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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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.