Factors associating with differences in the incidence of renal replacement therapy among elderly: data from the ERA-EDTA Registry.

Background: The incidence of renal replacement therapy (RRT) in the general population ≥75 years of age varies considerably between countries and regions in Europe. Our aim was to study characteristics and survival of elderly RRT patients and to find explanations for differences in RRT incidence. Methods: Patients ≥75 years of age at the onset of RRT in 2010-2013 from 29 national or regional registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry were included. Chi-square and Mann-Whitney U tests were used to assess variation in patient characteristics and linear regression was used to study the association between RRT incidence and various factors. Kaplan-Meier curves and Cox regression were employed for survival analyses. Results: The mean annual incidence of RRT in the age group ≥75 years of age ranged from 157 to 924 per million age-related population. The median age at the start of RRT was higher and comorbidities were less common in areas with higher RRT incidence, but overall the association between patient characteristics and RRT incidence was weak. The unadjusted survival was lower in high-incidence areas due to an older age at onset of RRT, but the adjusted survival was similar [relative risk 1.00 (95% confidence interval, 0.97-1.03)] in patients from low- and high-incidence areas. Conclusions: Variation in the incidence of RRT among the elderly across European countries and regions is remarkable and could not be explained by the available data. However, the survival of patients in low- and high-incidence areas was remarkably similar.

Biochemical variables and survival of patients with type 1 diabetes on renal replacement therapy.

BACKGROUND/AIMS: End-stage renal disease (ESRD) is one of the most serious complications of type 1 diabetes, but scarcely studied. Our aim was to estimate the association between biochemical variables and survival among these patients. METHODS: This was an incident cohort study of patients with type 1 diabetes entering chronic renal replacement therapy (RRT) in Finland 2000-2011 (n = 834). Biochemical variables were measured before the initiation of RRT. Adjusted relative risk of death according to biochemical variables was estimated by Cox regression. RESULTS: When adjusted for age, sex, comorbidities, and initial treatment modality of RRT, the most important predictors of death were low creatinine and albumin and high C-reactive protein. CONCLUSION: Among type 1 diabetes patients entering chronic RRT, biochemical variables independently associated with survival are creatinine, albumin and C-reactive protein. They reflect the nutritional status, proteinuria, liver function, and ongoing inflammatory process. Treatment of these might improve survival.

Modality of chronic renal replacement therapy and survival--a complete cohort from Finland, 2000-2009.

BACKGROUND: Studies on dialysis modality and survival have shown conflicting results, mostly due to insufficient and varying control of confounding factors. Using comprehensive data on a well-defined patient cohort, we therefore investigated the association of dialysis modality with survival on chronic renal replacement therapy (RRT) and whether this association varies between subgroups of patients. METHODS: Survival analyses included all adult patients entering chronic RRT in Finland between 2000 and 2009 and used information obtained from the Finnish Registry for Kidney Diseases and the Finnish Kidney Transplant Registry. In our primary intention-to-treat (ITT) analysis, we calculated relative risk of death according to dialysis modality on Day 91 from RRT start, comparing peritoneal dialysis (PD) to haemodialysis (HD). Relative risks were adjusted for putative confounders. Interactions between treatment groups and other variables were estimated. RESULTS: Of the total 4463 patients, 42% died during the 10 years of follow-up. Median survival time was 5.2 years. In unadjusted ITT analysis, relative risk of death of PD patients was 0.65 (95% CI 0.58-0.73, P < 0.001) compared with HD patients. With adjustment for 26 variables, the corresponding relative risk of death was 1.07 (95% CI 0.94-1.22, P = 0.33). When censoring at time of kidney transplantation, the result was similar with a relative risk of death of 1.09 (95% CI 0.95-1.25, P = 0.24) on PD compared with HD. CONCLUSIONS: PD is associated with several factors generally related to good prognosis. After comprehensive adjustment for putative confounding factors with the ITT analysis approach, we found no significant difference in survival between PD and HD patients.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.

BACKGROUND: Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. METHODS: This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. FINDINGS: 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74-0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76-1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60-0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68-0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10,000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). INTERPRETATION: Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. FUNDING: Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.

Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.

BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS: We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS: After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)

Employment of patients receiving maintenance dialysis and after kidney transplant: a cross-sectional study from Finland.

BACKGROUND: Associations between mode of renal replacement therapy and employment rate have not been well characterized. STUDY DESIGN: Cross-sectional registry analysis. SETTING & PARTICIPANTS: The employment status of all prevalent 15- to 64-year-old dialysis and kidney transplant patients in Finland at the end of 2007 (N = 2,637) was analyzed by combining data from the Finnish Registry for Kidney Diseases with individual-level employment statistics of the Finnish government. PREDICTOR: Prevalence rate ratios (PRRs) of employment according to treatment modality with adjustment for age, sex, cause of end-stage renal disease (ESRD), duration of ESRD, and comorbid conditions were estimated using Cox regression with a constant time at risk. OUTCOME: Employment status of patients on dialysis therapy or after transplant. MEASUREMENTS: Clinical data were collected from the Finnish Registry for Kidney Diseases, and employment data were acquired from Statistics Finland. RESULTS: 19% of hemodialysis patients, 31% of peritoneal dialysis patients, and 40% of patients with a functioning transplant were employed; the overall employment rate for the Finnish population aged 15-64 years is 67%. Home hemodialysis patients and those treated with automated peritoneal dialysis had employment rates of 39% and 44%, respectively. In adjusted analysis, patients on home hemodialysis therapy (PRR, 1.87), on automated peritoneal dialysis therapy (PRR, 2.14), or with a kidney transplant (PRR, 2.30) had higher probabilities of employment than in-center hemodialysis patients. Patients with type 1 or 2 diabetes as the cause of ESRD had the lowest probability of employment (PRR, 0.48-0.60 compared with glomerulonephritis). Patients aged 25-54 years more frequently were employed than those younger than 25 or older than 54 years. Sex did not predict employment. For transplant recipients, longer time since transplant was associated with higher employment in addition to the mentioned factors. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Employment rate of home dialysis patients was similar to that of transplant recipients and higher than that of in-center hemodialysis patients. Patients with diabetes were less likely to be employed.

Effect of vascular comorbidities on survival of type 2 diabetes patients on renal replacement therapy.

BACKGROUND: Atherosclerosis is an important predictor of mortality in patients with end-stage renal disease. The aim of this study was to determine how various vascular comorbidities such as coronary heart disease (CHD), peripheral vascular disease (PVD) or cerebrovascular disease (CeVD) affect survival of type 2 diabetic patients on renal replacement therapy (RRT). METHODS: Patients who entered RRT because of type 2 diabetes in 2000-2008 (n = 877) were identified within the Finnish Registry for Kidney Diseases. The patients were followed up until death or end of follow-up. Survival probabilities were calculated using Kaplan-Meier curves. Multivariate modeling was performed using Cox regression. RESULTS: 41% of the patients had CHD, 27% PVD and 16% CeVD at the start of RRT. Patients with PVD had a 1.9-fold (95% CI 1.6-2.3) risk of death compared to those without PVD when adjusting for age and gender, while patients with CHD had a 1.5-fold (95% CI 1.2-1.8) and those with CeVD a 1.4-fold (95% CI 1.1-1.8) risk compared to those without these diseases. The hazard ratio (HR) for death was highest in patients with the combination of PVD and either CHD (HR 2.8, 95% CI 2.1-3.8) or CeVD (HR 2.9, 95% CI 1.6-5.2) as compared to patients without any vascular comorbidities. CONCLUSION: PVD is the vascular comorbidity that increases risk of death the most among patients with type 2 diabetes starting RRT. Prevention of PVD in this patient group would merit further studies.

Decline in glomerular filtration rate during pre-dialysis phase and survival on chronic renal replacement therapy.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is widely used in follow-up and assessment of patients before start of chronic renal replacement therapy (RRT). Reported data on impact of eGFR decline pattern during pre-dialysis phase on consequent survival on RRT are, however, non-existent. METHODS: Using the database of the Finnish Registry for Kidney Diseases, we conducted a cohort study of all incident adult patients (n = 457) entering chronic RRT in Finland in 1998, with follow-up until 31 December 2008. We included those (n = 319) with three serum creatinine measurements (at ∼12 and 3 months and 1 to 2 weeks prior to RRT start) and calculated their slopes of eGFR using the modification of diet in renal disease formula. According to eGFR slopes (in mL/min/1.73m(2)/year), patients were divided into tertiles: most rapid (>8.5, n = 107), intermediate (3.4-8.5, n = 107) and slowest decline (<3.4, n = 105). RESULTS: Median survival time was 5.6 (95% confidence interval 4.2-7.0) years. Compared to the patient group with the slowest eGFR decline, age- and gender-adjusted relative risk of death was 1.1 (0.8-1.5) in the intermediate group and 1.7 (1.2-2.4, P = 0.002) in the most rapid decline group. When further adjusting for kidney disease diagnosis, comorbidities, use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, body mass index, blood haemoglobin and serum albumin, the association was no longer significant. CONCLUSIONS: Rapid decline in eGFR before entering chronic RRT associates with increased mortality on RRT. The elevated mortality appears to be caused by known risk factors for death on RRT.

New primary renal diagnosis codes for the ERA-EDTA.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry has produced a new set of primary renal diagnosis (PRD) codes that are intended for use by affiliated registries. It is designed specifically for use in renal centres and registries but is aligned with international coding standards supported by the WHO (International Classification of Diseases) and the International Health Terminology Standards Development Organization (SNOMED Clinical Terms). It is available as supplementary material to this paper and free on the internet for non-commercial, clinical, quality improvement and research use, and by agreement with the ERA-EDTA Registry for use by commercial organizations. Conversion between the old and the new PRD codes is possible. The new codes are very flexible and will be actively managed to keep them up-to-date and to ensure that renal medicine can remain at the forefront of the electronic revolution in medicine, epidemiology research and the use of decision support systems to improve the care of patients.

Improved survival of type 2 diabetic patients on renal replacement therapy in Finland.

BACKGROUND: Survival of type 2 diabetes mellitus patients on maintenance dialysis therapy is poor mainly due to cardiovascular events. The aim was to examine whether survival of type 2 diabetes patients on renal replacement therapy (RRT) in Finland has improved during 1995-2005. METHODS: Patients who entered RRT because of type 2 diabetes mellitus in 1995-99 (n = 314) and 2000-05 (n = 583) were identified within the Finnish Registry for Kidney Diseases. The two cohorts were followed up from start of RRT until death or end of follow-up on 31 December 2006. Survival probabilities and probabilities of receiving a kidney transplant were calculated using Kaplan-Meier curves. Multivariate modelling was performed using Cox regression. RESULTS: Patients who entered RRT in 2000-05 had lower risk of dying than those who entered in 1995-99; hazard ratio (HR) was 0.76 (95% CI 0.65-0.89) and 0.74 (95% CI 0.63-0.87) with adjustment for age and gender. The decreased risk of death was most obvious in age groups 55-64 (HR 0.67, 95% CI 0.49-0.92) and 65-74 years (HR 0.69, 95% CI 0.56-0.87). Adjustment for albumin in addition to age and gender only slightly weakened the effect of study periods (HR 0.83, 95% CI 0.69-1.01). The patients in 2000-05 were more obese, had lower total and LDL cholesterol and higher HDL cholesterol and albumin concentration in serum than patients in 1995-99. Patients' probability to receive a kidney transplant was low in both groups. CONCLUSIONS: Survival of type 2 diabetes patients on RRT improved during the time period 1995-2005 in Finland while the probability of receiving a kidney transplant remained low and unchanged.

An update on renal replacement therapy in Europe: ERA-EDTA Registry data from 1997 to 2006.

BACKGROUND: Recent studies have indicated a stabilization in the incidence rates of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in a number of European countries. The aim of this study was to provide an update on the incidence, prevalence and outcomes of RRT in Europe over the past decade. METHODS: Nineteen European national or regional renal registries with registry data from 1997 to 2006 participated in the study. Incidence and prevalence trends were analysed with Poisson and Joinpoint regression. Cox regression methods were used to examine patient survival. RESULTS: The total adjusted incidence rate of RRT for ESRD increased from 109.9 per million population (pmp) in 1997 to 119.7 pmp in 2000, i.e. an average annual percentage change (AAPC) of 2.9% (95% CI 2.1-3.8%). Thereafter, the incidence increased at a much lower rate to 125.4 pmp in 2006 [AAPC 0.6% (95% CI 0.3-0.8%)]. This change in the trend of the incidence of RRT was largely due to a stabilization in the incidence rates of RRT for females aged 65-74 years, males aged 75-84 years and patients receiving RRT for ESRD due to hypertension/renal vascular disease. The overall adjusted prevalence in Europe continued to increase linearly at 2.7% per year. Between the periods 1997-2001 and 2002-2006, the risk of death decreased for all treatment modalities, with the most substantial improvement in patients starting peritoneal dialysis [19% (95% CI 15-22%)] and in patients receiving a kidney transplant [17% (95% CI 11-23%)]. CONCLUSION: This European study shows that the annual rise of the overall incidence rate of RRT for ESRD has diminished and that in several age groups the incidence rates have now stabilized. The survival of dialysis patients and kidney transplant recipients has continued to improve.

The Nephrocare project: referral, patient case-mix, follow-up and quality of renal care in Nordic renal centres.

OBJECTIVE: Few studies have focused on patients actually attending renal units for their follow-up over time. This study reports the type of prevalent patients (case-mix) with a renal condition being followed up by 19 renal units in the Nordic countries during 1998-99. MATERIAL AND METHODS: In a joint quality of care development project between the renal societies of the five Nordic countries and the unit for Quality of Health Systems, WHO (Europe), 19 renal units collected data on a random sample of their prevalent patients. RESULTS: At follow-up, 56% had chronic kidney disease (CKD) not in renal replacement therapy (RRT). Seventeen per cent had haemodialysis (HD), 6% peritoneal dialysis (PD) and 21% a functioning kidney transplant (Tx). In the CKD group, 5.9% were CKD stage 1, 17.6% stage 2, 35.2% stage 3, 25.6% stage 4 and 15.7% stage 5. One-third had known cardiovascular disease, 30% known diabetes, half had a blood pressure >140/90 mmHg and 75% > 130/80 mmHg. Twenty eight per cent had left ventricular hypertrophy, 20% were smokers and 17% were anaemic. One-third of those with known cardiovascular disease were prescribed lipid-lowering therapy and half of those with proteinuria were prescribed an angiotensin-inhibiting drug. CONCLUSIONS: The data, collected in 1998-99, indicate that there is room for improvement in the quality of care provided by renal units to patients with CKD. The data may serve as a basis for assessing possible change in nephrological practice after the introduction of K/DOQI guidelines and staging of chronic renal disease.

IL5RA and TNFRSF6B gene variants are associated with sporadic IgA nephropathy.

Familial clustering and genome-wide linkage scans strongly support a genetic susceptibility to familial IgA nephropathy (IgAN), but genetic factors that predispose to sporadic IgAN are unknown. A high-throughput single nucleotide polymorphism (SNP) association study was conducted using a customized Illumina BeadChip in 732 white patients with biopsy-proven IgAN and 503 control subjects from Canada, France, and Finland. Approximately 93% of 1536 SNPs on the array were tag SNPs from Phase I+II of the HapMap with a minor allele frequency > or =5%, designed to capture the common variants of genes within the critical interval of IGAN1 on chromosome 6q22 and 69 biologic candidate genes for IgAN. SNPs of suggestive or significant association were identified by using logistic regression to adjust for age, gender, study site, and population stratification. Despite using a dense marker set that covered an average interval of 6.5 kb between SNPs, there was no strong and consistent association signal within the IGAN1 critical interval. Among the biologic candidate genes examined, two significant association signals were found at IL5RA and TNFRSF6B, the latter being particularly interesting because this gene encodes a decoy receptor for a TNF family ligand that causes IgAN in mice when overexpressed. Pending replication, these data suggest that variants of IL5RA and TNFRSF6B may predispose to sporadic IgAN.

Cumulative Risk of End-Stage Renal Disease Among Patients With Type 2 Diabetes: A Nationwide Inception Cohort Study.

OBJECTIVE: To estimate long-term cumulative risk of end-stage renal disease (ESRD) after diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: This nationwide population-based inception cohort study included 421,429 patients with type 2 diabetes diagnosed in 1990-2011; patients were followed until the end of 2013. Data linkage between several national health care registers in Finland, covering 100% of the population, enabled the inclusion of almost all inhabitants who started taking diabetes medication or were hospitalized for diabetes. Cumulative risk of ESRD and hazard ratios [HR] for ESRD and death were estimated according to age, sex, and time period of diabetes diagnosis. RESULTS: Among 421,429 patients with type 2 diabetes, 1,516 developed ESRD and 150,524 died during 3,458,797 patient-years of follow-up. Cumulative risk of ESRD was 0.29% at 10 years and 0.74% at 20 years from diagnosis of diabetes. Risk was higher among men than among women (HR 1.93 [95% CI 1.72-2.16]), decreased with older age at diagnosis (HR 0.70 [95% CI 0.60-0.81] for age 60-69 vs. 40-49 years), and was lower for those diagnosed in 2000-2011 than in 1990-1994 (HR 0.72 [95% CI 0.63-0.81]). Patients diagnosed with diabetes in 2000-2011 had lower risk of death during follow-up than those diagnosed in 1990-1994 (HR 0.64 [95% CI 0.63-0.65]). CONCLUSIONS: Cumulative risk of ESRD is minimal among patients with type 2 diabetes compared with their risk of death. Patients diagnosed with diabetes at an older age have a lower risk of ESRD due to higher competing mortality.

Type 2 diabetic patients on renal replacement therapy: Probability to receive renal transplantation and survival after transplantation.

BACKGROUND: Type 2 diabetic (T2DM) patients on renal replacement therapy (RRT) seldom receive a kidney transplant, which is partly due to age and comorbidities. Adjusting for case mix, we investigated whether T2DM patients have equal opportunity for renal transplantation compared to other patients on dialysis, and whether survival after transplantation is comparable. METHODS: Patients who entered RRT in Finland in 2000-2010 (n = 5419) were identified from the Finnish Registry for Kidney Diseases and followed until the end of 2012. Of these, 20% had T2DM, 14% type 1 diabetes (T1DM) and 66% other than diabetes as the cause of ESRD. Uni-/multivariate survival analysis techniques were employed to assess the probability of kidney transplantation after the start of dialysis and survival after transplantation. RESULTS: T2DM patients had a relative probability of renal transplantation of 0.18 (95% CI 0.15-0.22, P<0.001) compared to T1DM patients: this increased to 0.51 (95% CI 0.36-0.72, P<0.001) after adjustment for case mix (age, gender, laboratory values and comorbidities). When T2DM patients were compared to non-diabetic patients, the corresponding relative probabilities were 0.25 (95% CI 0.20-0.30, P<0.001) and 0.59 (95% CI 0.43-0.83, P = 0.002). After renal transplantation when adjusted for age and gender, relative risk of death was 1.25 (95% CI 0.64-2.44, P = 0.518) for T1DM patients and 0.72 (0.43-1.22, P = 0.227) for other patients compared to T2DM patients. CONCLUSIONS: T2DM patients had a considerably lower probability of receiving a kidney transplant, which could not be fully explained by differences in the patient characteristics. Survival within 5 years after transplantation is comparably good in T2DM patients.

Incidence of End-Stage Renal Disease in Patients With Type 1 Diabetes.

OBJECTIVE: To investigate how risk of end-stage renal disease (ESRD) among patients with type 1 diabetes has changed over time and further how the risk is affected by age, sex, and time period of diagnosis of diabetes. RESEARCH DESIGN AND METHODS: A cohort including all patients <30 years old diagnosed with type 1 diabetes in Finland in 1965-2011 was followed until start of renal replacement therapy, death, or end of follow-up at the end of 2013. Altogether, 29,906 patients were included. The main outcome was cumulative risk of ESRD, accounting for death as a competing risk. RESULTS: The patients were followed up for a median of 20 years. During 616,403 patient-years, 1,543 ESRD cases and 4,185 deaths were recorded. The cumulative risk of ESRD was 2.2% after 20 years and 7.0% after 30 years from the diabetes diagnosis. The relative risk of ESRD was 0.13 (95% CI 0.08-0.22) among patients diagnosed in 1995-2011 compared with those diagnosed in 1965-1979. Patients <5 years old at the time of diagnosis had the lowest risk of ESRD after diagnosis. With the cumulative risk of ESRD estimated from time of birth, the patients aged 5-9 years at diabetes diagnosis were at highest risk. CONCLUSIONS: The cumulative risk of ESRD has decreased markedly during the past five decades. This highlights the importance of modern treatment of diabetes and diabetic nephropathy.

One- and 2-Year Mortality Prediction for Patients Starting Chronic Dialysis.

INTRODUCTION: Mortality risk of patients with end-stage renal disease (ESRD) is highly elevated. Methods to estimate individual mortality risk are needed to provide individualized care and manage expanding ESRD populations. Many mortality prediction models exist but have shown deficiencies in model development (data comprehensiveness, validation) and in practicality. Therefore, our aim was to design 2 easy-to-apply prediction models for 1- and 2-year all-cause mortality in patients starting long-term renal replacement therapy (RRT). METHODS: We used data from the Finnish Registry for Kidney Diseases with complete national coverage of RRT patients. Model training group included all incident adult patients who started long-term dialysis in Finland in 2000 to 2008 (n = 4335). The external validation cohort consisted of those who entered dialysis in 2009 to 2012 (n = 1768). Logistic regression with stepwise variable selection was used for model building. RESULTS: We developed 2 prognostic models, both of which only included 6 to 7 variables (age at RRT start, ESRD diagnosis, albumin, phosphorus, C-reactive protein, heart failure, and peripheral vascular disease) and showed sufficient discrimination (c-statistic 0.77 and 0.74 for 1- and 2-year mortality, respectively). Due to a significantly lower mortality in the newer cohort, the models, to a degree, overestimated mortality risk. DISCUSSION: Mortality prediction algorithms could be more widely implemented into management of ESRD patients. The presented models are practical with only a limited number of variables and fairly good performance.

Increased urinary excretion of transforming growth factor-beta(1) in renal transplant recipients during cytomegalovirus infection.

AIMS: Cytomegalovirus (CMV) is a suggested risk factor for chronic allograft nephropathy, and transforming growth factor-beta (TGF-beta) is a key fibrogenic molecule in this process. CMV has been shown to induce the expression of TGF-beta and several cytokines. We analyzed the impact of CMV on urinary excretion of TGF-beta, ICAM-1, TNF-alpha and correlated findings with biopsy histology. MATERIAL: Urine samples from 46 renal transplant recipients were available for the study. Urine samples were taken when CMV infection was suspected, or for controlling of proteinuria or bacteriuria. METHOD: CMV was diagnosed by antigenemia and viral cultures. Patients with previous CMV infection were excluded from the analysis. Urine samples were analyzed by ELISA-method to detect the levels of TNF-alpha, ICAM-1 and TGF-beta(1). Banff '97 criteria were used for scoring of protocol biopsies taken 6 months after transplantation. RESULTS: At the time of the urine collection, 13/46 patients had CMV infection. Eight patients with no CMV infection were used as controls. TGF-beta(1) was significantly increased in the CMV group (samples taken mean 137+/-79 days post-transplantation) compared to controls (samples 139+/-64 days post-transplantation) (51.1+/-28.0 vs. 13.3+/-6.7 ng/mmol crea, p<0.001). No differences in the levels of other molecules were recorded. In the biopsies, interstitial fibrosis was significantly increased in the CMV group compared to controls. CONCLUSIONS: Urinary excretion of TGF-beta(1) was increased in patients during CMV infection. This was associated with increased fibrosis in the biopsies.

Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat. FINDINGS: After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups. INTERPRETATION: Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.

Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation: experience from the Assessment of Lescol in Renal Transplantation trial.

BACKGROUND: Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease. Traditional and nontraditional risk factors for cardiovascular disease are prevalent in renal patients. In renal-transplant recipients, immunosuppressive therapy can be nephrotoxic and aggravate cardiovascular disease risk factors. Renal dysfunction has been established as a risk factor for cardiovascular disease and mortality in different populations. We evaluated the effects of baseline renal-transplant function on mortality and cardiovascular and renal endpoints in 1,052 placebo-treated patients of the Assessment of Lescol in Renal Transplantation trial. METHODS: All renal-transplant recipients were on cyclosporine-based immunosuppressive therapy. Follow-up was 5 to 6 years, and endpoints included cardiac death, noncardiovascular death, all-cause mortality, major adverse cardiac event (MACE), stroke, nonfatal myocardial infarction, and graft loss. RESULTS: Baseline serum creatinine was strongly and independently associated with increased cardiac, noncardiovascular, and all-cause mortality, as well as MACE and graft loss. Serum creatinine was not a risk factor for stroke or nonfatal myocardial infarction. CONCLUSIONS: Elevated baseline serum creatinine in renal-transplant recipients is a strong and independent risk factor for all-cause, noncardiovascular and cardiac mortality, MACE, and graft loss.