Unilateral nephrectomy: effect on survival in NZB/NZW mice.

Male F1 New Zealand Black X New Zealand White mice, which spontaneously develop immune complex renal disease, underwent unilateral nephrectomy at 3 months of age and were compared with sham-operated controls. At 12 months of age only 24% of mice with a single kidney were alive, while 85% of sham-operated controls survived to the same age. Unilaterally nephrectomized mice had more severe renal histologic changes, as shown by light and immunofluorescence microscopy.

Adverse impact of hypertension on diabetic recipients of transplanted kidneys.

The effect of hypertension on patient and allograft survival in 60 diabetic recipients of transplanted kidneys was assessed by retrospective chart analysis. Hypertension was present in 81% of recipients. Of eight of these patients who became normotensive after transplantation, all had functioning allografts and one died. By contrast, persistent hypertension after transplantation was associated with a higher mortality rate (25 of 54, 48%) and loss of kidney graft function (19 of 54, 35%). At a mean of 21 months after transplantation, living hypertensive diabetic recipients had worse renal function (mean serum creatinine of 3.1 mg/dl) than did nonhypertensive recipients (mean serum creatinine of 1.6 mg/dl). It is concluded that hypertension is a significant risk factor for diabetic patients and kidneys after transplantation.

Reduction in hyperlipidemia in hemodialysis patients treated with charcoal and oxidized starch (oxystarch).

A combination of two oral sorbents, oxystarch 35 g/day plus activated charcoal 35 g/day, was administered to four patients undergoing maintenance hemodialysis during thrice weekly and once weekly treatments. Patients tolerated oxystarch and charcoal without complaint during the 4-week period of thrice weekly hemodialyses. All four patients became clinically uremic when hemodialyses were reduced to once weekly and only two patients were able to continue through the end of this 4-week period. Mean serum cholesterol concentration diminished significantly from 200 mg/dl during control periods to 140 mg/dl after each 4-week trial of sorbents (P less than 0.02). Hypertriglyceridemia (range 181 to 543 mg/dl) was corrected in three of four patients with triglyceride values falling to less than 150 mg/dl during ingestion of sorbents (P less than 0.05). Activated charcoal, which is inert as an intestinal nitrogen binding sorbent, may lower serum lipids by direct intragut binding of lipids and bile acids. The potential use of oral charcoal in long-term therapy to reduce hyperlipidemia and prevent vascular accidents due to atherosclerosis requires additional study.

Immune competence of the streptozotocin-induced diabetic rat. I. Absent second-set skin allograft response.

A study was designed to assess the cellular immune competence of Lewis rats with streptozotocin-induced diabetes. First-set Fischer skin allografts were rejected in 10.9 days by nondiabetic Lewis recipients and in 12.0 days by diabetic Lewis recipients. Second-set skin allografts in the same strain combination, utilizing the same recipients, were rejected in 8.1 days by nondiabetic recipients and in 13.0 days by diabetic recipients (P less than 0.01), indicating an absence of second-set rejection in the streptozotocin-induced diabetic rat. Treatment with NPH insulin, 3 units daily, although only slightly corrective of hyperglycemia, reduced second-set graft rejection to 8.0 days. These findings offer evidence of impaired cellular immune responsiveness in the streptozotocin-induced diabetic rat. Insulin was shown to correct deficient allograft immunity.

Charcoal-induced lipid reduction in uremia.

Charcoal, in divided oral doses totalling 35 g/day, was administered to six patients with renal insufficiency (creatinine clearance of 0 to 45 ml/min). Significant (P less than 0.01) reductions in serum cholesterol and triglycerides were observed in the three most hyperlipidemic patients. Maximal decreases in charcoal responders, as compared with control values, were for cholesterol (43%, 23.4% and 40.4%) and for triglycerides (76%, 60.3% and 64.3%). None of the patients showed altered concentrations of BUN, serum creatinine, uric acid, or vitamin A. Because of its safety and the profundity of its hypolipidemic action, it is suggested that charcoal may find applicability in the management of azotemic diabetic and nephrotic hyperlipidemia.

The mineral and mechanical properties of bone in chronic experimental diabetes.

The long-term effects of experimentally induced diabetes on bone were studied in eight male Lewis rats, intravenously (i.v.) injected with 65 mg/kg of streptozocin (STZ) and maintained for 12 months. Eight untreated age-matched rats served as controls. In the STZ-treated rats, experimentally induced diabetes was documented by the presence of hyperglycemia at 24 h and at 3 and 12 months. Significantly less weight was gained and less growth occurred in the STZ-treated rats despite careful attention to feeding and hydration. Mineral alterations were detected in the bones of the animals with experimental diabetes. Decreased hydroxyapatite crystal perfection, decreased Ca/P of the ash, and decreased ash content in the tibial metaphyses with increased ash content in the tibial diaphyses, was noted relative to controls. Bone osteocalcin content was increased in the metaphyses of the STZ-treated rats. While absolute measures of stiffness, torsional strength and energy absorption were decreased in the bones of the STZ-treated animals, when torsional strength and stiffness were normalized for differences in both growth and geometry, the normalized stiffness values for the diabetic bones were increased. The results suggest that in experimental diabetes certain aspects of bone mineralization are adversely affected and lead to reduced strength-related properties. However, a compensatory increase in stiffness occurs. The reason for this increase, although not known, may be related to changes in bone crystal structure.

Diabetic nephropathy.

It is estimated that about 50 per cent of all patients with Type I diabetes mellitus develop uremia during the course of their disease. Glomerular microvasculopathy is the most serious and predictable threat to longevity. Following a discussion of this disorder, the author outlines a plan for overall management of each phase of kidney disease so that the patient, his or her family, and all members of the medical team can achieve an understanding of what can be anticipated and accomplished.

Islet of Langerhans allotransplantation in the rat.

Normoglycemia in rats allotransplanted with islets of Langerhans was studied. It was found that pretreatment with donor liver extract and pertussis followed by a short course of ALS treatment results in much better overall survival of functioning islets of Langerhans allotransplants than with other forms of immunosuppression tested.

Uremia in diabetics: the prognosis improves.

Chronic uremia caused by diabetic glomerulopathy accounts for about 25 percent of new patients treated by maintenance hemodialysis. At the onset of glucose intolerance, insulin dependent diabetics have larger than normal kidneys, with a markedly increased glomerular filtration rate. During the subsequent 15 to 20 years of insulin use, glomerulosclerosis progresses silently, until a clinically overt nephrotic syndrome becomes evident. Thereafter, the clinical manifestations of nephropathy appear rapidly with an exponential decline in creatinine clearance to less than 5 ml/min within one to five years. Putting together a life plan for a nephrotic and azotemic diabetic involves awareness, and coordinated management of not only renal but extrarenal vasculopathic complications of diabetes, especially proliferative retinopathy. Carefully made preparations for hemodialysis and/or renal transplantation with increase changes for at least a short-term favorable outcome, which can now be anticipated in a growing proportion of patients.

Effect of antithymocyte globulin on islet of Langerhans transplantation.

Lewis rats were treated with streptozotocin to induce hyperglycemia and glycosuria (400-600 mg/dl). Transplantation of approximately 1,000 dissociated islets obtained from collagenase-treated pancreases from 4 donors will promptly correct induced diabetes. Functional survival of islet allografts is related to genetic disparity between donor and recipient strains. In the closely matched Fisher-to-Lewis combination, islets functioned for a mean of 4.2+/-1 days while in the AgB-incompatible Wistar/Furth-to-Lewis combination, islets functioned for a mean of only 2.1+/-0.5 days. Treatment of recipients with antithymocyte globulin (ATG) for 3 days extended islet survival to a mean of 11.8 +/- 1.9 days in the Wistar/Furth-to-Lewis combination and to as long as 184+/-87.5 days in the Fischer-to-Lewis combination. ATG may have a role in trials of clinical islet transplants.

Epsilon-aminocaproic acid in traumatic renal hematuria in the rabbit.

Epsilon-aminocaproic acid (EACA) was intravenously administered to rabbits subjected to bilateral renal crushing trauma. Posttraumatic hematuria in 10 control rabbits lasted a mean of 5.5 days (range 5 to 7 days). Rabbits treated with 1250 mg 5 min before renal trauma and with repeat EACA injections 1 hr (500 mg) and 24 hr (500 mg) after the injury had significantly less hematuria. Only eight of 20 EACA-treated rabbits had any hematuria, and this bleeding terminated by the 2nd posttrauma day in all. EACA may have an important role in the management of trauma-induced renal bleeding.