Sleep apnea is associated with residual kidney function and mortality in patients with peritoneal dialysis: Prospective cohort study.

INTRODUCTION: Fluid overload and sleep apnea (SA) are known risk factors for mortality in dialysis patients. Although incidence and severity of SA were shown higher in peritoneal dialysis (PD) patients than in hemodialysis patients, data regarding the association of SA with body fluid status and mortality are limited. Therefore, the association of SA with body fluid status and mortality were investigated in a prospective cohort with patients undergoing PD. METHODS: The present study included 103 prevalent PD patients who were followed up for median 70 months. At baseline, the subjects underwent in-home polysomnography, bioelectrical impedance analysis, and urea kinetics. Excessive daytime sleepiness and sleep quality were assessed using sleep questionnaires. SA was defined as apnea/hypopnea index higher than 15 events per hour. RESULTS: Sleep apnea was diagnosed in 57 (55.3%) patients (SA group); the subjects had significantly higher extracellular water (10.3 ± 1.4 vs. 9.2 ± 1.8, p = 0.001) and lower residual kidney function (RKF) (3.3 ± 3.3 vs. 5.9 ± 7.2, p = 0.02) compared with subjects in the non-SA group. SA was significantly associated with RKF [odds ratio, 0.84; 95% confidence interval (CI), 0.73-0.97] in multivariable logistic regression analysis. In multivariable Cox regression models, SA was a significant predictor of mortality in PD patients (adjusted hazard ratio, 5.74; 95% CI, 1.09-30.31) after adjusting for well-known risk factors. CONCLUSIONS: Sleep apnea was very common in PD patients and significantly associated with lower RKF. SA was also a novel risk predictor of mortality in PD patients.

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD.

BACKGROUND AND AIMS: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of "the lower, the better" strategy for statin intake. METHODS AND RESULTS: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70-99, 100-129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70-99, 100-129, and ≥130 mg/dL were 2.06 (1.14-3.73), 2.79 (1.18-6.58), and 4.10 (1.17-14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. CONCLUSIONS: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

Associations of Systolic Blood Pressure With Incident CKD G3-G5: A Cohort Study of South Korean Adults.

RATIONALE & OBJECTIVE: Clinical practice guidelines recommend a target blood pressure (BP)<130/80 mm Hg to reduce cardiovascular risk. However, the optimal BP to prevent chronic kidney disease (CKD) is unknown. STUDY DESIGN: Population-based retrospective cohort study. SETTING & PARTICIPANTS: 10.5 million adults who participated in the National Health Insurance Service National Health Checkup Program in South Korea between 2009 and 2015 and had an estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2 at the beginning of follow-up. PREDICTORS: Baseline and time-updated systolic BP (SBP) as a continuous variable and categorized as<110, 110 to 119, 120 to 129, 130 to 139, or≥140 mm Hg. OUTCOME: Incident CKD GFR categories 3 to 5 (CKD G3-G5), defined as de novo development of estimated GFR<60 mL/min/1.73 m2 for at least 2 consecutive assessments confirmed at least 90 days apart. ANALYTICAL APPROACH: Cox proportional hazards regression for baseline BP and marginal structural analysis for time-updated BP. RESULTS: During 49,169,311 person-years of follow-up, incident CKD G3-G5 developed in 172,423 (1.64%) individuals with a crude event rate of 3.51 (95% CI, 3.49-3.52) per 1,000 person-years. Compared to a baseline SBP of 120 to 129 mm Hg, HRs for incident CKD G3-G5 for the<110, 110 to 119, 130 to 139, and≥140 mm Hg categories were 0.84 (95% CI, 0.82-0.85), 0.92 (95% CI, 0.91-0.94), 1.11 (95% CI, 1.09-1.12), and 1.30 (95% CI, 1.28-1.31), respectively. For time-updated SBPs, corresponding HRs were 0.57 (95% CI, 0.56-0.59), 0.79 (95% CI, 0.78-0.80), 1.58 (95% CI, 1.55-1.60), and 2.49 (95% CI, 2.45-2.53), respectively. Treated as a continuous exposure, each 10-mm Hg higher SBP was associated with 35% higher risk for incident CKD G3-G5 (95% CI, 1.35-1.36). LIMITATIONS: Use of International Classification of Diseases codes to assess comorbid condition burden; residual confounding, and potential selection bias cannot be excluded. CONCLUSIONS: In this large national cohort study, higher SBPs were associated with higher risk for incident CKD G3-G5. These findings support evaluation of SBP-lowering strategies to reduce the development of CKD.

Health Insurance Status Is Related to Risk of Mortality and Hospitalization in Korean Maintenance Hemodialysis Patients: A Longitudinal Cohort Study.

BACKGROUND: There has been an increasing incidence of hemodialysis (HD) due to old age and comorbid condition such as diabetes. In general, socioeconomic status (SES) is known as one of the most important risk factors for patient mortality and morbidity. Whether low SES is associated with poorer outcome in HD patients is controversial. This study was performed to evaluate the association of health insurance status as a proxy indicator for SES upon mortality and hospitalization in maintenance HD patients. METHODS: We used HD-quality assessment data from the year of 2015 for collecting demographic and clinical data. The subjects were classified into Medical Aid (MA) recipients (low SES) and National Health Insurance (NHI) beneficiary (high SES). We analyzed mortality and hospitalization risk based on health insurance status using Cox proportional hazard model. A total of 35,454 adult HD patients ≥18 years old who received HD treatment more than twice weekly were included in the analysis. RESULTS: The ratio between MA recipient and NHI beneficiary was 76.7 versus 23.3%. The MA recipient group demonstrated younger age and lower proportion of female, diabetes, hypertension, and cerebrovascular accidents compared to the NHI beneficiary group. After adjusting for age, gender, comorbidity, and laboratory parameters, the MA recipient group showed a significantly higher mortality risk compared to the NHI beneficiary group (hazard ratio 1.073 [1.009-1.14], p = 0.025). The MA recipient group was also an independent risk factor for hospitalization after adjusting for age, gender, comorbidities, and laboratory parameters (hazard ratio 1.142 [1.108-1.178], p < 0.001). CONCLUSION: Low SES as measured by health insurance status was associated with an increased risk of patient mortality and hospitalization in Korean maintenance HD patients.

Relationship between complement deposition and the Oxford classification score and their combined effects on renal outcome in immunoglobulin A nephropathy.

BACKGROUND: Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. METHODS: We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up. RESULTS: Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1-2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1-2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1-2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. CONCLUSIONS: Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.

A Diet Rich in Vegetables and Fruit and Incident CKD: A Community-Based Prospective Cohort Study.

RATIONALE & OBJECTIVE: A diet rich in vegetables and fruit can lower blood pressure and may reduce cardiovascular risk. However, the association between this dietary pattern and incident chronic kidney disease in the general population is unknown. STUDY DESIGN: A community-based prospective cohort study. SETTING & PARTICIPANTS: 9,229 study participants with normal kidney function from the Korean Genome and Epidemiology Study database. PREDICTORS: Daily consumption of nonfermented and fermented vegetables and fruit classified into tertiles based on a validated semiquantitative food-frequency questionnaire. OUTCOMES: Incident occurrence of estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2, incident proteinuria (≥1+ by dipstick test), and repeated measures of estimated net endogenous acid production. ANALYTICAL APPROACH: Multivariable cause-specific hazards model to assess the association of vegetable and fruit intake with incident chronic kidney disease. RESULTS: During a mean follow-up of 8.2 years, 1,741 (21.9/1,000 person-years [PY]) participants developed eGFRs < 60mL/min/1.73m2. Incident eGFR < 60mL/min/1.73m2 occurred less frequently with higher intake of nonfermented vegetables, occurring at rates of 22.8/1,000 PY, 22.7/1,000 PY, and 20.1/1,000 PY for the lowest, middle, and highest tertiles, respectively; P for trend < 0.001. The incidence of proteinuria was also lower in the middle and highest tertiles. In a multivariable cause-specific hazards model, the highest tertile of nonfermented vegetable intake was associated with 14% lower risk for incident eGFR < 60mL/min/1.73m2 than the lowest tertile. The highest tertile was also associated with 32% lower risk for proteinuria than the lowest tertile. There were no associations of fermented vegetable and fruit intake with incidence of eGFR < 60mL/min/1.73m2. However, the highest tertiles of both fermented vegetable and fruit intake were associated with 14% and 45% lower risks for incident proteinuria compared with the lowest tertiles (both P < 0.001). During follow-up, estimated net endogenous acid production increased in the lowest tertile of intake of nonfermented or fermented vegetables and fruit, whereas it decreased in the highest tertile. LIMITATIONS: Self-reported dietary intake, single ethnicity population. CONCLUSIONS: A diet rich in vegetables and fruit may reduce the risk for kidney disease.

Lower serum beta-2 microglobulin levels are associated with worse survival in incident peritoneal dialysis patients.

Background: There is a general consensus that elevated serum beta-2 microglobulin (B2M) levels measured at a single time-point are significantly associated with mortality in patients on maintenance dialysis. To date, the majority of prior studies that have examined B2M-associated mortality have been conducted in prevalent hemodialysis patients with little residual renal function (RRF). However, studies in incident peritoneal dialysis (PD) patients are lacking. Moreover, changes in serum B2M levels over time have not been considered in this population. Methods: We examined the association of time-updated and baseline serum B2M levels with mortality in a 10-year cohort of 725 incident PD patients who were maintained on dialysis between January 2006 and December 2011 using Cox proportional hazards regression analyses. Patients were categorized into tertiles according to B2M levels. Results: During a median follow-up of 38 (interquartile range 23-64) months, 258 (35.4%) deaths occurred, including 106 (14.6%) and 86 (11.9%) deaths from cardiovascular and infectious causes, respectively. The lowest B2M tertile was associated with a higher risk of all-cause and infectious mortality compared with the middle tertile: the hazard ratios (95% confidence interval) for all-cause deaths were 2.12 (1.38-3.26) and 2.20 (0.96-5.05) in time-varying analyses and 1.52 (1.07-2.17) and 2.41 (1.19-4.88) in baseline analyses. Subgroup analyses showed that this association was particularly observed in females, older patients, those with comorbidities such as diabetes, a lower body mass index, lower albumin levels or those with higher RRF (all P for interactions <0.05). Conclusions: In incident PD patients, lower B2M levels were independently associated with overall and infectious mortality. These associations can be potentially modified by malnutrition, inflammation and RRF.

A case report of immunoglobulin M nephropathy manifesting as crescentic glomerulonephritis and nephrotic syndrome in an adult.

BACKGROUND: The nature of immunoglobulin M (IgM) nephropathy has been controversial for a long time, but it is now considered an independent disease like immunoglobulin A nephropathy. IgM nephropathy has been known to have various clinical manifestations ranging from asymptomatic hematuria and/or proteinuria to nephrotic syndrome. Recently, one case of IgM nephropathy manifesting as crescentic glomerulonephritis (GN) was reported in a child. CASE PRESENTATION: We experienced a case of IgM nephropathy that manifested clinically as nephritic and nephrotic syndrome with pathologically confirmed crescentic GN in a 30-year-old woman. We administered a calcineurin inhibitor and corticosteroids to treat the ongoing nephrotic syndrome after remission of crescentic GN. As a result, her proteinuria was significantly reduced and edema improved. CONCLUSIONS: We described a case of IgM nephropathy in an adult patient who initially developed crescentic GN with nephritic and nephrotic syndrome. This case report could contribute to a deeper understanding of IgM nephropathy.

Changes in obese metabolic phenotypes over time and risk of incident chronic kidney disease.

AIM: To examine the association between metabolically healthy obese (MHO) phenotype and incident chronic kidney disease (CKD) and study whether changes in metabolic phenotypes over time could affect CKD risk. METHODS: A total of 8589 subjects from the Korean Genome and Epidemiology Study were categorized into four groups based on the presence of obesity and metabolic abnormalities (MA). The primary endpoint was an onset of incident CKD defined as an estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m2 . Multivariable Cox analysis and time-varying Cox analysis were performed to delineate the relationship between obese metabolic phenotypes and incident CKD after adjustment for sociodemographic factors and clinical and laboratory parameters. RESULTS: During a mean follow-up duration of 9.3 years, CKD occurred in 782 (9.1%) participants. In the multivariable Cox model, the hazard ratio (HR) for incident CKD in the MHO, metabolically abnormal non-obese (MANO), and metabolically abnormal obese (MAO) groups was 1.42 (P = 0.002), 1.45 (P < 0.001), and 1.77 (P < 0.001), respectively, compared with the metabolically healthy non-obese (MHNO) group. Time-varying analysis with these four phenotypes as time-varying exposures showed the same results. Furthermore, subjects with persistent MHO through follow-up were at a 2.0-fold increased risk of CKD (P < 0.001). 41.0% of subjects experienced phenotype changes during follow-up. Over the long term, the MHO group had a higher proportion of transition to the MA phenotype and unfavourable metabolic profiles than the MHNO group. Among MHO subjects, those who transitioned to MAO were at a 4.1-fold increased risk of incident CKD than those who regressed to MHNO. In addition, transition to MHO from other groups carried a higher risk of CKD than persistent MHNO. CONCLUSION: MHO subjects are at increased risk for incident CKD.

Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. METHODS: Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. RESULTS: Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P=0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P=0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P=0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P=0.470). CONCLUSIONS: Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.

Dementia is a risk factor for major adverse cardiac and cerebrovascular events in elderly Korean patients initiating hemodialysis: a Korean national population-based study.

BACKGROUND: Dementia is common in end-stage renal disease (ESRD) patients on hemodialysis (HD) and is associated with worse outcomes. This study aimed to investigate the risk of major adverse cardiac and cerebrovascular event (MACCE) in elderly patients with dementia initiating HD. METHODS: Using the database from the Health Insurance Review & Assessment Service, we analyzed 10,171 patients aged 65 years or older who had initiated dialysis from 2005 to 2008. MACCE was defined as a composite outcome of all-cause mortality, nonfatal acute myocardial infarction, target vessel revascularization, and nonfatal ischemic and hemorrhagic stroke. The Kaplan-Meier method and Cox proportional hazards model were used, and further comparisons using propensity-score matching at 1:2 ratio were also performed. RESULTS: A total of 303 elderly patients (3.0%) had dementia at initiating HD. During follow-up, dementia was a significant predictor of MACCE after adjustment for confounding variables. In addition, further analyzed in the propensity-score matched groups, dementia was an independent predictor of both nonfatal ischemic stroke and all-cause mortality. CONCLUSIONS: Dementia is an independent risk factor for mortality and ischemic stroke in elderly ESRD patients initiating HD. Patients with dementia who start dialysis should be closely monitored to reduce the risk of mortality and ischemic stroke.

Clinical features and outcomes of focal segmental glomerulosclerosis pathologic variants in Korean adult patients.

BACKGROUND: Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations. METHODS: This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR). RESULTS: There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044). CONCLUSION: Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.

Association of sleep-disordered breathing with cognitive dysfunction in CKD stages 4-5.

BACKGROUND: Sleep-disordered breathing and cognitive impairment are common in patients with chronic kidney disease (CKD). Sleep-disordered breathing is known to be a risk factor for cognitive dysfunction in the general population, but this association has not been studied in patients with CKD. STUDY DESIGN: Cross-sectional study. SETTINGS & PARTICIPANTS: A cohort of 169 patients with CKD stages 4-5. PREDICTORS: Sleep-disordered breathing; covariates included demographics, diabetes, cardiovascular disease, depression, and dialysis modality. OUTCOMES: Cognitive impairment, generally defined as a score 1.5 standard deviations or more from the age- and education level-adjusted normative cognitive test score. MEASUREMENTS: Standardized health interview, neurocognitive assessment, sleep-related questionnaires, and polysomnography. RESULTS: Sleep-disordered breathing (apnea-hypopnea index >15) was diagnosed in 83 (49.1%) individuals. This group had a significantly higher prevalence of nocturnal hypoxemia (65.8% vs 26.8%; P < 0.001) and excessive daytime sleepiness (38.6% vs 20.7%; P = 0.01). In addition, this group had significantly lower scores in tests measuring verbal memory, working memory, attention, and psychomotor speed. Sleep-disordered breathing was associated with higher risk of immediate verbal memory impairment after adjustment for known confounders (adjusted OR, 2.67; 95% CI, 1.17-6.08). However, in a subgroup analysis of older adults (aged >60 years), there were no significant differences in cognitive testing between the groups with and without sleep-disordered breathing. LIMITATIONS: Cross-sectional design, limited sample size. CONCLUSIONS: Sleep-disordered breathing is associated with cognitive impairments, especially impaired verbal memory, in patients with advanced CKD. However, the impact appeared limited in older adults. Early evaluation and management of sleep-disordered breathing in patients with CKD may provide an opportunity to improve cognitive function.

Immunogenicity of recombinant human erythropoietin in Korea: a two-year cross-sectional study.

Immunogenicity of erythropoietin (EPO) is related with pure red cell aplasia (PRCA). We sought to determine the prevalence of antibody (Ab)-mediated PRCA in Korea and threshold diagnostic criteria by dual parameters: Ab titer and neutralizing activity. This study was a multi-center, cross-sectional study for two years. In the first year study (1 YS), 209 samples suspected to be EPO resistance were collected. In the second year study (2 YS), all the patients who consented to participate (N = 946) were enrolled. In 1 YS, we found three and six serum samples that were positive and borderline for anti-EPO Abs, respectively. The first three patients had neutralizing activity (NT) and were diagnosed as PRCA. In 2 YS, seven patients were anti-EPO positives and six had borderline levels. Among them, one patient with NT was diagnosed as PRCA and one with NT as aplastic anemia. The prevalence of PRCA was 0.106%. The correlation analysis of the 22 patients who had anti-EPO Ab showed that dual crossed cut-off lines (anti-EPO Ab titer ≥ 40 ng/ml, % NT ≥ 25%) were able to clearly isolate red cell aplasia. We suggest novel diagnostic criteria for diagnosis and prediction of Ab-mediated PRCA with data from both Ab titer assays and NT bioassays.

Spontaneous remission of nephrotic syndrome in patients with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) can be complicated by nephrotic syndrome. Because the spontaneous resolution of heavy proteinuria is rare, corticosteroid therapy should be considered in such cases, particularly when IgAN is combined with minimal-change disease. Here, we report our experience of spontaneous remission of nephrotic syndrome in patients with IgAN and the long-term outcomes of these patients. METHODS: Two hundred and thirty-three patients with biopsy-proven IgAN were enrolled between January 2001 and March 2009. Demographic, clinical and laboratory data were collected retrospectively based on medical records. In addition, pathologic findings were reviewed for glomerular and tubulointerstitial lesions. Outcome data for complete or partial remission, spontaneous remission, relapse, deterioration of renal function, and end-stage renal disease were recorded. RESULTS: Twenty-four patients (10.3%) presented nephrotic syndrome. Among them, five patients underwent spontaneous remission within 6 months after the presentation of nephrotic syndrome. Interestingly, spontaneous remission occurred even in two patients who had elevated serum creatinine levels and advanced renal damage. During follow-up, neither recurrence nor relapse occurred, and no patients showed progressive deterioration of kidney function. Conclusions. This study suggests that spontaneous remission of nephrotic syndrome may occur in any stage of IgAN and carries a favourable long-term outcome without relapse. Given the possibility of under-reported cases, large-scale studies are required, and careful attention should be paid to such complicated cases.

Combined vascular effects of HMG-CoA reductase inhibitor and angiotensin receptor blocker in non-diabetic patients undergoing peritoneal dialysis.

BACKGROUND: Statins and angiotensin receptor blockers (ARBs) are known to improve vascular dysfunction in patients with chronic kidney disease. However, these effects have been inconsistent in dialysis patients. Moreover, it is currently unknown whether adding statins to ARBs improves vascular dysfunction better than ARB monotherapy in these patients. METHODS: We conducted a prospective open randomized trial to investigate the effects of statin add-on to ARB on vascular protection in 124 nondiabetic patients undergoing peritoneal dialysis (PD). Initially, all patients received 80 mg/day of valsartan for 6 months. Excluding 10 patients who dropped out during this period, patients were randomly assigned to continue ARB treatment alone (n = 57) or to receive 10 mg/day of rosuvastatin (n = 57) added to ARB for the next 6 months. To assess vascular function, endothelium-dependent vasodilation and arterial stiffness were determined by brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV), respectively. RESULTS: Compared to baseline values, ARB treatment for the first 6 months significantly improved FMD% (2.97 ± 2.64 to 3.57 ± 2.58 %, P < 0.001). In addition, there was a small but significant decrease in baPWV during this period (1691.5 ± 276.3 to 1635.0 ± 278.6 cm/s, P = 0.048). After randomization, add-on treatment further improved FMD% (3.57 ± 2.73 to 4.24 ± 2.77 %, P = 0.003), whereas ARB monotherapy did not (P = 0.02 for between-group difference). Further slight improvement in baPWV (1617.0 ± 280.9 to 1528.9 ± 266.8 cm/s, P = 0.021) was observed only in the combined treatment group (P = 0.28 for between-group difference). CONCLUSIONS: Adding a statin to the ARB was of some help in improving vascular dysfunction more effectively than ARB monotherapy in nondiabetic PD patients. However, whether such limited improvements can lead to better clinical outcomes requires further investigation.

Clinical Associations between Serial Electrocardiography Measurements and Sudden Cardiac Death in Patients with End-Stage Renal Disease Undergoing Hemodialysis.

The rate of sudden cardiac death (SCD) for hemodialysis (HD) patients is significantly higher than that observed in the general population and have the highest risk for arrhythmogenic death. In this multi-center study, patients starting hemodialysis in each hospital were enrolled; they underwent regular check-ups in an open-patient clinic. We examined serial electrocardiography (ECG) data in patients undergoing HD and determined their associations with the occurrence of SCD. Of 678 enrolled subjects who underwent serial ECG before and after hemodialysis, 291 died and 39 developed SCD. In all subjects, the QT peak-to-end (QTpe) interval at all leads and QRS duration were shortened after hemodialysis. The SCD group showed a significant change in the QTpe interval of the inferior, anterior, and lateral leads before and after hemodialysis compared with the survivor group (p < 0.001). In the pre-hemodialysis ECG, SCD patients had significantly longer QTpe intervals in all leads (p < 0.001) and a longer QRS duration (92.6 ± 14.0 vs. 100.6 ± 14.9 ms, p = 0.015) than survivors. In conclusion, patients with a longer QTpe interval before hemodialysis and large changes in ECG parameters after hemodialysis might be at a higher risk of SCD. Therefore, changes in the ECG before and after hemodialysis could help to predict SCD.

Reduction in proteinuria after immunosuppressive therapy and long-term kidney outcomes in patients with immunoglobulin A nephropathy.

BACKGROUND/AIMS: Despite controversy regarding the benefits of immunosuppressive therapy in immunoglobulin A nephropathy (IgAN), clinical outcomes may vary depending on the patient's responsiveness to this therapy. This study evaluated long-term kidney outcomes according to the extent of proteinuria reduction after immunosuppression in IgAN patients. METHODS: Among 927 patients with biopsy-proven IgAN, 127 patients underwent immunosuppression. Time-averaged urine protein-creatinine ratio before and within 1 year after start of immunosuppression were calculated, and responsiveness to immunosuppression was assessed as the reduction of proteinuria between the two periods. Patients were classified into tertiles according to the extent of proteinuria reduction. We compared the slopes of estimated glomerular filtration rate (eGFR) decline using a linear mixed model, and estimated hazard ratios (HRs) for disease progression (defined as development of a ≥ 30% decline in eGFR or end-stage renal disease) using a Cox proportional hazard model. RESULTS: Median extent of proteinuria reduction was -2.1, -0.9, and -0.2 g/gCr in the first, second, and third tertiles, respectively. There were concomitant changes in the slopes of annual eGFR decline: -2.03, -2.44, and -4.62 mL/min/1.73 m2 among the first, second, and third tertiles, respectively. In multivariable Cox analysis, the HRs (95% confidence intervals) for disease progression were 0.30 (0.12 to 0.74) in the first tertile and 0.70 (0.34 to 1.45) in the second tertile compared with the thirdtertile. CONCLUSION: This study showed that greater proteinuria reduction after immunosuppression was associated with a lower risk of disease progression in patients with IgAN, suggesting that responsiveness to immunosuppression may be an important determinant of kidney outcomes.

Mixed- versus predilution hemodiafiltration effects on convection volume and small and middle molecule clearance in hemodialysis patients: a prospective randomized controlled trial.

BACKGROUND: The use of newly developed mixed-dilution hemodiafiltration (HDF) can supplement the weaknesses of pre- and postdilution HDF. However, it is unclear whether mixed-HDF performs well compared to predilution HDF. METHODS: We conducted a prospective, open-labeled, randomized controlled trial from two hemodialysis centers in Korea. Between January 2017 and September 2019, 60 patients who underwent chronic hemodialysis were randomly assigned at a 1:1 ratio to receive either predilution HDF (n = 30) or mixed-HDF (n = 30) for 6 months. We compared convection volume, changes in small- and medium-sized molecule clearance, high-sensitive C-reactive protein (hs-CRP) level, and dialysis-related parameters between the two dialysis modalities. RESULTS: A mean effective convection volume of 41.0 ± 10.3 L/session in the predilution HDF group and 51.5 ± 9.0 L/session in the mixed-HDF group was obtained by averaging values of three time-points. The difference in effective convection volume between the groups was 10.5 ± 1.3 L/session. This met the preset noninferiority criteria, suggesting that mixed-HDF was noninferior to predilution HDF. Moreover, the ß2-microglobulin reduction rate was greater in the mixed-HDF group than in the predilution HDF group, while mixed-HDF provided greater transmembrane pressure. There were no significant between-group differences in Kt/V urea levels, changes in predialysis hs-CRP levels, proportions of overhydration, or blood pressure values. Symptomatic intradialytic hypotension episodes and other adverse events occurred similarly in the two groups. CONCLUSION: Use of mixed-HDF was comparable to predilution HDF in terms of delivered convection volume and clinical parameters. Moreover, mixed-HDF provided better ß2-microglobulin clearance than predilution HDF.

Increased Risk of Chronic Kidney Disease Associated With Weight Gain in Healthy Adults: Insight From Metabolic Profiles and Body Composition.

Objective: Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD). Methods: For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories. Results: During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively (P = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06-1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06-1.87) and 2.2 (95% CI, 1.40-3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased. Conclusion: Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.