Browsing by Subject "STAGE RENAL-DISEASE"

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  • van Zuydam, Natalie R.; Ahlqvist, Emma; Sandholm, Niina; Deshmukh, Harshal; Rayner, N. William; Abdalla, Moustafa; Ladenvall, Claes; Ziemek, Daniel; Fauman, Eric; Robertson, Neil R.; McKeigue, Paul M.; Valo, Erkka; Forsblom, Carol; Harjutsalo, Valma; Perna, Annalisa; Rurali, Erica; Marcovecchio, M. Loredana; Igo, Robert P.; Salem, Rany M.; Perico, Norberto; Lajer, Maria; Karajamak, Annemari; Imamura, Minako; Kubo, Michiaki; Takahashi, Atsushi; Sim, Xueling; Liu, Jianjun; van Dam, Rob M.; Jiang, Guozhi; Tam, Claudia H. T.; Luk, Andrea O. Y.; Lee, Heung Man; Lim, Cadmon K. P.; Szeto, Cheuk Chun; So, Wing Yee; Chan, Juliana C. N.; Ang, Su Fen; Dorajoo, Rajkumar; Wang, Ling; Clara, Tan Si Hua; McKnight, Amy-Jayne; Duffy, Seamus; Pezzolesi, Marcus G.; Marre, Michel; Gyorgy, Beata; Hadjadj, Samy; Hiraki, Linda T.; Tuomi, Tiinamaija; Groop, Per-Henrik; Groop, Leif C. (2018)
    dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
  • Harjutsalo, Valma; Maric-Bilkan, Christine; Forsblom, Carol; Groop, Per-Henrik; FinnDiane Study Grp (2016)
    Aims/hypothesis The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Methods Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. Results There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p <0.0001). A non-linear relationship between the age of menarche and risk of diabetic microvascular complications was found in patients with diabetes onset before menarche, but there was no such association in patients with diabetes onset after menarche. Women with delayed menarche (> mean age+ 2 years) had a 2.30 (95% CI 1.27, 4.17; p <0.006) times higher risk of nephropathy compared with the women who underwent menarche at the mean age +/- 2 years. Delayed menarche also increased the risk of retinopathy (OR 2.34 [95% CI 1.36, 4.01]). After excluding patients with nephropathy, the OR for retinopathy was 2.11 (95% CI 1.15, 3.90). Earlier menarche (<mean age-2 years) did not have any effect on this risk. Conclusions/interpretation Delayed menarche was associated with an increased risk of diabetic nephropathy and retinopathy, whereas early menarche was not. Delayed menarche may be used as a new tool to identify women at risk of diabetic microvascular complications.
  • Boenink, Rianne; Stel, Vianda S.; Waldum-Grevbo, Bard E.; Collart, Frederic; Kerschbaum, Julia; Heaf, James G.; de Meester, Johan; Finne, Patrik; Garcia-Marcos, Sergio A.; Evans, Marie; Ambuhl, Patrice M.; Arici, Mustafa; Ayav, Carole; Steenkamp, Retha; Cases, Aleix; Traynor, Jamie P.; Palsson, Runolfur; Zoccali, Carmine; Massy, Ziad A.; Jager, Kitty J.; Kramer, Anneke (2020)
    The objective of this study was to investigate whether the improvement in survival seen in patients on kidney replacement therapy reflects the enhanced survival of the general population. Patient and general population statistics were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and the World Health Organization databases, respectively. Relative survival models were composed to examine trends over time in all-cause and cause-specific excess mortality, stratified by age and modality of kidney replacement therapy, and adjusted for sex, primary kidney disease and country. In total, 280,075 adult patients started kidney replacement therapy between 2002 and 2015. The excess mortality risk in these patients decreased by 16% per five years (relative excess mortality risk (RER) 0.84; 95% confidence interval 0.83-0.84). This reflected a 14% risk reduction in dialysis patients (RER 0.86; 0.85-0.86), and a 16% increase in kidney transplant recipients (RER 1.16; 1.07-1.26). Patients on dialysis showed a decrease in excess mortality risk of 28% per five years for atheromatous cardiovascular disease as the cause of death (RER 0.72; 0.70-0.74), 10% for non-atheromatous cardiovascular disease (RER 0.90; 0.88-0.92) and 10% for infections (RER 0.90; 0.87-0.92). Kidney transplant recipients showed stable excess mortality risks for most causes of death, although it did worsen in some subgroups. Thus, the increase in survival in patients on kidney replacement therapy is not only due to enhanced survival in the general population, but also due to improved survival in the patient population, primarily in dialysis patients.
  • Mocroft, Amanda; Lundgren, Jens D.; Ross, Michael; Law, Matthew; Reiss, Peter; Kirk, Ole; Smith, Colette; Wentworth, Deborah; Neuhaus, Jacqueline; Fux, Christoph A.; Moranne, Olivier; Morlat, Phillipe; Johnson, Margaret A.; Ryom, Lene; DAD Study Grp; Royal Free Hosp Clin Cohort; INSIGHT Study Grp; SMART Study Grp; ESPRIT Study Grp; Ristola, M. (2015)
    Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1: 47 and 1: 6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score >= 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.
  • Derner, Ondrej; Kramer, Anneke; Hruskova, Zdenka; Arici, Mustafa; Collart, Frederic; Finne, Patrik; Sanchez, Laura Fuentes; Harambat, Jerome; Hemmelder, Marc H.; Hommel, Kristine; Kerschbaum, Julia; De Meester, Johan; Palsson, Runolfur; Segelmark, Marten; Skrunes, Rannveig; Traynor, Jamie P.; Zurriaga, Oscar; Massy, Ziad A.; Jager, Kitty J.; Stel, Vianda S.; Tesar, Vladimir (2022)
    Rationale & Objective: There is a dearth of data characterizing patients receiving kidney replacement therapy (KRT) for kidney failure due to systemic lupus erythematosus (SLE) and their clinical outcomes. The aim of this study was to describe trends in incidence and prevalence of KRT among these patients as well as to compare their outcomes versus those of patients treated with KRT for diseases other than SLE. Study Design: Retrospective cohort study based on kidney registry data. Setting & Participants: Patients recorded in 14 registries of patients receiving KRT that provided data to the European Renal Association Registry between 1992 and 2016. Predictor: SLE as cause of kidney failure. Outcomes: Incidence and prevalence of KRT, patient survival while receiving KRT, patient and graft survival after kidney transplant, and specific causes of death. Analytical Approach: Kaplan-Meier methods and Cox regression models were fit to compare patient survival between the SLE and non-SLE groups, overall KRT, dialysis, and patient and graft survival after kidney transplant. Results: In total, 1,826 patients commenced KRT for kidney failure due to SLE, representing an incidence of 0.80 per million population (pmp) per year. The incidence remained stable during the study period (annual percent change, 0.1% [95% CI, -0.6% to 0.8%]). Patient survival among patients with SLE receiving KRT was similar to survival in the comparator group (hazard ratio [HR], 1.11 [95% CI, 0.99-1.23]). After kidney transplant, the risk of death was greater among patients with SLE than among patients in the comparator group (HR, 1.25 [95% CI, 1.02-1.53]), whereas the risk of all-cause graft failure was similar (HR, 1.09 [95% CI, 0.95-1.27]). Ten-year patient overall survival during KRT and patient and graft survival after kidney transplant improved over the study period (HRs of 0.71 [95% CI, 0.56-0.91], 0.43 [95% CI, 0.27-0.69], and 0.60 [95% CI, 0.430.84], respectively). Patients with SLE receiving KRT were significantly more likely to die of infections (24.8%) than patients in the comparator group (16.9%; P < 0.001). Limitations: No data were available on extrarenal manifestations of SLE, drug treatments, comorbidities, kidney transplant characteristics, or relapses of SLE. Conclusions: The prognosis of patients with SLE receiving KRT has improved over time. Survival of patients with SLE who required KRT was similar compared with patients who required KRT for other causes of kidney failure. Survival following kidney transplants was worse among patients with SLE.
  • Vidal, Enrico; van Stralen, Karlijn J.; Chesnaye, Nicholas C.; Bonthuis, Marjolein; Holmberg, Christer; Zurowska, Aleksandra; Trivelli, Antonella; Esteves Da Silva, Jose Eduardo; Herthelius, Maria; Adams, Brigitte; Bjerre, Anna; Jankauskiene, Augustina; Miteva, Polina; Emirova, Khadizha; Bayazit, Aysun K.; Mache, Christoph J.; Sanchez-Moreno, Ana; Harambat, Jerome; Groothoff, Jaap W.; Jager, Kitty J.; Schaefer, Franz; Verrina, Enrico; ESPN-ERA-EDTA Registryy (2017)
    Background: The impact of different dialysis modalities on clinical outcomes has not been explored in young infants with chronic kidney failure. Study Design: Cohort study. Setting & Participants: Data were extracted from the ESPN/ERA-EDTA Registry. This analysis included 1,063 infants 12 months or younger who initiated dialysis therapy in 1991 to 2013. Factor: Type of dialysis modality. Outcomes & Measurements: Differences between infants treated with peritoneal dialysis (PD) or hemodialysis (HD) in patient survival, technique survival, and access to kidney transplantation were examined using Cox regression analysis while adjusting for age at dialysis therapy initiation, sex, underlying kidney disease, and country of residence. Results: 917 infants initiated dialysis therapy on PD, and 146, on HD. Median age at dialysis therapy initiation was 4.5 (IQR, 0.7-7.9) months, and median body weight was 5.7 (IQR, 3.7-7.5) kg. Although the groups were homogeneous regarding age and sex, infants treated with PD more often had congenital anomalies of the kidney and urinary tract (CAKUT; 48% vs 27%), whereas those on HD therapy more frequently had metabolic disorders (12% vs 4%). Risk factors for death were younger age at dialysis therapy initiation (HR per each 1-month later initiation, 0.95; 95% CI, 0.90-0.97) and non-CAKUT cause of chronic kidney failure (HR, 1.49; 95% CI, 1.08-2.04). Mortality risk and likelihood of transplantation were equal in PD and HD patients, whereas HD patients had a higher risk for changing dialysis treatment (adjusted HR, 1.64; 95% CI, 1.17-2.31). Limitations: Inability to control for unmeasured confounders not included in the Registry database and missing data (ie, comorbid conditions). Low statistical power because of relatively small number of participants. Conclusions: Despite a widespread preconception that HD should be reserved for cases in which PD is not feasible, in Europe, we found 1 in 8 infants in need of maintenance dialysis to be initiated on HD therapy. Patient characteristics at dialysis therapy initiation, prospective survival, and time to transplantation were very similar for infants initiated on PD or HD therapy. (C) 2016 by the National Kidney Foundation, Inc.
  • Ortiz, Fernanda; Harjutsalo, Valma; Helanterä, Ilkka; Lempinen, Marko; Forsblom, Carol; Groop, Per-Henrik (2019)
    OBJECTIVE To examine time trends inmortality rates and causes of death in patients with type 1 diabetes and end-stage renal disease on dialysis and after kidney transplantation. RESEARCH DESIGN AND METHODS In a nationwide retrospective cohort analysis, all patients with type 1 diabetes in Finland who received a kidney transplant alone were compared with patients who remained on dialysis. The main outcome was patient survival after starting dialysis. The cohort was divided into dialysis, functioning kidney transplant, and dialysis after transplant loss. Causes of death were retrieved and standardized mortality ratios calculated. RESULTS We studied 2,383 patients. Patients survived a median of 15.9 years after a successful transplant, 11.2 years if transplant function was lost, and 2.9 years if they remained on chronic dialysis. Standardized mortality ratio decreased in all subgroups during the past four decades: from 2005 onwards, it was 3.9 in patients receiving a kidney transplant, 11.5 in patients with graft loss, and 32.5 in patients on dialysis. The most common cause of death in all patients was ischemic heart disease (45%) followed by infection (18%), which was more common in patients on dialysis. CONCLUSIONS Kidney transplantation is the treatment of choice for patients with type 1 diabetes and end-stage renal disease because it substantially reduces the excess death risk when compared with dialysis. Even when kidney graft function is lost, the excess death risk is still considerably lower. Although overall mortality has decreased over the years, premature death due to ischemic heart disease remains high.
  • Perkovic, Vlado; Agarwal, Rajiv; Fioretto, Paola; Hemmelgarn, Brenda R.; Levin, Adeera; Thomas, Merlin C.; Wanner, Christoph; Kasiske, Bertram L.; Wheeler, David C.; Groop, Per-Henrik; Conf Participants (2016)
    The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.
  • Haukka, Jani K.; Sandholm, Niina; Forsblom, Carol; Cobb, Jeffrey E.; Groop, Per-Henrik; Ferrannini, Ele (2018)
    Elevated urinary albumin excretion (microalbuminuria) is an early marker of diabetic nephropathy, but there is an unmet need for better biomarkers that capture the individuals at risk with higher accuracy and earlier than the current markers do. We performed an untargeted metabolomic study to assess baseline differences between individuals with type 1 diabetes who either developed microalbuminuria or remained normoalbuminuric. A total of 102 individuals progressed to microalbuminuria during a median follow-up of 3.2 years, whereas 98 sex-, age- and body mass index (BMI) matched nonprogressors remained normoalbuminuric during a median follow-up of 7.1 years. Metabolomic screening identified 1,242 metabolites, out of which 111 differed significantly between progressors and non-progressors after adjustment for age of diabetes onset, baseline glycosylated hemoglobin A1c (HbA(1c)), and albumin excretion rate (AER). The metabolites that predicted development of microalbumiuria included several uremic toxins and carnitine metabolism related molecules. Iterative variable selection indicated erythritol, 3-phenylpropionate, and N-trimethyl-5-aminovalerate as the best set of variables to predict development of microalbuminuria. A metabolomic index based on these metabolites improved the prediction of incident microalbuminuria on top of the clinical variables age of diabetes onset, baseline HbA1c and AER (ROCAUC = 0.842 vs 0.797), highlighting their ability to predict early-phase diabetic nephropathy.
  • Wessman, Maija; Forsblom, Carol; Kaunisto, Mari A.; Soderlund, Jenny; Ilonen, Jorma; Sallinen, Riitta; Hiekkalinna, Tero; Parkkonen, Maija; Maxwell, Alexander P.; Tarnow, Lise; Parving, Hans-Henrik; Hadjadj, Samy; Marre, Michel; Peltonen, Leena; Groop, Per-Henrik (2011)
  • Eriksson, Daniel; Karlsson, Linda; Eklund, Oskar; Dieperink, Hans; Honkanen, Eero; Melin, Jan; Selvig, Kristian; Lundberg, Johan (2017)
    Background: There is limited real-world data on the economic burden of patients with autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to estimate the annual direct and indirect costs of patients with ADPKD by severity of the disease: chronic kidney disease (CKD) stages 1-3; CKD stages 4-5; transplant recipients; and maintenance dialysis patients. Methods: A retrospective study of ADPKD patients was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Data on medical resource utilisation were extracted from medical charts and patients were asked to complete a self-administered questionnaire. Results: A total of 266 patients were contacted, 243 (91%) of whom provided consent to participate in the study. Results showed that the economic burden of ADPKD was substantial at all levels of the disease. Lost wages due to reduced productivity were large in absolute terms across all disease strata. Mean total annual costs were highest in dialysis patients, driven by maintenance dialysis care, while the use of immunosuppressants was the main cost component for transplant care. Costs were twice as high in patients with CKD stages 4-5 compared to CKD stages 1-3. Conclusions: Costs associated with ADPKD are significant and the progression of the disease is associated with an increased frequency and intensity of medical resource utilisation. Interventions that can slow the progression of the disease have the potential to lead to substantial reductions in costs for the treatment of ADPKD.
  • Manderbacka, Kristiina; Arffman, Martti; Lumme, Sonja; Lehikoinen, Markku; Winell, Klas; Keskimaki, Ilmo (2016)
    Objectives: Diabetes requires continuous medical care including prevention of acute complications and risk reduction for long-term complications. Diabetic complications impose a substantial burden on public health and care delivery. We examined trends in regional differences in hospitalisations due to diabetes-related complications among the total diabetes population in Finland. Research design: A longitudinal register-based cohort study 1996-2011 among a total population with diabetes in Finland. Participants: All persons with diabetes identified from several administrative registers in Finland in 1964-2011 and alive on 1 January 1996. Outcome measures: We examined hospitalisations due to diabetes-related short-term and long-term complications, uncomplicated diabetes, myocardial infarction, stroke, lower extremity amputation and end-stage renal disease (ESRD). We calculated annual age-adjusted rates per 10 000 person years and the systematic component of variation. Multilevel models were used for studying time trends in regional variation. Results: There was a steep decline in complication-related hospitalisation rates during the study period. The decline was relatively small in ESRD (30%), whereas rates of hospitalisations for short-term and long-term complications as well as uncomplicated diabetes diminished by about 80%. The overall correlation between hospital district intercepts and slopes in time was -0.72 (p Conclusions: Our study suggests that the prevention of complications among persons with diabetes has improved in Finland between 1996 and 2011. The results further suggest that the prevention of complications has become more uniform throughout the country.
  • Bonthuis, Marjolein; Cuperus, Liz; Chesnaye, Nicholas C.; Akman, Sema; Melgar, Angel Alonso; Baiko, Sergey; Bouts, Antonia H.; Boyer, Olivia; Dimitrova, Kremena; Carmo, Carmen do; Grenda, Ryszard; Heaf, James; Jahnukainen, Timo; Jankauskiene, Augustina; Kaltenegger, Lukas; Kostic, Mirjana; Marks, Stephen D.; Mitsioni, Andromachi; Novljan, Gregor; Palsson, Runolfur; Parvex, Paloma; Podracka, Ludmila; Bjerre, Anna; Seeman, Tomas; Slavicek, Jasna; Szabo, Tamas; Tönshoff, Burkhard; Torres, Diletta D.; Van Hoeck, Koen J.; Ladfors, Susanne Westphal; Harambat, Jérôme; Groothoff, Jaap W.; Jager, Kitty J. (2020)
    One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five-years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 66% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low, medium, and high risk) graft recipients from high-income countries.
  • Dauvilliers, Yves; Benes, Heike; Partinen, Markku; Rauta, Virpi; Rifkin, Daniel; Dohin, Elisabeth; Goldammer, Nadine; Schollmayer, Erwin; Schroeder, Hanna; Winkelman, John W. (2016)
    Background: Restless legs syndrome (RLS) has been associated with insomnia, decreased quality of life, and increased morbidity and mortality in end-stage renal disease. This randomized controlled trial investigated effects of rotigotine in patients with RLS and end-stage renal disease. Study Design: Double-blind placebo-controlled study. Setting & Participants: Adults with moderate to severe RLS (International RLS Study Group Rating Scale [IRLS] >= 15) and Periodic Limb Movement Index (PLMI) >= 15 who were receiving thrice-weekly hemodialysis enrolled from sites in the United States and Europe. Intervention: Following randomization and titration ( Outcomes & Measurements: Primary efficacy outcome: reduction in PLMI, assessed by ratio of PLMI at end of maintenance to baseline. Secondary/other outcomes (P values exploratory) included mean changes from baseline in PLMI, IRLS, and Clinical Global Impression item 1 (CGI-1 [severity of illness]) score. Results: 30 patients were randomly assigned (rotigotine, 20; placebo, 10); 25 (15; 10) completed the study with evaluable data. Mean (SD) PLMI ratio (end of maintenance to baseline) was 0.7 +/- 0.4 for rotigotine and 1.3 +/- 0.7 for placebo (analysis of covariance treatment ratio, 0.44; 95% CI, 0.22 to 0.88; P = 0.02). Numerical improvements were observed with rotigotine versus placebo in IRLS and CGI-1 (least squares mean treatment differences of -6.08 [95% CI, -12.18 to 0.02; P = 0.05] and -0.81 [95% CI, -1.94 to 0.33; P = 0.2]). 10 of 15 rotigotine and 2 of 10 placebo patients were CGI-1 responders (>= 50% improvement). Hemodialysis did not affect unconjugated rotigotine concentrations. The most common adverse events (>= 2 patients) were nausea (rotigotine, 4 [20%]; placebo, 0); vomiting (3 [15%]; 0); diarrhea (1 [5%]; 2 [20%]); headache (2 [10%]; 0); dyspnea (2 [10%]; 0); and hypertension (2 [10%]; 0). Limitations: Small sample size and short duration. Conclusions: Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients. (C) 2016 by the National Kidney Foundation, Inc.
  • Gillard, Pieter; Schnell, Oliver; Groop, Per-Henrik (2020)
    Prevalence of type 1 diabetes mellitus (T1DM) is globally continuously increasing. T1DM is accompanied by a high risk of developing cardiovascular and renal comorbidities and is one of the leading causes of end-stage renal disease (ESRD). However, current therapeutic approaches for chronic and/or diabetic kidney disease (CKD/DKD) existed for a long time, and offer room for improvement, particularly in T1DM. In 2019, the European Medicines Agency (EMA) approved a first sodium/glucose co-transporter 2 inhibitor (SGLT-2i) and a first dual SGLT-1/-2i to improve glycaemic control, as an adjunctive treatment to insulin in persons with T1DM and a body mass index >27 kg/m(2). Of note, SGLT-1/2is and SGLT-2is are not approved by the Food and Drug Administration (FDA) as an adjunct treatment in T1DM, nor approved for the treatment of CKD or DKD by EMA and FDA. SGLT is have shown to mediate different renoprotective effects in type 2 diabetes mellitus in corresponding cardiovascular and renal outcome trials. First efficacy trials offer insights into potential positive effects on renal function and kidney disease of SGLTis in T1DM. This review summarizes and discusses latest available data on SGLT inhibition and provides an update on the nephrological perspective on SGLTis, specifically in T1DM. (c) 2020 Published by Elsevier B.V.