Glomerular crescents are associated with the risk of type 2 diabetic kidney disease progression: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.

Short-term Blood Pressure Variability and Incident CKD in Patients With Hypertension: Findings From the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI) Study.

RATIONALE & OBJECTIVE: The association between short-term blood pressure variability (BPV) and kidney outcomes is poorly understood. This study evaluated the association between short-term BPV and kidney disease outcomes in people with hypertension. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 1,173 hypertensive participants in the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (2013-2018) Study with estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2. EXPOSURE: Short-term BPV assessed by average real variability (ARV). OUTCOME: Composite kidney disease outcome (30% decline in eGFR from baseline, new occurrence of eGFR <60mL/min/1.73m2, or onset of UACR >300mg/g). ANALYTICAL APPROACH: Multivariable Cox regression analyses to evaluate the association between systolic and diastolic BP ARV (SBP-ARV and DBP-ARV) and outcomes. RESULTS: During a median follow-up of 5.4 [4.1-6.5] years, 271 events of the composite kidney disease outcome occurred (46.5 per 1,000 person-years). Multivariable Cox analysis revealed that the highest SBP-ARV and DBP-ARV tertiles were associated with a higher risk of the composite kidney disease outcome than the lowest tertiles, independent of the 24-hour SBP or DBP levels (HR, 1.64 [95% CI, 1.16-2.33], and 1.60 [95% CI, 1.15-2.24] for SBP-ARV and DBP-ARV, respectively). These associations were consistent when SBP-ARV and DBP-ARV were treated as continuous variables (HR per 1.0-unit greater SBP-ARV, 1.03 [95% CI, 1.01-1.06]; HR per 1.0-unit greater DBP-ARV, 1.04 [95% CI, 1.01-1.08]). These associations were consistent, irrespective of subgroups (age, sex, 24-hour SBP or DBP, and moderate albuminuria). However, other measures of short-term BPV including SD, coefficient of variation, and dipping patterns were not associated with the composite kidney disease outcome. LIMITATIONS: Observational study design, the use of single measurement of 24-hour BP, lack of information on changes in antihypertensive medication during the follow-up. CONCLUSIONS: Short-term BPV is associated with the development of a composite kidney disease outcome in hypertensive patients.

Preoperative Ionized Magnesium Levels and Risk of Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Although postoperative acute kidney injury (AKI) is a serious complication after cardiac surgery, preventive measures are limited. Despite the known association of preoperative low magnesium levels with cardiac surgery-related atrial fibrillation, the association between preoperative magnesium concentration and postoperative AKI has not been fully elucidated. This study evaluated the association between preoperative serum magnesium level and the development of AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who underwent cardiac surgery at 2 South Korean tertiary hospitals between 2006 and 2020 were identified from medical records. Patients with missing information, an estimated glomerular filtration rate<15mL/min/1.73m2, receiving maintenance dialysis, or a history of AKI treated by dialysis within 1 year before surgery were excluded. EXPOSURE: Preoperative serum magnesium levels. OUTCOME: Postoperative AKI within 48 hours after surgery, defined using the Acute Kidney Injury Network (AKIN) criteria, and dialysis-treated AKI within 30 days after surgery. ANALYTICAL APPROACH: Multivariable logistic regression analysis. RESULTS: Among the 9,766 patients (median age, 64.0 years; 60.1% male), postoperative AKI and dialysis-treated AKI were observed in 40.1% and 4.3% patients, respectively. Postoperative AKI was more prevalent in patients with lower serum magnesium levels (44.9%, 41.4%, 39.4%, and 34.8% in quartiles 1-4, respectively). Multivariable logistic regression analysis revealed that the odds ratios (ORs) for postoperative AKI were progressively larger across progressively lower quartiles of serum magnesium concentration (adjusted ORs of 1.53 [95% CI, 1.33-1.76], 1.29 [95% CI, 1.12-1.48], 1.15 [95% CI, 1.01-1.31] for quartiles 1-3, respectively, relative to quartile 4, P for trend<0.001). Preoperative hypomagnesemia (serum magnesium level<1.09mg/dL) was also significantly associated with AKI (adjusted OR, 1.39 [95% CI, 1.10-1.77]) and dialysis-treated AKI (adjusted OR, 1.67 [95% CI, 1.02-2.72]). LIMITATIONS: Causality could not be evaluated in this observational study. CONCLUSIONS: Lower serum magnesium levels were associated with a higher incidence of AKI in patients undergoing cardiac surgery.

Colchicine use and the risk of CKD progression: a multicentre nested case-control study.

OBJECTIVES: Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout. METHODS: We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3-G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex. RESULTS: Overall, 3085 patients with CKD progression were matched to 11 715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3. CONCLUSION: Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout.

Effect of Psychosocial Distress on the Rate of Kidney Function Decline.

BACKGROUNDS: Chronic kidney disease is a growing global health problem. Psychosocial stress has been found to induce changes in biological processes and behavioral patterns that increase risks of cardiovascular and metabolic diseases. However, the association between psychosocial stress and kidney function is not well understood. OBJECTIVE: To evaluate the association between psychosocial stress and kidney function decline. DESIGN: In this prospective cohort study, psychosocial distress was assessed using the psychosocial well-being index short-form (PWI-SF). PARTICIPANTS: Data of a total of 7246 participants were retrieved from a community-based cohort (Korean Genome and Epidemiology Study). MAIN MEASURES: The rate of estimated glomerular filtration rate (eGFR) decline was calculated for each individual. Rapid eGFR decline was defined as a decrease of ≥ 3 mL/min/1.73 m2 per year. The presence of kidney disease was defined as eGFR < 60 mL/min/1.73 m2 at baseline or proteinuria of higher than trace levels from two consecutive urine test results. KEY RESULTS: A total of 7246 participants were analyzed. The mean eGFR was 92.1 ± 14.0 mL/min/1.73 m2. Rapid eGFR decline was observed in 941 (13.0%) participants during a median follow-up of 11.7 years. When the participants were categorized into tertiles according to PWI-SF score, rapid eGFR decline was more prevalent in the group with the highest PWI-SF score (15.8%) than in the group with the lowest score (12.2%). Multivariate logistic regression analysis revealed that the risk of rapid eGFR decline was significantly increased in the tertile group with the highest PWI-SF score compared to the lowest group (odds ratio, 1.35; 95% confidence interval, 1.15-1.59). This association was maintained even after adjusting for confounding variables and excluding participants with kidney disease. CONCLUSIONS: Higher levels of psychosocial distress were closely associated with an increased risk of rapid kidney function decline.

Effects of Intensive Individualized Nutrition Counseling on Nutritional Status and Kidney Function in Patients With Stage 3 and 4 Chronic Kidney Disease.

OBJECTIVE: Although dietary modification is a critical component of chronic kidney disease (CKD) management, compliance with dietary recommendations is often suboptimal. This prospective intervention study was conducted to evaluate the effects and adherence of intensive, individualized nutrition counseling in CKD patients from a single nation Asian ethnic group. METHODS: Patients with Stages 3 and 4 CKD were recruited from a tertiary hospital outpatient clinic in Korea. The intensive group received 3 monthly sessions of individualized intensive nutrition counseling. The control group received a one-time group program. The intensive group was compared with the control group at 3 months. RESULTS: A total of 59 patients were enrolled, and 42 (71.2%) completed the study (23/32 of the intensive group; 19/27 of the control group). The mean age of the patients was 64.7 ± 12.5 years, and 81% were male. The most common nutritional diagnosis was an excessive intake of sodium (Na, 97.6%), followed by potassium (K, 78.6%), protein (52.4%), and phosphorus (P, 31.0%). After 3 months of nutrition counseling, K and P intakes decreased significantly in both the intensive group (K, 2,760.9 ± 677.4 vs. 1,500.7 ± 398.5 mg/d, P < .001; P, 1,010.5 ± 247.4 vs. 631.3 ± 178.1 mg/d, P < .001) and the control group (K, 2,090.8 ± 765.3 vs. 1,703.9 ± 490.0 mg/d, P = .036; P, 807.2 ± 163.8 vs. 679.1 ± 175.9 mg/d, P = .044). Meanwhile, protein (68.3 ± 21.8 vs. 45.4 ± 10.1 g/d, P = .001), Na (4,009.8 ± 1,418.2 vs. 2,224.6 ± 759.8 mg/d, P < .001), and energy intakes (1,857.1 ± 411.5 vs. 1,273.7 ± 231.5 kcal, P < .001) decreased in the intensive group, but were comparable in the control group. Notably, BMI decreased (BMI, 25.4 ± 2.5 vs. 24.9 ± 2.9 kg/m2, P = .014) while eGFR (43.1 ± 11.8 vs. 48.9 ± 13.7 mL/min/1.73m2, P = .002) improved significantly in the intensive group only. CONCLUSION: Intensive individualized nutrition counseling results in better adherence to dietary recommendations and improvement in kidney function in CKD patients.

High-protein diet with renal hyperfiltration is associated with rapid decline rate of renal function: a community-based prospective cohort study.

BACKGROUND: The effect of a high-protein diet with renal hyperfiltration (RHF) on decline of kidney function has rarely been explored. We investigated the association between a high-protein diet, RHF and declining kidney function. METHODS: A total of 9226 subjects from the Korean Genome and Epidemiology Study, a community-based prospective study (2001-14), were enrolled and classified into quartiles according to daily amount of protein intake based on food frequency questionnaires. RHF was defined as estimated glomerular filtration rate (eGFR) with residuals of >95th percentile after adjustment for age, sex, history of hypertension or diabetes, height and weight. Rapid decline of renal function was defined as decline rate of eGFR >3 mL/min/1.73 m2/year. RESULTS: The relative risk of RHF was 3.48-fold higher in the highest than in the lowest protein intake quartile after adjustment for confounding factors [95% confidence interval (CI) 1.39-8.71]. The mean eGFR decline rate was faster as quartiles of protein intake increased. Furthermore, the highest quartile was associated with 1.32-fold increased risk of rapid eGFR decline (95% CI 1.02-1.73). When subjects were divided into two groups with or without RHF, the highest quartile was associated with a rapid decline in renal function only in RHF subjects (odds ratio 3.35; 95% CI 1.07-10.51). The sensitivity analysis using the Korean National Health and Nutrition Examination Survey (2008-15) data with 40 113 subjects showed that higher quartile was associated with increased risk for RHF. CONCLUSIONS: A high-protein diet increases the risk of RHF and a rapid renal function decline in the general population. These findings suggest that a high-protein diet has a deleterious effect on renal function in the general population.

The effect of interactions between proteinuria, activity of fibroblast growth factor 23 and serum phosphate on renal progression in patients with chronic kidney disease: a result from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease study.

BACKGROUND: Recent experimental study reported that proteinuria increases serum phosphate by decreasing biologic activity of fibroblast growth factor 23 (FGF-23). We examined this relationship in a large chronic kidney disease (CKD) cohort and evaluated the combined effect of proteinuria, FGF-23 activity and serum phosphate on CKD progression. METHODS: The activity of FGF-23, measured by the fractional excretion of phosphate (FEP)/FGF-23 ratio, was compared according to the degree of proteinuria in 1909 patients with CKD. Primary outcome was CKD progression defined as ≥50% decline of estimated glomerular filtration rate, doubling of serum creatinine and start of dialysis. RESULTS: There was a negative relationship between 24-h urine protein (24-h UP) and FEP/FGF-23 ratio (γ -0.07; P = 0.005). In addition, after matching variables associated with serum phosphate, patients with more proteinuria had higher serum phosphate (P < 0.001) and FGF-23 (P = 0.012), and lower FEP/FGF-23 ratio (P = 0.007) compared with those with less proteinuria. In the matched cohort, low FEP/FGF-23 ratio was an independent risk factor for CKD progression (hazard ratio 0.87 per 1 log increase; 95% confidence interval 0.79-0.95; P = 0.002), and there was significant interaction between 24-h UP and FEP/FGF-23 ratio (P = 0.039). Furthermore, 24-h UP and serum phosphate also had a significant interaction on CKD progression (P < 0.001). CONCLUSIONS: Proteinuria is associated with decreased biologic activity of FGF-23 and increased serum phosphate. Furthermore, diminished activity of FGF23 is an independent risk factor for renal progression in proteinuric CKD patients.

New oral spherical carbon adsorbent effectively reduces serum indoxyl sulfate levels in moderate to advanced chronic kidney disease patients: a multicenter, prospective, open-label study.

BACKGROUND: Elevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients. METHODS: This prospective, multicenter, open-label study enrolled patients with CKD stages 3-5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA. RESULTS: A total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0.406, P < 0.001) and increased with increasing CKD stages (stage 3, 0.21 ± 0.21 mg/dL; stage 4, 0.54 ± 0.52 mg/dL; stage 5, 1.15 ± 054 mg/dL; P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P < 0.001) and up to 8 weeks (31.9 ± 33.7% reduction from baseline, P < 0.001). This reduction effect was noted regardless of age, kidney function, or diabetes. No severe adverse effects were reported. Gastrointestinal symptoms were the most commonly reported adverse effects. In total, 21 patients withdrew from the study, with dyspepsia due to heavy pill burden as the most common reason. The medication compliance rate was 84.7 ± 21.2% (min 9%, max 101%) for 8 weeks among those who completed the study. CONCLUSIONS: OSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported. TRIAL REGISTRATION: Clinical Research Information Service ( KCT0001875 . 14 December 2015.).

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.

The Association of Glomerular Glucocorticoid Receptor Expression with Responsiveness to Corticosteroid Treatment in IgA Nephropathy.

BACKGROUND: Corticosteroids can be used to treat IgA nephropathy (IgAN). However, responsiveness to these drugs is highly variable and unpredictable. Corticosteroids act by binding glucocorticoid receptors (GCRs). Therefore, we evaluated the association between GCR expression and responsiveness to corticosteroid treatment in IgAN. METHODS: We screened 78 IgAN patients receiving steroid treatment between 2010 and 2016. Of these, 33 patients met study inclusion criteria. Glomerular GCR expression was assessed by real-time polymerase chain reaction. Complete remission (CR) and partial remission (PR) were defined as a spot urine protein-to-creatinine ratio (UPCR) of <0.3 g/g and a ≥50% reduction of proteinuria from baseline along with UPCR of ≥0.3 g/g, respectively. Disease progression was defined as a ≥30% decrease in estimated glomerular filtration rate (eGFR) from baseline. RESULTS: The mean age of study patients was 43.9 ± 11.6 years (25 males and 8 females). All 33 patients responded to steroid treatment; CR and PR occurred in 14 (42.4%) and 18 (54.5%) patients, respectively. One patient did not achieve PR, but proteinuria was decreased after treatment. There were no significant differences in baseline eGFR and proteinuria between CR and non-CR groups. GCR mRNA expression was significantly higher in the CR group compared to that in the non-CR group. Immunohistochemistry confirmed higher GCR expression in the CR group. During a median follow-up of 20.6 months, 1 (7.1%) patient in the CR group had disease progression, as compared to 8 (42.1%) patients in non-CR group (p = 0.03). CONCLUSION: This study suggests that responsiveness to corticosteroid may differ depending on the degree of glomerular GCR expression in IgAN.

The interactive effects of input and output on managing fluid balance in patients with acute kidney injury requiring continuous renal replacement therapy.

BACKGROUND: The interactive effect of cumulative input and output on achieving optimal fluid balance has not been well elucidated in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated the interrelation of fluid components with mortality in patients with AKI requiring CRRT. METHODS: This is a retrospective observational study conducted with a total of 258 patients who were treated with CRRT due to AKI between 2016 and 2018 in the intensive care unit of Ewha Womans University Mokdong Hospital. The amounts of fluid input and output were assessed at 24-h and 72-h from the initiation of CRRT. The study endpoints were 7- and 28-day all-cause mortality. RESULTS: The mean patient age was 64.7 ± 15.8 years, and 165 (64.0%) patients were male. During the follow-up, 7- and 28-day mortalities were observed in 120 (46.5%) and 157 (60.9%) cases. The patients were stratified into two groups (28-day survivors vs. non-survivors), and the cumulative fluid balances (CFBs) at 24 h and 72 h were significantly higher in the 28-day non-survivors compared with the survivors. The increase in 24-h and 72-h CFB was significantly associated with an increase in 7- and 28-day mortality risks. To examine the interactive effect of cumulative input or output on the impact of CFB on mortality, we also stratified patients into three groups based on the tertile of 24-h and 72-h cumulative input or output. The increases in 24-h and 72-h CFBs were still significantly related to the increases in 7-day and 28-day mortality, irrespective of the cumulative input. However, we did not find significant associations between increase in 24-h and 72-h CFB and increase in mortality risk in the groups according to cumulative output tertile. CONCLUSIONS: The impact of cumulative fluid balance on mortality might be more dependent on cumulative output. The physicians need to decrease the cumulative fluid balance of CRRT patients as much as possible and consider increasing patient removal.

Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: an observational prospective study.

BACKGROUND: Online haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cut-off (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF. METHODS: Six clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for ß2-microglobulin (ß2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs. RESULTS: All three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P <  0.001). Conversely, predilution OL-HDF showed the greatest RR for ß2M, whereas MCO HD and HF HD showed comparable RRs for ß2M (predilution OL-HDF vs. MCO HD: 80.1 ± 4.9% vs. 72.6 ± 3.8%, P = 0.01). There was no significant difference among MCO HD, HF HD, and predilution OL-HDF in the RRs for κFLC (63.2 ± 6.0%, 53.6 ± 15.5%, and 61.5 ± 7.0%, respectively; P = 0.37), and FGF-23 (55.5 ± 20.3%, 34.6 ± 13.1%, and 35.8 ± 23.2%, respectively; P = 0.13). Notably, MCO HD showed improved clearances for FLCs when compared to HF HD or OL-HDF. CONCLUSIONS: MCO HD showed significantly greater RR of large middle molecules and achieved improved clearance for FLCs than conventional HD and OL-HDF, without the need for large convection volumes or high blood flow rates. This would pose as an advantage for elderly HD patients with poor vascular access and HD patients without access to OL-HDF. TRIAL REGISTRATION: Clinical Research Information Service (CRIS): KCT 0003009. The trial was prospectively registered on the 21 Jul 2018.

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study.

BACKGROUND: Guidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD. METHODS: A total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline. RESULTS: Patients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (ß = - 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, ß = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07-1.55; P = 0.007). CONCLUSIONS: High activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.

High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension.

The association between salt intake and renal outcome in subjects with preserved kidney function remains unclear. Here we evaluated the effect of sodium intake on the development of chronic kidney disease (CKD) in a prospective cohort of people with normal renal function. Data were obtained from the Korean Genome and Epidemiology Study, a prospective community-based cohort study while sodium intake was estimated by a 24-hour dietary recall Food Frequency Questionnaire. A total of 3,106 individuals with and 4,871 patients without hypertension were analyzed with a primary end point of CKD development [a composite of estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2 and/or development of proteinuria during follow-up]. The median ages were 55 and 47 years, the proportions of males 50.9% and 46.3%, and the median eGFR 92 and 96 mL/min/1.73 m2 in individuals with and without hypertension, respectively. During a median follow-up of 123 months in individuals with hypertension and 140 months in those without hypertension, CKD developed in 27.8% and 16.5%, respectively. After adjusting for confounders, multiple Cox models indicated that the risk of CKD development was significantly higher in people with hypertension who consumed less than 2.08 g/day or over 4.03 g/day sodium than in those who consumed between 2.93-4.03 g/day sodium. However, there was no significant difference in the incident CKD risk among each quartile of people without hypertension. Thus, both high and low sodium intakes were associated with increased risk for CKD, but this relationship was only observed in people with hypertension.

High serum adiponectin is associated with anemia development in chronic kidney disease: The results from the KNOW-CKD study.

BACKGROUND: Adiponectin is an adipokine secreted by adipocytes. A low adiponectin level is a significant risk factor of diabetes mellitus and cardiovascular disease. Recent studies have shown that adiponectin is negatively associated with hematopoiesis and predicts the development of anemia in the general population. In chronic kidney disease (CKD) patients, circulating adiponectin level is paradoxically elevated and the role of adiponectin is complex. Therefore, we evaluated the relationship between adiponectin and anemia in these patients. METHODS: This prospective longitudinal study included 2113 patients from the KNOW-CKD study (KoreaN cohort study for Outcome in patients With CKD), after excluding 125 without data on adiponectin levels. Hemoglobin levels were measured yearly during a mean follow-up period of 23.7 months. Anemia was defined as hemoglobin levels of <13.0 and 12.0 g/dL for men and women, respectively. RESULTS: Mean patient age was 53.6 ±â€¯12.2 years, and 1289 (61%) were men. The mean estimated glomerular filtration rate (eGFR) was 50.4 ±â€¯30.2 mL min-1 1.73 m-2. Serum adiponectin level was inversely associated with body mass index, eGFR, log-transformed C-reactive protein, and positively with Charlson comorbidity index, urine protein to creatinine ratio, and high density lipoprotein cholesterol. In addition, serum adiponectin level was also negatively correlated with hemoglobin level and reticulocyte production index in both men and women. In multivariable linear regression analysis after adjustment of multiple confounders, adiponectin was negatively associated with hemoglobin (men, ß = -0.219, P < .001; women, ß = -0.09, P = .025). Among 1227 patients without anemia at baseline, 307 newly developed anemia during the follow-up period. In multivariable Cox regression analysis after adjustment of confounders, high adiponectin level was significantly associated with an increased risk of incident anemia (per 1 µg/mL increase, hazard ratio, 1.02; 95% confidence interval 1.01-1.04; P = .001). CONCLUSIONS: A high serum adiponectin level is independently associated with a low hemoglobin level and predicts the development of anemia in patients with CKD. These findings reveal the potential role of adiponectin in CKD-related anemia.

Permissive fluid volume in adult patients undergoing extracorporeal membrane oxygenation treatment.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a cardiorespiratory support technique for patients with circulatory or pulmonary failure. Frequently, large-volume fluid resuscitation is needed to ensure sufficient extracorporeal blood flow in patients initiating ECMO. However, excessive overhydration is known to increase mortality in critically ill patients. Therefore, in order to define a tolerant volume range in patients undergoing ECMO treatment, the association between cumulative fluid balance (CFB) and outcome was evaluated in patients undergoing ECMO. METHODS: This retrospective multicenter cohort study was conducted with 723 patients who underwent ECMO in three tertiary care hospitals between 2005 and 2016. CFB was calculated as total fluid input minus total fluid output during the first 3 days from ECMO initiation. The patients were divided into groups that initiated ECMO owing to cardiovascular disease (CVD)-related or non-cardiovascular disease (non-CVD)-related causes. The primary endpoint was mortality within 90 days after ECMO commencement. RESULTS: Totals of 406 and 317 patients were included in the CVD and non-CVD groups, respectively. In the CVD group, the mean age was 58.4 ± 17.7 years, and 68.2% were male. The mean age was 55.7 ± 15.7 years, and 65.3% were male in the non-CVD group. The median CFB values were 64.7 and 53.5 ml/kg in the CVD and non-CVD groups, respectively. Multivariable analysis using Cox proportional hazards models revealed a significantly increased risk of 90-day mortality in patients with higher CFB values in both the CVD and non-CVD groups. However, the risks were elevated only in the two CFB quartile groups with the largest CFB amounts. Cubic spline models showed that mortality risk began to increase significantly when CFB was 82.3 ml/kg in the CVD group. In patients with respiratory diseases, the mortality risk increase was significant for those with CFB levels above 189.6 ml/kg. CONCLUSIONS: Mortality risk did not increase until a certain level of fluid overload was reached in patients undergoing ECMO. Adequate fluid resuscitation is critical to improving outcomes in these patients.

THYROID HORMONE REPLACEMENT REDUCES THE RISK OF CARDIOVASCULAR DISEASES IN DIABETIC NEPHROPATHY PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM.

OBJECTIVE: Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN. METHODS: This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases. RESULTS: Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk. CONCLUSION: THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding. ABBREVIATIONS: CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.

The impact of disease severity on paradoxical association between body mass index and mortality in patients with acute kidney injury undergoing continuous renal replacement therapy.

BACKGROUND: Association between high body mass index (BMI) and survival benefit is confounded by comorbid conditions such as nutritional status and inflammation. Patients with acute kidney injury (AKI), particularly those receiving continuous renal replacement therapy (CRRT), are highly catabolic and more susceptible to loss of energy. Herein, we evaluated whether disease severity can modify the relationship between BMI and mortality. METHODS: We conducted an observational study in 1144 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. Patients were categorized into four groups; underweight (< 18.5 kg/m2), normal (18.5-22.99 kg/m2), overweight (23.0-24.99 kg/m2), and obesity (≥25 kg/m2) according to BMI classification by the Committee of Clinical Practice Guidelines and Korean Society for the Study of Obesity. More severe disease was defined as sepsis-related organ failure assessment (SOFA) score of ≥ a median value of 12. The study endpoint was death that occurred within 30 days after the initiation of CRRT. RESULTS: The mean age was 63.2 years and 439 (38.4%) were females. The median BMI was 23.6 (20.9-26.2) kg/m2. The obese group were younger and higher SOFA score than normal BMI group. In a multivariable Cox regression analysis, we found a significant interaction between BMI and SOFA score (P <  0.001). Furthermore, obese patients were significantly associated with a lower risk of death as compared to normal BMI group after adjusting confounding factors [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.68-0.97; P = 0.03]. This association was only evident among patients with high severity (HR, 0.61; 95% CI, 0.48-0.76, P <  0.001). In contrast, in those with low severity, survival benefit of high BMI was lost, whereas underweight was associated with an increased risk of death (HR, 1.74; 95% CI, 1.16-2.60; P = 0.007). CONCLUSION: In this study, we found a survival benefit of high BMI in AKI patients undergoing CRRT, particularly in those with more disease severity; the effect was not observed in those with less disease severity.

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.