1. ACUTE RENAL FAILURE University of Medicine and Pharmacy, Iasi School of Medicine ANESTHESIA and INTENSIVE CARE Conf. Dr. Ioana Grigoras MEDICINE 4 th year English Program Suport de curs

2. ACUTE RENAL FAILURE DEFINITION clinical syndrome induced by various causes and characterized by the incapacity of the kidney to maintain organism homeostasis manifested as retention of nitrogenous waste products and variable volume of diuresis.

3. ACUTE RENAL FAILURE CLASSIFICATION: –Prerenal acute renal failure Reduction of renal blood flow –Intrinsic acute renal failure Agression of renal parenchyma (toxic, ischemic, imunological, etc) –Postrenal acute renal failure Urinary tract obstruction

4. PRERENAL ACUTE RENAL FAILURE ( functional renal failure, prerenal azotemia) CAUSES: –Reduction of effective circulanting blood volume Hypovolemia due to hemorrhage Hipovolemia due to non-hemorrhagic losses (see hypovolemic shock) –Low cardiac output Cardiogenic shock or extracardiac obstructive shock Chronic heart failure Ischemic, toxic, dilated cardiomyopathy Cardiac disrhythmias, etc. –Blood flow maldistribution Excessive vasodilatation ( septic shock, excess of antihypertensive drugs) Cirrhosis

5. PRERENAL ACUTE RENAL FAILURE ( functional renal failure,prerenal azotemia) Functional renal dysfunction induced by alterations of renal perfusion. General features: –Functional deterioration without structural damage; –Prompt correction of the renal perfusion normalizes renal function; –Healing - complete recovery of renal function; –Good prognosis; –Dialysis is not necessary; –Form of acute renal failure in which prophylaxis and early treatment have maximum efficiency and the most chances of success; –Without early correction of renal hypoperfusion, intrinsic renal failure develops through ischemic mechanism (acute tubular necrosis).

6. INTRINSIC ACUTE RENAL FAILURE CAUSES: – Renal parenchymal ischemia Prerenal acute renal failure (late treatment) All shock states (late treatment) –Nephrotoxic agents Radiocontrast agents Antibiotics (aminoglycosides, vancomycin, cyclosporine) Toxins ( heavy metals: Pb, Cd, Hg, ethylene glycol, poisonous mushrooms) –Disorders of glomeruli and blood vessels Glomerulonephritis Vasculitis Diabetic nephropathy –Interstitial disorders Interstitial nephritis Antibiotics (cephalosporins)

7. Renal acute failure (intrinsic renal failure) Agression of renal parenchyma triggered by different mechanisms: ischemic, nephrotoxic, imunological, etc. General features: –Morphological alterations of the kidney are present; –Long time of evolution; –Dialysis often required; –Poor prognosis (variable mortality depending on cause); –Recovery can be complete or with residual functional deficit.

8. POSTRENAL ACUTE RENAL FAILURE (obstructive renal failure) CAUSES: –Nephrolithiasis –Prostate adenoma –Pelvic tumors –Retroperitoneal pathological process (retroperitoneal fibrosis, tumors, abcess, hematoma) –Accidental ureteral ligation,etc.

9. POSTRENAL ACUTE RENAL FAILURE (obstructive renal failure) result of bilateral ureteral obstruction or unilateral obstruction in patients with solitary kidney. – General features : –Obstruction results in renal parenchymal damage; –Prognosis depends on the precociousness of urinary output resumption and the presence of urinary infection –Early urinary output resumption results in complete recovery of renal function

10. ACUTE RENAL FAILURE FORMS: – Anuric renal failure urinary output < 100ml/24 ore – Oliguric renal failure urinary output < 500ml/24 ore – Renal failure with preserved diuresis urinary output >1000ml/24 ore

11. MONITORING OF THE PATIENT WITH RENAL FAILURE Respiratory monitoring Respiratorz rate Pattern of respiration Pulsoximetry Blood gas analysis Cardio-vascular monitoring BP, HR ECG Pulsoximetry Skin colour and temperature CVP Neurological monitoring State of consciousness Temperature monitoring Measurement of central/peripheral temperature Diuresis monitoring Hourly monitoring of diuresis – urinary catheter Acido-basic monitoring Blood gas analyses

12. ACUTE RENAL FAILURE PRINCIPILES OF TREATMENT Treatment of the causative disease Circulanting blood volume restoration –Volemic solutions (see hypovolemic shock) Correction of cardiac output and renal perfusion – inotropic drugs (dobutamine, dopamine) Removal of the nephrotoxic drugs Water, electrolytes and nutritional support Infection prophylaxis Dialysis (when necessary) Obstacle removal (when necessary)

13. PRERENAL ACUTE RENAL FAILURE

14. DEFINITION form of acute renal failure characterized by insufficient renal perfusion for the maintenance of adequate glomerular filtration rate.

15. PRERENAL ACUTE RENAL FAILURE MECHANISMS: hypovolemia reductions of effective circulanting blood volume reduction of cardiac output dysfunction of renal autoregulation

16. PRERENAL ACUTE RENAL FAILURE REDUCTION OF EFFECTIVE CIRCULANTING BLOOD VOLUME - HYPOVOLEMIA renal losses diuretics osmotic drugs renal diseases with salt losses adrenal insufficiency, etc. skin losses burns excessive sweating, etc. hemorrhagic losses trauma upper/lower GI bleeding epistaxis hemoptysis,etc. digestive losses vomiting diarrhea surgical drainages, etc.

17. PRERENAL ACUTE RENAL FAILURE REDUCTIONS OF EFFECTIVE CIRCULANTING BLOOD VOLUME - REDISTRIBUTION peripheral vasodilatation vasodilators, anaphylaxis, sepsis, anesthetics peripherical edema hipoalbuminemia, nephrotic syndrome, cirrhosis third space losses peritonites, pancreatits, intestinal oclussion,etc. REDUCTION OF CARDIAC OUTPUT cardiac tamponade, acute myocardial infarction, valvular heart disease, cardiomyopathys, arrhytmias, etc. DYSFUNCTION OF RENAL AUTOREGULATION treatment with cu NSAID or ACE inhibitors

18. PRERENAL ACUTE RENAL FAILURE - PATHOGENESIS Reduction of effective circulanting blood volume Reduction of cardiac output –Systemic arterial hypotension which reduces renal perfusion pressure –Compensatory mechanisms : sympathetic stimulation, stimulation of SRAA and ADH. Reduction of renal perfusion

19. PRERENAL ACUTE RENAL FAILURE - PATHOGENESIS Reduction of renal perfusion afferent arteriolar vasoconstriction glomerular hidrostatic pressure glomerular filtration rate predominantly in renal cortex Stimulation of SRAA and ADH renal vasoconstriction reabsorbtion of sodium, water and bicarbonate.

20. PRERENAL ACUTE RENAL FAILURE - PATHOGENESIS In prerenal acute renal failure the kidney tend to conserve water and sodium producing a small volume high concetration urine and decreased Na excretion.

21. PRERENAL ACUTE RENAL FAILURE CLINICAL FEATURES Clinical signs and symptoms of the causative disorder are prevalent (trauma, burns, acute surgical abdomen, acute myocardial infarction, anaphylactic shock, etc.) Patient history, clinical signs and hemodynamic parameters will identify the characteristic hemodynamic status for each mechanism (hypovolemia, reduction of effective circulanting blood volume through redistribution, reduction of cardiac output). urinary volume is variable, but most frequently is decreased (oliguria– urinary output <0,5ml/kg/hour).

22. PRERENAL ACUTE RENAL FAILURE Diagnosis: –Identification of etiology –variable amount of urine usual, oliguria ( urinary output <0,5ml/kg/hour) urinary output may be normal or elevated in the case of diuretics and osmotic drugs –Elevation of blood ureea nitrogen (BUN) and serum creatinine The elevation of blood ureea nitrogen is more pronunced than serum creatinine elevation Plasma BUN/serum creatinine is elevated (normal 10/1; in prerenal ARF 20/1) Differential diagnosis with diseases accompanied by BUN/serum creatinine elevations without glomerular filtration rate reduction (table 3) –Characteristic urinary analysis –Imagistic explorations for the exclusion of postrenal causes (chest Rx, abdominal ultrasound).

23. PRERENAL ACUTE RENAL FAILURE Causes of BUN/serum creatinine elevations without glomerular filtration rate reduction: Elevation of BUN synthesis –Gastro-intestinal bleeding –Drugs: steroids, tetraciclyne –Elevated protein intake –Elevated intake of aminoacids –Hypercatabolism and fever Elevation of creatinine synthesis Elevation of creatinine release from the muscles (rhabdomyolysis) Drugs which interfere with tubular secretion of creatinine Cimetidine, trimetoprim

24. PRERENAL ACUTE RENAL FAILURE –characteristic urinary analysis: urine specific gravity >1020 urine osmolarity>500mOsm/l plasma BUN/ plasma creatinine ratio >20/1 urine urea nitrogen /plasma urea nitrogen ratio >10 urinary sodium <10-20 mEq/l fractional Na excretion <1%; the ratio between sodium and creatinine excretion; FE Na = U Na : P Na / U cr : P cr FE Na = U Na x P cr / U cr x P Na

25. PRERENAL ACUTE RENAL FAILURE PRINCIPLES OF TREATMENT –early and agressive treatment of the causative disorder for normalization of renal perfusion before occurance of ischemic damage –Hemodynamic optimization: normalisation of intravascular volume, cardiac output and systemic vascular resistance - by volemic repletion, inotropic and vasoactive drugs –Promotion of urinary output with diuretics (manitol, furosemid)

26. ACUTE RENAL FAILURE PROPHYLAXIS Identification of high risk patients Early correction of hemodynamic disorders which can induce or aggravate renal dysfunction Promotion of urinary output - diuretics Use catecholamines for renal protection Other drugs used in renal protection

27. POSTRENAL ACUTE RENAL FAILURE

28. DEFINITION postrenal acute renal failure is the form of renal failure caused by urinary output obstruction

29. POSTRENAL ACUTE RENAL FAILURE Causes: Tumors –renal adenocarcinoma, limfomas, bladder cancer, gynecological tumors, prostate carcinoma, others pelvic tumors, so inflamatory process – tuberculosis, retroperitoneal abcess, retroperitoneal fibrosis, bowel inflammatory disease, so Vascular diseases –Renal artery aneurysm, aortic aneurysm Papilar necrosis –diabetes mellitus, hemoglobinopathy C, analgetic abuse, inhibition of prostaglandins, cirrhosis Intratubular obstruction –uric acid, calcium phosphate, Benes-Jones proteins, metotrexat, acyclovir, sulfonamide Others –nephrolithiasis, ureteral ligature, ureteral pielography, pielography with ureteral edema, neurological bladder,etc

30. POSTRENAL ACUTE RENAL FAILURE PATHOGENESIS Mechanisms of urinary output reduction –Urinary obstruction retrograde overpressure reduced or suspended glomerular filtration – Ureteral obstruction thromboxan mediated renal vasoconstriction –Long lasting obstruction – structural renal damage.

31. POSTRENAL ACUTE RENAL FAILURE CLINICAL FEATURES Clinical signs of the causative disorder –Frequently – slow progression, late and discreet signs of acute renal failure. Urinary output is variable. –Sometimes suddenly instalation of a complete anuria dominate clinical picture and in this case a complete obstruction must be suspected. –Other times the obstruction is incomplete and urinary output is present and even polyuria is possible

32. POSTRENAL ACUTE RENAL FAILURE DIAGNOSIS –Identification of the obstructive cause Ultrasonography is the screening test and often a diagnostic examination –level of obstruction –retrograde dilatation –the cause : lithiasis, tumors, so Investigations for complete diagnosis of the causative disorder –Variable urinary output; Sometimes compete anuria, suddenly instalated Other times polyuria (loss of urinary concentrating capacity) –Plasma BUN and creatinine are elevated; plasma BUN/ plasma creatinine ratio is elevated –Hyperkalemia –Variable and uncharacteristic urinary analysis: loss of urinary concentrating and dilution ability reduction of the urinary acidification capacity variable Na excretion (FENa 3% in late phases)

33. POSTRENAL ACUTE RENAL FAILURE PRINCIPlES OF TREATMENT Treatment of causative disorder Early removal of the obstruction –Emergency urine drainage through urinary catheter, cistostomy, ureteral stents or percutaneous nephrostomy Hemodynamic and renal perfusion optimization for functional renal recovery Treatment of urinary infection which is frequent associated with obstruction.

34. INTRINSIC ACUTE RENAL FAILURE

35. Causes Renal ischemia Nephrotoxic substances –Drugs : antibiotics, NSAID, cyclosporine, etc. –Radiocontrast agents –Toxins: ethylene glycol, heavy metals, pesticides, fungicides, etc. Glomerulonephritis and vasculitis: –poststreptococcal glomerulonephritis, bacterial endocarditis, systemic erythematosus lupus, malignant hypertension, thrombotic microanghiopathy, Henoch-Schönlein purpura, polyarteritis nodosa, rapidly progressive glomerulonephritis, Goodpasture syndrome, Wegener granulomatosis, etc. –bilateral thrombosis of renal veins, dissecting aneurysm of renal artery, renal artery embolism, etc. Interstitial nephritis: –antibiotics, furosemide, alopurinol, fenitoine,etc.

36. INTRINSIC ACUTE RENAL FAILURE PATHOGENESIS –afferent arterioles vasoconstriction catecholamines, angiotensin II, impaired prostaglandin regulation –decreased permeability of glomerulo-capillary membrane inflammatory/immunological processes –tubular basement membrane disrupption primary urine back leak to interstitium –intratubular obstruction cell debris

37. INTRINSIC ACUTE RENAL FAILURE DIAGNOSIS –history consistent with causative condition –clinical examination data according to causative disorder urine output according to form (anuria, oliguria, preserved urinary flow/polyuria) clinical signs of renal failure and complication –laboratory urinary specific gravity ~1010 (isosthenuria) urinary urea/blood urea nitrogen < 3 urinaru creatinine/blood creatinine < 20 urinary Na > 40mEq/l fractional sodium excretion > 3% –other diagnostic tests – to exclude postrenal causes

38. INTRINSIC ACUTE RENAL FAILURE CLINICAL SINGS AND COMPLICATIONS –water and electrolytes balance water and salt overload (anuria) –treatment: water restriction volume depletion (rare; vomiting, diarrhea, etc.) –treatment: volume repletion dillutional hyponatremia –treatment: fluid restriction hypernatremia –treatment: hemodialysis hyperkaliemia –treatment: correction of metabolic acidosis infusion of glucose + insulin, bicarbonate hemodialysis

39. INTRINSIC ACUTE RENAL FAILURE CLINICAL SINGS AND COMPLICATIONS –acid-base balance metabolic acidosis –treatment: sodium bicarbonate, hemodialysis –complications of nitrogen waste products retention –encephalopathy, pulmonary edema, pericarditis, HTA, etc. –absent in case of hemodialysis infections –sites: urinary, intravascular catheters, intraabdominal –no antibiotic prophylaxis –search for the source gastro-intestinal bleeding (stress ulcerations) –prophylaxis: aniacids, histamine H2 blockers, etc.

40. INTRINSIC ACUTE RENAL FAILURE PHASES –phase I dominated by the causative condition –phase II dominated by anuria and clinical signs of nitrogen waste products retention attenuated by the use of renal replacement therapies –phase III reappearance of urinary output, followed by polyuria

41. ACUTE RENAL FAILURE PROPHYLAXIS Identification of high risk patients Early correction of hemodynamic disorders which can induce or aggravate renal dysfunction Promotion of urinary output - diuretics Use catecholamines for renal protection Other drugs used in renal protection

42. INTRINSIC ACUTE RENAL FAILURE PATIENTS AT RISK FOR RENAL FAILURE chronic renal failure volume depletion diabetes mellitus elderly patients surgery chronic heart failure urinary tract infection prior history of acute renal failure

43. INTRINSIC ACUTE RENAL FAILURE USE OF DIURETICS IN PREVENTION / TREATMENT OF ACUTE RENAL FAILURE –MANITOL expands blood volume (colloid solution) may induce vasodilation (if vasoconstriction is present) promotes osmotic diuresis solutions: 10%, 20%; effective in high risk conditions, before occurrence of renal insult should not be use in anuric intrinsic renal failure –FUROSEMIDE may induce vasodilation (if vasoconstriction is present) may diminish renal oxygen demand (protects nephron during ischemia); redistribution of renal blood flow may convert oliguric ARF to ARF with preserved urinary flow

44. INTRINSIC ACUTE RENAL FAILURE PRINCIPLES OF TREATMENT Causative treatment Hemodynamic optimization Urinary output promotion Fluid-electrolyte treatment Prophylaxis and treatment of complications Nutritional support Renal replacement therapies

45. RENAL REPLACEMENT TECHNIQUES Indications of hemodialysis în ARF volume overloaded HTA, pulmonary edema electrolyte abnormalities : K> 7mEq/l, Na 155mEq/l acido-base abnormalities pH 7,54 retention of nitrogenous waste products BUN>200mg%, creatinine >8-10mg% Mnemotehnique formula for hemodialysis indications: A – metabolic acidosis E - electrolyte: hyperkalemia I - intoxications O - fluid overload U - uremia

46. RENAL REPLACEMENT TECHNIQUES PERITONEAL DIALYSIS TECHNIQUES WITH PARENTERAL ACCESS Renal replacement duration Intermittent (for 4-8 hours/day) Continous (24 hours/day) Type of vascular access arterial access and venous access venous access Type of renal replacement technique Hemodialysis Hemofiltration Hemodiafiltration