Proportion Of End-stage Renal Disease Research Articles

The Emerging Role of Bone-Derived Hormones in Diabetes Mellitus and Diabetic Kidney Disease.

Diabetic kidney disease (DKD) causes the greatest proportion of end-stage renal disease (ESRD)–related mortality and has become a high concern in patients with diabetes mellitus (DM). Bone is considered an endocrine organ, playing an emerging role in regulating glucose and energy metabolism. Accumulating research has proven that bone-derived hormones are involved in glucose metabolism and the pathogenesis of DM complications, especially DKD. Furthermore, these hormones are considered to be promising predictors and prospective treatment targets for DM and DKD. In this review, we focused on bone-derived hormones, including fibroblast growth factor 23, osteocalcin, sclerostin, and lipocalin 2, and summarized their role in regulating glucose metabolism and DKD.

MO049FUNCTIONAL IMPORTANCE OF MAPKBP1 PROTEIN DOMAINS IN NEPHRONOPHTHISIS

Abstract Background and Aims Nephronophthisis is an autosomal-recessive kidney disease that accounts for a significant proportion of end-stage renal disease (ESRD) in childhood, adolescence and early adulthood. Biallelic pathogenic variants in MAPKBP1, encoding the c-Jun N-terminale kinase (JNK)-binding protein 1, are associated with development of Nephronophthisis and subsequent chronic kidney disease (CKD) (Macia et al, AJHG, 2017). We recently characterized MAPKBP1 as microtubule-associated protein that is able to localize to centrioles and the base of primary cilia depending on dimerization via its C-terminal coiled-coil domain (Schönauer et al, Kidney Int, 2020). However, the physiological function of its N-terminal WD40 and intermediate JNK-binding domain is still poorly understood. By in vitro comparison of artificial domain deletions with known and novel patient variants, we aim at pinpointing functional consequences of pathogenic MAPKBP1 in cilia and cell cycle control. Method N-terminally GFP-tagged MAPKBP1 constructs with either full-domain deletions or patient-derived variants were expressed in non-ciliated HeLa and ciliated H69 cells for fluorescence microscopy studies. Furthermore, RNA-seq analysis using primary patient cells was conducted to investigate differentially regulated molecular pathways compared to healthy control individuals. Results Immunofluorescence microscopy revealed inappropriate intracellular localization upon single or combined deletion of any MAPKBP1 protein domain. Compared to wild type, all deletion variants showed reduced intensity at the centrosome and ciliary base. Despite preserved dimerization ability, loss of the intermediate JNK-binding domain (JBD) most effectively abolished centrosomal or ciliary targeting, whereas loss of the N-terminal WD40-domain induced strongest mitotic aberrations. Unlike wild type, both, artificial and patient-derived truncating variants were able to enter the nucleus. RNA-seq analysis using primary patient fibroblasts with varying C-terminal truncations will allow important insights into common gene expression profiles unveiling consequences of aberrant intracellular trafficking. Conclusion In the present work, we demonstrate that all protein domains are indispensable for appropriate MAPKBP1 intracellular localization and function. Most of clinically reported patient variants exhibiting C-terminal truncation of varying lengths resulted in comparable intracellular behavior in presence of an intact N-terminal WD40 domain. Surprisingly, deletion of the JNK-binding domain alone aggravated functional disturbances hinting at a prominent regulatory role of this protein part interdepending with dimerization. Further insights into domain-specific functions will explain molecular disease mechanisms of MAPKBP1.

Potential role of extracellular vesicles in the pathophysiology of glomerular diseases.

Extracellular vesicles (EVs) are membrane-bound vesicles released by most cells and are found in diverse biological fluids. The release of EVs provides a new mechanism for intercellular communication, allowing cells to transfer their functional cargoes to target cells. Glomerular diseases account for a large proportion of end-stage renal disease (ESRD) worldwide. In recent years, an increasing number of research groups have focused their effort on identifying the functional role of EVs in renal diseases. However, the involvement of EVs in the pathophysiology of glomerular diseases has not been comprehensively described and discussed. In this review, we first briefly introduce the characteristics of EVs. Then, we describe the involvement of EVs in the mechanisms underlying glomerular diseases, including immunological and fibrotic processes. We also discuss what functions EVs derived from different kidney cells have in glomerular diseases and how EVs exert their effects through different signaling pathways. Furthermore, we summarize recent advances in the knowledge of EV involvement in the pathogenesis of various glomerular diseases. Finally, we propose future research directions for identifying better management strategies for glomerular diseases.

Proteomic analysis of plasma proteins of high-flux haemodialysis and on-line haemodiafiltration patients reveals differences in transthyretin levels related with anaemia

A large proportion of end-stage renal disease (ESRD) patients under long-term haemodialysis, have persistent anaemia and require high doses of recombinant human erythropoietin (rhEPO). However, the underlying mechanisms of renal anaemia have not been fully elucidated in these patients. In this study, we will be focusing on anaemia and plasma proteins in ESRD patients on high-flux haemodialysis (HF) and on-line haemodiafiltration (HDF), to investigate using two proteomic approaches if patients undergoing these treatments develop differences in their plasma protein composition and how this could be related to their anaemia. The demographic and biochemical data revealed that HDF patients had lower anaemia and much lower rhEPO requirements than HF patients. Regarding their plasma proteomes, HDF patients had increased levels of a protein highly similar to serotransferrin, trypsin-1 and immunoglobulin heavy constant chain alpha-1, and lower levels of alpha-1 antitrypsin, transthyretin, apolipoproteins E and C-III, and haptoglobin-related protein. Lower transthyretin levels in HDF patients were further confirmed by transthyretin-peptide quantification and western blot detection. Since ESRD patients have increased transthyretin, a protein that can aggregate and inhibit transferrin endocytosis and erythropoiesis, our finding that HDF patients have lower transthyretin and lower anaemia suggests that the decrease in transthyretin plasma levels would allow an increase in transferrin endocytosis, contributing to erythropoiesis. Thus, transthyretin could be a critical actor for anaemia in ESRD patients and a novel player for haemodialysis adequacy.

Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis

OBJECTIVES:Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. In this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (αGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare αGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD.METHODS:The records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. The screening was performed based on the αGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. The two groups were compared using these parameters.RESULTS:The mean level of αGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88±1.2 μmol/L/h versus 3.79±1.9 μmol/L/h, p<0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2±1.22 ng/ml versus 1.7±0.66 ng/ml, p: 0.4). In the analysis of GLA mutations, a D313Y mutation [C(937G>T) in exon p] was found in one patient from the FSGS group.CONCLUSIONS:We found that αGAL activity in patients with FSGS is lower than that in patients undergoing HD. The low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury.

A Retrospective Study of Chronic Kidney Disease Burden in Saskatchewan's First Nations People.

Background:Chronic kidney disease is more prevalent among First Nations people than in non-First Nations people. Emerging research suggests that First Nations people are subject to greater disease burden than non-First Nations people.Objective:We aimed to identify the severity of chronic kidney disease and quantify the geographical challenges of obtaining kidney care by Saskatchewan’s First Nations people.Design:This study is a retrospective analysis of the provincial electronic medical record clinical database from January 2012 to December 2013.Setting:The setting involved patients followed by the Saskatchewan provincial chronic kidney care program, run out of two clinics, one in Regina, SK, and one in Saskatoon, SK.Patients:The patients included 2478 individuals (379 First Nations and 2099 non-First Nations) who were older than 18 years old, resident in Saskatchewan, and followed by the provincial chronic kidney care program. First Nations individuals were identified by their Indigenous and Northern Affairs Canada (INAC) Number.Measurements:The demographics, prevalence, cause of end-stage renal disease, severity of chronic kidney disease, use of home-based therapies, and distance traveled for care among patients are reported.Methods:Data were extracted from the clinical database used for direct patient care (the provincial electronic medical record database for the chronic kidney care program), which is prospectively managed by the health care staff. Actual distance traveled by road for each patient was estimated by a Geographic Information System Analyst in the First Nations and Inuit Health Branch of Health Canada.Results:Compared with non-First Nations, First Nations demonstrate a higher proportion of end-stage renal disease (First Nations = 33.0% vs non-First Nations = 21.4%, P < .001), earlier onset of chronic kidney disease (MFN = 56.4 years, SD = 15.1; MNFN = 70.6 years, SD = 14.7, P < .001), and higher rates of end-stage renal disease secondary to type 2 diabetes (First Nations = 66.1% vs non-First Nations = 39.0%, P < .001). First Nations people are also more likely to be on dialysis (First Nations = 69.7% vs non-First Nations = 40.2%, P < .001), use home-based therapies less frequently (First Nations = 16.2% vs non-First Nations = 25.7%; P = 003), and must travel farther for treatment (P < .001), with First Nations being more likely than non-First Nations to have to travel greater than 200 km.Limitations:Patients who are followed by their primary care provider or solely through their nephrologist’s office for their chronic kidney disease would not be included in this study. Patients who self-identify as Aboriginal or Indigenous without an INAC number would not be captured in the First Nations cohort.Conclusions:In Saskatchewan, First Nations’ burden of chronic kidney disease reveals higher severity, utilization of fewer home-based therapies, and longer travel distances than their non-First Nations counterparts. More research is required to identify innovative solutions within First Nations partnering communities.

Key factors for a high-quality peritoneal dialysis program--the role of the PD team and continuous quality improvement.

The proportion of end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) has increased very fast in China over the last decade. Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, is a recognized high-quality PD unit with a high PD utilization rate, excellent patient and technique survival (1-year and 5-year patient survival rate of 93% and 71%, and 1-year and 5-year technique survival of 96% and 82%, respectively), low peritonitis rate and a well-documented good quality of life of the treated patients. We believe that a dedicated and experienced PD team, a structured patient training program, continuous patient support, establishing and utilizing standardized protocols, starting PD with low dialysis dose, monitoring key performance indicators (KPIs), and continuous quality improvement (CQI) are the key factors underlying this successful PD program.

Individuals of Pacific Asian origin with IgA nephropathy have an increased risk of progression to end-stage renal disease

IgA nephropathy (IgAN) accounts for a far higher proportion of end-stage renal disease (ESRD) in Asia compared with North America. It is not known whether this is entirely because of differences in disease prevalence or a higher risk of disease progression. The lack of a racially diverse population cohort followed longitudinally has previously precluded the ability to address this question. To determine whether Asians in North America with IgAN are at higher risk for ESRD, we analyzed a cohort of 202 patients of self-reported Pacific Asian origin and 467 of other origin from the Toronto GN Registry followed up for a median of 46.4 months. The primary outcome of ESRD (dialysis, transplantation, or eGFR below 15) was analyzed using Cox regression analysis. Baseline eGFR was 59.6 ml/min/1.73 m(2), and median proteinuria was 1.8 g/day. ESRD occurred in 213 patients. By univariable analysis, the risk of ESRD was similar between the two groups (hazard ratio 0.98, 95% CI 0.73, 1.31); however, after adjusting for age, gender, eGFR, medication use, blood pressure, and proteinuria, the risk of ESRD was significantly higher in Pacific Asian individuals (hazard ratio 1.56, 95% CI 1.10, 2.22). This was supported by a significant 1.62 ml/min/1.73 m(2)/year faster rate of eGFR decline (95% CI -3.19, -0.5) and an increased risk of a reduction in eGFR by half (hazard ratio 1.81, 95% CI 1.25, 2.62). Thus, in a large multiracial cohort of patients with IgAN, individuals of Pacific Asian origin have a higher risk of progression to ESRD.

The Enigma of Hypertensive ESRD: Observations on Incidence and Trends in 18 European, Canadian, and Asian-Pacific Populations, 1998 to 2002

Despite improved treatment of hypertension and decreasing rates of stroke and coronary heart disease, the reported incidence of hypertensive end-stage renal disease (ESRD) increased during the 1990s. However, bias, particularly from variations in acceptance into ESRD treatment (ascertainment) and diagnosis (classification), has been a major source of error when comparing ESRD incidences or estimating trends. Age-standardized rates were calculated in persons aged 30 to 44, 45 to 64, and 65 to 74 years for 15 countries or regions (separately for the Europid and non-Europid populations of Canada, Australia, and New Zealand), and temporal trends were estimated by means of Poisson regression. For 10 countries or regions, population-based estimates of mean systolic blood pressures and prevalences of hypertension were extracted from published sources. Hypertensive ESRD, comprising ESRD attributed to essential hypertension or renal artery occlusion, was least common in Finland, non-Aboriginal Australians, and non-Polynesian New Zealanders; intermediate in most European and Canadian populations; and most common in Aboriginal Australians and New Zealand Maori and Pacific Island people. Rates correlated with the incidence of all other nondiabetic ESRD, but not with diabetic ESRD or community rates of hypertension. Between 1998 and 2002, hypertensive ESRD did not increase in Northwestern Europe or non-Aboriginal Canadians, although it did so in Australia. Despite the likelihood of classification bias, the probability remains of significant variation in incidence of hypertensive ESRD within the group of Europid populations. These between-population differences are not explained by community rates of hypertension or ascertainment bias.

Cardiac disease in diabetic patients with renal disease

Patients with diabetes represent an increasing proportion of end-stage renal disease (ESRD) patients. Cardiovascular risk, already formidable among patients on dialysis, is significantly higher among those who also have diabetes. Diabetic ESRD patients are not only at higher risk of ischaemic events, but are also subject to haemodynamic overload, because of anaemia, hypertension, and arteriovenous dialysis connections. Mortality rates are also significantly higher in these patients. Hypertension and anaemia stand out as opportunities for intervention in these patients. Anaemia per se is associated with an increased risk of cardiovascular abnormalities, including left ventricular hypertrophy, and with an increased risk of mortality. The interplay of multiple risk factors in diabetic patients with ESRD demands a multidisciplinary approach for the early identification and management of cardiovascular risk factors--hypercholsterolaemia, hypertension, blood glucose and anaemia--in order to optimise outcomes in these patients.

Methodological limitations of the ESRD core indicators project: An ESRD network's experience wtih implementing an ESRD quality survey

ESRD Network Number 1, composed of Maine, New Hampshire, Vermont, Massachusetts, Connecticut, and Rhode Island, developed a Network Core Indicator Pilot Project using the dialysis units represented on the Medical Review Board. Network 1's Core Indicator Pilot Project aimed to (1) estimate the proportion of end-stage renal disease (ESRD) patients in Network 1 receiving hemodialysis treatments associated with a urea reduction ratio less than 60% to 65%, (2) elucidate the patient characteristics associated with a hemodialysis dose less than 65%, (3) define the processes in the delivery of hemodialysis that limit the provision of an adequate dialysis dose, and (4) initiate the routine collection of measures of dialysis dose, the analysis of those data, and feedback to the participating dialysis units. In the course of the Core Indicator Pilot Project, we observed little uniformity in the sampling method for the postdialysis blood urea nitrogen sample. Thirty-three percent of the hemodialysis units reported that this critical blood sample was drawn immediately before the dialysis treatment was terminated; 25% were obtained immediately at the end of the dialysis treatment and 42% drew the sample ≥ 5 minutes after all blood was reinfused to the patient. Especially in the presence of unappreciated blood recirculation in the angioaccess or postdialysis urea rebound, the lack of standardization in obtaining this critical blood sample to support the urea reduction ratio calculation greatly compromises any comparisons of performance across dialysis facilities and may jeopardize patient care. Future ESRD quality improvement efforts must focus not only on the results of the outcome measure but also on the process by which the measure is achieved. These fundamental principles of qualtiy assessment should be considered by policy specialists, payers, providers, and developers of clinical practice guidelines.

A study on optimal maintenance of system with exponential distribution : Michio Horigome. Proc. 15th Symp. Reliab. Maintainab. (Union of Japanese Scientists and Engineers, Tokyo), 85 (1985)

ESRD Network Number 1, composed of Maine, New Hampshire, Vermont, Massachusetts, Connecticut, and Rhode Island, developed a Network Core Indicator Pilot Project using the dialysis units represented on the Medical Review Board. Network 1's Core Indicator Pilot Project aimed to (1) estimate the proportion of end-stage renal disease (ESRD) patients in Network 1 receiving hemodialysis treatments associated with a urea reduction ratio less than 60% to 65%, (2) elucidate the patient characteristics associated with a hemodialysis dose less than 65%, (3) define the processes in the delivery of hemodialysis that limit the provision of an adequate dialysis dose, and (4) initiate the routine collection of measures of dialysis dose, the analysis of those data, and feedback to the participating dialysis units. In the course of the Core Indicator Pilot Project, we observed little uniformity in the sampling method for the postdialysis blood urea nitrogen sample. Thirty-three percent of the hemodialysis units reported that this critical blood sample was drawn immediately before the dialysis treatment was terminated; 25% were obtained immediately at the end of the dialysis treatment and 42% drew the sample ≥ 5 minutes after all blood was reinfused to the patient. Especially in the presence of unappreciated blood recirculation in the angioaccess or postdialysis urea rebound, the lack of standardization in obtaining this critical blood sample to support the urea reduction ratio calculation greatly compromises any comparisons of performance across dialysis facilities and may jeopardize patient care. Future ESRD quality improvement efforts must focus not only on the results of the outcome measure but also on the process by which the measure is achieved. These fundamental principles of qualtiy assessment should be considered by policy specialists, payers, providers, and developers of clinical practice guidelines.