Joint association of hyperuricemia and reduced GFR on cardiovascular morbidity: a historical cohort study based on laboratory and claims data from a national insurance provider.

BACKGROUND: Hyperuricemia is common in patients with chronic kidney disease (CKD). We assessed the relationship of increased serum uric acid levels with cardiovascular risk across levels of kidney function. STUDY DESIGN: Historical cohort study. SETTING & PARTICIPANTS: Study data were drawn from administrative records of a national private health insurer (2003-2006). We included all adult beneficiaries with concurrently measured serum creatinine and serum uric acid. Patients with acute kidney failure or undergoing renal replacement therapy at baseline were excluded. PREDICTORS: Serum uric acid concentration and estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS: Cardiovascular diagnoses (myocardial infarction, subacute coronary heart disease, heart failure, cerebrovascular disease, or peripheral arterial disease) ascertained from billing claims. Cox proportional hazard models were used to test the association of predictors with cardiovascular morbidity. Models were adjusted for sociodemographic characteristics, selected comorbid conditions, and laboratory results. RESULTS: In 148,217 eligible patients, mean eGFR was 84 mL/min/1.73 m(2) and the prevalence of CKD stages 3-5 was 6.0%. Hyperuricemia (serum uric acid >7 mg/dL) was found in 15.6% of patients. The 40-month cumulative incidence of cardiovascular events (mean follow-up, 15.3 months) was 8.1%. Cardiovascular risk was associated independently with uric acid level, and this association was stronger in patients with lower eGFRs. LIMITATIONS: Observational design, lack of information for mortality and potential confounders, single creatinine and uric acid assessment. CONCLUSIONS: Serum uric acid concentration was an independent correlate of cardiovascular morbidity, and this association was stronger in patients with severely decreased eGFR. This investigation provides a rationale for further study of serum uric acid-lowering interventions on cardiovascular risk in the general population and patients with CKD.

Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: application of statistical approaches to reduce bias in observational comparisons.

BACKGROUND: Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching. METHODS: We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching. RESULTS: All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients. CONCLUSIONS: Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable.

Obesity and cardiac risk after kidney transplantation: experience at one center and comprehensive literature review.

BACKGROUND: The cardiac implications of obesity in kidney transplant recipients are not well-described. METHODS: We examined associations of body mass index (BMI) at transplant with posttransplant cardiac risk among 1102 renal allograft recipients at a single center in 1991 to 2004. Cumulative posttransplant incidences of congestive heart failure (CHF), atrial fibrillation (AF), myocardial infarction, and a composite of these cardiac diagnoses were estimated by the Kaplan-Meier method. Bivariate (hazards ratio) and covariate (adjusted hazards ratio) relationships of BMI increments with cardiac risk were modeled by Cox's regression. We also systematically reviewed the literature on BMI and cardiac events after transplant. RESULTS: In the local data, 5-year cumulative incidence of any cardiac diagnosis rose from 8.67% to 29.35% across the lowest to highest BMI quartiles (P=0.02), driven primarily by increases in CHF and AF. In contrast, the rate of myocardial infarction did not differ by BMI quartile (P=0.56). Each 5 U BMI increase predicted 25% higher risk of the cardiac composite (hazards ratio 1.25, 95% CI 1.07-1.47, P=0.005), a relationship that persisted with significance after covariate adjustment (adjusted hazards ratio 1.19, 95% CI 1.00-1.43, P=0.049). BMI independently predicted cardiac risk in subcohorts with pretransplant heart disease and with nondiabetic renal failure. Data from 26 original articles support BMI as a risk factor for posttransplant CHF and AF, whereas findings for coronary/ischemic outcomes are inconsistent and predominantly negative. CONCLUSIONS: High BMI at transplant predicts increased cardiac risk, especially of CHF and AF. Further research should examine whether obesity treatment modifies cardiac risk after kidney transplantation.

Variations in the risk for cerebrovascular events after kidney transplant compared with experience on the waiting list and after graft failure.

BACKGROUND AND OBJECTIVES: This study examined the risks, predictors, and mortality implications of cerebrovascular disease events after kidney transplantation in a national cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This analysis used United States Renal Data System registry data to study retrospectively Medicare-insured kidney transplant candidates (n = 51,504), recipients (n = 29,614), and recipients with allograft failure (n = 2954) in 1995 through 2002. New-onset cerebrovascular disease events including ischemic stroke, hemorrhagic stroke, and transient ischemic attacks were ascertained from billing records, and participants were followed until Medicare-end or December 31, 2002. Multivariable survival analysis was used to compare cerebrovascular disease event incidence and risk profiles among the study samples. RESULTS: The cumulative, 3-yr incidence of de novo cerebrovascular disease events after transplantation was 6.8% and was lower than adjusted 3-yr estimates of 11.8% on the waiting list and 11.2% after graft loss. In time-dependent regression, transplantation predicted a 34% reduction in subsequent, overall cerebrovascular disease events risk compared with remaining on the waiting list, whereas risk for cerebrovascular disease events increased >150% after graft failure. Similar relationships with transplantation and graft loss were observed for each type of cerebrovascular disease event. Smoking was a potentially preventable correlate of posttransplantation cerebrovascular disease events. Women were not protected. All forms of cerebrovascular disease event diagnoses after transplantation predicted increased mortality. CONCLUSIONS: Along with known benefits for cardiac complications, transplantation with sustained graft function seems to reduce risk for vascular disease events involving the cerebral circulation.

Increased risk of graft failure in kidney transplant recipients after a diagnosis of dyspepsia or gastroesophageal reflux disease.

BACKGROUND: Gastrointestinal complications are common in patients who undergo kidney transplantation and may affect posttransplant outcomes. We examined the incidence and predictors of gastroesophageal reflux disease (GERD) and dyspepsia and their associations with graft survival and mortality after transplant. METHODS: We examined United States Renal Data System data and Medicare billing claims to identify diagnoses of dyspepsia and GERD among Medicare beneficiaries transplanted in 1995-2002 (n=42,257). Among GERD cases, we identified patients with reflux esophagitis (RE). We determined independent predictors of upper gastrointestinal complications and modeled these conditions as time-dependent outcomes predictors with Cox regression. RESULTS: The 3-year cumulative incidences of GERD, RE, and dyspepsia were 20%, 5%, and 6%, respectively. Overall, 23% of transplant recipients received a diagnosis of at least one of these complications by 3 years after transplant. Female gender and a pretransplant upper gastrointestinal disease diagnosis predicted posttransplant gastrointestinal complications. Older age, obesity, Caucasian, and African-American race were associated to increased risk of developing GERD. Patients diagnosed with any of the examined upper gastrointestinal complications experienced an increased risk of graft-failure (hazard ratio 1.58; 95% confidence interval 1.48-1.69) and death (hazard ratio 1.61; 95% confidence interval 1.46-1.77). CONCLUSIONS: Upper gastrointestinal complications are relatively common after kidney transplantation and are associated with a significantly increased risk of graft loss and death. Further research is needed to elucidate mechanisms underlying the observed adverse prognoses conferred by diagnosis of upper gastrointestinal complications after kidney transplant.

Delivery patterns of recommended chronic kidney disease care in clinical practice: administrative claims-based analysis and systematic literature review.

BACKGROUND: Clinical practice guidelines for management of chronic kidney disease (CKD) have been developed within the Kidney Disease Outcomes Quality Initiative (K/DOQI). Adherence patterns may identify focus areas for quality improvement. METHODS: We retrospectively studied contemporary CKD care patterns within a private health system in the United States, and systematically reviewed literature of reported practices internationally. Five hundred and nineteen patients with moderate CKD (estimated GFR 30-59 ml/min) using healthcare benefits in 2002-2005 were identified from administrative insurance records. Thirty-three relevant publications in 2000-2006 describing care in 77,588 CKD patients were reviewed. Baseline demographic traits and provider specialty were considered as correlates of delivered care. Testing consistent with K/DOQI guidelines and prevalence of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) medication prescriptions were ascertained from billing claims. Care descriptions in the literature sample were based on medical charts, electronic records and/or claims. RESULTS: KDOQI-consistent measurements of parathyroid hormone (7.1 vs. 0.6%, P = 0.0002), phosphorus (38.2 vs. 1.9%, P < 0.0001) and quantified urinary protein (23.8 vs. 9.4%, P = 0.008) were more common among CKD patients with versus without nephrology referral in the administrative data. Nephrology referral correlated with increased likelihood of testing for parathyroid hormone and phosphorus after adjustment for baseline patient factors. Use of ACEi/ARB medications was more common among patients with nephrology contact (50.0 vs. 30.0%; P = 0.008) but appeared largely driven by higher comorbidity burden. The literature review demonstrated similar practice patterns. CONCLUSIONS: Delivery of CKD care may be monitored by administrative data. There is opportunity for improvement in CKD guideline adherence in practice.