Impact of initial dialysis modality on mortality: a propensity-matched study

Background Whether the choice of dialysis modality in patients with end stage renal disease may impact mortality is undecided. No randomized controlled trial has properly addressed this issue. Propensity-matched observational studies could give important insight into the independent effect of peritoneal (PD) opposed to haemodialysis (HD) on all-cause and cardiovascular mortality. Methods To correct for case-mix differences between patients treated with PD and HD, propensity-matched analyses were utilized in all patients who initiated dialysis as first renal replacement therapy in Norway in the period 2005–2012. PD patients were matched in a 1:1 fashion with HD patients, creating 692 pairs of patients with comparable baseline variables. As-treated and intention-to treat analyses were undertaken to assess cardiovascular and all-cause mortality. Interaction analyses were used to assess differences in the relationship between initial dialysis modality and mortality, between strata of age, gender and prevalent diabetes mellitus. Results In the as-treated analyses, initial dialysis modality did not impact 2-year (PD vs. HD: HR 0.87, 95 % CI 0.67–1.12) or 5-year all-cause mortality (HR 0.95, 95 % CI 0.77–1.17). In patients younger than 65 years, PD was superior compared to HD with regard to both 2-year (HR 0.39, 95 % CI 0.19–0.81), and 5-year all-cause mortality (HR 0.49, 95 % CI 0.27–0.89). Cardiovascular mortality was also lower in the younger patients treated with PD (5-year HR 0.38, 95 % CI 0.15–0.96). PD was not associated with impaired prognosis in any of the prespecified subgroups compared to HD. The results were similar in the as-treated and intention-to-treat analyses. Conclusion Survival in PD was not inferior to HD in any subgroup of patients even after five years of follow-up. In patients below 65 years, PD yielded superior survival rates compared to HD. Increased use of PD as initial dialysis modality in ESRD patients could be encouraged

Health related quality of life in patients in dialysis after renal graft loss and effect of gender

BACKGROUND: An increasing number of dialysis patients have returned to dialysis after renal graft loss, and the transition in disease state could likely be associated with reduced health related quality of life (HRQOL). Furthermore, gender differences in HRQOL have been observed in dialysis and kidney transplanted patients, but whether transition in disease state affects HRQOL differently in respect to gender is not known. The aims of this study were to compare HRQOL in dialysis patients with graft loss to transplant naïve dialysis patients, and to explore possible gender differences. METHODS: In a cross-sectional study, HRQOL was measured in 301 prevalent dialysis patients using the Kidney Disease and Quality of Life Short Form version 1.3. Adjusted comparisons were made between dialysis patients with previous graft loss and the transplant naïve patients. Multiple linear regression analyses were performed with HRQOL as outcome variables. Interaction analyses using product terms were performed between gender and graft loss. HRQOL was analysed separately in both genders. RESULTS: Patients with renal graft loss (n = 50) did not experience lower HRQOL than transplant naïve patients after multiple adjustments. Among patients with graft loss, women (n = 23) reported lower HRQOL than men (n = 27) in the items physical function (40 vs. 80, p = 0.006), and effect of kidney disease (49 vs. 67, p = 0.017). Women with graft loss reported impaired kidney-specific HRQOL compared to transplant naïve women (n = 79) in the items effect of kidney disease (50 vs. 72, p = 0.002) and cognitive function (80 vs. 93, p = 0.006), and this observation persisted after multiple adjustments. Such differences were not apparent in the male counterparts. CONCLUSIONS: Patients who resumed dialysis after renal graft loss did not have lower HRQOL than dialysis patients not previously transplanted. However, losing graft function was associated with reduced HRQOL in females, and important interactions were identified between graft loss and gender. This needs to be further explored in prospective studies

From dialysis to transplantation: a 5-year longitudinal study on self-reported quality of life

Background Little is known how health related quality of life (HRQOL) change in the transition from dialysis to renal transplantation (RTX). Longitudinal data addressing the patient-related outcomes are scarce, and particularly data regarding kidney-specific HRQOL are lacking. Thus, the aim of the current study was to assess HRQOL in patients followed from dialysis to RTX. Furthermore, to compare HRQOL in RTX patients and the general population. Methods In a prospective study, HRQOL was measured in a cohort of 110 patients (median age 53.5 (IQR 39–62) years, GFR 54 (45–72) ml/min/1.73 m2) in dialysis and after RTX using the self-administered Kidney Disease and Quality of Life Short Form version 1.3 (KDQOL-SF). Generic HRQOL in the RTX patients was compared to that of the general population (n = 5903) using the SF-36. Clinical important change after RTX was defined as difference in HRQOL of SD/2. Results Follow-up time was 55 (IQR 50–59) months, and time after RTX was 41 (34–51) months. Four of nine domains in kidney-specific HRQOL improved after RTX, i.e. burden of kidney disease, effect of kidney disease, symptoms and work status. In SF-36, general health, vitality, social function and role physical improved after RTX, but none of the domains improved sufficiently to be regarded as clinically relevant change. There were highly significant differences in HRQOL between RTX patients and the general population after adjustment for age and gender for all items of SF-36 except for bodily pain and mental health. Conclusions HRQOL improved in the transition from dialysis to transplantation, but clinical relevant change was only obtained in the kidney specific domains. HRQOL was perceived considerably poorer in RTX patients than in the general population. Our observations point to the need of improving HRQOL even after RTX, and should encourage further longitudinal research and clinical attention during treatment shift

Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

Background Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population. Methods In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics. Results Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine). The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein) were significantly up-regulated in association with AR (P = 0.03) while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74) tended to be up-regulated ( P = 0.13). Conclusion The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis. Trial registration ClinicalTrials.gov number NCT0013900

Should patients older than 65 years be offered a second kidney transplant?

Background: Age and number of recipients in need of kidney re-transplantation are increasing. Re-transplantation practices and outcomes in elderly recipients are not previously explored. We aimed to retrospectively evaluate the outcomes of recipients 65 years and older receiving their second deceased donor allograft. Methods: The study was designed as a retrospective registry based study. All recipients 65 years or older who received a deceased donor kidney transplant at Oslo University Hospital between 2000 and 2014 were included in the study. Survival outcomes were compared between recipients of first (TX1) and second (TX2) allograft. Survival analyses were performed using the Kaplan–Meier method and Cox proportional hazard models with patient survival, uncensored graft survival and death-censored graft survival as outcomes in the analyses. Results: Seven hundred and thirty-tree recipients > 65 years received a first (n = 687) or second (n = 46) deceased donor kidney transplant. Five years uncensored graft survival rates were 64% in TX 2 and 67% in TX 1 (P= 0.789). Estimated five years graft survival rates censored for death with functioning graft were 88% in TX2 and 90% in TX1 (P=0.475). Adjusted hazard ratio for uncensored graft loss (TX2 vs. TX1) was 1.24 (95% CI 0.77 – 2.00). Adjusted hazard ratio for graft loss censored for death with functioning graft (TX2 vs. TX1) was 1.70 (0.72-4.02). Conclusions: Older recipients of second transplants have outcomes that are comparable to the outcomes of age-matched first transplant recipients, and far better than previously documented for older transplant candidates remaining on dialysis treatment. Advanced age by itself should not be a contraindication for re-transplantation. Best results are achieved with short time on dialysis before re-transplantation

Elevated Terminal C5b-9 Complement Complex 10 Weeks Post Kidney Transplantation Was Associated With Reduced Long-Term Patient and Kidney Graft Survival

Background: The major reason for graft loss is chronic tissue damage, as interstitial fibrosis and tubular atrophy (IF/TA), where complement activation may serve as a mediator. The association of complement activation in a stable phase early after kidney transplantation with long-term outcomes is unexplored. Methods: We examined plasma terminal C5b-9 complement complex (TCC) 10 weeks posttransplant in 900 patients receiving a kidney between 2007 and 2012. Clinical outcomes were assessed after a median observation time of 9.3 years [interquartile range (IQR) 7.5–10.6]. Results: Elevated TCC plasma values (≥0.7 CAU/ml) were present in 138 patients (15.3%) and associated with a lower 10-year patient survival rate (65.7% vs. 75.5%, P Conclusions: Early complement activation, assessed by plasma TCC, was associated with impaired long-term patient and graft survival

Elevated Terminal C5b-9 Complement Complex 10 Weeks Post Kidney Transplantation Was Associated With Reduced Long-Term Patient and Kidney Graft Survival

Background: The major reason for graft loss is chronic tissue damage, as interstitial fibrosis and tubular atrophy (IF/TA), where complement activation may serve as a mediator. The association of complement activation in a stable phase early after kidney transplantation with long-term outcomes is unexplored. Methods: We examined plasma terminal C5b-9 complement complex (TCC) 10 weeks posttransplant in 900 patients receiving a kidney between 2007 and 2012. Clinical outcomes were assessed after a median observation time of 9.3 years [interquartile range (IQR) 7.5–10.6]. Results: Elevated TCC plasma values (≥0.7 CAU/ml) were present in 138 patients (15.3%) and associated with a lower 10-year patient survival rate (65.7% vs. 75.5%, P < 0.003). Similarly, 10-year graft survival was lower with elevated TCC; 56.9% vs. 67.3% (P < 0.002). Graft survival was also lower when censored for death; 81.5% vs. 87.3% (P = 0.04). In multivariable Cox analyses, impaired patient survival was significantly associated with elevated TCC [hazard ratio (HR) 1.40 (1.02–1.91), P = 0.04] along with male sex, recipient and donor age, smoking, diabetes, and overall survival more than 1 year in renal replacement therapy prior to engraftment. Likewise, elevated TCC was independently associated with graft loss [HR 1.40 (1.06–1.85), P = 0.02] along with the same covariates. Finally, elevated TCC was in addition independently associated with death-censored graft loss [HR 1.69 (1.06–2.71), P = 0.03] as were also HLA-DR mismatches and higher immunological risk. Conclusions: Early complement activation, assessed by plasma TCC, was associated with impaired long-term patient and graft survival

The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

BACKGROUND AND OBJECTIVES: Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. RESULTS: There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality. CONCLUSIONS: Higher plasma phospholipid marine n-3 polyunsaturated fatty acid levels were independently associated with better patient survival