Incidence Of End-stage Renal Disease Research Articles

Risk factors and renal outcomes of low bone mineral density in patients with non-dialysis chronic kidney disease.

Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ - 1.0), osteopenia (- 1.0 > T score > - 2.5), and osteoporosis (T score ≤ - 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < - 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD). Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12years; male 61%). Over a median follow-up of 4.3years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49-0.77)) and spot urine Na/K ratio (1.07 (1.00-1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92-1.41) for osteopenia; 1.43 (1.01-2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification. Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.

Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial.

The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3-4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.

Cardiovascular System Affection and Its Relation to First-Year Mortality in Patients Initiating Maintenance Hemodialysis.

BackgroundThe incidence of end-stage renal disease (ESRD) has increased by 30–40% in the last decade. These patients have a higher mortality rate of 3–8 times compared to the general population. In the present study, we aimed to detect cardiovascular complications and their relation to the first-year mortality rate in patients on hemodialysis in Aswan University Hospital, upper Egypt.Patients and MethodsOur study was a cross-sectional study which was done at the hemodialysis unit in Aswan University Hospital from May 2016 to May 2018. The study included 100 patients with ESRD on regular hemodialysis (first year on programmed hemodialysis). All patients were subjected to full clinical examination and laboratory studies includngd complete blood count (CBC), kidney function tests, serum calcium and phosphorus level, parathormone (PTH) hormone, serum albumin level, C-reactive protein (CRP), echocardiography and electrocardiogram (ECG), and lateral abdominal x-ray for detection of aortic calcification. ResultsThe present study included 47 males and 53 females, with a mean age of 50.6 ±13.89 years. The main risk factors for patients with ESRD were hypertension (48%) followed by diabetic nephropathy (36%), glomerulonephritis (15%), idiopathic etiology (11%), obstructive uropathy (8%), lupus nephritis (6%), polycystic kidney disease (4%) and cardio renal syndrome (1%). Twenty-seven deaths have been noted during the first year of dialysis treatment. The leading causes of death were cardio-vascular events (66, 67%), infection (22, 22%) and malignancy (11, 11%), The most common cardiovascular events were myocardial infarction (27.8%), sudden cardiac death (SCD) (27.8%) and heart failure (22.2%).ConclusionIn conclusion, our study showed that the main risk factors for ESRD patients in Aswan University Hospital are hypertensive nephrosclerosis, diabetic nephropathy, glomerulonephritis and idiopathic etiology, and the main causes of first-year mortality were cardiovascular events followed by infection and malignancy.

Characterization of the renal cortical transcriptome following Roux-en-Y gastric bypass surgery in experimental diabetic kidney disease.

IntroductionRoux-en-Y gastric bypass surgery (RYGB) reduces albuminuria and the long-term incidence of end-stage renal disease in patients with obesity and diabetes. Preclinical modeling in experimental diabetic kidney disease demonstrates that improvements in glomerular structure likely underpin these findings.Research design and methodsIn adult male Zucker diabetic fatty (ZDF) rats, we profiled the effect of RYGB on weight and metabolic control as well biochemical, structural and ultrastructural indices of diabetic renal injury. Furthermore, we sequenced the renal cortical transcriptome in these rats and used bioinformatic pathway analyses to characterize the transcriptional alterations governing the renal reparative response to RYGB.ResultsIn parallel with improvements in weight and metabolic control, RYGB reduced albuminuria, glomerulomegaly, podocyte stress and podocyte foot process effacement. Pathway analysis of RYGB-induced transcriptomic changes in the renal cortex highlighted correction of disease-associated alterations in fibrosis, inflammation and biological oxidation pathways. RYGB reversed disease-associated changes in the expression of transforming growth factor (TGF)-β superfamily genes that strongly correlated with improvements in structural measures of glomerulopathy.ConclusionsImproved glomerular structure in ZDF rats following RYGB is underpinned by pathway level changes, including interruption of the TGF-β-driven early profibrotic programme. Our data provide an important layer of experimental support for clinical evidence demonstrating that RYGB arrests renal damage in patients with obesity and type 2 diabetes.

Trends in Living Donation by Race and Ethnicity Among Children With End-stage Renal Disease in the United States, 1995-2015.

Living donor kidney transplants have declined among adults with end-stage renal disease (ESRD), with increases in racial/ethnic disparities over time. Secular trends in racial/ethnic disparities in living donor kidney transplantation have not been well studied in children. Using multivariable Cox modeling, we examined changes in living donor kidney transplant rates over time and probability of receiving living donor kidney transplantation within 2 years of incident ESRD by race/ethnicity among 19 772 children in the US Renal Data System, 1995-2015. We also examined racial/ethnic concordance between donors and recipients. Overall, living donor kidney transplant rates declined by 3% annually since 1995 for all racial/ethnic groups except Asians for whom living donor kidney transplant rates remained stable; however, disparities persist. Compared with non-Hispanic white children, Hispanics were 42% less likely (adjusted hazard ratio: 0.58; 95% confidence interval: 0.49-0.67), Asians 39% less likely (0.61; 0.47-0.79), and blacks 66% less likely (0.34; 0.28-0.42) to receive living kidney donor transplantation within 2 years, even when accounting for deceased donor transplantation as a competing risk. Additionally, while 95% of non-Hispanic white children had non-Hispanic white donors, only 56% of Asian recipients had Asian donors (P < 0.001). Asian recipients were more likely to have nonrelated donors (P < 0.001). There are ongoing declines in living donation for children with ESRD for uncertain reasons, and minority populations experience significantly reduced access to timely living donor transplant, even when accounting for changes in deceased donation and donor-recipient relationships.

New-onset ESRD secondary to reflux nephropathy has decreased in incidence in the United States

Vesicoureteral reflux (VUR) has been associated with the development and progression of reflux nephropathy (RN). Management of VUR has become more conservative over time as therapies have not been reliably proven to prevent renal scarring. We sought to examine the incidence of end stage renal disease (ESRD) due to RN over recent decades in the United States. The United States Renal Data System (USRDS) is a national data system that collects information about chronic kidney disease and ESRD. Since 1995, the USRDS has mandated that all dialysis centers enroll and submit data on new-onset ESRD patients. Of the over 2.5 million patients enrolled since 1996, 7314 were enrolled with a diagnosis code for RN as the primary cause of ESRD. We examined the trends seen in this patient population from 1996 to 2014 and used US census data to calculate incidence. The incidence of patients with new-onset ESRD attributed primarily to RN saw a steady decrease over time: from 1.9 per million in 1996 to 0.6 per million in the US population in 2014 (exp(B)=0.941, p<0.001). 58.8% of the patients were female, 87.4% white. The mean age at the time of ESRD onset was 47 years (IQR 30-65) and this did not significantly vary over the period (P>0.05). When comparing pediatric new-onset ESRD to adult-onset, a non-significant trend (p=0.093) was seen with a decrease in incidence of adult ESRD, but a relatively stable incidence of pediatric ESRD (mean age 12, incidence 0.2-0.6 cases per million US children/year). 44.5% of patients received renal transplantation at a mean age of 36 years, 18.9 months (IQR 5-40) after ESRD diagnosis. The mean age of mortality was 62 years old (IQR 50-76), and 5-year survival after RN ESRD diagnosis was 65.8%. As with any public database study, our findings may be limited by disease coding or reporting practices. Medical and surgical management trends practiced since the 1960s may have contributed to a decrease in the incidence of ESRD primarily attributed to RN in the United States between 1996 and 2014. Our findings may also reflect changes in diagnostic practices. ESRD attributed primarily to RN has gradually decreased in incidence in the United States between 1996 and 2014, but the age of ESRD onset has been unchanged.

Sphingomyelin and progression of renal and coronary heart disease in individuals with type 1 diabetes

Aims/hypothesisLipid abnormalities are associated with diabetic kidney disease and CHD, although their exact role has not yet been fully explained. Sphingomyelin, the predominant sphingolipid in humans, is crucial for intact glomerular and endothelial function. Therefore, the objective of our study was to investigate whether sphingomyelin impacts kidney disease and CHD progression in individuals with type 1 diabetes.MethodsIndividuals (n = 1087) from the Finnish Diabetic Nephropathy (FinnDiane) prospective cohort study with serum sphingomyelin measured using a proton NMR metabolomics platform were included. Kidney disease progression was defined as change in eGFR or albuminuria stratum. Data on incident end-stage renal disease (ESRD) and CHD were retrieved from national registries. HRs from Cox regression models and regression coefficients from the logistic or linear regression analyses were reported per 1 SD increase in sphingomyelin level. In addition, receiver operating curves were used to assess whether sphingomyelin improves eGFR decline prediction compared with albuminuria.ResultsDuring a median (IQR) 10.7 (6.4, 13.5) years of follow-up, sphingomyelin was independently associated with the fastest eGFR decline (lowest 25%; median [IQR] for eGFR change: <−4.4 [−6.8, −3.1] ml min−1 [1.73 m−2] year−1), even after adjustment for classical lipid variables such as HDL-cholesterol and triacylglycerols (OR [95% CI]: 1.36 [1.15, 1.61], p < 0.001). Similarly, sphingomyelin increased the risk of progression to ESRD (HR [95% CI]: 1.53 [1.19, 1.97], p = 0.001). Moreover, sphingomyelin increased the risk of CHD (HR [95% CI]: 1.24 [1.01, 1.52], p = 0.038). However, sphingomyelin did not perform better than albuminuria in the prediction of eGFR decline.Conclusions/interpretationThis study demonstrates for the first time in a prospective setting that sphingomyelin is associated with the fastest eGFR decline and progression to ESRD in type 1 diabetes. In addition, sphingomyelin is a risk factor for CHD. These data suggest that high sphingomyelin level, independently of classical lipid risk factors, may contribute not only to the initiation and progression of kidney disease but also to CHD.Graphical abstract

Joint Longitudinal Low Calcium High Phosphorus Trajectory Associates with Accelerated Progression, Acute Coronary Syndrome and Mortality in Chronic Kidney Disease

The effects of long-term disturbance of the mineral metabolism on patients with chronic kidney disease (CKD) are unclear. We investigated whether the longitudinal Ca-P (joint calcium and phosphorus) trajectories are associated with incident end-stage renal disease (ESRD), acute coronary syndrome (ACS), and all-cause mortality in patients with CKD. We conducted a prospective cohort study by using data from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 4,237 CKD patients aged 20–90 years with data gathered from 2003 to 2015. Individuals’ Ca-P trajectories were defined using group-based multi-trajectory modeling into three distinct patterns: reference, moderately abnormal, and severely abnormal. Times to ESRD, ACS, and death were analyzed using multiple Cox regression. Compared with those with a “reference” Ca-P trajectory, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for incidental ESRD were 5.92 (4.71–7.44) and 15.20 (11.85–19.50) for “moderately abnormal” and “severely abnormal” Ca-P trajectories, respectively. The corresponding aHRs for ACS were 1.94 (1.49–2.52) and 3.18 (2.30–4.39), and for all-cause mortality, they were 1.88 (1.64–2.16) and 2.46 (2.05–2.96) for “moderately abnormal” and “severely abnormal” Ca-P trajectories, respectively. For outcomes of progression to ESRD, the detrimental effects of abnormal Ca-P trajectories were more substantial in patients with CKD stage 3 than those with CKD stage 4 or 5 (p-value for interaction < 0.001). Future studies should validate reliable longitudinal cut-offs of serum phosphorus and consider the “lowering phosphorus— the lower the better, the earlier the better” approach to phosphorus control in CKD.

White-coat hypertension and incident end-stage renal disease in patients with non-dialysis chronic kidney disease: results from the C-STRIDE Study

BackgroundControversy remains whether white coat hypertension (WCH) is associated with renal prognosis in patients with chronic kidney disease (CKD).MethodsIn the present multicenter, prospective study, we analyzed data of participants with CKD stage 1–4 from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE). WCH was defined according to two criteria as follows: A, clinical blood pressure (BP) ≥ 140/90 mm Hg and average 24-h ambulatory BP < 130/80 mm Hg; B, clinical BP ≥ 130/80 mm Hg and daytime ambulatory BP < 130/80 mm Hg. Renal outcome was defined as initiation of renal replacement therapy. The association of WCH with renal events was evaluated by Cox regression model.ResultsA total of 1714 patients with CKD were included in the present analysis. The mean age of the population was 48.9 ± 13.8 years and 56.8% were men. The mean baseline estimated glomerular filtration rate (eGFR) was 52.2 ± 30.1 ml/min/1.73 m2 and urinary protein was 1.0 (0.4, 2.4) g/day. The overall prevalence of WCH was 4.7% and 16.6% according to criteria A and B, respectively. Incidence rates of renal events were 49.58 and 26.51 according to criteria A and B, respectively, per 1000 person-years during a median follow-up of 4.8 years. After full adjustment, WCH was associated with an increased risk of renal event (criterion A: hazard ratio 2.36, 95% confidence interval 1.29–4.34; for criterion B: hazard ratio 1.90, 95% confidence interval 1.04–3.49) compared with patients with normal BP.ConclusionsWCH is associated with a greater risk for renal events in non-dialysis dependent Chinese patients with CKD.

The Effects of Shared Decision Making on Different Renal Replacement Therapy Decisions in Patients With Chronic Kidney Disease.

The prevalence and incidence of end-stage renal disease (ESRD) in Taiwan are the highest of any country in the world. The different renal replacement therapies that are adopted by patients with ESRD significantly affect their social roles and daily life. However, because of the complexities of different renal replacement therapies, patients may be unsure of which to choose. The aim of this study was to explore the effectiveness of a shared decision-making (SDM) program regarding different renal replacement therapies for patients with chronic kidney disease. A quasi-experimental design was conducted at two similar regional hospitals in Miaoli County, Taiwan. One hospital hosted the intervention group, and the other hospital hosted the control group. The 31 participants in the intervention group took part in a SDM program. The 36 control group participants took part in the pre-ESRD care program. Data collection included demographic and disease characteristics, decisional conflict scale, and decision self-efficacy scale. Results were analyzed using independent t test, Fisher's exact test, generalized estimating equation, and paired t tests. The study results revealed that the intervention group experienced a significant increase in decision self-efficacy and a significant decrease in decisional conflict at 1 month after receiving the SDM intervention in comparison to before and immediately after receiving the intervention. Moreover, the intervention group had higher decision self-efficacy and lower decisional conflict than the control group. The SDM program may be an effective intervention for complex decision-making processes, such as the process involved in making renal replacement treatment decisions. The SDM program group intervention improved decisional conflict and decision self-efficacy. Thus, to improve patients' decision-making processes, the application of an SDM program focused on the personal values and opinions of patients with ESRD will be necessary. Physicians and case managers of patients with ESRD should act in complementary and cooperative roles in SDM programs.

P0180U-SHAPED RELATIONSHIP BETWEEN SERUM URIC ACID LEVEL AND THE RISK OF END STAGE RENAL DISEASE AND ALL-CAUSE MORTALITY IN MEN

Abstract Background and Aims High uric acid level was known as a risk factor to incident chronic kidney disease, mortality, or cardiovascular mortality. However, it is obscure which level of uric acid (UA) is safe to prevent end stage renal disease (ESRD) and mortality. We searched the optimal range of UA level to escape the incident ESRD and death in a large cohort of general population. Method We enrolled 143,762 adult subjects participated in voluntary health check-up program from three referral hospitals in Korea between 1995 and 2009. We defined 48,147 control subjects (CONTROL) without risk factors of high UA level, to calculate 5, 20, 80, and 95 percentiles of UA level and allocated whole participants into five groups (G1, G2, G3, G4, G5) according to the criteria in each gender. We merged the incident data of ESRD from the Korean ESRD registry by December 2017 and the mortality data from the Ministry of the Interior and Safety by May 2018 based on the identifier of Koreans. This project was approved by institutional review boards of the three hospitals. Results The UA levels of 5, 20, 80, 95 percentiles in CONTROL were 2.9 mg/dL, 3.5 mg/dL, 4.9 mg/dL, and 5.7 mg/dL in females, and 4.1 mg/dL, 5.0 mg/dL, 6.8 mg/dL, and 7.8 mg/dL in males. There were 76,784 (53.4%) males and 66,978 (46.6%) females. The age was 50.5 ± 12.2 years and the level of GFR by CKD-EPI equation was 94.3 ± 15.2 ml/min/1.73 m2 at enrollment. Among females, ESRD was developed in 110 subjects (0.2%) and 1,922 subjects (2.9%) were dead during more than 12 years. The level of UA and groups of UA were not independent risk factors to mortality or incident ESRD in females. Among males, there were 162 subjects with ESRD (0.2%) and 4293 subjects (5.6%) were dead. Compared to G3 group (5.0 mg/dL ≤ UA&amp;lt;6.8 mg/dL), other groups showed higher risk of incident ESRD adjusted with related factors by Cox’s hazard proportional model in males (p=0.016). The Hazard ratios (HRs) for incident ESRD in G1 group (&amp;lt;4.1 mg/dL), G4 group (6.8 mg/dL ≤ UA&amp;lt; 7.8 mg/dL), and G5 group (7.8 mg/dL ≤ UA) were 2.409 (95% CI, 1.312-4.423, P=0.005), 1.710 (95% CI, 1.080-2.707, P=0.022), and 1.742 (95% CI, 1.098-2.762, P=0.018), respectively. The HRs for all-cause mortality in G1, G4, and G5 group were 1.203 (95% CI, 1.017-1.346, P=0.001), 1.099 (95% CI, 1.006-1.201, P=0.037), and 1.137 (95% CI, 1.015-1.272, P=0.026), respectively. We found there were 591 subjects died from cardiovascular disease (CVD) among 3,352 deaths with valid cause of death. G1 and G5 group showed higher risk for CVD-mortality compared to G3 group in men (p&amp;lt;0.001). Conclusion Serum uric acid level showed U-shaped pattern of HRs for incident ESRD and all-cause mortality in men, only. The appropriate uric acid level might be 4.1-6.7 mg/dL in men.

P0503PROGNOSTIC VALUE OF HISTOPATHOLOGICAL CLASSIFICATION OF ANCA-ASSOCIATED GLOMERULONEPHRITIS: A SINGLE-CENTER RETROSPECTIVE STUDY

Abstract Background and Aims Kidney biopsy is the gold standard for establishing the diagnosis of ANCA-associated glomerulonephritis (GN). Previous studies have validated the prognostic significance of histopathological classification for the development of end stage renal disease (ESRD). We sought to evaluate the prognostic value of the EUVAS histopathological classification in terms of renal and overall survival (OS) in a single center retrospective cohort study. Method Forty-six consecutive patients (mean age 69, range; 29-84 years) with biopsy-proven ANCA-associated GN diagnosed at our hospital between January 2003 and January 2019 were included in the study. All biopsies had ≥10 glomeruli and were reviewed by two independent pathologists blinded to clinical data. Renal morphology was classified as sclerotic (if ≥50% globally sclerotic glomeruli), focal (if ≥50% normal glomeruli), crescentic (if ≥50% crescents with cellular component) and mixed. Probabilities of renal and overall survival were estimated using Kaplan-Meier method. Cumulative incidence function for ESRD was estimated using death as competing risk. Results Three biopsies were classified as focal (6%), twenty-nine as crescentic (63%), ten as mixed (22%) and four as sclerotic (9%). With a median follow-up of 39 months the 3-year probability of renal survival was 100% for the focal class, 66,37% for the crescentic class, 64% for the mixed class and 50% for the sclerotic class (p&amp;gt;0.05). Other parameters associated with increased probability of ESRD were interstitial fibrosis (IF) and eGFR at time of diagnosis. IF of ≥40% at diagnosis was associated with high incidence of ESRD, while IF of 20-40% and &amp;lt;20% had significantly lower incidence of ESRD (100% vs 34.2% vs 17.6%, p=0.014). Half (50%) of the patients with eGFR&amp;lt;15ml/min at diagnosis developed ESRD at 36 months compared to only 8% of the patients with eGFR≥15ml/min (p=0.024) at diagnosis. Median overall survival for the entire cohort reached 128 months (95% CI; 35-221). Twelve patients died at median time of 19,5 months (range; 3-129) after diagnosis. Three patients died before developing ESRD and nine patients developed ESRD prior to death. Leading cause of death was sepsis (8/12). Other causes included sudden death (n=2), malignancy (n=1) and intestinal obstruction (n=1). In terms of histopathological classification, OS at 3 years was 100% (95% CI; N/A) for the focal class, 73.5% (95% CI; 57-94.8) for the crescentic class, 100% (95% CI; N/A) for the mixed class and 37,5% (95% CI; 83,9-100) for the sclerotic class (p&amp;gt;0.05). Conclusion Our results suggest that the focal class has the best and the sclerotic the worst outcome, while both crescentic and mixed subtype are of intermediate risk. Although our results did not reach statistical significance, due to primarily the small number of patients included, the incidence of ESRD and the probability of renal survival in each histopathological subtype in our cohort are comparable to those reported by larger studies. Thus, the EUVAS histological classification of ANCA-associated glomerulonephritis appears to be a useful predictor of renal outcome at the time of diagnosis. As previously reported, no significant prognostic difference was observed between the crescentic and mixed subtype. Thus, this classification system should be optimized by inclusion of other histological characteristics, such as the specific percentage of normal glomeruli, tubular atrophy and interstitial fibrosis. These characteristics may prove useful in highlighting significant differences between mixed and crescentic classes.

P0397OUTCOMES OF PROTEINASE 3- AND MYELOPEROXIDASE ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY ASSOCIATED VASCULITIS IN DENMARK 2014-2017

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody associated vasculitis (AAV) defines an uncommon group of autoimmune diseases with antibodies directed against proteinase 3 (PR3) or myeloperoxidase (MPO). Incidence rates of PR3- and MPO-AAV differ geographically, and current evidence based on genetic variations and cluster analyses supports discrimination of associated vasculitis based on PR3- and MPO-positivity. Such discrimination could provide insights of scope for clinical trials with ramifications for improvement of treatment. With the aim of comparing patient characteristics and outcomes between PR3- and MPO-AAV, we report on results from a nationwide retrospective cohort study. Method Incident patients positive for PR3- and MPO-anti-neutrophil cytoplasmic antibodies were identified in central laboratories of three of four administrative regions (covering 80% of the population) in Denmark between 1/1-2014 and 31/12-2017. Patient characteristics were identified by cross-referencing of data from multiple national health care registers. Baseline renal function was calculated based on the CKD-EPI equation using plasma creatinine measurements recorded 365 to 7 days prior to index. Incidences of all-cause mortality and end-stage renal disease stratified on baseline eGFR were computed using the Aalen-Johansen estimator. Hazard ratios for specific predictors including strata of baseline eGFR were calculated based on a multiple Cox proportional hazards model adjusted for relevant confounders. Results In total 770 patients were included in the study (PR3 n=399 and MPO n=371). Annual incidence rates of PR3- and MPO-AAV were 22.6 and 21.1 per million, respectively. PR3-AAV was associated with greater preponderance for male gender (54.4% vs. 42.3%, p=0.001), lower patient age (61.9 years [IQR 41.6-73.0 years] vs. 64.9 years [IQR 50.0-74.0 years], p=0.016), and greater baseline renal function (eGFR 87 ml/min [IQR 56-101 ml/min] vs. 75 ml/min [IQR 36-92 ml/min] compared with MPO-AAV. Comorbid burden was comparable; 26% of patients had history of hypertension, 15% of patients had a history of ischemic heart disease, and 12% of patients had a history of cancer. Acute dialysis was initiated in 5.3% and 6.7%, plasmapheresis in 12.8% and 13.7%, and mechanical ventilation in 4.8% and 4.3% of patients with PR3- and MPO-AAV, respectively. Median follow-up was 564 days [234 – 932]. A total of 86 deaths and 25 end-stage renal disease endpoints were recorded during follow-up. Cumulative incidences of all-cause mortality and end-stage renal disease stratified on baseline eGFR are shown in Figure 1. Adjusted hazard ratios for all-cause death and/or end-stage renal disease showed increased risk associated with PR3-AAV, HR 1.51 (95% CI 1.03 – 2.25, p=0.036), non-European descent, HR 3.63 (95% CI 1.29-10.25, p=0.015) and patient age, HR 1.05 (95% CI 1.03-1.07, p&amp;lt;0.001). In both PR3- and MPO-AAV, only baseline eGFR ≤ 20ml/min/1.73m2 was associated with poorer prognosis (ref.: baseline eGFR &amp;gt;90 ml/min/1.73m2); MPO-AAV: eGFR 51-90 ml/min/1.73m2: HR 2.34 (95% CI 0.75 – 7.34, p=0.145), eGFR 21-50 ml/min/1.73m2: HR 2.11 (95% CI 0.60 – 7.47, p=0.246), and eGFR ≤ 20ml/min/1.73m2: 5.05 (95% CI 1.55 – 16.45, p=0.007); PR3-AAV: eGFR 51-90 ml/min/1.73m2: HR 1.54 (95%CI 0.53 – 4.46, p=0.427), eGFR 21-50 ml/min/1.73m2: HR 1.70 (95% CI 0.51 – 5.64, p=0.386), and eGFR ≤ 20ml/min/1.73m2: 8.06 (95% CI 2.83 – 23.0, p=&amp;lt;0.001). Conclusion In a nationwide cohort study comparing PR3- and MPO-AAV, PR3-AAV was associated with poorer 24-month outcomes in spite of superior renal function at baseline. Overall, poor prognosis was limited to patients with severe renal insufficiency (eGFR ≤20ml/min/1.73m2) at time of diagnosis in both PR3- and MPO-AAV.

P0385CLINICAL DIFFERENCES OF MEMBRANOPROLIFERATIVE GLOMERULONEPHROPATHY (MPGN) ACCORDING TO PRESENCE OF HEPATITIS B VIRUS INFECTION

Abstract Background and Aims Traditional definition of MPGN by morphologic changes on light microscopic examination was reclassified into MPGN caused by immunoglobulin/immune complex injury and C3 glomerulopathy (C3G) with alternative complement pathway abnormality based on immunofluorescence staining. MPGN might be caused by various causes such as malignancy, infection, autoimmune diseases, etc. It was rarely known the clinical characteristics of MPGN according to the possible causes excluding C3G. Method We enrolled 20,481 adult patients having native kidney biopsy for diagnosis of nephritis between 1979 and 2018, retrospectively. Among them, there were 553 patients with MPGN whom we reclassified into 18 patients with C3G and 535 MPGN patients. We excluded patients with cancer, autoimmune disease, hepatitis C virus infection, C3G, or combined pathologic diagnosis other than MPGN. Finally, we enrolled 156 patients without hepatitis B surface antigen (HBsAg)[MPGN] and 48 patients with HBsAg [MPGN_HBV]. The final outcomes were incidences of end stage renal disease (ESRD) and death. Results Patients with MPGN_HBV are younger than MPGN (45.5 ± 15.8 years vs 54.6 ± 15.7 years, p=0.001) and included more males (43 (89.6%) vs 97 (62.2%), p&amp;lt;0.001). The systolic blood pressure was not different between groups but the diastolic blood pressure was higher in MPGN_HBV (85.4 ± 10.4 mmHg vs 80.7 ± 13.4 mmHg, p=0.018). The level of urine protein to creatinine ratio was not different between groups but the level of glomerular filtration rate (GFR) was higher in patients with MPGN_HBV compared to patients with MPGN (65.8 ± 29.0 ml/min/1.73 m2 vs 57.5 ± 34.8 ml/min/1.73 m2, p=0.039). Mortality was observed in 2 patients with MPGN_HBV (4.2 %) and 9 patients with MPGN (5.8%)(p=1.000) during 64.9 months (median). Incident ESRD was notified in 6 patients with MPGN_HBV (13.3 %) and 39 patients with MPGN (26.5 %)(p=0.067) during 47.8 months (median). HBV positivity was not a risk factor to mortality (p=0.847) and was not a risk factor to incident ESRD (p=0.108), either, by Cox’s hazard proportional model adjusted with related factors to mortality. The most important risk factor was hemoglobin and GFR at renal biopsy. Conclusion The clinical characteristics of MPGN according to presence of HBsAg were different, however, the prognosis was not dependent on HBsAg positivity, which suggested the severity of renal injury was more important than the cause of renal injury.

P0155CHARACTERISTICS OF HYPERTENSIVE NEPHROSCLEROSIS DIAGNOSED BY RENAL BIOPSY BASED ON 40-YEAR EXPERIENCE

Abstract Background and Aims Hypertensive nephrosclerosis (HT-N) is known as the second common cause of end stage renal disease (ESRD) in Korea as well as in other countries. However, the HT-N is assumed by clinical findings which are not well correlated to the pathologic findings. Therefore, we report the clinical characteristics of HT-N diagnosed by renal biopsy and compare the prognosis between patients with HT-N and hypertensive patients with focal segmental nephrosclerosis (FSGS) without pathologic HT-N. Method We enrolled 21,617 patients having native kidney biopsy for diagnosis of nephritis between 1979 and 2018, retrospectively. Among them, we selected 267 adult hypertensive patients with only HT-N and 984 hypertensive patients with FSGS without HT-N or other diagnoses (FSGS-HT). The estimated glomerular filtration rate (GFR) was calculated by original MDRD equation. The final outcomes were incidences of end stage renal disease (ESRD) and death. We matched blood pressures and GFR between two groups and analyzed the difference of outcomes within the matched cohort (mHT-N and mFSGS-HTN), also. Results The age of patients with HT-N was 49.5 ± 15.3 years at renal biopsy. There were 175 (65.5 %) men. Systolic blood pressure (SBP) was 139.1 ± 24.0 mmHg and diastolic blood pressure (DBP) was 83.7 ± 15.6 mmHg at renal biopsy. Levels of serum creatinine, GFR, and urine protein to creatinine ratio were 3.17 ± 3.05 mg/dl, 40.7 ± 32.5 ml/min/1.73 m2, and 2.277 ± 2.803 g/g cr, respectively. During follow-up period of 64.1 months (median), there were 52 (22.7%) patients progressed to ESRD and 8 (3.1%) patients were dead. Age, SBP, and hemoglobin were risk factors to mortality by Cox’s hazard proportional model adjusted with related factors to mortality. With increase of 10 mmHg in the level of SBP at renal biopsy, hazard ratio(HR) of mortality was increase by 1.645 folds (95% CI: 1.192-2.270, P=0.002). Presence of diabetes mellitus, serum albumin, and GFR were risk factors to incident ESRD. Compared to patients with FSGS-HT, patients with HT-N showed higher levels of SBP, DBP, and serum creatinine and lower levels of GFR, serum albumin, hemoglobin, and UPCR (all p-values &amp;lt;0.05), however, the risk of incident ESRD and mortality was not different. Therefore, we matched BP and GFR between groups and selected 235 patients in each group. The matched groups were not different in the values of age, SBP, DBP, and GFR. The risk of mortality was not different between groups (p-value =0.502), however, HR of incident ESRD was 1.558-fold higher (95% CI: 1.004-2.419, P=0.048) in mFSGS-HT compared to mHT-N by Cox’s hazard proportional model adjusted by factors related to ESRD. Conclusion Hypertensive nephrosclerosis was diagnosed in more advanced stage of CKD compared to hypertensive FSGS. Considering levels of GFR and SBP as risk factors to hard outcomes, we should consider early pathologic diagnosis for proteinuric and/or azotemic hypertensive patients and control blood pressures and renal dysfunction in more aggressive manners.

P1007CHANGES IN METABOLIC SYNDROME COMPONENTS AND RISK OF END STAGE RENAL DISEASE: A NATIONWIDE COHORT STUDY

Abstract Background and Aims Few studies have investigated the impact of a change in metabolic syndrome (MetS) components on clinical renal outcomes in the general population. Method Using nationally representative data from the Korean National Health Insurance System, 13,310,924 subjects who underwent two health examinations over 2 years and were free from end-stage renal disease (ESRD) from 2009 to 2012 were followed to the end of 2016. The subjects were divided into four groups according to the change in MetS components between the two visits over 2 years: no MetS (–/–), post-MetS (–/+), pre-MetS (+/–), and both MetS (+/+). Results After a median follow up of 5.11 years, 18,582 incident ESRD cases were identified. In the multivariate adjusted model, the hazard ratio (HR) and 95% confidence interval (CI) for the development of ESRD in the both-MetS (+/+) group compared with the no-MetS (–/–) group was 5.65 (95% CI, 5.42–5.89), which was independent of age, sex, and baseline estimated glomerular filtration rate. Additionally, the HR for the pre-MetS (+/-) group versus the no-MetS (–/–) group was 2.28 (2.15–2.42). In subgroup analysis according to renal function, the impact of a change in MetS on the incidence of ESRD was more pronounced in individuals with advanced renal dysfunction. Subjects with resolved MetS components had a decreased risk of ESRD, but not as low as those that never had MetS components. Conclusion This provides evidence supporting the strategy of modulating MetS in the general population to prevent the development of ESRD.

P0468RENAL OUTCOME AND MORTALITY OF GLOMERULONEPHRITIS IN A THAI TERTIARY CARE CENTER

Abstract Background and Aims Glomerulonephritis (GN) is a common cause of End-stage renal disease (ESRD) in Asia and around the world. Most studies from renal registries have focused on the prevalence or clinical characteristics of patients with GN. Only a few registry-based data have focused on mortality and ESRD risks of different types of GN. There is limited data from low to middle income countries or from Southeast Asia. The objectives of this study were to evaluate the mortality and ESRD rates among patients with different types of GN referred for a kidney biopsy at a Thai tertiary care hospital. Method In this retrospective study, the data of patients (n=1,025) referred for a kidney biopsy at Ramathibodi Hospital from 1 January 2011 to 31 December 2017 were reviewed. Patients were classified in to 11 different types of GN. Patient death and cause of death data was obtained from National Census office. ESRD data was obtained from the Thailand Nephrology Society ESRD registry which includes all patients on renal replacement therapies for greater than 3 months. Results Patients with inadequate specimen (n=66) or non-glomerular diseases (n=95) were excluded. Data from 864 patients with GN was analyzed. The age at kidney biopsy was 43.9 ± 16.8 years, median eGFR (CKD-EPI) was 42 (IQR 13-83) mL/min/1.73m2. The male:female ratio was 0.6. The prevalence of GN were: Lupus nephritis (26.8%), IgA nephropathy (18.2%), focal segmental glomerulosclerosis (FSGS 12.6 %), membranous nephropathy (11.9 %), diabetic nephropathy (10.8%), minimal change disease (9.7%), hypertensive nephrosclerosis (4.3%), pauci-immune complex glomerulonephritis (2.3%), membranoproliferative glomerulonephritis (MPGN 1.6%) and multiple myeloma (1.4%) Median time follow up was 42 (IQR 23-62) months. Overall mortality was 13 %. Lupus nephritis accounted for highest proportion of all deaths (25%), followed by diabetic nephropathy (19.1%), FSGS (9%). Listed causes of deaths were: sepsis 22% and chronic kidney disease 8%. Mortality rates by disease were: multiple myeloma (50%), diabetic nephropathy (28.7%), MPGN (21.4%), pauci-immune complex GN (20%), hypertensive nephrosclerosis (15.8%), lupus nephritis (14.6%), membranous nephropathy (8.7%), FSGS (8.2%), minimal change disease (5.8%), IgA nephropathy (4.4%) The incidence of ESRD was 14 %. LN accounted for the highest proportion (29%) of all ESRD, followed by IgA nephropathy (14%), and membranous nephropathy (13%). The rates of ESRD by disease were: multiple myeloma (33.3%), lupus nephritis (15%), membranous nephropathy (14.5%), minimal change disease (14.3%), MPGN (14.2%), IgA nephropathy (10.1%), FSGS (10.1%), diabetic nephropathy (7.4%), pauci-immune complex glomerulonephritis (5%), hypertensive nephroclerosis (2.6%). Conclusion Lupus nephritis is the most common GN and accounted for the highest proportion of all deaths and ESRD in this Thai cohort. IgA nephropathy is the most common primary GN and an important cause of ESRD, but the mortality rate is low compared to other GN. Membranous nephropathy has comparable prevalence to FSGS, but is a more important contributor to ESRD. Diabetic nephropathy has higher rate of mortality than ESRD. Multiple myleloma has the highest rate of both death and ESRD.

P0405CURRENT STATUS OF NEPHRITIS IN KOREA: EXPERIENCE OF 18 CENTERS DURING LAST 40 YEARS

Abstract Background and Aims Glomerulonephritis (GN) is one of common causes of end-stage renal disease (ESRD) in Korea as well as in the world, however, it is underdiagnosed as a cause of chronic kidney disease. The incidence and prevalence of GNs are different according to periods and countries. We report trends of pathologic diagnosis of nephritis from 18 centers throughout Korea during last 40 years. Method We enrolled 21,617 patients having native kidney biopsy for diagnosis of nephritis between 1979 and 2018, retrospectively. We excluded 191 patients diagnosed as cancer or tumor and analyzed the data of 21,426 patients. We defined the primary GN as IgA nephropathy (IGAN), minimal change disease (MCD), membranous nephropathy (MGN), focal segmental glomerulosclerosis (FSGS), membranoproliferative GN (MPGN), and C3 glomerulopathy (C3G). The estimated glomerular filtration rate (GFR) was calculated by original MDRD equation for adults and by height-independent equation for children. The final outcomes were incidences of end stage renal disease (ESRD) and death. Results There were 22,203 pathologic diagnoses including 777 patients with two kinds of pathologic diagnosis. The age was 42.1 ± 17.7 years at renal biopsy. There were 11565 (54.0 %) men and 976 (4.6 %) children &amp;lt;18 years. The frequencies of hypertension and diabetes mellitus were 53.0 % (10994) and 14.0 % (2833), respectively. Mean levels of serum creatinine, GFR, and urine protein to creatinine ratio were 1.62 ± 1.89 mg/dl, 77.1 ± 60.4 ml/min/1.73 m2, and 3.305 ± 4.164 g/g cr, respectively. The prevalence of GN was 78.45% (17419 diagnoses), followed by tubulointerstitial nephritis (8.84 %), abnormality in glomerular basement membrane (3.43 %), ischemic nephropathies (1.73 %), paraproteinemia related lesions (1.36 %), infection (0.12 %). There were non-specific GN (3.65 %), normal pathology (2.46 %), advanced global sclerosis (1.77 %), inadequate specimen (0.96 %), and miscellaneous lesions (0.12 %), also. The most frequent diagnosis was IGAN (34.17%, 7586 diagnoses), followed by MGN (9.17%), MCD (9.13 %), FSGS (7.65 %), lupus nephritis (LN) (6.30 %), diabetic nephropathy (DMN) (3.99 %), MPGN and C3G (2.79 %), therefore, prevalence of primary GN was 62.90 %. The frequency of IGAN had been increased from 19.9 % at the period of 1979-1989 to 41.4 % at the period of 2005-2009 and then stabilized to 36.0-36.7%. The frequencies of MCD, MGN, and FSGS were not changed since 1990. However, the frequency of MPGN was decreased from 4.7-5.7 % at the period of 1979-1999 to 2.5 % at the period of 2015-2018. The frequency of LN was decreased and that of DMN was increased from 2.5-3.1% during 1990-2009 to 6.3 % during 2015-2018 which might be related to the pathologic classification of DMN, published at 2010 by Tervaert TW et al. The incidences of ESRD and death were 13.3 % (2663/20010 patients) and 2.9 % (608/20884 patients) during follow-up period of 82.6 months (median) for ESRD and 91.5 months (median) for mortality after biopsy. Among patients with primary GN, patients with MCD showed the best prognosis for ESRD, followed by patients with MN, IGAN, FSGS, MPGN, and C3G (p &amp;lt;0.001) by Cox’s hazard proportional model adjusted by risk factors related to ESRD. Prognosis for mortality was not different among patients with MCD, MN, IGAN, and FSGS, but, patients with C3G showed the worst prognosis for mortality (p=0.006). Conclusion IGAN was the most frequent diagnosis followed by MGN and MCD. Compared to Western countries, IGAN and MCD are more prevalent in Korea, while MGN and FSGS are less prevalent. The frequencies of MPGN and LN had been decreased since 2000. The patients with MPGN and C3G showed the worst prognosis.

1512-P: Severe Hypoglycemia and Hyperglycemia among U.S. Adults with Diabetes and ESRD on Dialysis, 2010-2015

Glycemic management in patients with diabetes and end-stage renal disease (ESRD) is challenging. There is limited evidence about the incidence of severe hypoglycemia and hyperglycemia in this population. Here, we examine rates of emergency department visits and hospitalizations for severe hypoglycemia and hyperglycemia (ascertained using validated ICD-9/10 codes) in a national cohort of adults with diabetes and incident ESRD, included in the United States Renal Data System, between 2010-2015. We then examine risk factors for these events using logistic regression. Among 678,376 patients with ESRD, 59.5% (n=403,490) had diabetes (63.6±13.0 years, 56.4% male, 26.8% Black, and 18.0% Hispanic). Rates of severe hypoglycemia and hyperglycemia were 126.2 and 35.5 per 1000 person-years, respectively. Strongest risk factors for hypoglycemia were insulin therapy (OR 4.5 [95% CI, 4.4-4.6] vs. no medications) and non-insulin diabetes medications (OR 3.7 [3.6-3.8]); Black race (OR 1.3 [1.3-1.4] vs. Caucasian); older age: 65-74 years (OR 1.2 [1.1-1.3] and ≥75 years OR 1.1 [1.1-1.1] vs. 18-44 years); and history of amputation (OR 1.4 [1.4-1.5]) or retinopathy (OR 1.2 [1.2-1.3]). Strongest risk factors for hyperglycemia were insulin (OR 7.7 [7.4-8.2]) and non-insulin diabetes medication use (OR 2.8 [2.6-3.1]) and retinopathy (OR 1.5 [1.4-1.5]). Older age was protective for hyperglycemia (OR 0.1 [0.1-0.1] for age ≥75 and 0.2 [0.2-0.2] for age 65-74 vs. 18-44 years). Patients on peritoneal dialysis had a lower risk (OR 0.8 [0.8-0.9]) of hypoglycemia, but no difference in odds of hyperglycemia, compared to patients on hemodialysis. Hypoglycemia requiring ED/hospital care was 3.6-fold more prevalent than severe hyperglycemia, greatly exceeding rates previously reported for older adults and those with non-end stage chronic kidney disease. There is a critical need for proactive interventions to reduce hypoglycemia and related ED/hospital use in this high-risk population. Disclosure R.J. Galindo: Advisory Panel; Self; Lilly Diabetes. Consultant; Self; Valeritas, Inc. Research Support; Self; Novo Nordisk Inc. Other Relationship; Self; UpToDate. M.K. Ali: Research Support; Self; Merck &amp; Co., Inc. N. Shah: None. S. Funni: None. G.E. Umpierrez: None. R.G. McCoy: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024)

P0832FINAL OUTCOME OF CKD STAGE 5 PATIENTS WHO CHOSE PALLIATIVE TREATMENT-EXPERIENCE FROM ONE MEDICAL CENTER IN TAIWAN

Abstract Background and Aims Taiwan has a high incidence and prevalence of ESRD (end stage renal disease) in the world and all the medical expenses are covered by national insurance. Therefore, many old ESRD(end stage renal disease) patients received dialysis even had multiple co- morbidity. However, still some old late CKD patients withhold dialysis and chose palliative treatment. This study elucidate the experience of final outcome for those late CKD patients who chose palliative treatment in Taiwan. Method We enrolled 137 CKD stage 5 patients (age: 80.2±8.8 y/o, male/female:85/52) who were interested about palliative treatment since Oct, 2010 till July 2019. We reviewed their co-morbidity to calculate Modified Charlson comorbidity index by medical record and record their laboratory data at enrollment. The differences between two groups were calculated using a Chi-square test for categorical variables and a Mann-Whitney test for continuous variables. All statistical tests were two-tailed and a P value of less than .05 was considered a significant difference. Results After fully discussion, 82(59.9%) patients can accept palliative treatment, 46(33.6%) refuse palliative treatment, 9(6.6%) patients cannot decided palliative treatment or not at first. 79 patient died during study period, median survival time is 163 days. 22 death patients(27.8%) received dialysis before end of life. 10 patients (12.2%) who asked palliative treatment at first and changed their mind to received dialysis. 80% of these patients receive dialysis by double lumen catheter. For those refuse palliative treatment, 43 patient received dialysis and 24(55.8%) patients received dialysis by temporary catheter. These percentage is much higher(55.8%) than other CKD stage 5 patients (26.6%) following at our hospital. Only 13 patient(16.5%) died at home, 24 patients(30.4%) diet at hospice ward and 39(49.4%) patients diet at ordinary ward or intensive care unit. Older age, lower albumin and higher Charlson comorbidity index are found in mortality patients. The median survival time for those patients received dialysis is 467 days. Conclusion After fully explanation, only 59.9% patients can accept withhold dialysis and 12.2% regret later. Those who had interested in palliative treatment had higher percentage to use double lumen catheter for first dialysis. The median survival time for those patients who ever think about withhold dialysis is only 467 days even receiving dialysis. To minimize suffering before end of life and decrease medical expense burden, we still need to do more effort to popularize the concept of withhold dialysis in older and multiple comorbidity patients.