Salvage of clotted jugular vein hemodialysis catheters.

Jugular venous catheters (JVC) provide rapid, vascular access for both emergency and maintenance hemodialysis in both acute and end-stage renal disease. Clotting and occlusion of JVC is a common problem necessitating alternate vascular access. Urokinase will declot 80-90% of central venous catheters; however, recurrence of catheter occlusion is frequent. We successfully employed a guide wire insertion technique to salvage occluded JVC after failed urokinase infusion. In 24 patients JVCs, inserted for either temporary or permanent vascular access, clotted within 6-55 days of initiating hemodialysis. Urokinase (5,000 IU) instilled into both arterial and venous limbs of the catheter had been unsuccessful in restoring patency. In these patients, we inserted a soft-tipped guide wire into both lumina. In 21 of 24 patients (87.5%), guide wire insertion opened the occluded JVC, permitting immediate initiation of hemodialysis. We conclude that for clotted JVC unresponsive to urokinase infusion, guide wire insertion can salvage most catheters thereby facilitating hemodialysis.

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.

Variations of susceptibility to alloxan induced diabetes in the rabbit.

The variations of susceptibility to alloxan induced Diabetes in a total of seventeen rabbits was described. Our study was designed to explore dosage schedules which might improve rabbit responsiveness to and survival after alloxan treatment. A wide range of response to intravenously administered alloxan was observed. Permanent diabetes (blood glucose 350 mg/dl) was found in three rabbits after a single injection (60 mg/kg in one, 100 mg/kg in two). This effect has persisted for eight months. By contrast, two other rabbits injected with a single dose of alloxan (60 mg/kg) developed only transient hyperglycemia. Similarly, four other rabbits either did not respond or had an incomplete response after receiving a total dose of 120 mg/kg. These data suggest that there is extreme variability in individual rabbits susceptibility to the diabetogenic affects of alloxan.

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.

Posttransplant diabetes in kidney transplant recipients.

We retrospectively reviewed the course of 1,000 renal transplants performed in 835 recipients (758 nondiabetics) to assess the incidence of new onset posttransplant diabetes in former nondiabetics. A total of 119 (15.7%) recipients manifested posttransplant diabetes, of whom 64 (53.8%) became hyperglycemic within 3 weeks of transplantation. Actuarial survival analysis indicated a statistically significant selection of blacks; 68 (57.1%) in the group of posttransplant diabetics contrasted with 30.4% of the overall series who were black (p = less than 0.01). Males comprised 73 (61.3%) of posttransplant diabetics, consistent with the male proportion of 66.6% in the entire series. The total dose of methylprednisolone administered before onset of posttransplant diabetes was less than 2.5 g in 86 (69%) and less than 5 g in 110 (92%) patients. Familial diabetes had been noted in 12 (10%) posttransplant diabetics and in 10 (9%) controls. New cases of posttransplant diabetes occurred at a relatively constant annual rate over the decade of study (+/- 15%/year). Patient survival in controls was greater than in posttransplant diabetics, reaching significance (83 vs. 67%) at 2 years. Kidney graft survival in controls and posttransplant diabetics was similar. We conclude that posttransplant diabetes is of greater prevalence in blacks, is not proportional to total dose or duration of intravenous methylprednisolone therapy, and imposes a threat to recipient survival.

Treatment of the uremic diabetic.

Improved patient survival and rehabilitation have been continuously reported over the last decade for diabetics in irreversible kidney failure. There have, however, been no controlled prospective trials of the relative merits of CAPD, maintenance hemodialysis, or kidney transplantation in the uremic diabetic. As a generalization, younger, more rehabilitatable diabetics have been offered a kidney transplant, while older, often sicker diabetics have been relegated to CAPD, leaving most diabetics in the subset managed by maintenance hemodialysis. Treatment preference has reasonably been based on a team's experience and available facilities. Furthermore, nonuniform criteria for patient selection, and timing of the onset of uremia therapy, preclude direct comparisons between series of treated diabetics. While survival of diabetics treated with maintenance hemodialysis or peritoneal dialysis has improved substantially in recent years, survival and rehabilitation after kidney transplantation are superior to other forms of uremia therapy. Cumulative data suggest that a treated uremic diabetic patient has a 50% chance of living 3 years on hemodialysis, a 50% chance of surviving 5 years if he receives a well functioning cadaveric kidney transplant, and an even longer anticipated survival of 50% for 7.5 years if transplanted with a well-functioning living-related kidney. Even better results may be attainable with kidneys from HLA-identical siblings, particularly when transplanted early and employing cyclosporine rather than azathioprine, thereby allowing reduction of steroid dosage to minimal levels. Kidney transplantation, when judiciously undertaken by a team skilled in overall diabetic management, is the treatment of choice for the uremic diabetic. Dialytic therapy, however, has appreciable value, not only as an alternative in patients in whom transplantation is contraindicated, or for whom a kidney is not available, but as life-sustaining therapy while awaiting surgical intervention. No matter how treated, diabetic nephropathy need no longer be viewed as a disease of desperation. Unfortunately, proffering a substitute for the diabetic patient's own renal function does not, in and of itself, diminish progression of preexisting multisystem micro- and macrovascular disease. Implantation of a functioning kidney transplant in a failing diabetic with the renal-retinal syndrome provides a firm base upon which, with careful attention to regulation of blood glucose, reduction of hypertensive blood pressure, and provision of emotional support, a new, tenuous life may be built.

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.

Hypertension jeopardizes diabetic patients following renal transplant.

Hypertension is highly prevalent in both types I (87%) and type II (95) uremic diabetics at the time of kidney transplantation. Hypertension was diagnosed a mean of 16.9 yrs in type I, and 2.9 yrs in type II diabetics after the clinical diagnosis of diabetes was made. The majority (81%) of our patients were hypertensive postkidney transplant. Only 13% of hypertensive recipients became normotensive post-transplant. This group had a lower mortality rate (1/8, 12.5%), and all survivors (100%) had good graft function (mean creatinine = 1.6 +/- 0.6, range 0.9 to 2.5 mg/dl). By contrast, recipients who remained hypertensive post-transplantation had a much higher mortality rate (25/54, 48%), and loss of graft function necessitating dialysis occurred frequently (19/54, 35%). Of hypertensive diabetic recipients alive at a mean of 21 mos post-transplant, renal function was worse (mean creatinine = 3.1 +/- 3.0, range 1.0 to 13.7 mg/dl) than in nonhypertensive recipients. We conclude that while renal transplantation may be the treatment of choice in patients with diabetes mellitus, failure to control hypertension negatively biases the ultimate post-transplant course.

Pathology of the penis in long-term diabetic rats.

Pathological changes in the penis of long-term diabetic rats (greater than 1 year) include epidermal atrophy and lipid droplets in erectile tissue and dermis, as well as thickening of capillary basement membranes, dilatation and microaneurysms of capillaries, and atrophy and degeneration of erectile smooth muscle. These changes are similar to those previously described as occurring in other organs, but damage to nerves and smooth muscle can best be appreciated with electron microscopy.

Intact antibody response to pneumococcal capsular polysaccharides in uremia and diabetes.

To test their immune responsiveness to pneumococcal polysaccharide antigens, eight azotemic patients, ten dialysis patients, and five insulin-dependent diabetics were vaccinated with a 14-valent vaccine. When compared with nonazotemic, nondiabetic control subjects, both diabetics and uremic patients responded with normal antibody titers to each antigen type. Therefore, we are advising immunization with commercially available vaccine in our patients with diabetes, renal failure, or both, although long-term efficacy has yet to be proved.

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.

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.

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.

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.

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.

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.