Background

Few reports have shown an association between access type and inflammatory marker levels in a longitudinal cohort. We investigated the role of access type on serial levels of inflammatory markers and the role of inflammatory markers in mediating the association of access type and risk of mortality in a prospective study of incident dialysis patients.

Study design

Cohort study, post hoc analysis of the CHOICE (Choices for Healthy Outcomes in Caring for ESRD) Study.

Setting & participants

In 583 participants, inflammation was assessed by measuring serum C-reactive protein (CRP) and interleukin 6 (IL-6) after access placement and at multiple times during 3 years' follow-up. Type of access was categorized as central venous catheter (CVC), arteriovenous graft (AVG), and arteriovenous fistula (AVF), and changes over time were recorded.

Predictor

Access type, age, sex, race, body mass index, diabetes, cardiovascular disease, and serum albumin level.

Outcomes

CRP level, IL-6 level, and mortality.

Measurements

We used mixed-effects pattern mixture models to study the association between access type and repeated measurements of inflammation and survival analysis to investigate the association of access type and mortality, adjusting for predictors.

Results

In a mixed-effects pattern mixture model, compared with AVFs, the presence of CVCs and AVGs was associated with 62% (P=0.02) and 30% (P=0.05) increases in average CRP levels, respectively. A Cox proportional hazards model yielded nonsignificant associations of CVC and AVG use (vs AVFs) with risk of mortality when adjusted for inflammatory marker levels. Higher CRP levels were associated with increased risk of CVC failure than lower CRP levels.

Limitations

CRP and IL-6 measurements not performed for all hemodialysis patients.

Conclusions

CVCs, compared with AVFs, are associated with a greater state of inflammation in incident hemodialysis patients, and the association of catheter use and mortality may be mediated by access-induced inflammation. Our findings support recommendations for the early removal or avoidance of CVC placements.

Although the United States possesses one of the most comprehensive transplant registries in the world, nationally representative data on how transplant care is structured and delivered is lacking. Therefore, we surveyed all 208 adult kidney transplant centers in the United States, excluding 37 pediatric and 58 inactive adult centers. Respondents were asked about the characteristics of their kidney transplant programs (25 items), the structure and process of care (18 items), coordination of care (10 items), and the characteristics of transplant physicians and surgeons (9 items). The survey was completed by directors of 156 transplant centers (75% response). The results demonstrated significant variation between centers in several domains. Sixty-five percent of transplant centers do not have a dedicated transplant pharmacist in outpatient care. Two thirds of transplant centers do not see the kidney transplant recipients at least monthly during the first year. Less than 30% of centers perform joint sit-down or walking rounds between nephrology and transplant surgery. There was significant variation in the structure and process of care in kidney transplantation. This implies variation in the use of resources at the transplant centers. This variation should be studied to determine best practices associated with optimal kidney allograft and patient survival.

Background

We examined if African or Asian ethnicity was associated with lower access to kidney transplantation (KT) in a Canadian setting.

Methods

Patients referred for KT to the Toronto General Hospital from January 1, 2003, to December 31, 2012, who completed social work assessment, were included (n = 1769). The association between ethnicity and the time from referral to completion of KT evaluation or receipt of a KT were examined using Cox proportional hazards models.

Results

About 54% of the sample was white, 13% African, 11% East Asian, and 11% South Asian; 7% had "other" (n = 121) ethnic background. African Canadians (hazard ratio [HR], 0.75; 95% CI: 0.62-0.92]) and patients with "other" ethnicity (HR, 0.71; 95% CI, 0.55-0.92) were less likely to complete the KT evaluation compared with white Canadians, and this association remained statistically significant in multivariable adjusted models. Access to KT was significantly reduced for all ethnic groups assessed compared with white Canadians, and this was primarily driven by differences in access to living donor KT. The adjusted HRs for living donor KT were 0.35 (95% CI, 0.24-0.51), 0.27 (95% CI, 0.17-0.41), 0.43 (95% CI, 0.30-0.61), and 0.34 (95% CI, 0.20-0.56) for African, East or South Asian Canadians and for patients with "other" ethnic background, respectively.

Conclusions

Similar to other jurisdictions, nonwhite patients face barriers to accessing KT in Canada. This inequity is very substantial for living donor KT. Further research is needed to identify if these inequities are due to potentially modifiable barriers.

In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant-naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant-naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work-up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant-naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis.

Rationale & objective

Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain.

Study design

Post hoc longitudinal cohort analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial.

Setting & participants

Stable kidney transplant recipients with elevated homocysteine levels from 30 sites in the United States, Canada, and Brazil.

Predictor

Urine albumin-creatinine ratio (ACR) at randomization.

Outcomes

Allograft failure, CVD, and all-cause death.

Analytical approach

Multivariable Cox models adjusted for age; sex; race; randomized treatment allocation; country; systolic and diastolic blood pressure; history of CVD, diabetes, and hypertension; smoking; cholesterol; body mass index; estimated glomerular filtration rate (eGFR); donor type; transplant vintage; medications; and immunosuppression.

Results

Among 3,511 participants with complete data, median ACR was 24 (Q1-Q3, 9-98) mg/g, mean eGFR was 49±18 (standard deviation) mL/min/1.73m², mean age was 52±9 years, and median graft vintage was 4.1 (Q1-Q3, 1.7-7.4) years. There were 1,017 (29%) with ACR < 10mg/g, 912 (26%) with ACR of 10 to 29mg/g, 1,134 (32%) with ACR of 30 to 299mg/g, and 448 (13%) with ACR ≥ 300mg/g. During approximately 4 years, 282 allograft failure events, 497 CVD events, and 407 deaths occurred. Event rates were higher at both lower eGFRs and higher ACR. ACR of 30 to 299 and ≥300mg/g relative to ACR < 10mg/g were independently associated with graft failure (HRs of 3.40 [95% CI, 2.19-5.30] and 9.96 [95% CI, 6.35-15.62], respectively), CVD events (HRs of 1.25 [95% CI, 0.96-1.61] and 1.55 [95% CI, 1.13-2.11], respectively), and all-cause death (HRs of 1.65 [95% CI, 1.23-2.21] and 2.07 [95% CI, 1.46-2.94], respectively).

Limitations

No data for rejection; single ACR assessment.

Conclusions

In a large population of stable kidney transplant recipients, elevated baseline ACR is independently associated with allograft failure, CVD, and death. Future studies are needed to evaluate whether reducing albuminuria improves these outcomes.

Background

Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs).

Methods

The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome.

Results

The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77).

Conclusions

Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.