Biomedical subjects
Publications and source records attributed to M M Avram.
Ligandinuria is a useful index of acute tubular injury. Ligandin probably enters the urine at the time of initial necrosis and should be looked for soon after the toxic or ischemic event. Periodic examination of perfusates for this substance might yield useful information about techniques for storage of cadaver kidneys.
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Pulmonary nocardiosis occurred in a renal homotransplant patient and was diagnosed by persistently positive blood cultures. Infection developed at a time when efforts were being made with moderate dosages of immunosuppressive drugs to prevent rejection of the transplant. The subsequent nocardemia lasted for one week. The remaining kidney function was preserved, and the patient had a very favorable outcome because of early diagnosis and prompt treatment with sulfisoxazole.
In a retrospective analysis to determine whether secondary hyperparathyroidism in uremia has a role in uremic peripheral neuropathy, we simultaneously measured motor-nerve conduction velocity and serum parathormone level in 42 uremic patients. We compared age-matched groups of nondiabetic uremic patients, divided into three groups according to serum parathyroid hormone, for degree of impairment of motor-nerve conduction velocity, and 12 diabetic patients with uremia. The group with highest levels had a significantly (P less than 0.01) lower conduction velocity (25.3 +/- 4.9 m per second) than the group with normal or slightly elevated parathyroid hormone, who had only mild depression of nerve conduction (45.1 +/- 1.3 m per second). Mean serum calcium and creatinine were not significantly different between groups. Nerve conduction velocity was similarly depressed in 17 patients on additional dialysis studied prospectively and divided into groups according to parathyroid hormone levels. These results suggest a relation between high parathormone levels and uremic neuropathy and implicate parathyroid hormone as a uremic toxin.
Significant hypertriglyceridemia, the most common lipid abnormality in renal failure, first occurs when the creatinine clearance falls to 50 ml/min. The prevalence of hypertriglyceridemia continues to rise as creatinine clearance falls further with the highest rate developing at a creatinine clearance less than 10 ml/min. Hypertriglyceridemia is correlated with plasma glucagon levels but not growth hormone or insulin. Plasma cholesterol values remain normal in the face of deteriorating renal function and show no correlation with any of the hormones measured. Although all three hormones became elevated as renal function diminished, none were directly correlated with glomerular filtration rate. There was a distinct decrease in the prevalence of hyperlipidemia after 5 years of maintenance hemodialysis therapy. Plasma growth hormone and glucagon through an effect on plasma triglyceride and plasma insulin by effecting plasma cholesterol may play a role in this decline of hyperlipidemia with duration of hemodialysis.
In a randomized, double-blind multicenter trial, 284 patients and 282 staff members of renal dialysis units who lacked detectable hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) were randomly assigned to receive two 3-ml injections of immune serum globulin with high, intermediate, or low titers of anti-HBs four months apart. The incidence of infection with hepatitis B and of development of HBsAg was significantly lower in both patients and staff who received the high-titer material than in subjects who received the low-titer preparation eight but not 12 months after randomization (P less than 0.01 for patients and P less than 0.04 for staff, low-titer vs. high-titer at eight months). The high-titer hepatitis B immune globulin preparation did not appear to affect the severity of the cases of hepatitis that did occur, the proportion of subjects who developed persistent antigenemia, or the magnitude or timing of primary anti-HBs responses.
In order to detect metabolic aberrations which could account for the poor therapeutic response of the diabetic to dialysis, a comparative study of nondiabetic and diabetic uremia patients treated with hemodialysis was undertaken. Plasma renin activity and levels of growth hormone, glucose and insulin were investigated.
A retrospective analysis of the mortality and morbidity experience with maintenance hemodialysis as treatment for uremia in systemic disease was conducted. Between 1962 and 1977, a total of 141 patients with chronic glomerulonephritis and 120 patients with uremia caused by renal involvement in systemic disease were treated. With the exception of two patients with bacterial endocarditis who died early in their course, survival in the diagnostic categories studied ranged from acceptable, in diabetics with 29 of 53 (54.7%) patients living, to excellent in tuberculosis where all of six patients are alive and well. Overall, it is concluded that uremia in systemic disease is responsive to maintenace hemodialysis.
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Forty-seven patients with chronic renal failure presenting with a loss of vascular access precluding hemodialysis were subjected to 105 surgical procedures to establish and to maintain an arteriovenous fistulae. 67 bovine heterografts were implanted over a 30 month period and observed for 6 or more months. Fifteen, or 32% of the patients, died during the study period. Eleven patients died with a functional fistula. Twenty fistulae continued to function at the end of 36 months constituting a 46.3% graft survival rate. Hemodialysis was continued in 11 of 12 patients via a P.T.F.E. Goretex graft or via a matured Brescia Fistula. The remaining patient experienced graft failure at the end of the study period. Graft thrombosis was observed in 31 of 67 grafts placed (46%). Successful thrombectomy was achieved in 52%. Fourteen grafts developed frank aneurysms with overt rupture in 8. All patients with aneurysms were negro. Six of 8 patients with aneurysm presented with severe hypertension. Thirteen aneurysms were resected without loss of life or limb. The use of bovine grafts in hypertensive negro patients is believed to be contraindicated.
The prevalence of pancreatic disease was determined in 21 autopsied uremic patients who had died during the course of maintenance hemodialysis, as compared with 60 autopsied patients without kidney or pancreatic disease. Histologic criteria of pancreatic disease included. (1) duct ectasia; (2) periductal fibrosis; (3) ductular proliferation; (4) acinar ductalar metaplasia, and (5) interstitial inflammation or fibrosis. Significant pancreatic disease was present in 56% of the uremic patients and only 11.8% of the controls (p less than 0.01). Two uremic patients had abscesses in the tail of the pancreas. The clinical significance of the high prevalence of pancreatic pathologic alterations in uremia remains to be assessed.
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Our study indicates that in renal failure elevated plasma triglyceride can first be detected when the GFR falls to 50 ml/min. Hypertriglyceridemia is the commonest abnormality found and increases further when the GFR falls below 10 ml/min. Plasma cholesterol levels remain normal even at low levels of renal function. Although plasma growth hormone, glucagon, and insulin levels become elevated when renal function diminishes, there is no definite correlation of their levels and GFR. A decreased incidence of hyperlipidemia observed in patients sustained by maintenance hemodialysis for over 5 yrs may in part be due to the triglyceride lowering effect of growth hormone and glucagon and/or the cholesterol lowering effect of insulin.
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By studying the metabolic values of a nondiabetic and diabetic uremic population we demonstrated the following: 1. Insulin is higher in diabetic than nondiabetic uremic patients. A slight arteriovenous difference across the dialyzer membrane suggests that insulin is dialyzable in small amounts in man. 2. C-peptides are highest in nondiabetics, lower in maturity onset diabetics, and lowest in juvenile diabetics. 3. Growth hormone is higher in diabetics than nondiabetics, decreased in both groups during hemodialysis, and returns to pre-dialysis levels 2 hrs after the completion of dialysis treatment. 4. Plasma triglycerides are elevated in both popualtions during the fasting state anddrop during hemodialysis, rising slowly towards the end of hemodialysis. 5. The majority of diabetics on hemodialysis have low renin levels and do not respond to volume reduction. In the high renin diabetics and high and low renin nondiabetics the plasma renin levels rise in response to volume reduction during hemodialysis. Renin is not dialyzable in man. 6. Thyroid function tests show that diabetic and nondiabetic patients have measurements in the low normal range. Our results reveal significant information concerning metabolic changes which take place in diabetic and nondiabetic uremic patients on hemodialysis and helps to characterize these populations. This report may have implications in better understanding the nature of the problems encountered in these populations and in their management (Table III).