Low Incidence of End-Stage Renal Disease in Childhood-Onset Type 1 Diabetes Followed for Up to 42 Years.

OBJECTIVE: End-stage renal disease (ESRD) is one of the most severe complications in type 1 diabetes. We aimed to estimate the cumulative incidence of ESRD in individuals with childhood-onset type 1 diabetes followed for up to 42 years. RESEARCH DESIGN AND METHODS: Data were based on the nationwide, population-based Norwegian Childhood Diabetes Registry and included case patients with new-onset type 1 diabetes (age <15 years) who had received a diagnosis during the periods 1973-1982 and 1989-2012. Follow-up took place until the development of ESRD, death, emigration, or 30 November 2015. We estimated the cumulative incidence of ESRD by linking to the Norwegian Renal Registry. RESULTS: Among the 7,871 patients, representing 147,714 person-years of follow-up, ESRD developed in 103 individuals (1.3%). The mean time from the diagnosis of diabetes to the development of ESRD was 25.9 years (range 12.7-39.1). The cumulative incidence of ESRD was 0.7% (95% CI 0.4-1.0) at 20 years' diabetes duration, 2.9% (2.3-3.7) at 30 years' duration, and 5.3% (4.3-6.5) at 40 years' duration. The risk of the development of ESRD was lower in women than in men (hazard ratio [HR] 0.61; 95% CI 0.41-0.91) and higher in individuals in whom diabetes had been diagnosed at 10-14 years of age compared with those in whom it was diagnosed before 10 years of age (HR 1.29; 1.06-1.56). We did not identify any significant difference in the risk of the development of ESRD between those in whom diabetes was diagnosed in 1973-1982 and in 1989-2012 (HR 0.80; 0.45-1.45). CONCLUSIONS: We report a very low incidence of ESRD among patients with childhood-onset diabetes in Norway. The risk was lower in women compared with men and in individuals in whom diabetes was diagnosed at a younger age.

Long-term Change in the Risk of Skin Cancer After Organ Transplantation: A Population-Based Nationwide Cohort Study.

Importance: The high risk of skin cancer after organ transplantation is a major clinical challenge and well documented, but reports on temporal trends in the risk of posttransplant cutaneous squamous cell carcinoma (SCC) are few and appear contradictory. Objective: To study temporal trends for the risk of skin cancer, particularly SCC, after organ transplantation. Design, Setting, and Participants: Population-based, nationwide, prospective cohort study of 8026 patients receiving a kidney, heart, lung, or liver transplant in Norway from 1968 through 2012 using patient data linked to a national cancer registry. The study was conducted in a large organ transplantation center that serves the entire Norwegian population of approximately 5.2 million. Exposures: Receiving a solid organ transplant owing to late-stage organ failure, followed by long-term immunosuppressive treatment according to graft-specific treatment protocols. Main Outcomes and Measures: Occurrence of first posttransplant SCC, melanoma, or Kaposi sarcoma of the skin. Risk of skin cancer was analyzed using standardized incidence ratios (SIRs) and, for SCC, multivariable Poisson regression analysis of SIR ratios, adjusting for 5-year time period of transplantation, different follow-up time, age, sex, and type of organ. Results: The study cohort included 8026 organ transplant recipients, 5224 men (65.1%), with a mean age at transplantation of 48.5 years. Median follow-up time was 6.7 years per recipient; total follow-up time, 69 590 person-years. The overall SIRs for SCC, melanoma, and Kaposi sarcoma were 51.9 (95% CI, 48.4-55.5), 2.4 (95% CI, 1.9-3.0), and 54.9 (95% CI, 27.4-98.2), respectively. In those who underwent transplantation in the 1983-1987 period, the unadjusted SIR for SCC was 102.7 (95%, 85.8-122.1), declining to 21.6 (95% CI, 16.8-27.0) in those who underwent transplantation in the 2003-2007 period. Adjusting for different follow-up times and background population risks, as well as age, graft organ, and sex, a decline in the SIR for SCC was found, with SIR peaking in patients who underwent transplantation in the 1983-1987 period and later declining to less than half in patients who underwent transplantation in the 1998-2002, 2003-2007, and 2008-2012 periods, with the relative SIRs being 0.42 (95% CI, 0.32-0.55), 0.31 (95% CI, 0.22-0.42), and 0.44 (95% CI, 0.30-0.66), respectively. Conclusions and Relevance: The risk of SCC after organ transplantation has declined significantly since the mid-1980s in Norway. Less aggressive and more individualized immunosuppressive treatment and close clinical follow-up may explain the decline. Still, the risk of SCC in organ transplant recipients remains much higher than in the general population and should be of continuous concern for dermatologists, transplant physicians, and patients.

Association Between Pretransplant Cancer and Survival in Kidney Transplant Recipients.

BACKGROUND: Kidney transplantation in recipients with a previous malignancy is often deferred 2 to 5 years after cancer treatment due to fear of cancer recurrence. In Norway, the required waiting period has been 1 year. METHODS: We compared patient and graft survival of recipients with pretransplant cancer to the outcomes of matched recipients without such cancer (comparators) using Cox regression. RESULTS: From 1963 to 2010, 377 (6.4%) of 5867 recipients had a pretransplant cancer. During a median follow-up of 6.8 years, 256 recipients died, 35 (13.7%) from recurrent cancer and 27 (10.5%) from de novo cancer. Uncensored and death-censored graft loss occurred in 263 and 46 recipients, respectively. All-cause mortality was similar as in comparators (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.93-1.20]; P = 0.40), death-censored graft loss was lower (HR, 0.63; 95% CI, 0.47-0.84; P = 0.002), and uncensored graft loss was similar (HR, 0.99; 95% CI, 0.87-1.12; P = 0.87). Cancer mortality was higher than in comparators (HR, 1.97; 95% CI, 1.51-2.56; P < 0.001), particularly during the first 5 years of follow-up (HR, 3.44; 95% CI, 2.36-5.03; P < 0.01). Waiting period was not associated with recurrent cancer mortality or all-cause mortality (both P > 0.45). Results were similar within cancer subgroups, with most data in patients with a history of kidney cancer, prostate cancer, urothelial cancer, and skin squamous cell carcinoma. CONCLUSIONS: Kidney transplant recipients with a pretransplant cancer had a similar overall patient and graft survival as recipients without such cancer. Cancer mortality was increased, particularly during the first 5 years after transplantation. A short waiting period was not associated with mortality.

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.

Long-term Mortality and End-Stage Renal Disease in a Type 1 Diabetes Population Diagnosed at Age 15-29 Years in Norway.

OBJECTIVE: To study long-term mortality, causes of death, and end-stage renal disease (ESRD) in people diagnosed with type 1 diabetes at age 15-29 years. RESEARCH DESIGN AND METHODS: This nationwide, population-based cohort with type 1 diabetes diagnosed during 1978-1982 (n = 719) was followed from diagnosis until death, emigration, or September 2013. Linkages to the Norwegian Cause of Death Registry and the Norwegian Renal Registry provided information on causes of death and whether ESRD was present. A clinical committee reviewed the causes of death. We calculated standardized mortality ratios (SMRs) for comparison with the background population. RESULTS: During 30 years' follow-up, 4.6% of participants developed ESRD and 20.6% (n = 148; 106 men and 42 women) died. Cumulative mortality by years since diagnosis was 6.0% (95% CI 4.5-8.0) at 10 years, 12.2% (10.0-14.8) at 20 years, and 18.4% (15.8-21.5) at 30 years. The SMR was 4.4 (95% CI 3.7-5.1). Mean time from diagnosis of diabetes to ESRD was 23.6 years (range 14.2-33.5). Death was caused by chronic complications (32.2%), acute complications (20.5%), violent death (19.9%), or any other cause (27.4%). Death was related to alcohol in 15% of cases. SMR for alcohol-related death was 6.8 (95% CI 4.5-10.3), for cardiovascular death was 7.3 (5.4-10.0), and for violent death was 3.6 (2.3-5.3). CONCLUSIONS: The cumulative incidence of ESRD was low in this cohort with type 1 diabetes followed for 30 years. Mortality was 4.4 times that of the general population, and more than 50% of all deaths were caused by acute or chronic complications. A relatively high proportion of deaths were related to alcohol.

Cardiac Assessment of Patients With Type 1 Diabetes Median 10 Years After Successful Simultaneous Pancreas and Kidney Transplantation Compared With Living Donor Kidney Transplantation.

BACKGROUND: In recipients with type 1 diabetes, we aimed to determine whether long-term normoglycemia achieved by successful simultaneous pancreas and kidney (SPK) transplantation could beneficially affect progression of coronary artery disease (CAD) when compared with transplantation of a kidney-alone from a living donor (LDK). METHODS: In 42 kidney transplant recipients with functioning grafts who had received either SPK (n = 25) or LDK (n = 17), we studied angiographic progression of CAD between baseline (pretransplant) and follow-up at 7 years or older. In addition, computed tomography scans for measures of coronary artery calcification and echocardiographic assessment of left ventricular systolic function were addressed at follow-up. RESULTS: During a median follow-up time of 10.1 years (interquartile range [IQR], 9.1-11.5) progression of CAD occurred at similar rates (10 of 21 cases in the SPK and 5 of 14 cases in the LDK group; P = 0.49). Median coronary artery calcification scores were high in both groups (1767 [IQR, 321-4035] for SPK and 1045 [IQR, 807-2643] for LDK patients; P = 0.59). Left ventricular systolic function did not differ between the 2 groups. The SPK and LDK recipients were similar in age (41.2 ± 6.9 years vs 40.5 ± 10.3 years; P = 0.80) and diabetes duration at engraftment but with significant different mean HbA1c levels of 5.5 ± 0.4% for SPK and 8.3 ± 1.5% for LDK patients (P < 0.001) during follow-up. CONCLUSIONS: In patients with both type 1 diabetes and end-stage renal disease, SPK recipients had similar progression of CAD long-term compared with LDK recipients. Calcification of coronary arteries is a prominent feature in both groups long-term posttransplant.

Are Octogenarians With End-Stage Renal Disease Candidates for Renal Transplantation?

BACKGROUND: Elderly patients are the fastest-growing group in need of renal transplantation. This study puts focus on renal transplant recipients in their 80th year or longer at time of engraftment. Is there evidence to support an absolute upper age limit for renal transplantation? METHODS: Recipients in their 80th year or longer, transplanted between 1983 and 2015, were included. Data were retrieved from the Norwegian Renal Registry in the end of October 2015. Graft and patient survivals were compared with recipients aged 70 to 79 years at transplantation. RESULTS: Forty-seven patients older than 79 years were transplanted in the defined period. Median age 80.1 years, 81% were men. Median time on dialysis before transplantation was 18.5 months. All patients received an allograft from a deceased donor (median donor age, 61.8 years). In the death-censored graft survival model, there was no statistical difference between the groups. We found improved patient and graft survivals after introduction of mycophenolate mofetil and induction with basiliximab. Patients transplanted before 2000 had increased risk of death compared with those transplanted after 2000 (hazard ratio, 3.2; 95% confidence interval, 1.2-8.7). Median uncensored graft survival for patients transplanted after the year 2000 was 5.0 year (95% confidence interval, 2.4-7.6). Median patient survival was 5.0 years (3.1-6.9) and 5-year patient survival was 55%. CONCLUSIONS: Age by itself should not be an absolute contraindication against renal transplantation. An estimated 5-year survival rate of 55% post-engraftment for an 80-year-old patient is in our opinion more than acceptable.

The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry.

BACKGROUND: This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. METHODS: Eighteen national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression. RESULTS: From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998-2002 and 2003-2007 [adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86]. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients ≥65 years. CONCLUSION: This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population.

Long-term cardiovascular outcomes in type 1 diabetic patients after simultaneous pancreas and kidney transplantation compared with living donor kidney transplantation.

AIMS/HYPOTHESIS: Mortality due to cardiovascular disease (CVD), particularly coronary artery disease (CAD), is high in type 1 diabetic patients with end-stage renal disease (ESRD). We aimed to determine whether normoglycaemia, as achieved by successful simultaneous pancreas and kidney (SPK) transplantation, could improve long-term outcomes compared with living donor kidney-alone (LDK) transplantation. METHODS: We studied 486 type 1 diabetic patients with ESRD who underwent a first SPK (n = 256) or LDK (n = 230) transplant between 1983 and 2012 and were followed to the end of 2014. Data were retrieved from the Norwegian Renal Registry and hospital records. Kaplan-Meier plots and multivariate Cox regression, with correction for recipient, donor and transplant factors, were used to examine potential associations between transplant type and all-cause and CVD- and CAD-related mortality. RESULTS: Median follow-up time was 7.9 years (interquartile range 4.3, 12.9). The adjusted HR for CVD-related deaths in SPK recipients compared with LDK recipients was 0.63 (95% CI 0.40, 0.99; p = 0.047), while the HRs for all-cause and CAD-related mortality were 0.81 (95% CI 0.57, 1.16; p = 0.25) and 0.63 (95% CI 0.36, 1.12; p = 0.12), respectively. Compared with the LDK group, SPK recipients were younger and received grafts from younger donors. Cardiovascular mortality was higher in patients transplanted between 1983 and 1999 compared with those who received their grafts in subsequent years. CONCLUSIONS/INTERPRETATION: In patients with type 1 diabetes and ESRD, SPK transplantation was associated with reduced long-term cardiovascular mortality compared with LDK transplantation.

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.

Renal replacement therapy in Europe: a summary of the 2012 ERA-EDTA Registry Annual Report.

BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. Individual patient level data were received from 31 renal registries, whereas 14 renal registries contributed data in an aggregated form. The incidence, prevalence and survival probabilities of patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp in Montenegro. The proportion of incident patients ≥75 years varied from 15 to 44% between countries. The overall unadjusted prevalence on 31 December 2012 was 716.7 pmp (n = 451 270), ranging from 1670.2 pmp in Portugal to 146.7 pmp in the Ukraine. The proportion of prevalent patients ≥75 years varied from 11 to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59.7% (95% confidence interval, CI: 59.3-60.0) which fell to 39.3% (95% CI: 38.7-39.9) in patients 65-74 years and 21.3% (95% CI: 20.8-21.9) in patients ≥75 years.

Aortic Stiffness in a Mortality Risk Calculator for Kidney Transplant Recipients.

BACKGROUND: The association between aortic stiffness and all-cause mortality in kidney transplant recipients (KTRs) is uncertain, and aortic stiffness has not yet been incorporated into risk prediction tools. METHODS: During 2007 to 2012, we measured carotid-femoral pulse wave velocity (PWV; SphygmoCor apparatus) 8 weeks after transplantation. The association between PWV and mortality was assessed in a Cox regression analysis adjusting for seven risk factors from a previously validated model. Internal validation was performed by bootstrap resampling, and discrimination and overfitting evaluated by Harrell's C and the calibration slope. RESULTS: Of 1497 KTRs, 1040 (69%) had a valid PWV measurement. During a median follow-up of 4.2 years, 82 patients died. The association between PWV and mortality showed a ceiling effect, and PWV was truncated at 12 m/sec. Each 1 m/sec increase in PWV, up to 12 m/sec, was associated with mortality, hazard ratio (HR) 1.36 (95% CI, 1.14-1.62; P = 0.001). An interquartile range increase (3.8 m/sec) tripled the hazard of mortality, HR, 3.21 (95% CI, 1.63-6.31), similar to the effect of being approximately 20 years older (interquartile range increase (21.6 years); HR, 3.06 [95% CI, 1.87-5.29]). The PWV improved model discrimination with an increase in Harrell's C from 0.76 to 0.78; C difference, 0.024 (95% CI, 0.005-0.043; P = 0.01). Overfitting was moderate with a calibration slope of 0.89, and the final model was adjusted accordingly. A spreadsheet version is presented to estimate expected 5-year survival. CONCLUSIONS: The PWV is a strong risk factor for mortality in KTRs.

Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry.

BACKGROUND: Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex. METHODS: We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression. RESULTS: Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies. CONCLUSION: Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required.

Regional differences in renal replacement therapy in northern Norway 2000-2012.

OBJECTIVES: Distance from residence location to a centre for renal replacement therapy (RRT) may influence patients' quality of life and prognosis. Northern Norway constitutes 45% of Norway's landmass, but has less than 10% of the population. METHODS: In this study, we analysed all patients in northern Norway consecutively registered in the Norwegian Renal Registry during 2000-2012. A total of 634 patients (Nordland County 321 patients, Troms County 215 patients and Finnmark County 98 patients) were investigated. RESULTS: There were more smokers (31% vs. 22%) and patients with diabetes (32% vs. 22%) in Finnmark, but the difference did not reach statistical significance. Patients undergoing RRT and living in Finnmark County had a significantly worse outcome (P=0.03). The median survivals after initiation of RRT were 3.8 years (Finnmark), 6.4 years (Troms) and 5.4 years (Nordland), respectively. The most common causes of death were cardiovascular disease (53%), infections (16%), withdrawal from therapy (15%) and malignancy (13%). In a Cox analysis, age (P<0.0001), diabetes (P=0.008) and smoking at any time (P<0.004) were individual factors correlated with inferior prognosis. CONCLUSION: Age, smoking and diabetes were prognostic factors. Residents of the northernmost county (Finnmark) experienced an inferior prognosis. Long distance from residence location to hospital may be another factor, but this could not be documented. Preventive strategies should be improved.

Use of vascular access for haemodialysis in Europe: a report from the ERA-EDTA Registry.

BACKGROUND: Although arteriovenous fistulas (AVFs) are actively promoted, their use at the start of haemodialysis (HD) seems to be decreasing worldwide. In this paper, we describe recent trends in incidence and prevalence of vascular access types in Europe from 2005 to 2009 and their relationship with patient characteristics and survival. METHODS: Ten European renal registries participating in the ERA-EDTA Registry provided data on incidence (n = 13,044) and/or prevalence (n = 75,715) of vascular access types. We used logistic regression to assess which factors influence the likelihood to be treated with an AVF rather than another type. RESULTS: The use of AVFs at the start of HD showed a significant decreasing trend from 42% in 2005 to 32% in 2009 (P < 0.0001), while the use of central venous catheters (CVCs) increased from 58 to 68% (P < 0.0001). A similar evolution pattern was observed for the prevalence; use of AVFs decreased from 66 to 62% and use of CVCs increased from 28 to 32%. There was a large international variation in the use of the different vascular access types. Female patients [adjusted odds ratio: 0.84, 95% confidence interval (CI): 0.78-0.90] and those ≥80 years (0.77, 95% CI: 0.67-0.90) were least likely to start HD with an AVF. CONCLUSION: In Europe, there is a decreasing trend in the use of AVFs and an increasing trend in the use of CVCs at the start and after the start of HD. We cannot explain all between-country variations we found, and more research is needed to clarify how healthcare around vascular access is organized in Europe.

Parathyroid hormone and clinical outcome in kidney transplant patients with optimal transplant function.

BACKGROUND: The aim of the study was to investigate whether serum levels of intact parathyroid hormone (iPTH) are associated with an increased risk of cardiovascular events, graft loss, or mortality in kidney transplant patients with optimal transplant function. METHODS: From the Norwegian Renal Registry, we identified 522 patients who received a first kidney transplant from 2001 to 2008 with optimal transplant function defined as an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2, more than one yr after transplantation. Cox's proportional hazard models were used to assess the association between iPTH measured 10 wk after transplantation and the composite endpoint. The estimates were adjusted for age, gender, serum calcium, serum phosphate, diabetes mellitus, cardiovascular disease, and time on dialysis prior to transplantation. RESULTS: Median follow-up time was 3.9 yr (interquartile range, IQR: 2.0-6.0 yr). Patients in the third iPTH quartile (9.3-14.4 pM) had the lowest risk for reaching the composite endpoint. Patients in the fourth iPTH quartile (>14.4 pM) had an increased risk compared to those in the third quartile (HR: 2.60, 95% CI: 1.10-6.16, p=0.03). CONCLUSION: In patients with optimal transplant function, iPTH levels are associated with a clinical outcome consisting of cardiovascular events, graft loss, and all-cause mortality.

CD11c(+) dendritic cells rather than Langerhans cells are reduced in normal skin of immunosuppressed renal transplant recipients.

The increased risk of squamous cell carcinomas (SCC) in renal transplant recipients (RTR) is related to impaired immunosurveillance as a consequence of immunosuppressive therapy. Since dendritic cells (DC) play an important role in immunosurveillance, we investigated the quantity of DC subsets and macrophages in normal skin of RTR and immunocompetent controls by immunohistochemistry. In this comparative study Langerhans' cells (LC) were present in similar numbers in RTR and controls. The number of CD11c+ DC was significantly reduced in RTR, particularly in patients on triple treatment therapy, compared with controls. Macrophages were significantly increased. Plasmacytoid DC were not detected in normal skin. The reduced quantity of CD11c+ DC and increased number of macrophages in normal skin of immunosuppressed RTR may contribute to the increased incidence of SCC in RTR. This finding underlines the role of DC subsets in immunosurveillance, and may have implications for our understanding of the effect of immunosuppression on DC subsets.