Thomas G. Murray

Risk factors and outcome of hospital-acquired acute renal failure: Clinical epidemiologic study:

In order to evaluate potential risk factors for the development of hospital-acquired acute renal failure, a case-control study was performed, comparing patients with hospital-acquired acute renal failure with control subjects matched on age, sex, hospital, service of admission, and baseline renal function. The same patients were then reanalyzed utilizing a cohort study design to investigate outcomes from this syndrome. The following elevated odds ratios (95 percent confidence interval) were found while simultaneously adjusting for possible confounding variables using logistic regression: volume depletion, 9.4 (2.1 to 42.8); aminoglycoside use, 5.6 (1.3 to 23.7); congestive heart failure 9.0 (2.1 to 38.9); radiocontrast exposure, 4.9 (1.2 to 19.7); and septic shock, approached infinity, p less than 0.0001. The effect of volume depletion was markedly accentuated in those with diabetes (odds ratio = 1.9) (p less than 0.05). The risk from aminoglycoside use markedly increased with increasing age (p less than 0.002). Finally, the development of hospital-acquired acute renal failure was associated with a marked increase in the risk of dying--the relative risk (95 percent confidence interval) was 6.2 (2.6 to 14.9)--and a marked increase in length of stay, from a median of 13 days in control subjects to a median of 23 days in case subjects (p = 0.005). In conclusion, hospital-acquired acute renal failure is a serious illness. Attempts to prevent it should focus on proved risk factors.

Spontaneous increase in erythropoietin and hematocrit value associated with transient liver enzyme abnormalities in an anephric patient undergoing hemodialysis

An anephric patient undergoing hemodialysis experienced an increase in his hematocrit value (19 +/- 1 per cent to 31 +/- 1 per cent) as a result of increased erythropoiesis (reticulocyte count 1.8 per cent to 7.4 per cent). This increase occurred in concert with an elevation of the patients liver enzyme levels and was maintained for four months. The hematocrit value returned to its base line only after the liver function tests showed improvement. During the period when the hematocrit value was increasing, the circulating level of erythropoietin was elavated to 71.0 mU/ml--a level higher than that seen in either anephric or nephric patients undergoing dialysis. When the hematocrit value and liver enzyme levels had returned to their base line values, the erythropoietin level was 4.3 mU/ml--a level in the range seen in anephric patients undergoing dialysis. The observations in this patient suggest that under certain circumstances, the liver can produce erythropoietin in the anephric patient; and, more importantly, that the bone marrow of at least some uremic patients is capable of responding to the endogenous erythropoietin.

Renal disease, age, and oxazepam kinetics

Effects of renal insufficiency and age on oxazepam kinetics were assessed in 13 normal subjects (21 to 72 yr old), four patients with renal insufficiency, and eight patients on hemodialysis. Normal intact oxazepam results were: mean elimination half‐life (t½), 10 hr; area under the curve (AUC), 6.0 μg·hr/ml; unbound oxazepam fraction (fup), 3.2%; maximum concentration of unbound oxazepam (Cmax, u), 16 ng/ml; and intrinsic (unbound drug) clearance (Clint), 2.9 llhrlkg. Less than 1% of the dose was excreted intact in urine. Age differences had no influence on results. In renal insufficiency patients, t½ was prolonged to 25 hr, fup increased to 7%, and Cmax, u and Clint were unchanged. Volume of distribution of unbound oxazepam (Vu) increased, thereby prolonging t½. In dialysis patients, t½ was prolonged to 33 hr, fup increased to 6.2%, and Cmax, u and Clint again were unchanged. Oxazepam was undialyzable; since unbound oxazepam disposition kinetics are not altered, no dosage adjustment for patients is necessary.

Analgesic-associated nephropathy. An important cause of renal disease in the United States?

Since 1953, when Spuhler and Zollinger reported from Switzerland the association of chronic interstitial nephritis with the ingestion of certain analgesic drugs,1 analgesic-associated nephropathy h...

Multiple-Dose Kinetics and Dialyzability of Oxazepam in Renal Insufficiency

7 patients with chronic renal insufficiency (4 of whom were on maintenance hemodialysis) and 6 healthy controls received single 15-mg oral doses of oxazepam for 7 consecutive days. Multiple venous blo

Ticrynafen in anephric patients: Effects on uric acid and pharmacokinetics

Ticrynafen was given to 6 anephric patients undergoing maintenance hemodialysis. Ticrynafen was given daily for the 3 days between hemodialyses. Ticrynafen had no effect on the interdialysis rise in serum uric acid levels. Ticrynafen did not accumulate in serum, but levels of metabolites continued to rise over the 3 days. Hemodialysis (5 hr) reduced levels of ticrynafen by 38% but had less effect on metabolite levels. There was no effect on serum cholesterol or triglycerides.

Analgesic-Associated Nephropathy-Reply

—I agree with Dr Regester that analgesic nephropathy may be underrepresented in the population requiring dialysis (relating to the population with chronic renal disease) because of an increased mortality in patients who take large doses of analgesics. Neither the data of Nanra nor those outlined by Dr Regester include appropriate controls; therefore it is difficult at this time to assess the effect of increased mortality on the preponderance of analgesic nephropathy in the population requiring dialysis. This problem deserves further study. As Dr Regester points out, analgesic nephropathy is an important public health problem. It is a problem that every physician should be aware of, since it can be prevented.