Roentgenographic manifestations of maxillomandibular renal osteodystrophy.

We examined 30 male chronic hemodialysis patients and 18 male controls without known bone or renal disease to determine the utility of maxillomandibular, non-dominant hand, shoulder and pelvis films in the evaluation of renal osteodystrophy. We used panoramic periapical radiographs to examine the maxilla and mandible and sensitive rapid processing films for the hand, shoulder and pelvis. Films were evaluated by experienced personnel without knowledge of the patients. There were significant differences between patients and controls in creatinine, urea nitrogen, total protein, albumin, alkaline phosphatase and phosphorus. Twenty-three patients had abnormal hand radiographs and 22 patients had abnormal jaw radiographs (p less than 0.05 vs. controls). Four patients had changes in the hands, but not in the jaw; 4 had opposite findings. Changes in the jaw tended to be more severe than in the hands in those with involvement of both. We concluded that dental and hand radiography are good screening techniques for evaluating bone disease. They may be useful in evaluating treatment for renal osteodystrophy.

Primary glomerulonephritis complicating diabetic nephropathy: report of seven cases and review of the literature.

Glomerulonephritis has been recognized as a rare complication of diabetes mellitus. The clinical, pathologic, and laboratory findings for 18 diabetic patients were reviewed. Eight of these patients (44 per cent) were found to have primary glomerulonephritis in addition to diabetic nephropathy. Although this series may not represent the true incidence of complicating glomerulonephritis in diabetes, it is probable that the incidence of this condition has been underestimated. An additional 26 previously reported cases are reviewed.

The renin-angiotensin system in aminoglycoside-induced acute renal failure.

To examine the role of the renin-angiotensin system in aminoglycoside-induced acute renal failure, we gave rats gentamicin (80 mg/kg/day), gentamicin + captopril (an angiotensin-converting enzyme inhibitor), captopril alone or saline sham injections, for 10 days. Blood pressure, sodium excretion, urine osmolality and creatinine clearance were measured four times during treatment. Plasma renin activity, angiotensin I-converting enzyme and renal histology were determined at sacrifice. Although angiotensin I-converting enzyme activity was markedly suppressed by captopril treatment, the addition of captopril failed to consistently influence blood pressure or urine osmolality. In addition, it did not promote natriuresis in the face of gentamicin toxicity. Creatinine clearance decreased progressively in groups receiving gentamicin and was lowest (P less than .05) in the groups receiving gentamicin + captopril. Captopril did not prevent the development of tubular epithelial nor glomerular endothelial changes associated with gentamicin toxicity. In a separate experiment rats received captopril for 3 days prior, before receiving the gentamicin + captopril regimen for 10 days. Captopril pretreatment did not influence the results. This study does not support a pivotal role for the renin-angiotensin system in the production of the decreased glomerular filtration rate observed in nephrotoxic acute renal failure induced by gentamicin in rats.

Moxalactam pharmacokinetics during hemodialysis.

To establish dosage recommendations, moxalactam elimination kinetics were studied in six anephric patients during hemodialysis and in four anephric patients during the interdialytic period. After a single 1-g intravenous bolus injection, moxalactam elimination half-life was 18.0 plus or minus 0.6 h with a volume of distribution of 20.2 plus or minus 3.6 liters and a plasma clearance of 12.8 plus or minus 2.0 ml/min in four nondialyzed patients. Moxalactam elimination half-life was decreased to 2.7 plus or minus 0.2 h during hemodialysis in six patients. After 4 h, 48.5% of the dose was recovered in the dialysate. The maintenance dose of moxalactam should be decreased to 15% of a normal dose in patients with creatinine clearances less than 10 ml/min, and 50% of a loading dose should be given after hemodialysis.

Mezlocillin pharmacokinetics in renal impairment.

Mezlocillin kinetics was examined in 28 adult subjects with varying renal function. Mezlocillin 3 gm, was infused over 30 min. Mean peak plasma concentrations ranged from 204 to 253 mg/I. When the area under the curve (AUC) was plotted against creatinine clearance (CCr), the relationship found was expressed by the equation AUC = 656e(-0.01)(CCr). From this relationship a dosage nonogram was derived describing a power function with the following equaton: Dose fraction = 1.32--e(-0.01)(CCr). Therapeutic guidelines are suggested.

Hypoxanthine-arabinoside pharmacokinetics after adenine arabinoside administration to a patient with renal failure.

Hypoxanthine arabinoside pharmacokinetics were measured during an adenine arabinoside continuous intravenous infusion and during hemodialysis in a patient with renal failure. Therapeutic guidelines for adenine arabinoside in renal failure are provided based on an elimination half-life of 4.7 h and a plasma clearance of 87.9 ml/min for the hypoxanthine metabolite.

Prevailing patterns and predictor variables in patients with acute tubular necrosis.

The courses of 276 acute tubular necrosis patients referred for dialysis were reviewed in search for prognostic indicators. Sixty-three percent survived. Of 28 possible predictor variables, a posttoxic cause and nonoliguria were favorable, whereas myocardial infarction and peritonitis affected survival unfavorably. Total pareneral nutrition influenced survival favorably only in those with multiple complications or peritonitis. No single variable or combination predicted a lethal outcome. Since survivors were frequently restored to complete health, we advocate an aggressive therapeutic approach even in the face of multiple complications.

Iatrogenic factors in acute renal failure: can vigilance equal avoidance?

Physicians can aid substantially in reducing morbidity and mortality from acute renal failure by exercising particular care when using potentially nephrotoxic procedures or agents, by identifying patients at high risk before undertaking elective surgical procedures, and by acting promptly to correct predisposing conditions.

Intra-abdominal infection and acute renal failure.

The course of 76 consecutive patients with acute renal failure and severe intra-abdominal infection was reviewed to identify the microorganisms responsible, the factor precipitating reoperation, and prognostic indicators. Peritonitis occurred in 75 patients, 48 of whom had abscesses. Twenty-four patients (32%) survived. Anaerobes and fungi were commonly grown from blood. Gram-negative aerobic blood isolates were associated with the highest mortality. Leukocytosis, physical findings, and fever were factors that prompted reexploration whereas diagnostic procedures played an ancillary role. The finding of specifically correctable conditions at reoperation improved survival (P less than .05). Myocardial infarction and disseminated intravascular coagulation affected survival unfavorably whereas hyperalimentation had a favorable influence (P less than .05). Aggressive medical, nutritional, and surgical management results in improved survival rates in these patients.

Factors affecting prognosis in acute renal failure following cardiac operations.

Twenty-five patients with acute renal failure following cardiac operations using cardiopulmonary bypass were analyzed retrospectively to identify predictors of survival or mortality. Age and the number of postoperative medical complications served as predictors of mortality, p less than 0.05. A low survival rate occurred if the patient was in the seventh decade of life. Nonsurvivors had a higher number of postoperative medical complications. However, only cardiac failure and bacteremia occurred in a significantly greater proportion of those patients who died, p less than 0.05. The presence of non-oliguric renal failure was associated with a 100 per cent survival rate, p less than 0.05. The mortality of these 25 patients was 28 per cent, which is lower than that generally reported. Although an extremely serious postoperative complication, acute renal failure following cardiac operations does not imply a hopeless prognosis. A vigorous therapeutic effort is warranted.

The effect of concomitant mercuric chloride and gentamicin on kidney function and structure in the rat.

In order to define the possible effects of gentamicin on the course of experimental acute renal failure, the interaction between gentamicin and mercuric chloride was studied in rats. Acute renal failure was induced with 1 mg. of HgCl2 per kilogram intravenously. When given alone, HgCl2 produced a uniform, reproducible, nonoliguric, acute renal failure with a low mortality rate. Animals receiving gentamicin over the course of HgCl2-induced acute renal failure, in doses sufficient to produce a 1 hour postinjection serum concentration of 10 mug/ml., recovered glomerular filtration in a fashion similar to animals receiving only HgCl2(p greater than 0.05). Animals that recovered from HgCl2-induced acute renal failure were given 10 mg./Kg. of gentamicin every 4 hours for 15 days and developed proteinuria and decline in urine osmolality to the same degree as animals given gentamicin alone, but failed to develop azotemia. Nevertheless, morphological changes associated with gentamicin nephrotoxicity were found which were similar in severity to those seen with gentamicin alone. Animals pretreated with 10 mg./Kg. of gentamicin every 4 hours for 7 days were then given HgCl2. Acute renal failure in these animals was more severe than in animals receiving HgCl2 alone, as manifest by a greater degree of azotemia and death (p less than 0.05). The data indicate that in the rat the concomitant administration of gentamicin did not interfere with recovery from HgCl2-induced renal failure. Rats recovering from HgCl2-induced acute renal failure were resistant to a depression in glomerular filtration when given gentamicin. The prior administration of gentamicin enhanced the nephrotoxicity of HgCl2.

Gentamicin gradient patterns and morphological changes in human kidneys.

The gentamicin gradient pattern was studied in ten autopsied patients who expired during gentamicin therapy. Although two of the patients had acute renal failure, none was thought to have gentamicin-related nephrotoxicity. Gentamicin concentrations in cortex significantly exceeded those in medulla or serum (p less than 0.05 and p less than 0.01, respectively). No correlation was found between the cortical concentrations and the total drug dose, the time interval between the last injection and death, or the plasma creatinine concentrations in this heterogeneous group of patients. In addition, two specimens were suitable for electron microscopy which displayed cytosegrosomes and myeloid bodies previously noted in experimental animals. We conclude that gentamicin forms a gradient pattern in human kidney similar to that described in experimental animals. Furthermore, it evokes similar morphological changes.

Comparative nephrotoxicities of netilmicin and gentamicin in rats.

The relative nephrotoxicities of netilmicin (Sch 20569) and gentamicin were compared in rats at doses of 30, 60, 90, and 120 mg/kg per day for 15 days. Both drugs caused proteinuria and a decrease in urine osmolality; however, netilmicin produced significantly less changes at all doses than gentamicin. Whereas gentamicin resulted in a decline in creatinine clearance at all doses, netilmicin failed to cause a decline in creatinine clearance. Renal-cortical concentrations of antibiotic at sacrifice were similar in animals receiving either drug. Light-microscopic changes were less severe with netilmicin than gentamicin. Cytosegresomes with myeloid bodies were identified electron microscopically in the kidneys of animals receiving either netilmicin or gentamicin at all doses. Electron-microscopic manifestations were similar. The data indicate that in the rat, netilmicin is distinctly less nephrotoxic than gentamicin.

Hyperlactatemia and hemolysis in G6PD deficiency after nitrofurantoin ingestion.

A 69-year-old man with glucose-6-phosphate dehydrogenase deficiency was treated with nitrofurantoin for pyuria. Four days later he presented with metabolic acidosis due to excess lactic acid, a decline in curculating hemoglobin, reticulocytosis, elevated serum transaminase levels, and hyperbilirubinemia. The drug was withdrawn and the hyperlactatemia subsided in three days without specific treatment. In vitro, nitrofurantoin is capable of stimulating erythrocyte glucose utilization aand lactate production, and inhibiting the generation of reduced glutathione. In vivo, this drug is capable of producing hemolysis in susceptible subjects and hepatocellular injury. The temporal proximity of drug ingestion and hemolysis, increased glucose utilization, lactate excess, and hepatic insufficiency suggests that nitrofurantoin may have been responisble for precipitating the clinical and chemical abnormalities observed.

Intussusception in chronic renal failure.

Spontaneous intussusception in adults is rare. Recently, we managed two patients with chronic uremia in whom intussusception developed. Histologic examination of the resected segments showed intestinal intramural hemorrhage. We postulate that the coagulopathy associated with uremia may allow for intestinal intramural hemorrhage, thus forming a nidus from which intussusception may be initiated.

The influence of selective thrombocytopenia on nephrotoxic nephritis.

Anticoagulation with agents that interfere with fibrin formation inhibit the development of the autologous phase of nephrotoxic nephritis (NTN). Platelet participation in the nephritic process has been suggested but not proved, therefore, the influence of selective thrombocytopenia on the autologous phase in rabbits was evaluated. NTN was produced with goat antirabbit glomerular basement membrane antiserum. Thrombocytopenia was induced with goat antirabbit platelet antiserum 24 hours prior to the onset of nephritis. Platelet accumulation within the nephritic kidney was quantitated using chromium labeled platelets. Thrombocytopenia has no inhibitory effect on the development of the autologous phase of NTN in rabbits. There was no platelet accumulation within the nephritic kidney in the presence of thrombocytopenia. Pharmacologic inhibition of platelet aggregation may be of no benefit in glomerulonephritis produced by a fixed antigen-antibody reaction within the glomerular capillary wall.