Cyril H. Barton

Hypomagnesemia and renal magnesium wasting in renal transplant recipients receiving cyclosporine

Following the adoption and use of cyclosporine as the drug of choice in the management of renal allograft recipients, several cases of symptomatic hypomagnesemia were noted. These observations prompted the current prospective study of serum concentration and urinary excretion of magnesium in 27 renal transplant recipients treated with cyclosporine and prednisone. Relevant laboratory measurements were obtained shortly before and regularly after transplantation. The results were compared with those obtained in a group of 17 allograft recipients treated with azathioprine and prednisone. The cyclosporine-treated patients showed a significant reduction in the serum magnesium concentration and an inappropriately increased urinary excretion and fractional excretion of magnesium, suggesting renal magnesium wasting. The observed hypomagnesemia required magnesium supplementation in nearly all cyclosporine-treated patients. In contrast, azathioprine-treated patients showed normal serum magnesium concentrations and required no magnesium supplementation. In conclusion, administration of cyclosporine in renal allograft recipients appears to be commonly associated with renal magnesium wasting and hypomagnesemia. Therefore, it is recommended that serum levels of magnesium be monitored regularly in renal allograft recipients receiving cyclosporine and that magnesium supplementation be employed as needed to avoid magnesium depletion.

Renal magnesium wasting associated with amphotericin B therapy

The effect of amphotericin B on magnesium metabolism was studied in 10 patients (aged 30 to 68 years) with systemic fungal infections. Renal magnesium wasting resulting in mild to moderate hypomagnesemia was demonstrated by the second week of therapy following relatively small cumulative dosages of amphotericin B (208 +/- 40 mg). The lowest serum levels and largest fractional excretions of magnesium were observed by the fourth week of therapy after cumulative dosages of 510 +/- 118 mg. A plateauing of the renal magnesium wasting is suggested, as there were no further increases or reductions in fractional magnesium excretion and serum magnesium level, respectively, despite continued amphotericin B administration. Reversibility of the magnesium wasting is indicated by data in three of the patients approximately one year following discontinuation of amphotericin B therapy, in whom the serum magnesium level and fractional magnesium excretion had returned to pretreatment baseline values. Although the available data do not allow precise localization of this defect, increased urinary excretion of magnesium despite its reduced filtered load suggests a tubular defect in magnesium reabsorption. Therefore, routine monitoring of the serum magnesium level during treatment with amphotericin B is recommended.

Prediction of creatinine clearance from serum creatinine in spinal cord injury patients.

Measured endogenous creatinine clearance (Ccr) was compared with the predicted Ccr in 22 paraplegic, 36 tetraplegie and n ambulatory male individuals as well as 11 ambulatory females all of whom had normal renal function. While the predicted and measured values closely matched in the ambulatory patients the predicted values in the spinal cord injured patients consistently exceeded the measured values. It thus appears that the original Cockcroft and Gault formula;when applied to SCI patients can be misleading. Modification of the original formula using a correction factor of 0.8 in paraplegics and 0.6 in tetraplegics was found to allow prediction of Ccr from age, sex, body weight, and serum creatinine in these patients with reasonable accuracy.

Thyroid function studies in the nephrotic syndrome.

Total serum and urinary thyroxine (T4), triiodothyronine (T3), and thyroxine-binding globulin (TBG) as well as serum free T4, thyroid-stimulating hormone (TSH), and T3 resin uptake (T3RU) were measured in seven patients with the nephrotic syndrome. The nephrotic syndrome was defined by proteinuria exceeding 3 g/24 h. All patients were clinically euthyroid. Most values for total serum T4, free T4, T3, T3RU, TBG, and TSH were within normal limits. However, the mean serum T3 and TBG values were significantly lower in patients compared with the control group. The values (mean +/- 2 SD) for urinary T4 were 24.3 +/- 20.3 in the patient group and 1.5 +/- 0.7 microgram/24 h in the control group. Urinary T3 values for patients and the control group were 2100 +/- 856 and 848 +/- 253 ng/24 h respectively. Urinary TBG was 2.1 +/- 1.8 mg/24 h in the patients and undetectable in the control group. There was no correlation between daily urinary T3 and T4 and urinary TBG. There was a weak correlation between daily urinary protein excretion and urinary T4 (r = 0.5).

Plasma concentration and urinary excretion of erythropoietin in adult nephrotic syndrome

Abstract purpose: Nephrotic syndrome (NS) is associated with a significant alteration of protein metabolism. While lowering the plasma concentrations of certain proteins, the disease often raises the level of certain other proteins. The current study was undertaken to determine the effect of NS on erythropoietin (EPO) metabolism. patients and methods: We measured the EPO concentration in plasma and urine of 26 patients with NS by an immunologic assay using a rabbit antiserum against recombinant human EPO. The results were compared with those obtained in a group of 12 normal control subjects. results: Despite a significant reduction in the hemoglobin concentration in the NS group compared with the control group (125 ± 25 g/L versus 148 ± 11 g/L, p conclusion: We conclude that plasma EPO is inappropriately low in patients with NS. This is due, at least in part, to the urinary/renal losses of this protein and can potentially contribute to anemia in NS patients or compound the problem in those with concurrent renal insufficiency and diminished EPO production.

Bicarbonate-buffered peritoneal dialysis: An effective adjunct in the treatment of lactic acidosis

Severe lactic acidosis is associated with poor prognosis. Usually, the patient is treated with massive amounts of intravenous sodium bicarbonate, which in itself carries many undesirable consequences such as fluid overload and hypernatremia. We have successfully used peritoneal dialysis with a bicarbonate-buffered dialysate in the management of severe acidosis. Bicarbonate-buffered peritoneal dialysis provided an unlimited supply of physiologic buffer over a prolonged period without causing hypervolemia or hypernatremia. Furthermore, significant amounts of lactate were removed by dialysis. We, therefore, recommend the use of bicarbonate-buffered peritoneal dialysis as an adjunct in the treatment of severe lactic acidosis.

Effects of Long-Term Testosterone Administration on Pituitary-Testicular Axis in End-Stage Renal Failure

The endocrine effects of long-term testosterone administration were studied in 6 end-stage renal failure patients. During a 3-month control period where no androgens were administered the mean plasma testosterone level (7.3 nmol/l) was depressed while mean plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were elevated at 41.2 mU/ml, 105.5 mU/ml, and 63 ng/ml, respectively. These values were repeated during a 6-month study period where each subject was administered testosterone enanthate (400 mg) intramuscularly once a week. Plasma testosterone levels markedly increased in all subjects with a mean elevation of 72.4 nmol/l, while reductions were observed in FSH and LH levels with values of 2.7 and 16.3 mU/ml, respectively. When compared with control period values, these changes were statistically significant (p less than 0.05). Although the mean plasma PRL level of 49.0 ng/ml was reduced when compared with the control period values, this reduction was not statistically significant. Our control period findings of low plasma testosterone levels coupled with high plasma LH and FSH are consistent with Leydig cell dysfunction. The significant reductions in plasma FSH and LH noted during the study period indicate a negative feedback effect produced by the pharmacologic doses of testosterone. Long-term testosterone administration, however, did not significantly affect the elevated mean PRL levels observed in these subjects.

Renal pathology in end-stage renal disease associated with Paraplegia

In the present study we report the renal pathological findings from autopsy material along with relevant clinical data on 21 spinal cord injury patients with end-stage renal disease (SCI-ESRD) treated with maintenance haemodialysis. These data are compared with the relevant clinical and post-mortem findings on 43 ambulatory dialysis patients who expired during the same time period.The SCI-ESRD patients exhibited markedly different clinical and renal histo-pathological data when compared to the ambulatory—ESRD group. Chronic pyelonephritis and amyloidosis dominated the findings and were the major causes of renal insufficiency. Acute pyelonephritis, papillary necrosis, calculous disease, pyonephrosis and perinephric abscess formation were also more frequently present in the SCI-ESRD patients. Hypertension and nephrosclerosis, which were common findings in the ambulatory—ESRD patients were comparatively rare in the SCI-ESRD patients. In addition, the incidence of acquired cystic disease (ACD) was considerably less in the SCI-ESRD group. Although the reasons for these findings are not entirely clear several possible explanations are given.Infection with gram negative sepsis was the predominant cause of death in the SCI-ESRD patients, while death secondary to cardiovascular disease predominated in the ambulatory-ESRD group. Furthermore, the urinary tract and infected decubitus ulcers were determined to be the major source for sepsis in the SCI patients. From these findings it would follow that more effective prevention and control of these infections would result in not only a lower incidence of renal failure but also a substantially reduced morbidity and mortality in chronic SCI.

Femoral Neuropathy: a Complication of Renal Transplantation

Femoral neuropathy occurred in 3 patients after renal transplantation. This appeared to be due to compression of the femoral nerve by medial and inferior blades of the self-retaining retractors used during renal transplantation surgery. The condition resulted in weakness of quadriceps muscles, loss of patellar reflex, and sensory deficit on the side of transplantation surgery. The rate of recovery from neurologic deficits appeared to depend on the level of transplant renal function.

Phencyclidine intoxication: clinical experience in 27 cases confirmed by urine assay

Medical records of 107 consecutive patients with a diagnosis of phencyclidine (PCP) intoxication were reviewed and in 27 of these the diagnosis was confirmed by positive urine assay. In the 27 confirmed cases, the most common abnormalities present on physical examination were mental/behavioral (89%) and nystagmus (85%). Elevations in blood pressure, temperature, and heart rate that were statistically significant when compared with an age-matched control group also were noted. Review of available medical records disclosed that 13 of these patients had been evaluated previously at our institution for PCP intoxication. Toxicological screening tests including blood alcohol level, hypnotic screen, and urine test for alkaloids, were performed on 11 patients and found positive in four. The most common serious medical complication requiring hospitalization was rhabdomyolysis which occurred on three patients, two of whom developed acute renal failure. This complication may occur more frequently than previously recognized and should be excluded in patients with PCP intoxication.