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Background Elevated uric acid concentration is associated with higher rates of cardiovascular (CV) morbidity and mortality in the general population. It is not known whether hyperuricemia increases the risk for CV death or transplant failure in kidney transplant recipients. Study Design Post hoc cohort analysis of the FAVORIT Study, a randomized controlled trial that examined the effect of homocysteine-lowering vitamins on CV disease in kidney transplantation. Setting & Participants Adult recipients of kidney transplants in the United States, Canada, or Brazil participating in the FAVORIT Study, with hyperhomocysteinemia, stable kidney function, and no known history of CV disease. Predictor Uric acid concentration. Outcomes The primary end point was a composite of CV events. Secondary end points were all-cause mortality and transplant failure. Risk factors included in statistical models were age, sex, race, country, treatment assignment, smoking history, body mass index, presence of diabetes mellitus, history of CV disease, blood pressure, estimated glomerular filtration rate (eGFR), donor type, transplant vintage, lipid concentrations, albumin-creatinine ratio, and uric acid concentration. Cox proportional hazards models were fit to examine the association of uric acid concentration with study end points after risk adjustment. Results 3,512 of 4,110 FAVORIT participants with baseline uric acid concentrations were studied. Median follow-up was 3.9 (IQR, 3.0-5.3) years. 503 patients had a primary CV event, 401 died, and 287 had transplant failure. In unadjusted analyses, uric acid concentration was significantly related to each outcome. Uric acid concentration was also strongly associated with eGFR. The relationship between uric acid concentration and study end points was no longer significant in fully adjusted multivariable models ( P =0.5 for CV events; P =0.09 for death, and P =0.1 for transplant failure). Limitations Unknown use of uric acid–lowering agents among study participants. Conclusions Following kidney transplantation, uric acid concentrations are not independently associated with CV events, mortality, or transplant failure. The strong association between uric acid concentrations with traditional risk factors and eGFR is a possible explanation.

Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group. The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease. A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology. The average follow-up was 2.2 years. Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m2 who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded. The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d). Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death. Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d). In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease. A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected. If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure. Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease. In patients with GFR less than 25 mL/min/1.73 m2, we suggest a prescribed dietary protein intake of 0.6 g/kg/d.

CsA has now been used in this country for about four years and has been widely available for a little more than one year. Both the experience of those centers that have been using it longest, and total US national experience, suggest that CsA is now, with the sole exception of recipients matched for both HLA-DR antigens, the immunosuppressive of choice for all cadaveric renal allografts, conferring approximately a 10% advantage in graft survival. The advantages of CsA seem particularly apparent in the management of high-risk patients such as those over 50 years old and those with diabetes. CsA appears to reduce the frequency of rejection episodes and to permit reduction of steroid dosage. These factors, together with the improved graft survival rate, may contribute to a substantially higher rate of patient rehabilitation. The role of transfusion and HLA matching in association with CsA remains somewhat controversial. While large multicenter studies show the continued importance of both transfusion and optimal HLA matching, it has been argued that avoidance of pretransplant transfusions has avoided presentation of potential recipients, and that simplification of matching requirements has saved money and has permitted speedier transplantation of patients, favoring improved rehabilitation. Careful monitoring of the experience with this major new immunosuppressive agent over the next several years may answer these remaining questions.