Acute renal failure and

Identifying patients at high risk for development of acute renal failure and implementing preventive methods to decrease its occurrence or severity is critical. 

Hemolytic uremic syndrome A syndrome characterized by microangiopathic hemolytic anemia, acute renal failure, and a low platelet count (thrombocytopenia). 

Osmotic diuretics such as mannitol act on the proximal tubule and, in particular, the descending limb of the Loop of Henle — portions of the tubule permeable to water. These drugs are freely filtered at the glomerulus, but not reabsorbed therefore, the drug remains in the tubular filtrate, increasing the osmolarity of this fluid. This increase in osmolarity keeps the water within the tubule, causing water diuresis. Because they primarily affect water and not sodium, the net effect is a reduction in total body water content more than cation content. Osmotic diuretics are poorly absorbed and must be administered intravenously. These drugs may be used to treat patients in acute renal failure and with dialysis disequilibrium syndrome. The latter disorder is caused by the excessively rapid removal of solutes from the extracellular fluid by hemodialysis. 

The pathophysiology, clinical manifestations, diagnosis, and treatment of acute renal failure and chronic kidney disease (CKD) or end-stage renal disease are discussed in Chaps. 75 and 76, respectively. 

Continuous renal replacement therapy is used for the management of fluid overload and removal of uremic toxins in patients with acute renal failure and other conditions. Drug therapy individualization for patients receiving continuous renal replacement therapy is discussed in Chap. 75. 

Hypercalcemia of malignancy develops quickly and is associated with anorexia, nausea and vomiting, constipation, polyuria, polydipsia, and nocturia. Hypercalcemic crisis is characterized by acute elevation of serum calcium to greater than 15 mg/dL, acute renal failure, and obtundation. Untreated hypercalcemic crisis can progress to oliguric renal failure, coma, and life-threatening ventricular arrhythmias. 

Assessment of renal function is not required prior to first administration to man or even during clinical development however, based on the potential implications of acute renal failure and the challenges in assessing it in normal healthy animals or humans, it would make sense to consider a proper assessment of renal function prior to first administration to humans. 

Chertow, G.M., Levy, E.M., Hammermeister, K.E., et al (1998) Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104, 343-348. 

Noiri et al. used AS-ODN to inhibit production of inducible nitric oxide synthase (INOS) in an attempt to prevent NO production in an ischaemic kidney. A single intravenous injection of iNOS AS-ODN attenuated acute renal failure and reduced the morphological abnormalities [129],... 

Renai function impairment Dosage reduction is recommended with renal impairment (see Administration and Dosage). Acute renal failure and CNS symptoms have been reported in patients with underlying renal disease who have received inappropriately high doses for their level of renal function. Exercise similar caution when administering valacyclovir to elderly patients and patients receiving potentially nephrotoxic agents. 

Renal function impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported in association with the use of tenofovir. Avoid tenofovir with concurrent or recent use of a nephrotoxic agent. Carefully monitor patients at risk for, or with a history of, renal dysfunction and patients... 

Concomitant use with sympathomimetic drugs, p-adrenoceptor antagonists, calcium channel-entry blockers and other cardioactive drugs may result in bradyarrhythmias, bigemini, or tachyarrhythmias. Cardiac rhythm should be closely monitored and drug dosages carefully adjusted. Digoxin is mainly excreted by the kidneys and plasma levels should be closely monitored in patients with acute renal failure and in those whose renal function is compromised. 

The most important indications for the use of the loop diuretics include acute pulmonary edema, other edematous conditions, and acute hypercalcemia. The use of loop diuretics in these conditions is discussed in Clinical Pharmacology. Other indications for loop diuretics include hyperkalemia, acute renal failure, and anion overdose. 

Giving intravenous phosphate is probably the fastest and surest way to reduce serum calcium, but it is a hazardous procedure if not done properly. Intravenous phosphate should be used only after other methods of treatment (bisphosphonates, calcitonin, and saline diuresis) have failed to control symptomatic hypercalcemia. Phosphate must be given slowly (50 mmol or 1.5 g elemental phosphorus over 6-8 hours) and the patient switched to oral phosphate (1-2 g/d elemental phosphorus, as one of the salts indicated below) as soon as symptoms of hypercalcemia have cleared. The risks of intravenous phosphate therapy include sudden hypocalcemia, ectopic calcification, acute renal failure, and... 

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

Adverse effects are not a major concern with the use of tenofovir. The occurrence of acute renal failure and Fanconi syndrome is rare. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have also been observed. 

Price G. Metformin lactic acidosis, acute renal failure and rofecoxib. Br J Anaesth 2003 91 909-10. 

Fig. 64. Proteomic analysis with a SELDI-TOF-MS. In single marker analysis left), the relative intensity of the 3.5 KDa peptide was high in the ALPE group. In the hierarchical clustering analysis with marker candidates, the heat map in the ALPE group differed from those in the myoglobinuric acute renal failure and normal groups (p. 69)...

Some patients have nontypical ALPE. Some do not clearly remember having exercised [1,28,29], and others do not complain of loin pain [30,31]. In addition, others concurrently develop myoglobinuric acute renal failure and exercise-induced acute renal failure (ALPE), and show the characteristics of both disorders [32,33],... 

Fig. 63. Single marker analysis with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) in the ALPE, myoglobinuric acute renal failure, and normal groups. In the ALPE group, the relative intensity of a 3.5 KDa/4.3 KDa peptide was higher than that in the other groups...

As shown in Fig. 76, exercise-related acute renal failure is classified into two types myoglobinuric acute renal failure and non-myoglobinuric acute renal failure. The latter is represented by ALPE. The grade of rhabdomyolysis and the type/grade of muscle fibers affected are shown in Fig. 76. Pathogenetic factors for ALPE should be investigated in the future. 

Fig. 76. Comparison of the pathogenesis between myoglobinuric acute renal failure and non myoglobinuric acute renal failure represented by ALPE (hypothesis)...

Kim SH, Han MC, Han JS, Kim S, Lee JS (1991) Exercise-induced acute renal failure and patchy renal vasoconstriction CT and MR findings. J Comput Assist Tomogr... 

Yeun JY, Hasbargen JA (1995) Renal hypouricemia prevention of exercise-induced acute renal failure and a review of the literature. Am J Kidney Dis 25 937-946... 

Izumi M, Yokoyama K, Yamauchi A, HorioM, Imai E (1997) A young man with acute renal failure and severe loin pain. Nephron 76 215-217... 

Ueda O, Oka T, Kyan H (1997) A case of renal hypouricemia with exercise-induced acute renal failure and cerebral infarction (in Japanese with English abstract). J Jpn Pediatr Soc 101 1620-1625... 

Kikuchi Y, Koga H, Yasutomo Y, Kawabata Y, Shimizu E, Naruse M, Kiyama S, Nonoguchi H, Tomita K, Sasatomi Y, Takebayashi S (2000) Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction. Clin Nephrol 53 467-472... 

Koyama M, Ishii M, Watanabe K (2003) A case of exercise-induced acute renal failure and patchy renal vasoconstriction (Japanese abstract). J Jpn Radiol Soc 63 S413... 

The immunosuppressant agents, cyclosporin A (cys A) and FK506 both have the potential to induce acute renal failure and endothelin has been proposed as the mediator. Cys A and FK506 have both been shown to stimulate ET-1 release from cultured kidney cells [200]. An endothelin antibody prevented the reduction in function induced by cys A in a rat kidney perfusion model [201]. In the same model, BQ 123 also prevented the detrimental renal effects of cys A [202]. 

Although the pneumonia affects the lungs. Legionnaires disease is accompanied by symptoms that affect other areas of the body. About half the victims experience diarrhea and a quarter have nausea and vomiting and abdominal pain. In about 10% of cases, acute renal failure and scanty urine production accompany the disease. Changes in mental status, such as disorientation, conftision, and hallucinations, also occur in about a quarter of cases. 

Biswas CK, Milligan DA, Agte SD, Kenward DH, TiUey PJ. Acute renal failure and myopathy after treatment with aminocaproic acid. BMJ 1980 281(6233) 115-16. 

Hruz P, Mayr M, Low R, Drewe J, Huber G. Fanconi s syndrome, acute renal failure, and tonsil ulcerations after colloidal bismuth subcitrate intoxication. Am J Kidney Dis 2002 39(3) E18. 

Payne CR, Ackrill P, Ralston AJ. Acute renal failure and rise in alkaline phosphatase activity caused by cimetidine. BMJ (Clin Res Ed) 1982 285(6335) 100. 

Stein HD. Dextran-40, acute renal failure, and elevated plasma oncotic pressure. N Engl J Med 1988 318(4) 253. 

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