Risks and benefits of preemptive second kidney transplantation.

BACKGROUND: Information to guide the timing of a second kidney transplantation is limited. METHODS: We compared outcomes of 3509 preemptive and 14,075 nonpreemptive second kidney transplant recipients in the U.S. Renal Data System between 1995 and 2007. RESULTS: Preemptive recipients had less acute rejection (12% vs. 16%; P<0.0001) and delayed graft function (8% vs. 23%; P<0.0001). Preemptive transplantation was associated with a lower multivariate adjusted risk of allograft failure from any cause including death (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.81-0.96) and death with a functioning graft (HR [95% CI], 0.76 [0.66-0.87]) but a similar risk of death-censored graft loss (HR [95% CI], 0.98 [0.88-1.08]). The benefits of preemptive transplantation were evident in all patients groups with first transplant survival equal to or more than 1 year; however, a 34% increased risk of death-censored graft loss was observed in preemptive recipients when first transplant survival was less than 1 year. CONCLUSIONS: Benefits and risks of preemptive transplantation vary between primary and second transplant recipients. Benefits in second transplant recipients are primarily due to decreased death with a functioning graft, with no difference in death-censored graft survival. Preemptive transplantation was beneficial when first transplant survival was equal to or more than 1 year but associated with increased risk when graft survival was less than 1 year.

Utilization and outcome of 'out-of-center hemodialysis' in the United States: a contemporary analysis.

BACKGROUND: There is increasing interest in the delivery of out-of-center hemodialysis (HD), particularly in the home setting, but little systematic information about its use and outcome in contemporary incident patients is available. PATIENTS AND METHODS: Out-of-center HD was defined as HD delivered in a residential setting, mainly at home or in a long-term care facility (such as a nursing home) irrespective of the length and frequency of therapy. All-cause mortality was determined in an observational cohort study of 458,329 adult patients initiating dialysis in the United States with Medicare as a primary payer. RESULTS: Between 1995 and 2004, out-of-center HD was the initial modality in 1,641 (0.4%) of eligible participants, although there was significant geographic variation. Patients initiating out-of-center HD were younger, more likely to be nonwhite, had fewer comorbidities, a higher median income, and were more likely to be employed than patients initiating in-center HD or peritoneal dialysis (PD). In multivariate analysis, out-of-center HD patients had a higher overall risk of death compared to in-center HD or PD patients (HR = 1.10, 95% CI 1.04, 1.17), although the relative risk of death was lower in younger and healthier patients (HR = 0.78; 95% CI 0.61, 1.00). CONCLUSION: Out-of-center HD is not associated with a survival advantage among unselected patients initiating dialysis in the United States. These results call for better characterization of out-of-center HD in national registries, primarily to effectively compare the use, outcomes and potential benefits of home HD to standard therapies.

Survival among nocturnal home haemodialysis patients compared to kidney transplant recipients.

BACKGROUND: Kidney transplantation is the gold standard renal replacement therapy. Nocturnal haemodialysis (NHD) is an intensive dialysis modality (6-8 h/session, 3-7 sessions/week) associated with a significant improvement of clinical and biochemical parameters compared to conventional dialysis. To date, no studies have compared survival in patients treated with NHD and kidney transplantation. METHODS: Using data from two regional NHD programmes and the USRDS from 1994 to 2006, we performed a matched cohort study comparing survival between NHD and deceased and living donor kidney transplantation (DTX and LTX) by randomly matching NHD patients to transplant recipients in a 1:3:3 ratio. The independent association of treatment modality with survival was determined using Cox multivariate regression. RESULTS: The total study population consisted of 177 NHD patients matched to 1062 DTX and LTX recipients (total 1239 patients) followed for a maximum of 12.4 years. During the follow-up period, the proportion of deaths among NHD, DTX and LTX patients was 14.7%, 14.3% and 8.5%, respectively (P = 0.006). We found no difference in the adjusted survival between NHD and DTX (HR 0.87, 95% CI 0.50-1.51; NHD reference group), while LTX survival was better (HR 0.51, 95% CI 0.28-0.91). CONCLUSIONS: These results indicate that NHD and DTX survival is comparable, and suggest that this intensive dialysis modality may be a bridge to transplantation or even a suitable alternative in the absence of LTX in the current era of growing transplant waiting lists and organ shortage.

Focal segmental glomerulosclerosis in mild IgA nephropathy: a clinical-pathologic study.

BACKGROUND: The significance of focal segmental glomerulosclerosis (FSGS) in mild IgA nephropathy is uncertain. METHODS: All consecutive renal biopsies performed between 1996 and 2005 in adults with a diagnosis of mild IgA nephropathy (Lee Grade 1 or 2) at St Paul's Hospital, Vancouver, Canada, were reviewed. RESULTS: Seventy-five patients were included, 26 (35%) with IgA nephropathy and FSGS (FSGS+ group) and 49 (65%) with IgA nephropathy without FSGS (FSGS- group). The mean follow-up was 3 years. At the time of renal biopsy the FSGS+ group had a lower eGFR (60 versus 73 mL/min, P = 0.02), lower serum albumin (38 versus 41 g/L, P = 0.02), higher mean arterial pressure (103 versus 97 mmHg, P = 0.03) and greater protein excretion (3.0 versus 1.3 g/day, P < 0.01) than the FSGS- group. On histology, the FSGS+ group had a higher percentage of obsolete glomeruli (23.4% versus 12.7%, P < 0.01), and 31% of FSGS+ biopsies had >or=25% tubular atrophy/interstitial fibrosis while this was not observed in the FSGS- group (P < 0.01). The primary outcome measure, DeltaGFR, was -2.56 mL/ min/year in the FSGS+ group and +1.14 mL/min/year in the FSGS- group, difference: 3.70 mL/min/year (P = 0.03) (univariate). In the multivariate model, the FSGS+ group declined at 0.19 mL/min/year (-14.16, 13.78) and the FSGS- group improved at 2.85 mL/min/year (-11.64, 17.34), difference 3.04 mL/min/year, P = 0.18. CONCLUSIONS: Our study suggests that the focal segmental glomerulosclerosis lesion and associated clinical and pathologic findings in patients with mild IgA nephropathy are associated with a worse renal outcome.

Sirolimus is associated with new-onset diabetes in kidney transplant recipients.

New-onset diabetes (NOD) is associated with transplant failure. A few single-center studies have suggested that sirolimus is associated with NOD, but this is not well established. With the use of data from the United States Renal Data System, this study evaluated the association between sirolimus use at the time of transplantation and NOD among 20,124 adult recipients of a first kidney transplant without diabetes. Compared with patients treated with cyclosporine and either mycophenolate mofetil orazathioprine, sirolimus-treated patients were at increased risk for NOD, whether it was used in combination with cyclosporine (adjusted hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.36 to 1.90),tacrolimus (adjusted HR 1.66; 95% CI 1.42 to 1.93), or an antimetabolite (mycophenolate mofetil orazathioprine; adjusted HR 1.36; 95% CI 1.09 to 1.69). Similar results were obtained in a subgroup analysis that included the 16,861 patients who did not have their immunosuppressive regimen changed throughout the first posttransplantation year. In conclusion, sirolimus is independently associated with NOD. Given the negative impact of NOD on posttransplantation outcomes, these findings should be confirmed in prospective studies or in meta-analyses of existing trials that involved sirolimus.

Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival.

BACKGROUND AND OBJECTIVES: Development of new therapeutic strategies to improve long-term transplant outcomes requires improved understanding of the mechanisms by which these complications limit long-term transplant survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The association of acute rejection and new-onset diabetes was determined in the first posttransplantation year with the outcomes of transplant failure from any cause, death-censored graft loss, and death with a functioning graft in 27,707 adult recipients of first kidney-only transplants, with graft survival of at least 1 yr, performed between 1995 and 2002 in the United States. RESULTS: In multivariate analyses, patients who developed acute rejection or new-onset diabetes had a similar risk for transplant failure from any cause, but the mechanisms of transplant failure were different: Acute rejection was associated with death-censored graft loss but only weakly associated with death with a functioning graft. In contrast new-onset diabetes was not associated with death-censored graft loss but was associated with an increased risk for death with a functioning graft. CONCLUSIONS: Acute rejection and new-onset diabetes have a similar impact on long-term transplant survival but lead to transplant failure through different mechanisms. The mechanisms by which new-onset diabetes leads to transplant failure should be prospectively studied. Targeted therapeutic strategies to minimize the impact of various early posttransplantation complications may lead to improved long-term outcomes.

Outcomes of acute coronary syndrome in a large Canadian cohort: impact of chronic renal insufficiency, cardiac interventions, and anemia.

BACKGROUND: Chronic renal insufficiency (CRI) has been identified as an important risk factor for cardiac events. Studies in the United States reported decreased survival and decreased use of surgical and medical interventions after myocardial infarction in patients with CRI. METHODS: We studied the impact of renal function on health outcomes in a Canadian cohort of consecutive patients admitted with acute coronary syndrome (ACS) between October 1997 and October 1999. The study design is an observational cohort of 5,549 adult patients who survived to discharge with a discharge diagnosis of ACS. Renal function is classified into 4 levels: (1) normal, glomerular filtration rate (GFR) greater than 80 mL/min/1.73 m2 (>1.33 mL/s); (2) mild CRI, GFR of 60 to 80 mL/min/1.73 m2 (1.00 to 1.33 mL/s); (3) moderate CRI, GFR of 30 to 59 mL/min/1.73 m2 (0.50 to 0.98 mL/s); and (4) severe CRI, GFR less than 30 mL/min/1.73 m2 (<0.50 mL/s). The primary outcome is death. RESULTS: Advanced and moderate CRI independently predicted death (hazard ratio, 1.06; 95% confidence interval [CI], 1.01 to 1.12; and hazard ratio, 1.23; 95% CI, 1.18 to 1.29). Severe anemia (hemoglobin level < 9.0 g/dL [<90 g/L]) also was an independent risk factor for death (hazard ratio, 1.38; 95% CI, 1.18 to 1.61). Use of beta-blockers (hazard ratio, 0.91; 95% CI, 0.86 to 0.97), acetylsalicylic acid (hazard ratio, 0.90; 95% CI, 0.84 to 0.97), lipid-lowering therapy (hazard ratio, 0.84; 95% CI, 0.78 to 0.89), and medical thrombolysis (hazard ratio, 0.89; 95% CI, 0.81 to 0.97) were associated with reduced risk for death. Medical interventions with beta-blockers, acetylsalicylic acid, lipid-lowering therapy, and thrombolysis and surgical intervention were significantly less likely to be used in patients with CRI. CONCLUSION: Despite universal access to health care, Canadian patients with CRI are more likely to die after a cardiac event and less likely to receive important interventions.