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Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) and accounts for 35% of the ESRD population in the United States. It results in considerable morbidity, mortality, and expense. The average cost of managing one diabetic patient with ESRD is approximately $50,000 a year. Over the last decade, several advances in the management of diabetic nephropathy have allowed physicians to intervene and retard the progression of renal failure in patients with diabetic nephropathy. Stalling the progression of renal failure allows patients to maintain a superior quality of life and saves society millions of dollars that can be allocated to other aspects of health care. The prevalence of diabetes mellitus continues to increase. With the continued advances in medical technology and care, persons with this disease will live longer, and the incidence of diabetic nephropathy will increase. Primary care physicians will have the most frequent contact with these patients and therefore will have the greatest potential to favorably affect their clinical course. This review focuses on the therapeutic interventions available to delay the progression of diabetic nephropathy. Clinicians should strive to secure euglycemia and obtain optimal blood pressure control in their patients. The unique renal-protective effects of angiotensin-converting enzyme inhibitors will be reviewed, as will the salutary effects of a low-protein diet, normalizing serum cholesterol, and the cessation of smoking. The optimal timing of dialysis access placement and the initiation of dialysis and transplantation will also be discussed.

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BACKGROUND: Mechanisms by which delayed allograft function reduces renal allograft survival are poorly understood. This study evaluated the relationship of delayed allograft function to acute rejection and long-term survival of cadaveric allografts. METHODS: 338 recipients of cadaveric allografts were followed until death, resumption of dialysis, retransplantation, loss to follow-up, or the study's end, which ever came first. Delayed allograft function was defined by dialysis during the first week following transplantation. Multivariate Cox proportional hazards survival analysis was used to assess the relationship of delayed allograft function to rejection and allograft survival. RESULTS: Delayed allograft function, recipient age, preformed reactive antibody levels, prior kidney transplantation, recipient race, rejection during the first 30 days and rejection subsequent to 30 days following transplantation were predictive of allograft survival in multivariate survival models. Delayed allograft function was associated with shorter allograft survival after adjustment for acute rejection and other covariates (relative rate of failure [RR]+1.72 [95% CI, 1.07, 2.76]). The adjusted RR of allograft failure associated with any rejection during the first 30 days was 1.99 (1.23, 3.21), and for rejection subsequent to the first 30 days was 3.53 (2.9 08, 6.00). The impact of delayed allograft function did not change substantially (RR=1.84 [1.15, 2.95]) in models not controlling for acute rejection. These results were stable among several subgroups of patients and using alternative definitions of allograft survival and delayed allograft function. CONCLUSIONS: This study demonstrates that delayed allograft function and acute allograft rejection have important independent and deleterious effects on cadaveric allograft survival. These results suggest that the effect of delayed allograft function is mediated, in part, through mechanisms not involving acute clinical rejection.

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There is a clear need for well-tolerated immunomodulatory agents that can aid in the prevention of acute solid organ rejection. Extracorporeal photopherosis is an apheresis-based therapy that is currently available at many medical centers worldwide. Preliminary studies utilizing photopheresis with standard immunosuppressives have shown this therapy to successfully reverse acute cellular rejection of cardiac allografts with minimal toxicity. No formal evaluation of the role of extracorporeal photopheresis had been performed in renal transplantation. In this report, photopheresis was successfully utilized to treat acute cellular rejection in a patient with a renal allograft. This lends further support to the existing literature suggesting that photopheresis may be useful for the reversal of acute solid organ rejection. Although our experience with this patient is anecdotal, photopheresis merits further study as treatment for severe renal allograft rejection.

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Noncompliance has been implicated in modifying morbidity and mortality in end stage renal disease patients; however, the data are conflicting, and measurement of compliance has been difficult. Traditional measurements of compliance include serum potassium (K) and phosphorus (P) concentrations, and interdialytic fluctuations in weight gain (IWG). This study correlated three indices: 1) Adequacy of dialysis (Kt/V); 2) protein ingestion (PCR); and 3) the percentage of time dialyzed compared with the total dialysis time prescribed (% Time) with the traditional measurements of compliance. Correlations were calculated among pre- and post-BUN (blood urea nitrogen), Kt/V, K and P, PCR, IWG, and % Time. As expected, BUN levels correlated with Kt/V, K, P, PCR, IWG, and % Time. Protein ingestion correlated with K and IWG, but not with % Time. Adequacy of dialysis correlated with P levels, but not with PCR, WG, or % Time. Phosphorus correlated with pre- and post-BUN, Kt/V, and % Time, but not with K. Potassium, P, and IWG did not correlate internally. The authors conclude that standard biochemical measures of compliance reflect different compliance behaviors (dietary selection and restriction, restriction of fluid and salt intake, and adherence to medication regimens). Percent time may be a powerful, independent measure of patient compliance with the dialysis regimen.

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Orally administered calcium carbonate tablets are commonly prescribed as a calcium supplement and for their phosphate-binding effects in renal failure patients. Two cases are reported in which a commercially available brand of calcium carbonate tablets appeared to be ineffective. Formal investigation of the bioavailability of this product revealed it to have impaired disintegration and dissolution and a lack of clinical efficacy. Recommendations that will enable physicians to avoid prescribing and pharmacists to avoid dispensing ineffective calcium carbonate tablets are proposed.

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Hyperphosphatemia is practically a universal problem in patients with chronic renal failure. Conventional treatment of hyperphosphatemia in this situation is either only partially effective or may be associated with potentially serious adverse effects. The authors examined the effect of inducing a metabolic alkalosis on serum phosphate in chronic hemodialysis patients by increasing the concentration of bicarbonate in dialysate. Seven patients participated in the study. Each patient was on dialysis for 2 weeks with each of 2 dialysate regimens. Regimen A contained a bicarbonate concentration of 25 mEq/L and Regimen B a bicarbonate concentration of 40 mEq/L. Despite Regimen B resulting in a significant increase in predialysis and postdialysis serum bicarbonate concentration and arterial pH, no significant difference in serum phosphate was demonstrated after 2 weeks of therapy.

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Conventional methods of measuring recirculation in hemodialysis access include a three site method performed during dialysis, and a two site technique conducted at the end of a hemodialysis treatment. This study describes a two site procedure performed at the beginning of a hemodialysis session. Blood samples are drawn from the arterial side of the hemodialysis access immediately prior to hemodialysis (AIPD), and from the same arterial line (A+5) and venous line (V+5) when maximal blood flows are reached 5 min after starting hemodialysis. Blood urea nitrogen (BUN) is measured in these samples, and the results entered into the formula AIPD - A+5/AIPD - V+5 X 100% to calculate the percent recirculation. Percent recirculation calculated by this method compared favorably with, and may hold several advantages over conventional techniques.

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