ACUTE RENAL FAILURE

JAKUB ZÁVADA

KLINIKA NEFROLOGIE 1.LF UK

ACUTE RENAL FAILURE (ARF)

• ARF IS A CLINICAL SYNDROME CHARACTERIZED BY A RAPID DECLINE IN GLOMERULAR FILTRATION RATE (OVER HOURS TO WEEKS)

• ARF IS ACCOMPANIED BY – DISTRUBANCES OF

• EXTRACELLULAR FLUID VOLUME• ELECTROLYTE HOMEOSTASIS• ACID-BASE BALANCE

– ACCUMULATION OF NITROGENOUS WASTE PRODUCTS

• ARF IS OFTEN REVERSIBLE• ARF INCREASES MORBIDITY AND MORTALITY

ACUTE RENAL FAILURE

• PRERENAL – PHYSIOLOGICAL RESPONSE TO RENAL HYPOPERFUSION IN WHICH INTEGRITY OF RENAL PARENCHYMA IS PRESERVED

• INTRINSIC RENAL – CAUSED BY DISEASES OF RENAL PARENCHYMA

• POSTRENAL – ACUTE OBSTRUCTION OF URINARY TRACT

CAUSES OF PRERENAL ARF

• INTRAVASCULAR VOLUME DEPLETION– HEMORRHAGE, GASTROINTESTINAL, RENAL, SKIN AND

MUCOUS MEMBRANE, THIRD SPACE LOSSES

• DECREASED CARDIAC OUTPUT– DISEASES OF MYOCARDIUM, PERICARDIUM, VALVES ETC.

• SYSTEMIC VASODILATION– DRUGS, SEPSIS, LIVER FAILURE, ANAPHYLAXIS

• IMPAIRED RENAL AUTOREGULATION– ACEI, ATRA, NSAID

CAUSES OF INTRINSIC RENAL ARF

• SEVERE RENAL HYPOPERFUSION (+SIRS)• TOXINS

– EXOGENOUS (RADIOCONTRAST, NEFROTOXIC ANTIBIOTICS, ANTICANCER AGENTS )

– ENDOGENOUS (RHABDOMYOLYSIS, HEMOLYSIS, TUMORLYSIS, HYPERCALCEMIA, LIGHT Ig CHAINS)

• DISEASES OF LARGE RENAL VESSELS:– ATHEROEMBOLISM, THROMBOSIS OF RENAL ARTERY AND

VEIN• DISEASES OF SMALL VESSELS AND GLOMERULI

– GLOMERULONEPHRITIS AND VASCULITIS, TTP-HUS, MALIGNANT HYPERTENSION

• ACUTE DISEASES OF THE TUBULOINTERSTITIUM– ALLERGIC INTERSTICIAL NEPHRITIS, ACUTE BILATERAL

PYELONEPHRITIS

CAUSES OF POSTRENAL ARF

• BILATERAL OBSTRUCTION OF URETHERS

• OBSTRUCTION OF BLADDER NECK

• DISEASES OF PROSTATE GLAND

• OBSTRUCTION OF URETHRA

DIFFERENTIAL DIAGNOSIS OF ARF

• IS THE RENAL FAILURE ACUTE, ACUTE ON CHRONIC OR CHRONIC?

• IS THERE RENAL TRACT OBSTRUCTION?• IS THERE EVIDENCE OF TRUE

HYPOVOLEMIA OR REDUCED EFFECTIVE ARTERIAL BLOOD VOLUME?

• HAS THERE BEEN A MAJOR VASCULAR OCCLUSION?

• IS THERE EVIDENCE OF PARENCHYMAL RENAL DISEASE OTHER THAN ATN?

DIFFERENTIAL DIAGNOSIS OF ARF

IS THE RENAL FAILURE ACUTE, ACUTE ON CHRONIC OR CHRONIC?

• ARF:– RECENT INCREASE OF BUN AND SERUM CREATININ– CLINICAL AND HISTORY DATA CONSISTENT WITH ARF

• CRF:– PREVIOUSLY RECORDED ALTERED RENAL

PARAMETRES– HISTORY CONSISTENT WITH POSSIBLE CHRONIC

KIDNEY DISEASE (DM, HT, AMYLOIDOSIS, NSAID)– SEVERE ANEMIA, HYPERPHOSPHATEMIA,

HYPOCALCEMIA– ULTRASONOGRAPHY: SMALL, SHRUNKEN OR

POLYCYSTIC KIDNEYS

DIFFERENTIAL DIAGNOSIS OF ARF

IS THERE URINARY TRACT OBSTRUCTION?

• CLINICAL POINTS: – SUPRAPUBIC PAIN, PALPABLE BLADDER DISTENTION– HISTORY OF PROSTATIC DISEASE (NOCTURIA,

FREQUENY, HESITANCY)– COLICKY PAIN WITH IRADIATION TO THE GROIN– HISTORY OF MALIGNANCY IN PELVIS– HISTORY OF NEUROGENIC BLADDER

• IMAGING– ULTRASOUND, CT, MRI, IVU

DIFFERENTIAL DIAGNOSIS OF ARFIS THERE EVIDENCE OF TRUE HYPOVOLEMIA OR REDUCED EFFECTIVE ARTERIAL BLOOD VOLUME?

• HISTORY– BLEEDING, LOSS OF SOLUTES, LOW FLUID INTAKE – HEART OR LIVER FAILURE– NSAID, ACEI, ATRA

• SIGNS– ORTOSTATIC HYPOTENSION, TACHYCARDIA, DRY

MUCOUS MEMBRANES, LOW JUGULAR VENOUS PRESSURE, OLIGURIA, SEPSIS/SIRS

• LABORATORY AND URINARY FINDINGS– HEMOCONCENTRATION, UREA/KREATININ, SPEC.

GRAVITY OF URINE, U-Na

• INVASIVE MONITORING– CENTRAL VENOUS PRESSURE, SWAN-GANZ CATHETR

DIFFERENTIAL DIAGNOSIS OF ARF

HAS THERE BEEN A MAJOR VASCULAR OCCLUSION?

• ATHEROEMBOLISM– RECENT INSTRUMENTATION IN AORTA, AGE OVER 50,

SEVERE ATHEROSCLEROSIS, WARFARIN– PURPURA, LIVEDO RETIKULARIS– EOSINOPHILIA, HYPOCOMPLEMENTEMIA– RENAL BIOPSY

• TROMBOSIS OF RENAL ARTERY– HISTORY OF ATRIAL FIBRILLATION, RECENT MI– NAUSEA, ABDOMINAL PAIN, FLANK PAIN– ANGIOGRAPHY, AG-CT, MRI

• TROMBOSIS OF RENAL VEIN– NEPHROTIC SYNDROME, PULMONARY EMBOLISM– AG, AG-CT, MRI, DOPPLER US

DIFFERENTIAL DIAGNOSIS OF ARF

IS THERE EVIDENCE OF PARENCHYMAL RENAL DISEASE OTHER THAN ATN?

• HISTORY AND PHYSICAL EXAM– ARTHRALGIAS– SKIN CHANGES– PULMONARY AND ETN DISORDER– MALIGNANT HYPERTENSION

• URINANALYSIS– ACTIVE URINE SEDIMENT (PRU>1g/d, ERY-U)

• LAB – SIGNS OF MICROANGIOPATIC HEMOLYSIS– IMUNOLOGY (ANCA, ANA, C3, C4, ANTI-GBM, APLA)

• RENAL BIOPSY

ACUTE TUBULAR NECROSIS (ATN)

• ETIOLOGY– ISCHEMIA– TOXINS– SIRS/SEPSIS

• PATOPHYSIOLOGY– VACUOLATION, LOSS OF BRUSH BORDER,

APOPTOSIS/NECROSIS OF TUBULÁR CELLS– INTRARENAL VASOCONSTRICTION, IMPAIRED RENAL

AUTOREGULATION– INTRATUBULAR OBSTRUCTION – INFILTRATION BY NEUTROPHILS AND MACROPHAGES

• PROGNOSIS– UNCOMPLICATED ATN REVERSES IN 2-3 WEEKS– CORTICAL NECROSIS IS IRREVERSIBLE

ACUTE TUBULAR NECROSIS (ATN)

DIFF.DG. OF PRERENAL AZOTEMIA AND ATN:

• PRERENAL AZOTEMIA:– ADEQUATE KIDNEY RESPONSE TO VOLUME DEPLETION:

• ↑ URINE OSMOLALITY (U-OSM>500 mOsm/kg)• ↑ SPECIFIC GRAVITY (>1,018)• LOW URINARY SODIUM (U-Na<10 mmol/l, FeNa <1%)

– RAPID RESTORATION AFTER VOLUMEXPANSION

• ATN:– DISTURBED CONCENTRATING AND

VOLUMEREGULATORY KIDNEY FUNCTION:• ↓ URINE OSMOLALITY (U-OSM<250 mOsm/kg)• ↓ SPECIFIC GRAVITY (< 1,012)• HIGH URINARY SODIUM (U-Na > 20 mmol/l, FeNa > 2%)

NEFROTOXIC AGENTS• HEME PIGMENTS

– MYOGLOBIN – RHABDOMYOLYSIS• MUSCLE TRAUMA, ETHANOL, SEIZURES, LIMB ISCHEMIA,

STATINS, FIBRÁTES• ↑ CK, MYOGLOBIN IN PLASMA

– HEMOGLOBIN – HEMOLYSIS• INKOMPATIBILE TRANSFUSION, AIHA, SNAKE VENOM,

MALÁRIA, G6PDH DEFICIENCY, PNH

• RADIOCONTRAST• NEPHROTOXIC DRUGS

– NSAID, ACEI, ATRA– AMINOGLYKOSIDS, AMFOTERICIN B, PENTAMIDIN,

ACYCLOVIR– CYCLOSPORINE, TAKROLIMUS– CISPLATINE, IFOSFAMIDE

• ETHYLENGLYKOL, HEAVY METALS, HERBAL REMEDIES

ACUTE RENAL FAILURE – COMPLICATIONS

• HYPERVOLEMIA• HYPERKALEMIA• METABOLIC ACIDOSIS• UREMIA• HYPERURICEMIA• HYPOCALCEMIA, HYPERPHOSFATEMIA• RECOVERY PHASE OF ARF

– POLYURUIA– HYPERNATREMIA, HYPOKALEMIA, HYPOMAGNESEMIA,

HYPOPHOSFATEMIA

ACUTE RENAL FAILURE– MANAGEMENT

• PRERENAL ARF → RESTORATION OF RENAL PERFUSION– REPLACEMENT OF FLUID LOSSES (CRYSTALOIDS,

COLLOIDS)– MANAGEMENT OF CIRCULATORY FAILURE (INVASIVE

HEMODYNAMIC MONITORING, TREATMENT OF HEART FAILURE, IONOTROPES, VASOACTIVE DRUGS)

• POSTRENAL ARF → RELIEVE OBSTRUCTION – MULTIDISCIPLINARY APPROACH (RADIOLOGIST,

UROLOGIST, NEPROLOGIST)– URINARY BLADDER CATHETER– NEPHROSTOMY

ACUTE RENAL FAILURE– MANAGEMENT

INTRARENAL ARF • PREVENTION

– OPTIMAL HYDRATION OF PATIENTS AT RISK – MONITORING OF LEVELS OF AMINOGLYCOSIDES AND

CYKLOSPORINE – N-ACETYLCYSTEINE? – CAVE ACEI, NSAID, DIURETICS

• SUPPORTIVE TREATMENT– ADRESSING COMPLICATIONS (ACIDOSIS, ELECTROLYTE

ABNORMALITIES, HYPERVOLEMIA)– DIALYSIS (OR HEMOFILTRATION)

• TREATMENT OF SPECIFIC CAUSES OF ARF– TTP-HUS, RPGN, ATIN

ACUTE RENAL FAILURE – INDICATIONS OF DIALYSIS

• UREMIA

• HYPERKALEMIA

• HYPERVOLEMIA

• SEVERE ACIDOSIS