organ failure among critically ill patients

Murugan, R. & Kellum, J. A. (2011) Acute kidney injury: whats the prognosis? Nat. Rev. Nephrol. doi:10.1038/nrneph.2011.13

Key Points
The absolute incidence of acute renal failure (ARF) has increased in the

past two decades, while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of

identifying the factors that underlie changes in epidemiology of this condition.

Despite the use of different definitions in different studies, various

factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs

developing countries; community vs hospital vs intensive care unit), patient age, infections (HIV, malaria, leptospirosis and hantavirus), concomitant illnesses (cardiopulmonary failure, hematooncological disease), and interventions (hematopoietic progenitor cell and solid organ transplantation)

Prerenal Acute Renal Failure

 GFR is reduced as a result of hemodynamic

disturbances that decrease glomerular perfusion.

The defining feature of prerenal ARF is the absence

of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors.

Intravascular volume depletion

Altered intrarenal hemodynamics

Etiologies of Prerenal ARF Decreased effective arterial blood volume Abdominal compartment syndrome

Pathophsiology of Prerenal ARF

Diagnosis of Prerenal ARF

Hx P/E Urine sediment (usually normal, without cellular

elements or abnormal casts, unless chronic kidney disease is present) UNa< 15 meq/L (>20 in ATN) U/Pcreat> 20 (<15 in ATN) FeNa <1% (>1% in ATN) UNa/K <1/4 BUN/creat >20

Diagnosis of Prerenal ARF

BUN/CREAT of >20 is typical, BUT is not specific to prerenal ARF and may also be seen: Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea production.

FE Urea
Patients on diuretics

Prerenal azotemia due to vomiting on NG

suctioning. FE Na may be low in sepsis, RCN, myoglobinuria, nonoliguric ATN, acute GN, urinary tract obstruction and renal allograft rejection

FE UREA
Low FE urea <=35% is a more sensitive and

specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN, especially if diuretics have been administered.

ARF Associated with ACE Inhibitors and Angiotensin Receptor Blockers

ARF Associated with ACE Inhibitors and Angiotensin Receptor Blockers

Acute renal failure can develop acutely, when ACEI or

ARB therapy is initiated, or in patients receiving chronic therapy, especially in patients with underlying CHF

ARF Associated with ACE Inhibitors and Angiotensin Receptor Blockers

Predisposing factors:
Advanced cardiac failure with low mean arterial

pressure Volume depletion due to diuretic therapy The presence of renal vascular disease The concomitant use agents with vasoconstrictor effects (NSAIDs, cyclooxygenase-2 inhibitors, cyclosporine, and tacrolimus) CKD: The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function

ARF Associated with ACE Inhibitors and Angiotensin Receptor Blockers

Serum creatinine and electrolyte concentrations

should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of >0.5 mg/dl if the

initial serum creatinine is <2.0 mg/dl, or a rise of >1.0 mg/dl if the baseline serum creatinine is >2.0 mg/dl, has been suggested as a threshold for discontinuation of therapy

ARF Associated with ACE Inhibitors and Angiotensin Receptor Blockers

The development of ARF should prompt an

evaluation for cardiac failure, hypotension, volume depletion, use of a concomitant vasoconstrictive agent, or renovascular disease.

Acute Renal Failure Associated with NSAIDS

Acute Renal Failure Associated with NSAIDS

Nonsteroidal anti-inflammatory drugs (NSAID)

agents inhibit the synthesis of vasodilatory prostaglandins in the kidney.

Acute Renal Failure Associated with NSAIDS

Risk factors: Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD

Acute Renal Failure Associated with NSAIDS

Elderly patients are at increased risk due to

the increased prevalence of cardiac dysfunction, occult renal vascular disease, and subclinical chronic kidney disease.

Postrenal Acute Renal Failure

Anatomy of Urinary Tract

Etiologies of Postrenal ARF

Intrinsic Extrinsic
Lower tract obstruction

Stone Papillary necrosis Blood clot TCC

Retroperiton eal fibrosis Aortic aneurysm Retroperiton eal or pelvic malignancy

Urethral stricture BPH Prostate CA TCC of bladder Bladder stones Blood clot Fungus ball Neurogenic bladder Malpositioned catheter

Urine output?
If the obstruction is : Complete

Anuria

Incomplete

Norm al
Polyur ia
Fluctuati ng

InComplete

Pathophysiology
After the acute onset of obstruction, GFR declines

progressively, but it does not fall to zero.

Factors that maintain GFR include continued salt and

water reabsorption along the nephron, dilatation of the collecting system, and alterations in renal hemodynamics.
Intratubular pressure rises acutely, but it begins to

decline within the first 4 to 8 h, returning to nearly normal by 24 h.

Pathophysiology Of Postrenal Failure

Ureteral Pressure 1- 2 H RBF Renal Blood GFR

2-5 H

Late phase

Complete obstruction

Recovery after relief of obstruction depends on: Severity Duration

Less than 1 wk duration, recovery complete. Little or no recovery after 12 wk.

Partial obstruction
The course after relief of partial obstruction is less predictable Depends on Severity Duration Presence of infection or preexisting renal disease.

 Relief of obstruction may be accompanied by

a post-obstructive diuresis; Excretion of salt and water retained during the obstruction. Persistent salt-wasting and impaired urinary concentrating ability .

Diagnosis
Elderly male patients
Measurement of a post-voiding residual

bladder volume, either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter.

Diagnosis
Ultrasonography Sensitivity and specificity are high Non diagnostic Early in the course of postrenal ARF. Severe volume depletion. Obstruction is due to retroperitoneal disease (e.g., retroperitoneal fibrosis, tumors, adenopathy) encasing the ureter and preventing dilatation

Diagnosis

Computed tomography
Contrast CT scanning may be particularly useful for the

identification of obstructing kidney stones

Etiology of Intrinsic ARF

Proximal Part of Nephron

Acute tubular necrosis

Ischemic

Acute interstitial nephritis

Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related

hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass

Nephrotoxic

drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis

bacterial infection
viral infections rickettsial disease tuberculosis

Systemic diseases
systemic lupus erythematosus sarcoidosis Sjgren syndrome

Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis endocarditis-associated glomerulonephritis systemic vasculitis

tubulointerstitial nephritis
and uveitis (TINU) syndrome

hemolytic uremic syndrome/thrombotic thrombocytopenic purpura

rapidly progressive glomerulonephritis (RPGN)

Malignancy
malignant infiltration of interstitium multiple myeloma

Acute vascular syndromes

renal artery thromboembolism renal artery dissection renal vein thrombosis atheroembolic disease

Idiopathic

Acute Tubular Necrosis

Acute Tubular Necrosis

Acute tubular necrosis is the most common

form of intrinsic ARF (85 %) Tubular injury

Nephrotoxic (35%) Ischemic (50%) Multifactorial.

Profound ischemic injury may result in

bilateral cortical necrosis.

Acute Tubular Necrosis

Preren al
Prolonged hypoperfusi on

ATN

Ischemic ATN
Medical
Cardiogenic shock Sepsis Burns Severe volume depletion

Surgical
Cardiac Vascular

Nephrotoxic ATN

Exogenous
RCN Aminoglycosides Others meds

Endogenous
Heme pigment (rhabdo, or massive intavascular hemolysis)

Clinical course

Initiation

Maintenance

Recovery

Pathogenesis of ATN

Intrarenal vasoconstrition

Intratubular obstruction

ATN

Reduction in Kf

Backleak of glomerular filtrate

Recovery from Ischemic Injury

In contrast to the heart and brain, where ischemic injury results in permanent cell loss, the kidney is able to completely restore its structure and function after acute ischemic or toxic injury. The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity, normal histologic appearance, and physiologic function.

Short-term Outcomes after ATN

The outcome of ATN is highly dependent on

the severity of comorbid conditions. Uncomplicated ATN is associated with mortality rates of 7 to 23% Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80%. Mortality rates increases with the number of failed organ systems

Long-term Outcomes after ATN

Long-term outcomes of patients who survive

are good. Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN), in-hospital mortality was 69%. Patients who survived to hospital discharge, 6-mo survival was 77%, 1-yr survival was 69%, and 5-yr survival was 50% 59% of surviving patients had no residual renal insufficiency, and only 10% required chronic dialysis therapy. Long term outcomes in ARF in patients treated with continuous RRT. Am J Kidney
Dis, 2002

Radiocontratst Nephropathy

(Prevention is better !!!)

Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is

the third highest cause of hospital-acquired acute renal failure. In nearly half of these patients, CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention.

Radiocontratst Nephropathy

Radiocontratst Nephropathy
CHF Large volume of contrast

DM

NSAIDs or ACEI

Baseline renal insufficiency

Risk factors

Volume depletion

ARF:increase in serum creat of>50 % above baseline or >1 mg/dl if baseline>2 mg/dl
Normal baseline creatinine Mild to moderate CKD Mild to moderate CKD + DM Advanced renal insufficiency

negilgible risk 5-10 % risk 10- 40 % >50 % risk

Pathogenesis of Radiocontratst Nephropathy

Haemodynamic Alterations And

Tubuloglomerular Feedback
The injection of CM induces early, rapid renal

vasodilatation followed by prolonged vasoconstriction, with an increase in intrarenal vascular resistances, a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR). Conversely, the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances. The resulting renal ischaemia due to these haemodynamic effects is, in part, responsible for nephropathy

Pathogenesis of Radiocontratst Nephropathy

Endothelial dysfunction Vasoactive mediators

Free radicals and reperfusion damage

Haemorheological factors Tubular toxicity and immunological

mechanisms

Treatment
The best treatment of contrast-induced renal

failure is prevention! The use, if clinically possible, of ultrasonography, magnetic resonance imaging or CT scanning without radiocontrast agents, particularly in highrisk patients. The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours). Avoidance of volume depletion or nonsteroidal antiinflammatory drugs, both of which can increase renal vasoconstriction. The use of low or iso-osmolal nonionic contrast agents.

Treatment
The administration of Intravenous Saline.

Isotonic saline at a rate of 1 mL/kg per hour, begun at least two and preferably 6 to 12 hours prior to the procedure, and continuing for 6 to 12 hours after contrast administration. The administration of the antioxidant Acetylcysteine. Dose of 600 to 1200 mg orally twice daily, administered the day before and the day of the procedure, based upon its potential for benefit and low toxicity and cost.

Treatment
Routine hemofiltration or hemodialysis for the

prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended. More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD, can be considered,provided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy: a systematic review. Am J Kidney Dis 2006; 48:361. Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis. A randomized controlled trial. J Am Coll Cardiol 2007; 50:1015.

Treatment
NO indication for prophylactic dialysis

There is

for the prevention of volume overload in dialysisdependent patients.

Treatment
The volume of contrast administered to the

patien also appears to correlate with the incidence of nephrotoxicity. In patients who undergo only diagnostic coronary procedures, the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL).

Heme Pigment-induced Acute Tubular Necrosis Myoglobinuria: Hemoglobinuria: hemolysis. rhabdomyolysis. intravascular

Rhabdomyolysis
The release of muscle cell contents as the result

of traumatic or nontraumatic injury of skeletal muscle Physical findings may consist of

Tender, doughy muscles

Edema
weakness Compartmental compression symptoms with signs

and symptoms of neurovascular compromise may develop, necessitating the need for emergent fasciotomy.

The Majority Of Cases Of Rhabdomyolysis Are Nontraumatic

Alcohol abuse Massive muscle compression from immobilization in drug induced coma Drug-induced Seizures Occlusive peripheral vascular disease. Combination therapy with itraconazole, simvastatin, and cyclosporine Conversion from one fibric acid to another, or from one statin-fibrate combination to another Detergent ingestion

Hemolysis
Transfusion reactions due to ABO incompatible blood

are probably the most frequently encountered hemolytic processes that can lead to acute renal failure.
Severe acute hemolytic episodes in patients with

glucose-6-phosphate dehydrogenase deficiency.

Laboratory abnormalities

Hypovolemia and High AG acidosis

Hemolysis
The urine may have a low FENa despite

tubular injury. Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria. Heme-pigmented granular casts. Plasma is normal color in myoglobinuria and red brown in hemoglobinuria

Treatment
IVF
Isotonic saline at 1 to 2 liters per hour Fluids are titrated to maintain a urine output of

200 to 300 mL/hour Continue until the urine discoloration clears, and plasma creatine kinase decreases to less than 5,000 to 10,000 U/L (or there is cessation of hemolysis), or symptomatic fluid overload develops.

Treatment
Alkalinization.
Mannitol diuresis.

Acute Interstitial Nephritis

Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium

Drug hypersensitivity
Penicillin NSAIDs

Cephalosporin
Sulfonamide Fluoroquinolone Rifampin

Phenytoin
Furosemide Thiazide diuretics Allopurinol Alpha interferon Cimetidine Omeprazole

Others

Bacterial
Streptococcus Staphylococcus Diphteria Mycoplasma Legionella

Viral CMV EBV Rubeola HIV Hantaan

Others Tuberculosis Rickettsia Leptospirosis

Systemic Diseases Sjogrens SLE Sarcoidosis Polyangiitis

Methicillin Induced AIN

Renal symptoms typically develop 2 to 3 weeks after the initiation of treatment:

Hematuria Pyuria with white blood cell casts Proteinuria < 1g/d (can be nephrotic with NSAIDs) Renal failure in 50% of patients

Extrarenal manifestations:

Fever in 80% Eosinophilia in 80% Rash in 25%

Methicillin Induced AIN

Renal failure is the most prominent feature

Develops within 3 wk of initiation of drug

therapy in 80% Hematuria and pyuria each are present in only 50% of patients. Extrarenal manifestations, including fever, maculo-papular rash, arthralgias, and eosinophilia are each present in fewer than 50%
All of them together in <5%

Methicillin Induced AIN

Eosinophiluria (Diagnostic value is poor) Other conditions associated with Eosinophiluria Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease

Treatment Methicillin Induced AIN

Supportive

Dicontinue offending drug

Prednisone 1mg/kg/d for 4 weeks
Controversial:Rcommended if biopsy proven AIN

and who have persistent renal failure 1 week after DC the offending medication
? Adjunct cyclophosphamide

Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys. Although many of the features of HRS resemble prerenal azotemia, the defining feature is a lack of improvement in renal function with volume expansion. Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation

Type I HRS
Doubling of the serum creatinine concentration to a level of >2.5 mg/dl, or a reduction of the creatinine clearance by 50% or more to a value of <20 ml/min, over a duration of <2 wk Develops in hospitalized patients In 2/3 an inciting events is identified

Type II HRS
Moderate and stable reduction in GFR Insidious onset and slow progression of renal insufficiency in the setting of refractory ascites Better prognosis

Diagnostic criteria of HRS

Chronic or acute hepatic disease with advanced hepatic

failure and portal hypertension A plasma creatinine concentration above 1.5 mg/dL (133 mol/L) that progresses over days to weeks. The absence of any other apparent cause for the renal disease, including shock, ongoing bacterial infection, current or recent treatment with nephrotoxic drugs, and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease. Urine red cell excretion of less than 50 cells/HPF and protein excretion less than 500 mg/day. Lack of improvement in renal function after volume expansion with intravenous albumin (1 g/kg of body weight per day up to 100 g/day) for at least two days and withdrawal of diuretics. Urine Na<10

Treatment of HRS
Management of underlying cause
Stop diuretics Low salt diet and free water restriction if

hyponatremia Terlipressin + Albumin RRT TIPS

Treatment of ARF

Prevention is the Key!

Renal hypoperfusion is a predisposing factor to the

development of renal failure. Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure. Avoidance or discontinuation of drugs that increase renal vaso-constriction, such as NSAID and selective COX-2 inhibitors. Potentially nephrotoxic medications should be avoided, particularly in high-risk patients, whenever possible. Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast .

Indications for RRT

Refractory fluid overload
Hyperkalemia (plasma potassium concentration

>6.5 meq/L) or rapidly rising potassium levels Metabolic acidosis (pH less than 7.1) Signs of uremia, such as pericarditis, neuropathy, or an otherwise unexplained decline in mental status

Timing of Initiation of RRT

It is not possible to specify a specific duration of

renal injury or level of azotemia at which RRT should be optimally initiated. It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit.

Summary
Understand the limitations of serum creatinine
Formulate a DDx Understand the pathophysiology of ARF Prevent ARF Initiate RRT at optimal time ( not too late! )

Thank you