ACUTE RENAL ACUTE RENAL FAILUREFAILURE

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Acute renal failure (ARF) is a syndrome Acute renal failure (ARF) is a syndrome characterized by rapid decline in GFR characterized by rapid decline in GFR hours to days, retention of nitrogenous hours to days, retention of nitrogenous waste products and disturbances in the waste products and disturbances in the extra cellular volume, electrolyte and extra cellular volume, electrolyte and acid base homeostasis.acid base homeostasis.

Is seen as a complication in about 5% of Is seen as a complication in about 5% of hospital admissions, and up to 30% of hospital admissions, and up to 30% of intensive care admissions.intensive care admissions.

OliguriaOliguria is a common finding but not is a common finding but not necessary. ARF is sometimes asymptomatic necessary. ARF is sometimes asymptomatic and is diagnosed by increase in the urea and and is diagnosed by increase in the urea and creatininecreatinine. .

CLASSIFICATION AND MAJOR CAUSES CLASSIFICATION AND MAJOR CAUSES OF ACUTE RENAL FAILURE (ARF)OF ACUTE RENAL FAILURE (ARF)

I: PRERENAL ARF:I: PRERENAL ARF: A: A: HypovolemiaHypovolemia 1: Hemorrhage, burns, dehydration1: Hemorrhage, burns, dehydration 2: GIT fluid loss; vomiting, surgical drainage, 2: GIT fluid loss; vomiting, surgical drainage,

diarrheadiarrhea 3: Renal fluid loss; diuretics, osmotic 3: Renal fluid loss; diuretics, osmotic diuresisdiuresis

(Diabetes mellitus), (Diabetes mellitus), hypoadrenalismhypoadrenalism 4: Sequestration in 4: Sequestration in extravascularextravascular space; space;

pancreatitispancreatitis, peritonitis, trauma, burns, severe , peritonitis, trauma, burns, severe hypoalbuminemiahypoalbuminemia

B: Low cardiac output:B: Low cardiac output: 1: Diseases of myocardium, valves, and 1: Diseases of myocardium, valves, and

pericardium, arrhythmias, pericardium, arrhythmias, tamponadetamponade 2: Other: pulmonary hypertension, massive 2: Other: pulmonary hypertension, massive

pulmonary embolus, positive pressure pulmonary embolus, positive pressure mechanical ventilationmechanical ventilation

C: Altered Renal systemic vascular C: Altered Renal systemic vascular resistance ratioresistance ratio

1: Systemic 1: Systemic vasodilationvasodilation; Sepsis, ; Sepsis, antihypertensivesantihypertensives, , afterloadafterload reducers, reducers, anesthesia, anaphylaxisanesthesia, anaphylaxis

2: Renal vasoconstriction: 2: Renal vasoconstriction: HypercalcemiaHypercalcemia, , norepinephrinenorepinephrine, epinephrine, cyclosporine, , epinephrine, cyclosporine, FK 506, FK 506, amphoterecinamphoterecin BB

3: Cirrhosis with 3: Cirrhosis with ascitesascites ((hepatorenalhepatorenalsyndrome)syndrome)

D: Renal D: Renal hypoperfusionhypoperfusion: with : with impairementimpairement of of renal renal autoregulatoryautoregulatory responsesresponses

1: 1: CyclooxygenaseCyclooxygenase inhibitors, ACE inhibitorsinhibitors, ACE inhibitors

E: E: HyperviscosityHyperviscosity syndromesyndrome 1: Multiple 1: Multiple myelomamyeloma, , macroglobenemiamacroglobenemia, ,

polycythemiapolycythemia

II: INTRINSIC RENAL ARFII: INTRINSIC RENAL ARF 1: Reno1: Reno--vascular obstruction (vascular obstruction (Bilateral or Bilateral or

unilateral in the setting of one functioning unilateral in the setting of one functioning kidney)kidney)

A: Renal artery obstruction: Atherosclerotic A: Renal artery obstruction: Atherosclerotic plaque, thrombosis, embolism, dissecting plaque, thrombosis, embolism, dissecting aneurysms, aneurysms, vasculitisvasculitis

B: Renal vein obstruction: Thrombosis, B: Renal vein obstruction: Thrombosis, compressioncompression

2: Diseases of the 2: Diseases of the glomeruliglomeruli or renal or renal microvasculaturemicrovasculature

A: A: GlomeruloGlomerulo nephritis and nephritis and vasculitisvasculitis

B: Hemolytic B: Hemolytic uremicuremic syndrome: syndrome: ThromboticThromboticthrombocytopenic thrombocytopenic purpurapurpura, DIC, toxemia of , DIC, toxemia of pregnancy, accelerated hypertension, radiation pregnancy, accelerated hypertension, radiation nephritis, SLE, sclerodermanephritis, SLE, scleroderma

3: Acute tubular necrosis:3: Acute tubular necrosis: A: Ischemia: As per preA: Ischemia: As per pre--renal ARF, Obstetric renal ARF, Obstetric

complications (abruption placenta, post partum complications (abruption placenta, post partum hemorrhage)hemorrhage)

B: Toxins: B: Toxins: 1: Exogenous: radio contrast, cyclosporine, 1: Exogenous: radio contrast, cyclosporine,

antibiotics (antibiotics (aminoglycosidesaminoglycosides), chemotherapy ), chemotherapy ((cisplatincisplatin), organic solvents (Ethylene glycol), ), organic solvents (Ethylene glycol), acetaminophen, illegal acetaminophen, illegal abortificientsabortificients

2: Endogenous: 2: Endogenous: RhabdomyolysisRhabdomyolysis, , hemolysishemolysis, , uric acid, oxalate, plasma cell uric acid, oxalate, plasma cell dyscrasiadyscrasia((myelomamyeloma))

4: Interstitial nephritis4: Interstitial nephritis A: Allergic; Antibiotics (beta A: Allergic; Antibiotics (beta lactumslactums, sulfonamides, , sulfonamides,

trimethoprimtrimethoprim, , rifampicinrifampicin), NSAID, diuretics, ), NSAID, diuretics, captoprilcaptopril B: Bacterial; (acute B: Bacterial; (acute pyelonephritispyelonephritis, , leptospirosisleptospirosis), viral ), viral

(cytomegalovirus), fungal ((cytomegalovirus), fungal (candidiasiscandidiasis)) C: Infiltration: Lymphoma, leukemia, C: Infiltration: Lymphoma, leukemia, sarcoidosissarcoidosis.. D: Idiopathic: D: Idiopathic: 5: 5: IntratubularIntratubular deposition and obstructiondeposition and obstruction MyelomaMyeloma proteins, uric acid, oxalate, acyclovir, proteins, uric acid, oxalate, acyclovir,

methotrexatemethotrexate, , sulphonamidessulphonamides 6: Renal allograft rejection6: Renal allograft rejection

III: POST RENAL ARF (OBSTRUCTION)III: POST RENAL ARF (OBSTRUCTION)

1: 1: UretericUreteric: Calculi, blood clot, sloughed : Calculi, blood clot, sloughed papillae, cancer, external compression papillae, cancer, external compression (retroperitoneal fibrosis)(retroperitoneal fibrosis)

2: Bladder neck ; 2: Bladder neck ; NeurogenicNeurogenic bladder, bladder, ProstaticProstatichypertrophy, calculi, cancer, blood clothypertrophy, calculi, cancer, blood clot

3: Urethra: stricture, Congenital valve, 3: Urethra: stricture, Congenital valve, phimosisphimosis

Clinical features and differential diagnosisClinical features and differential diagnosis 1: Determine whether decline in GFR it is acute 1: Determine whether decline in GFR it is acute

or chronic. Findings that suggest of chronic renal or chronic. Findings that suggest of chronic renal failure are anemia, neuropathy, and failure are anemia, neuropathy, and radiologicradiologicevidence of evidence of osteoosteo--dystrophy, small scarred dystrophy, small scarred kidney.kidney.

2: Once ARF is established identify the 2: Once ARF is established identify the cause of ARF, eliminate the triggering cause of ARF, eliminate the triggering insult (insult (nephrotoxinnephrotoxin) and/or institution of ) and/or institution of disease specific therapies, prevention and disease specific therapies, prevention and management of management of uremicuremic complicationscomplications

Clinical assessmentClinical assessment PrerenalPrerenal ARF: ARF: Thirst, orthostatic dizziness, Thirst, orthostatic dizziness,

tachycardia, reduced jugular venous pressure, tachycardia, reduced jugular venous pressure, decreased skin decreased skin turgorturgor, dry mucous membrane, , dry mucous membrane, reduced reduced axillaryaxillary sweating, sweating,

Intrinsic renal ARF: Intrinsic renal ARF: Ischemic and Ischemic and nephrotoxicnephrotoxiccauses should be ruled out which constitute 90% causes should be ruled out which constitute 90% of causesof causes

Post renal ARF: Post renal ARF: SuprapubicSuprapubic and flank pain, and flank pain, colicky pain, colicky pain, NeurogenicNeurogenic bladder should be ruled bladder should be ruled out in patients on out in patients on anticholinergicanticholinergic..

Urine analysisUrine analysis AnuriaAnuria suggests complete urinary tract suggests complete urinary tract

obstructionobstruction

PrerenalPrerenal: contains transparent hyaline casts : contains transparent hyaline casts formed in concentrated urine from normal formed in concentrated urine from normal constituents of urine mainly constituents of urine mainly TammTamm--HorsfallHorsfallprotein secreted by the epithelial cells of the protein secreted by the epithelial cells of the loop of loop of HenleHenle..

LabarotaryLabarotary findings: findings: CreatinineCreatinine: peak : peak creatininecreatinine is observed is observed

after 3after 3--5 days after contrast nephropathy, 5 days after contrast nephropathy, and 7and 7--10 days after ischemic ARF and 10 days after ischemic ARF and atheroathero embolic disease.embolic disease.

HyperkalemiaHyperkalemia, , hyperphosphatemiahyperphosphatemia, , hypocalcemiahypocalcemia, increased uric acid, and , increased uric acid, and creatininecreatinine kinasekinase at the time of at the time of presentation suggests diagnosis of presentation suggests diagnosis of rhabdomyolisisrhabdomyolisis..

HyperurecemiaHyperurecemia > 15mg/dL in association with > 15mg/dL in association with hyperkalemiahyperkalemia, , hyperphophatemiahyperphophatemia, and raised , and raised levels of LDH indicate acute levels of LDH indicate acute urateurate nephropathy nephropathy and tumor and tumor lysislysis syndrome following syndrome following chemotherapy.chemotherapy.

RadilogyRadilogy::

Renal biopsyRenal biopsy

ComplicationsComplications ARF impairs renal excretion of Na, K, and water, ARF impairs renal excretion of Na, K, and water,

disturbs divalent disturbs divalent cationcation homeostasis and urinary homeostasis and urinary acidification mechanisms. acidification mechanisms.

Hence ARF presents with intravascular volume Hence ARF presents with intravascular volume overload, overload, hyponatremiahyponatremia, , hyperkalemiahyperkalemia, , hyperphosphatemiahyperphosphatemia, , hypocalcemiahypocalcemia, , hypermagnesemiahypermagnesemia, and metabolic acidosis, rise , and metabolic acidosis, rise in nitrogenous waste products leading to in nitrogenous waste products leading to uremicuremicsyndromesyndrome

Expansion of Expansion of ExtracellularExtracellular fluid volume:fluid volume: Diminished salt and water excretion in Diminished salt and water excretion in oliguricoliguric or or

anuricanuric patients is characterized by weight gainpatients is characterized by weight gain Bilateral basal Bilateral basal creptscrepts Raised JVPRaised JVP Dependent edemaDependent edema Pulmonary edemaPulmonary edema Cerebral edemaCerebral edema NeurologicNeurologic abnormalities including seizuresabnormalities including seizures

HyperkalemiaHyperkalemia Serum K rises by 0.5 Serum K rises by 0.5 mmolmmol/L per day in /L per day in oliguricoliguric

and and anuricanuric patients due to impaired excretion of patients due to impaired excretion of ingested or infused K and K released from the ingested or infused K and K released from the injured tissue. Coexisting metabolic acidosis will injured tissue. Coexisting metabolic acidosis will exaggerate exaggerate hyperkalaemiahyperkalaemia by promoting K efflux by promoting K efflux from cells.from cells.

Metabolism of dietary protein yields 50Metabolism of dietary protein yields 50--100 100 mmol/dmmol/d of fixed non volatile acids.of fixed non volatile acids.

Mild Mild hyperphosphatemiahyperphosphatemia is always seen in ARF, is always seen in ARF, and also in patients with and also in patients with rhabdomyolysisrhabdomyolysis, , hemolysishemolysis, tumor , tumor lysislysis. . MetastaticMetastatic deposition of deposition of calcium phosphate leads to calcium phosphate leads to hypocalcemiahypocalcemia..

Anemia: is due to impaired Anemia: is due to impaired erythropoesiserythropoesis, , hemolysishemolysis, bleeding, , bleeding, hemodilutionhemodilution, and reduced , and reduced red cell survival timered cell survival time

Increased bleeding time, Increased bleeding time, leukocytosisleukocytosis..

InfectionInfection

Cardiopulmonary complicationsCardiopulmonary complications

GIT bleedingGIT bleeding

UremicUremic syndromesyndrome

TREATMENTTREATMENT

Prevention: Prevention: No specific therapy for ischemic or No specific therapy for ischemic or nephrotoxicnephrotoxic

ARF except preventing the etiologic factors.ARF except preventing the etiologic factors.

Preventing hypotension by aggressive volume Preventing hypotension by aggressive volume replacementreplacement

Judicious use of Judicious use of nephrotoxicnephrotoxic drugsdrugs

Adjusting dosage of the Adjusting dosage of the nephrotoxicnephrotoxic drugsdrugs

AllupurinolAllupurinol and forced alkaline and forced alkaline diuresisdiuresis in in patients at high risk of patients at high risk of urateurate nephropathy nephropathy (cancer chemotherapy, (cancer chemotherapy, hematologichematologicmalignancies)malignancies)

NN--acetylcysteineacetylcysteine limits acetaminophen induced limits acetaminophen induced injuryinjury

DimercaprolDimercaprol prevents the metal prevents the metal nephrotoxicitynephrotoxicity

Specific therapiesSpecific therapies PrerenalPrerenal: : Correction of Correction of hypovolemiahypovolemia depends upon the depends upon the

etiology that has caused it. etiology that has caused it. Corrected with blood if it is due to hemorrhageCorrected with blood if it is due to hemorrhage Isotonic saline is appropriate replacement for Isotonic saline is appropriate replacement for

mild to moderate hemorrhage or plasma loss.mild to moderate hemorrhage or plasma loss. Serum K and acid base status should be Serum K and acid base status should be

correctedcorrected

Cardiac failure needs aggressive Cardiac failure needs aggressive management with positive management with positive ionotropesionotropes, , preload and preload and afterloadafterload reducing agents, reducing agents, antiarrhythmicantiarrhythmic agents, IABP.agents, IABP.

Fluid management may be difficult in Fluid management may be difficult in patients with cirrhosis and patients with cirrhosis and ascitesascites. . HepatorenalHepatorenal syndrome should be ruled outsyndrome should be ruled out

Intrinsic renal ARFIntrinsic renal ARF ANP therapyANP therapy

Low dose dopamineLow dose dopamine

Loop diureticLoop diuretic

Calcium channel blockersCalcium channel blockers

Alpha Alpha adrenoadreno--receptor blockerreceptor blocker

Prostaglandin analoguesProstaglandin analogues

AntioxidantsAntioxidants

Antibodies against leukocyte adhesion Antibodies against leukocyte adhesion moleculesmolecules

Insulin like growth factorsInsulin like growth factors

ARF due to ARF due to glomerulonephritisglomerulonephritis, and , and vasculitisvasculitisrespond better with respond better with glucocorticoidsglucocorticoids, , alkylatingalkylatingagents, and plasma agents, and plasma pheresispheresis

Hypertension and ARF due to scleroderma is Hypertension and ARF due to scleroderma is sensitive to ACE inhibitorssensitive to ACE inhibitors

Post Renal ARFPost Renal ARF Can be detected by collaboration of Can be detected by collaboration of

nephrologists, urologist, and radiologist. nephrologists, urologist, and radiologist. Obstruction of the urethra and bladder neck is Obstruction of the urethra and bladder neck is managed initially by catheterization. managed initially by catheterization.

Supportive measures:Supportive measures: Salt water intake is titrated as requiredSalt water intake is titrated as required

Diuretics to correct Diuretics to correct hypovolemiahypovolemia

Management of Management of hyperkalemiahyperkalemia

Correction of metabolic acidosisCorrection of metabolic acidosis

HyperphosphatemiaHyperphosphatemia is corrected by is corrected by AlluminiumAlluminium hydroxide, calcium carbonatehydroxide, calcium carbonate

Nutrition therapy to prevent the catabolism Nutrition therapy to prevent the catabolism and starvation and starvation ketoacidosisketoacidosis, by restricting , by restricting the protein intake to 0.6g/kg, and giving the protein intake to 0.6g/kg, and giving high carbohydrate diethigh carbohydrate diet

Blood transfusion if anemiaBlood transfusion if anemia

DialysisDialysis

Outcome and long term prognosisOutcome and long term prognosis

Mortality rate with ARF is about 50%, Mortality rate with ARF is about 50%, patients usually die of the patients usually die of the sequelaesequelae of of primary illness that lead to ARF and not primary illness that lead to ARF and not ARF per say.ARF per say.

Patients with Patients with oliguriaoliguria UOP< 400ml/d and UOP< 400ml/d and rise in serum rise in serum creatininecreatinine > 3mg/dl at the > 3mg/dl at the time of admission have a poor prognosistime of admission have a poor prognosis