Conversion to a sirolimus-based regimen is associated with lower incidence of BK viremia in low-risk kidney transplant recipients.

BACKGROUND: BK viral nephropathy is an increasingly recognized cause of early allograft loss in kidney transplantation. This study aimed to determine whether a sirolimus (Sir)-based calcineurin inhibitor-sparing regimen is associated with a lower incidence of BK viremia. METHODS: This was a single-center retrospective study. Patients were either on tacrolimus (Tac)-based or on Sir-based immunosuppression. Conversion from Tac to Sir occurred at or after 3 months if patients were <62 years of age, had calculated panel reactive antibodies of <20%, and did not have acute early rejection. RESULTS: Incidence of clinically significant BK viremia was 17.9% in the Tac group and 4.3% in the Sir group. Cox regression multivariate analysis showed that male gender (hazard ratio [HR] = 2.87) and switch to Sir (HR = 0.333) impacted the incidence of BK viremia. Kaplan-Meier analysis showed a higher BK-free survival in the Sir group. A trend was seen toward shorter time to resolution of BK viremia and lower peak viremia in the Sir group. Patients on Sir had a higher estimated glomerular filtration rate at each time point; 34% of patients discontinued Sir because of side effects. CONCLUSION: Conversion to Sir-based maintenance immunosuppression at or about 3 months after kidney transplantation correlates with a lower incidence of BK viremia.

Recommendations for the assessment and reporting of multivariable logistic regression in transplantation literature.

Multivariable logistic regression is an important method to evaluate risk factors and prognosis in solid organ transplant literature. We aimed to assess the quality of this method in six major transplantation journals. Eleven analytical criteria and four documentation criteria were analyzed for each selected article that used logistic regression. A total of 106 studies (6%) out of 1,701 original articles used logistic regression analyses from January 1, 2005 to January 1, 2006. The analytical criteria and their respective reporting percentage among the six journals were: Linearity (25%); Beta coefficient (48%); Interaction tests (19%); Main estimates (98%); Ovefitting prevention (84%); Goodness-of-fit (3.8%); Multicolinearity (4.7%); Internal validation (3.8%); External validation (8.5%). The documentation criteria were reported as follows: Selection of independent variables (73%); Coding of variables (9%); Fitting procedures (49%); Statistical program (65%). No significant differences were found among different journals or between general versus subspecialty journals with respect to reporting quality. We found that the report of logistic regression is unsatisfactory in transplantation journals. Because our findings may have major consequences for the care of transplant patients and for the design of transplant clinical trials, we recommend a practical solution for the use and reporting of logistic regression in transplantation journals.

Effects of antihypertensive therapy on serum lipids.

PURPOSE: To compare and contrast the effects of antihypertensive agents on serum lipids and blood pressure in different patient populations. DATA SOURCES: A MEDLINE search and bibliographies from recent comprehensive reviews were used to identify trials that provided sufficient data to calculate the change in one or more serum lipid values measured before and after antihypertensive therapy. STUDY SELECTION: 474 controlled and uncontrolled clinical trials investigated the effects of 85 antihypertensive agents on lipids and blood pressure in more than 65,000 patients. DATA EXTRACTION: Data on triglyceride and total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; blood pressure; patient characteristics; and study design. DATA SYNTHESIS: Differences in the effects of agents, adjusted for differences in patient populations and study design, were examined using multiple linear regression analysis that was weighted by study quality and inverse variance. Diuretics caused relative increases in cholesterol levels (regression coefficient = 0.13 mmol/L; 95% CI, 0.09 to 0.18 mmol/L) that were greater with higher doses (additional effect of high dose, 0.12 mmol/L; CI, 0.04 to 0.20 mmol/L) and were worse in blacks than in nonblacks (additional effect in blacks, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Beta-blockers caused increases in triglyceride levels (0.35 mmol/L; CI, 0.31 to 0.39 mmol/L) that were substantially smaller for agents with intrinsic sympathomimetic activity (amelioration of beta-blocker increase, -0.21 mmol/L; CI, -0.27 to -0.16 mmol/L). When combined with cardioselectivity, beta-blockers with intrinsic sympathomimetic activity favorably affected lipids and reduced both total (-0.14 mmol/L; CI, -0.24 to -0.04 mmol/L) and LDL cholesterol levels (-0.17 mmol/L; CI, -0.28 to -0.07 mmol/L). alpha-Blockers beneficially affected total cholesterol (-0.23 mmol/L; CI, -0.28 to -0.18 mmol/L), LDL cholesterol (-0.20 mmol/L; CI, -0.25 to 0.15 mmol/L), triglycerides (-0.07 mmol/L; CI, -0.11 to -0.03 mmol/L), and, in younger persons, HDL cholesterol (0.02 mmol/L; 0.01 to 0.04 mmol/L). Converting enzyme inhibitors reduced triglycerides (-0.07 mmol/L; CI, -0.12 to -0.02 mmol/L), and, in patients with diabetes, total cholesterol (-0.22 mmol/L; CI, -0.34 to -0.10 mmol/L). Vasodilators reduced total (-0.22 mmol/l; CI, -0.30 to -0.10 mmol/L) and LDL cholesterol (-0.22 mmol/L; CI, -0.29 to -0.11 mmol/L) and increased HDL cholesterol (0.06 mmol/L; CI, 0.02 to 0.09 mmol/L). CONCLUSION: With the exception of calcium antagonists, nearly all antihypertensive agents affect serum lipids. These effects differ among patient populations.

Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis.

OBJECTIVE: To assess the relative effect of different antihypertensive agents on proteinuria and renal function in patients with diabetes. DATA SOURCES: We used MEDLINE and bibliographies in recent articles to identify studies of the effects of antihypertensive agents on renal function in patients with diabetes. STUDY SELECTION: We selected 100 controlled and uncontrolled studies that provided data on renal function, proteinuria, or both, before and after treatment with an antihypertensive agent. DATA EXTRACTION: Data on blood pressure, renal function, proteinuria, patient characteristics (for example, age, sex, and type of diabetes), and study design (for example, random allocation and the use of a placebo) were extracted from selected studies. DATA SYNTHESIS: Multiple linear regression analysis indicated that angiotensin-converting enzyme (ACE) inhibitors decreased proteinuria independent of changes in blood pressure, treatment duration, and the type of diabetes or stage of nephropathy, as well as study design (P < 0.0001). Reductions in proteinuria from other antihypertensive agents could be entirely explained by changes in blood pressure. Blood pressure reduction in itself was associated with a relative increase in glomerular filtration rate (regression coefficient [+/- SE], 3.70 +/- .92 mL/min for each reduction of 10 mm Hg in mean arterial pressure; P = 0.0002); however, compared with other agents, ACE inhibitors had an additional favorable effect on glomerular filtration rate that was independent of blood pressure changes (3.41 +/- 1.71 mL/min; P = 0.05). CONCLUSION: Angiotensin-converting enzyme inhibitors can decrease proteinuria and preserve glomerular filtration rate in patients with diabetes. These effects occur independent of changes in systemic blood pressure.

Patients with a low income have reduced renal allograft survival.

The impact of socioeconomic factors on long-term outcome after renal transplantation is unknown. We examined the effects of family income among 202 patients transplanted between 1976 and 1982 who had an allograft that functioned for at least 1 year. Compared with patients with an adequate income, recipients of medical assistance at the time of transplantation were more likely to return to dialysis after 1 year (16/45 [36%] v 26/157 [17%], P less than 0.01), or after 5 years of graft function (10/38 [26%] v 12/116 [10%], P less than 0.01). Patients who complied with fewer than 85% of visits during the first 2 years were also more likely to return to dialysis after 1 year (17/49 [35%] v 25/153 [16%], P less than 0.01), or after 5 years (8/31 [26%] v 14/123 [11%], P less than 0.05) than were more compliant patients. However, noncompliance was not different in patients with and without a low income (37/157 [24%] v 12/45 [27%], P greater than 0.05). The relative risk for returning to dialysis after 5 years was 2.4 (P less than 0.05) for low income and 3.0 (P less than 0.05) for less than 85% compliance using a Cox proportional hazards model. These effects were independent of prior transplantation, mismatches, pre-formed antibodies, delayed graft function, age, sex, diabetes, alcohol or drug abuse, education, race, distance from the transplant center, and living in an urban environment (relative risk = 2.5, P less than 0.05). Neither income nor compliance could be linked to death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjunctive therapy with intravenous human immunoglobulin G improves survival of patients with acute renal failure.

The objective of this prospective, randomized, double-blind, placebo-controlled clinical trial was to evaluate the efficacy of adjunctive therapy with iv human immunoglobulin G in reducing the morbidity and mortality associated with acute renal failure. Forty patients greater than or equal to 18 yr of age who were identified within 48 h of the onset of acute renal failure and who met the enrollment criteria were enrolled in the study. Thirty-five patients were considered evaluable. Patients were grouped according to the admitting service (medical or surgical/trauma) and were randomized to receive either immunoglobulin G (400 mg/kg body wt) or placebo (normal saline; 8 mL/kg body wt) at study entry and then weekly thereafter for a maximum of 4 doses. The groups were well balanced with respect to demographics, clinical presentation, and severity of illness (APACHE II scores). A significant reduction in mortality at 42 days after study entry was observed. Two of 17 (12%) patients in the immunoglobulin G-treated group compared with 8 of 18 (44%) patients in the placebo-treated group died (P = 0.025). No differences were observed in the frequency of major complications that occurred in association with acute renal failure. However, in patients who manifested infection, greater survival was observed in the immunoglobulin G treatment group. The results suggest that immunoglobulin G administered at the onset of acute renal failure reduced mortality possibly by decreasing the severity of infectious complications associated with the occurrence of of acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathologic findings associated with a chronic, progressive decline in renal allograft function.

The relationship between specific histopathologic findings of chronic rejection (CR) and the clinical course of renal transplant recipients with a chronic progressive decline in allograft function (CPDAF) is unknown. We used one or two hinged regression lines, fitted by least-squares to serial creatinine clearances, to define the onset and clinical course of CPDAF. Biopsies (N = 100) from patients transplanted from 1978 to 1982 were studied retrospectively. Interstitial fibrosis, tubular atrophy, and fibrointimal arterial narrowing were more pronounced in biopsies obtained after, but not before the onset of CPDAF. Interstitial hemorrhage, an infrequent finding in acute vascular rejection, preceded the onset of CPDAF, but the more common histologic findings of acute cellular rejection did not. The severity of histologic features of CR (as reflected by a score combining fibrointimal arterial narrowing, interstitial fibrosis, tubular atrophy, glomerular sclerosis, glomerular mesangial expansion, and glomerular basement membrane reduplication) correlated with the duration of subsequent allograft survival (r = -0.65, P less than 0.001). Glomerular size increased after transplantation, but was not different in patients with or without CPDAF, suggesting that mechanisms related to compensatory hypertrophy did not play a major role in the pathogenesis of CR. In summary, the histologic findings of CR did not predict the onset of CPDAF, did not distinguish whether the pathogenesis was mediated by immune or nonimmune events, but did correlate with the duration of subsequent allograft survival.