In acute renal failure

There is no evidence that supports drug therapy in hastening the recovery period, decreasing length of hospitalization, or improving survival in acute renal failure. 

Loop diuretics are the diuretics of choice for the management of volume overload in acute renal failure. 

Mehta RL, Pascual MT, Soroko S, et al. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA 2002 288 2547-2553. 

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. 

Uremia results in increased permeability of the blood-brain barrier to sucrose and insulin K+ transport is enhanced whereas Na+ transport is impaired. There is an increase in brain osmolarity in acute renal failure due to the increase in urea concentrations. However, in contrast to acute renal failure, the increase in osmolarity in chronic renal failure results from the presence of idiogenic osmoles in addition to urea. CBF is increased in uremic patients but CMR02 and CMR are decreased. In the brains of rats with acute renal failure, ATP, phosphocreatine and glucose are increased whereas AMP, ADP and lactate are decreased, most probably as a result of decreased energy demands. 

Parathyroid hormone (PTH) produces CNS effects in normal subjects and neuropsychiatric symptoms are frequently encountered in patients with primary hyperparathyroidism, where EEG changes resemble those described in acute renal failure. Circulating PTH is not removed by hemodialysis. In uremic patients both EEG changes and neuropsychiatric symptoms are improved by either parathyroidectomy or medical suppression of PTH. The mechanism whereby PTH causes disturbances of CNS function is not well understood, but it has been suggested that increased PTH might facilitate the entry of Ca2+ into the cell resulting in cell death. 

Renal dysfunctions can be diagnosed by different methods, depending on the severity of the condition. Examination of urine, which is produced by the kidneys, provides an important indication of renal insufficiency. The urine output, color, odor, acidity, specific gravity, and constituents are important prognostic factors of kidney status. However, in critically ill patients and in acute renal failures induced by several diseases including multiple organ failures and diabetes, urine examination may be impractical and redundant. Such patients require reliable and simple methods to diagnose the onset of renal failure. 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

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