Renal Diseases Listen to Audio Acute Renal Failure Prerenal azotemia Renal azotemia Postrenal azotemia Chronic Renal Failure General/causes Clinical manifesations Acute Renal Failure General -rapid deterioration in renal function which results in retention in nitrogenous waste products (azotemia) -nitrogenous waste products (azotemia) act like toxins and are by-products of protein metabolism and amin acids ex. urea, guanidine compounds, urates, aliphatic amines along with other peptides of aromatic amino acid metabolism -causes of acute renal failure vary but the progression may be generalised -oliguria phase usually last around 2 weeks -diuretic phase with increased urine output (usually absent in nonoliguric renal failure) -then improvement in urinary function within several weeks upto one year PRERENAL AZOTEMIA causes treatment Causes -acute decrease in renal perfusion: ex. hypovolemia, decreased cardiac output, hypotension -increased renal vascular resistance: ex. neural, humoral, pharmacologic, thromboembolic -most common causes are decreased arterial blood pressure, increased venous pressuse or renal artery vasoconstriction resultant decreased renal perfusion leads to compensatory mechanisms: -inc plasma levels of norepinephrine, angiotensin II, AVP, and endothelin -kidneys respond to increased levels of catecholamines and release prostaglandins and nitric oxide -prostaglandins (PGE2 and prostacyclins) help maintain GFR -nitric oxide vasodilation also helps to maintain GFR -if COX inhibitors or ACE inhibitors used during the compensatory condition of the kidneys thet may precipitate ARF Treatment of prerenal azotemia: -correcting intravenous volume deficits -improving cardiac function -restoring normal blood pressure -reversing the increase in renal vascular resistance RENAL AZOTEMIA causes pathogenesis oliguria vs nonoliguria treatment Causes -renal ischemia about 50% of the cases (ex. hypotension, hypovolemia, impaired cardiac output) -nephrotoxins about 35% of the cases (ex. endogenous pigments, radiographic contrast, drugs, tubular crystals) -intrinsic renal disease about 15% of the cases (ex. glomerular disease, interstitial nephritis) Pathogenesis -prone to injury due to very high metabolic rate and ability to concentrate potentially toxic substances -renal ischemia and hypoxia may likely intiate renal damage by the following pathways: -ATP imbalance within epithelial cells due to an imbalance between oxygen supply and demand -resultant ATP imbalance may alter ion transport which may lead to: -altered metabolism of phospholipids and accumulation of intracellular calcium concentrations -reperfusion injury are reoxygenation may lead to free radical mediated cellular injury -backload of filtered solutes through damaged portions of renal tubules may allow reabsorptions of: -creatinine, urea, and nitrogenous waste products Oliguria vs nonoliguria ARF nonoliguria urinary volume > 400 ml /day oliguric urinary volume < 400 ml/ day anuria urinary volume < 100 ml/ day Nonoliguric ARF -upto 50% of all cases typically have lower urinary sodium concentrations than oliguric ARF -usually have lower complication rates and generally require shorter hospitalisation visits -may represent less severe renal injury Oliguric ARF -possible to convert oliguric ARF to nonoliguric ARF with mannitol, furosemide, and 'renal doses' of dopamine (ex. 1-2 ug/kg/min) -increases in urine output may be therapeutic by preventing tubular obstruction -mannitol may decrease cellular swelling and free radical scaveging action Treatment of ARF glomerulonephritis and vasculitis may respond to supportive treatments and glucocorticosteroids -if oliguric and anuric renal failure patients do not respond to diuretics then can try restricting fluids and electrolytes: -fluid restriction intake to about 500 ml + urine output -sodium restriction to about 1 mEq/kg/day intake -potassium restriction to about 1 mEq/kg/day intake -protein restriction to about < 0.7 g/kg/ day intake patients with hyponatremia: treat with water restriction patients with hypokalemia : treat with ion exchange resin ( sodium polystyrene) glucose + insulin calcium gluconate possibly bicarbonate patients with hyperphophatemia treat with dietary restrictions phosphate binding antacids (aluminum hydroxide) Dialysis: treat or prevent uremic complications Indications for hemodialysis: -fluid overload -hyperkalemia -drug toxicity -severe acidosis -pericarditis -metabolic encephalopathy -coagulopathy CRRT: continous renal replacement therapy CVVHF: continous venovenous hemofiltration CVVHD: continous venovenous hemodialysis POSTRENAL AZOTEMIA general/causes treatment General -caused by urinary tract obstruction -usually obstruction to both kidneys are necessary to develop azotemia and oligura/anuria -complete obstruction to the urinary tract eventually will lead to ARF -prolonged partial obstruction may eventually lead to chronic renal impairment -rapid diagnosis and relief of acute urinary obstruction usually restores normal kidney function -physical examination normally reveals a distended urinary bladder -abdominal x-ray may show bilateral renal calculi -confirmation is dilation of urinary tract proximal to the site of obstruction -commonly used studies: renal US, CT, cystoscopy with retrograde uterogram Treatment of postrenal azotemia -obstruction at the urinary bladder outlet: catherization of the bladder or straight suprapubic cystotomy -ureteral obstruction : nephrostomy or utereral stent placement Chronic Renal Failure General -progressive, irreversible decline in renal function -usually occurs over a course of at least 3 - 6 months -most common causes: -hypertension nephrosclerosis -diabetic nephropathy -chronic glomerulonephritis -polycystic renal disease GFR x < 25 ml/min usually manifest uremia x < 10 ml/min usually manifest ESRD ESRD is dependant on hemodialysis until recieving a kidney transplant CLINICAL MANIFESTATIONS OF RENAL FAILURE CNS: -autonomic neuropathy -peripheral neuropathy -encephalopathy -muscle twitching -aterexis -myoclonus -lethargy -confusion -coma CVS: -fluid overload -heart failure -hypertension -pericarditis -arryhthmias -conduction heart blocks -vascular calcifications -accelerated progression of atherosclerosis PULMONARY: -hyperventilation -interstitial edema -alveolar edema -pleural effusion GI: -anorexia -nasusea and vommiting -hyperacidity -mucosal ulcerations -hemmorhage -adynamic ileus METABOLIC: -metabolic acidosis -hyperkalemia -hyponatremia -hypermagnesemia -hyperphosphatemia -hypocalcemia -hyperuricemia -hypoalbuminemia HEMATOLGIC: -anemia -platelet dysfunction -leukocyte dysfunction ENDOCRINE: -glucose intolerance -secondary hyperparathyroidism -hypertriglyceridemia SKELETAL: -ostedystrophy -periarticular calcification SKIN: -hyperpigmentation -ecchymosis -pruritis