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.

Risk of incident chronic kidney disease among patients with urolithiasis: a nationwide longitudinal cohort study.

Background: Urolithiasis has been infrequently implicated to have a causal association with chronic kidney disease (CKD). Recently, several studies have demonstrated the relationship between urolithiasis and CKD. However, the generalizability of their results is limited. This study aimed to investigate the association between urolithiasis and the risk of incident CKD. Methods: This longitudinal cohort study used the National Health Insurance Service data, including 219 570 Korean adults with incident urolithiasis requiring procedural interventions and without prior kidney disease and 219 570 age- and sex-matched controls without urolithiasis between 1 January 2002 and 31 December 2020. Primary outcome was the development of CKD, defined by an estimated glomerular filtration rate <60 ml/min/1.73 m2 for at least two consecutive measurements at least 90 days apart. The risk for incident CKD was further examined using the outcome defined by newly occurring diagnostic codes indicating CKD. Results: Over a mean follow-up of 6 years, 12 338 (2.8%) primary outcome events of CKD were observed (incidence rate 4.6/1000 person-years). Per multivariable Cox analysis, urolithiasis was associated with a higher risk of incident CKD [adjusted hazard ratio 1.41 (95% confidence interval 1.36-1.46)]. This association remained consistent across all clinically relevant subgroups and when the CKD outcome was defined based on the diagnostic codes in the sensitivity analysis. Conclusions: In this large national cohort study, patients with urolithiasis were associated with a higher risk of incident CKD than those without urolithiasis. Further studies are warranted to establish the benefits of preventing urolithiasis in reducing CKD development.

Association of Plant Protein Intake With Risk of Incident CKD: A UK Biobank Study.

RATIONALE & OBJECTIVE: Data suggest that various dietary interventions slow kidney disease progression and improve clinical outcomes for those with chronic kidney disease (CKD). However, the association between plant protein intake and incident CKD has been uncertain. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 117,809 participants who completed at least 1 dietary questionnaire and had an estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m2, a urinary albumin-creatinine ratio (UACR)<30mg/g, and no history of CKD. EXPOSURE: Daily plant protein intake in g/kg/day. OUTCOME: Incident CKD based on the International Classification of Diseases, 10th Revision (ICD-10) or the Office of Population Censuses and Surveys Classification of Interventions and Procedures, version 4 (OPCS-4) codes. ANALYTICAL APPROACH: A cause-specific proportional hazards analysis incorporating competing risks that treated death occurring before incident CKD as a competing event. RESULTS: During a median follow-up period of 9.9 years, incident CKD occurred in 3,745 participants (3.2%; incidence rate, 3.2 per 1,000 person-years). In a multivariable model, the adjusted hazard ratio (AHR) for the second, third, and highest quartiles of plant protein intake was 0.90 (95% CI, 0.82-0.99), 0.83 (95% CI, 0.75-0.92), and 0.82 (95% CI, 0.73-0.93), respectively, compared with the lowest quartile. Modeled as a continuous variable, the AHR per 0.1g/kg/day plant protein intake increase was 0.96 (95% CI, 0.93-0.99). This beneficial association was also consistent in secondary analyses for which CKD was defined based on codes or 2 consecutive measures of eGFR<60mL/min/1.73m2 or UACR>30mg/g. Various sensitivity analyses demonstrated consistent findings. LIMITATIONS: Potential incomplete dietary assessments; limited generalizability due to the characteristics of participants in the UK Biobank Study. CONCLUSIONS: In this large, prospective cohort study, greater dietary plant protein intake was associated with a lower risk of incident CKD. Further interventional studies demonstrating the kidney-protective benefits of plant protein intake are warranted. PLAIN-LANGUAGE SUMMARY: Plant-based diets confer various health benefits, including lowering the risk of cardiovascular disease and certain cancers. However, the relationship between plant protein intake and the risk of chronic kidney disease (CKD) remains unclear. Our study investigated the association between plant protein intake and the development of CKD. Using the UK Biobank Study data, we found that participants with a higher plant protein intake had a lower risk of developing CKD. Our finding suggests that a higher dietary intake of plant-based protein may be beneficial for kidney health and provides insight into dietary interventions to prevent CKD in primary care settings.

Erythropoiesis stimulating agent recommendation model using recurrent neural networks for patient with kidney failure with replacement therapy.

In patients with kidney failure with replacement therapy (KFRT), optimizing anemia management in these patients is a challenging problem because of the complexities of the underlying diseases and heterogeneous responses to erythropoiesis-stimulating agents (ESAs). Therefore, we propose a ESA dose recommendation model based on sequential awareness neural networks. Data from 466 KFRT patients (12,907 dialysis sessions) in seven tertiary-care general hospitals were included in the experiment. First, a Hb prediction model was developed to simulate longitudinal heterogeneous ESA and Hb interactions. Based on the prediction model as a prospective study simulator, we built an ESA dose recommendation model to predict the required amount of ESA dose to reach a target hemoglobin level after 30 days. Each model's performance was evaluated in the mean absolute error (MAE). The MAEs presenting the best results of the prediction and recommendation model were 0.59 (95% confidence interval: 0.56-0.62) g/dL and 43.2 µg (ESAs dose), respectively. Compared to the results in the real-world clinical data, the recommendation model achieved a reduction of ESA dose (Algorithm: 140 vs. Human: 150 µg/month, P < 0.001), a more stable monthly Hb difference (Algorithm: 0.6 vs. Human: 0.8 g/dL, P < 0.001), and an improved target Hb success rate (Algorithm: 79.5% vs. Human: 62.9% for previous month's Hb < 10.0 g/dL; Algorithm: 95.7% vs. Human:73.0% for previous month's Hb 10.0-12.0 g/dL). We developed an ESA dose recommendation model for optimizing anemia management in patients with KFRT and showed its potential effectiveness in a simulated prospective study.

Synergic association of diabetes mellitus and chronic kidney disease with muscle loss and cachexia: results of a 16-year longitudinal follow-up of a community-based prospective cohort study.

Muscle loss is a serious complication in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). However, studies on a long-term change in muscle mass presence or absence of DM and CKD are scarce. We included 6247 middle-aged adults from the Korean Genome and Epidemiology Study (KoGES) between 2001 and 2016. Bioimpedance analysis (BIA) was performed biennially. Patients were classified into four groups according to the presence or absence of DM and CKD. The primary outcome was muscle depletion, which was defined as a decline in fat-free mass index (FFMI) below the 10th percentile of all subjects. The secondary outcomes included the occurrence of cachexia, all-cause mortality, and the slopes of changes in fat-free mass and weight. During 73,059 person-years of follow-up, muscle depletion and cachexia occurred in 460 (7.4%) and 210 (3.4%), respectively. In the multivariable cause-specific hazards model, the risk of muscle depletion was significantly higher in subjects with DM alone than in those without DM and CKD (HR, 1.37; 95% CI, 1.04-1.80) and was strongly pronounced in subjects with both conditions (HR, 3.38; 95% CI, 1.30-8.75). The secondary outcome analysis showed consistent results. The annual decline rates in FFMI, fat mass, and body mass index (BMI) were the steepest in subjects with DM and CKD among the four groups. DM and CKD are synergically associated with muscle loss over time. In addition, the mortality risk is higher in individuals with muscle loss.

Smoking Cessation and Coronary Artery Calcification in CKD.

BACKGROUND AND OBJECTIVES: Smoking is associated with vascular calcification and a higher risk of cardiovascular disease. In this study, we investigated the association of smoking dose and cessation with coronary artery calcification (CAC) in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From a nationwide, prospective cohort of Korean patients with CKD, 1914 participants were included. Prevalent CAC was defined as an Agatston score >0, using computed tomography. CAC progression was defined as ≥30%/yr increase in Agatston score at the 4-year follow-up examination in patients with baseline CAC. RESULTS: Prevalent CAC was observed in 952 (50%) patients. Compared with never smokers, former smokers had a similar prevalence ratio for CAC, but current smokers had a 1.25-fold higher prevalence ratio (95% confidence interval [95% CI], 1.10 to 1.42). Among former smokers, a lower smoking load of <10 pack-years (prevalence ratio, 0.77; 95% CI, 0.65 to 0.90) and longer duration of smoking cessation (prevalence ratio for 10 to <20 years, 0.85; 95% CI, 0.73 to 0.98: prevalence ratio for ≥20 years, 0.83; 95% CI, 0.73 to 0.96) were associated with lower risk of prevalent CAC compared with current smoking. The prevalence ratios did not differ between never smoking and long-term cessation. However, short-term cessation with heavy smoking load was associated with a higher risk of prevalent CAC (prevalence ratio, 1.21; 95% CI, 1.03 to 1.40) compared with never smoking. CAC progression was observed in 111 (33%) patients with baseline CAC. Compared with never smokers, former smokers showed a similar risk of CAC progression, but current smokers had a higher risk (relative risk, 1.92; 95% CI, 1.30 to 2.86). CONCLUSIONS: In CKD, former smoking with a lower smoking load and long-term cessation were associated with a lower risk of prevalent CAC than current smoking. CAC progression was more pronounced in current smokers.

Systolic blood pressure and chronic kidney disease progression in patients with primary glomerular disease.

INTRODUCTION: Many current guidelines on optimal target blood pressure (BP) for chronic kidney disease (CKD) patients are largely based on studies in diabetic and hypertensive patients. However, there have been few studies in patients with glomerular diseases. METHODS: We retrospectively studied the longitudinal association between BP and CKD progression in 1,066 biopsy-proven patients diagnosed with primary glomerular diseases, including IgA nephropathy, membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), between 2005 and 2017. The main predictor was time-updated systolic blood pressure (SBP) at every clinic visit. The primary outcome was a composite one including ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from the baseline, and end-stage kidney disease (ESKD). RESULTS: During 5009 person-years of follow-up, the primary outcome occurred in 157 (14.7%) patients. In time-varying Cox model, the adjusted hazard ratios (HRs) (95% confidence interval (CI)) for the primary outcome were 1.48 (0.96-2.29), 2.07 (1.22-3.52), and 2.53 (1.13-5.65) for SBP of 120-129, 130-139, and ≥ 140 mmHg, respectively, compared with SBP < 120 mmHg. This association was particularly evident in patients with elevated proteinuria. However, there was no association between baseline SBP and adverse kidney outcomes. Finally, prediction models failed to show the improvement of predictive performance of SBP compared with that of remission status. Moreover, patients with remission and less controlled SBP had better kidney outcomes than those with non-remission and well-controlled SBP. CONCLUSION: Among patients with glomerular disease, higher time-updated SBP was significantly associated with higher risk of CKD progression. However, the clinical significance of blood pressure was less powerful than remission status.

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.

Smoking, Smoking Cessation, and Progression of Chronic Kidney Disease: Results From KNOW-CKD Study.

INTRODUCTION: In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce. AIMS AND METHODS: We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation. RESULTS: There were 967 never-smokers and 369, 276, and 339 smokers who smoked <15, 15 to 29, ≥30 pack-years, respectively. During a mean follow-up of 3.0 years, the incidence rates (95% confidence interval [CI]) of the primary outcome were 54.3 (46.4-63.5), 46.9 (35.9-61.4), 69.2 (52.9-90.6), and 76.3 (60.7-96.0) events per 1,000 person-yr in never-, <15, 15 to 29, and ≥30 pack-year smokers. In cause-specific hazard model after adjustment of confounding factors, smokers were associated with 1.09 (0.73-1.63), 1.48 (1.00-2.18), and 1.94 (1.35-2.77) fold increased risk (95% CI) of primary outcome in <15, 15-29, and ≥30 pack-year smokers compared with never-smokers. The association of longer smoking duration with higher risk of CKD progression was evident particularly in patients with eGFR < 45 mL/min/1.73 m2 and proteinuria ≥ 1.0 g/g. In contrast, the risk of adverse kidney outcome decreased with longer smoking-free periods among former-smokers. CONCLUSIONS: These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD. IMPLICATIONS: Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression.

CD71 mesangial IgA1 receptor and the progression of IgA nephropathy.

The transferrin receptor (CD71) is known as a receptor for IgA1 on mesangial cells, but the role of CD71 in IgA nephropathy (IgAN) is unknown. We studied clinical implication of mesangial CD71 in 282 patients with biopsy-proven IgAN (2005-2018). The transcript and protein expression of glomerular CD71 was determined by real-time polymerase chain reaction and immunohistochemistry. Ten subjects with microscopic hematuria only and no evidence of histologic abnormalities on kidney biopsy were considered as controls. Human mesangial cells (HMCs) were treated with sera from IgAN patients and expression levels of CD71 and inflammatory cytokine markers were compared according to disease status. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate from the baseline value. During a mean follow up of 53.5 (18.3-75.9) months, 80 (28.4%) patients developed disease progression. The mRNA expression of CD71 was significantly higher in progressors than in nonprogressors (P = 0.001). Among the Oxford classification scores, patients with M1 had significantly higher CD71 expression levels than those with M0. In a multivariable Cox model, elevated transcript levels of CD71 were significantly associated with 4.32-fold higher risk of disease progression (P = 0.009). Furthermore, CD71 expression levels independently predicted the increase in proteinuria of ≥50% from the baseline (P = 0.03). Finally, HMCs treated with sera from IgAN patients with the higher Oxford score (M1E1S1T0) more increased the mRNA expression of CD71 and inflammatory markers than those with sera from negative score (M0E0S0T0). However, silencing CD71 significantly reduced expression levels of the inflammatory cytokine genes. Our results show that mesangial CD71 is significantly associated with disease progression and may play a biologic role in IgAN.

Polypharmacy, hospitalization, and mortality risk: a nationwide cohort study.

Polypharmacy is a growing and major public health issue, particularly in the geriatric population. This study aimed to examine the association between polypharmacy and the risk of hospitalization and mortality. We included 3,007,620 elderly individuals aged ≥ 65 years who had at least one routinely-prescribed medication but had no prior hospitalization within a year. The primary exposures of interest were number of daily prescribed medications (1-2, 3-4, 5-6, 7-8, 9-10, and ≥ 11) and presence of polypharmacy (≥ 5 prescription drugs per day). The corresponding comparators were the lowest number of medications (1-2) and absence of polypharmacy. The study outcomes were hospitalization and all-cause death. The median age of participants was 72 years and 39.5% were men. Approximately, 46.6% of participants experienced polypharmacy. Over a median follow-up of 5.0 years, 2,028,062 (67.4%) hospitalizations and 459,076 (15.3%) all-cause deaths were observed. An incrementally higher number of daily prescribed medications was found to be associated with increasingly higher risk for hospitalization and mortality. These associations were consistent across subgroups of age, sex, residential area, and comorbidities. Furthermore, polypharmacy was associated with greater risk of hospitalization and death: adjusted HRs (95% CIs) were 1.18 (1.18-1.19) and 1.25 (1.24-1.25) in the overall and 1.16 (1.16-1.17) and 1.25 (1.24-1.25) in the matched cohorts, respectively. Hence, polypharmacy was associated with a higher risk of hospitalization and all-cause death among elderly individuals.

Idiopathic membranous nephropathy in older patients: Clinical features and outcomes.

BACKGROUND: Various factors can affect renal and patient outcome in idiopathic membranous nephropathy (iMN). We aimed to identify predictors of renal and patient survival in patients with iMN, with a special focus on outcomes among older patients. METHODS: We retrieved data on 1,776 patients (mean age 53.0 ± 14.7 years; 1,075 [60.5%] males) diagnosed with iMN from the Korean GlomeruloNEphritis sTudy (KoGNET), a database compiled from 18 centers in Korea. RESULTS: The cohort included 428 (24.1%) patients over 65 years old. Compared to younger patients, this group had lower hemoglobin and serum albumin levels, a higher incidence of nephrotic-range proteinuria, and higher prevalences of hypertension and diabetes. At last follow-up, complete or partial remission rates were not significantly different between the older and younger groups. Older age (HR: 0.98, 95%CI: 0.97-0.99), elevated hemoglobin (HR: 0.82, 95%CI: 0.72-0.93), high serum albumin (HR: 0.66, 95%CI: 0.44-0.99), and a high estimated glomerular filtration rate (HR: 0.96, 95%CI: 0.95-0.97) at biopsy were good predictors of renal outcomes. Significant risk factors for patient survival were older age (HR: 1.04, 95%CI: 1.01-1.10) and hypertension at biopsy (HR: 2.76, 95%CI: 1.30-5.90). CONCLUSIONS: Older patients with iMN had favorable renal outcomes, but poor patient survival, compared to younger patients. Prognostic information on outcomes in this study might be helpful for optimizing the management of patients with iMN.

Association of smoking with incident CKD risk in the general population: A community-based cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a public health problem, and an unfavorable lifestyle has been suggested as a modifiable risk factor for CKD. Cigarette smoking is closely associated with cardiovascular disease and cancers; however, there is a lack of evidence to prove that smoking is harmful for kidney health. Therefore, we aimed to determine the relationship between cigarette smoking and CKD among healthy middle-aged adults. METHODS: Using the database from the Korean Genome and Epidemiology Study, we analyzed 8,661 participants after excluding those with baseline estimated glomerular filtration rate (eGFR)<60 ml/min/1.72 m2 or proteinuria. Exposure of interest was smoking status: never-, former-, and current-smokers. Primary outcome was incident CKD defined as eGFR <60 ml/min/1.73 m2 or newly developed proteinuria. RESULTS: The mean age of the subjects was 52 years, and 47.6% of them were males. There were 551 (6.4%) and 1,255 (14.5%) subjects with diabetes and hypertension, respectively. The mean eGFR was 93.0 ml/min/1.73 m2. Among the participants, 5,140 (59.3%), 1,336 (15.4%), and 2,185 (25.2%) were never-smokers, former-smokers, and current-smokers, respectively. During a median follow-up of 11.6 years, incident CKD developed in 1,941 (22.4%) subjects with a crude incidence rate of 25.1 (24.0-26.2) per 1,000 person-years. The multivariable Cox regression analysis after adjustment of confounding factors showed hazard ratios (95% confidence interval) of 1.13 (0.95-1.35) and 1.26 (1.07-1.48) for CKD development in the former- and current-smokers, compared with never-smokers. CONCLUSION: This study showed that smoking was associated with a higher risk of incident CKD among healthy middle-aged adults.

Efficacy and Safety of a Balanced Salt Solution Versus a 0.9% Saline Infusion for the Prevention of Contrast-Induced Acute Kidney Injury After Contrast-Enhanced Computed Tomography.

RATIONALE & OBJECTIVE: We aimed to elucidate whether a balanced salt solution decreases the occurrence of contrast-induced acute kidney injury (CI-AKI) after contrast-enhanced computed tomography (CE-CT) as compared to 0.9% saline solution. STUDY DESIGN: A randomized clinical trial. SETTING & PARTICIPANTS: The study was performed in 14 tertiary hospitals in South Korea. Patients with estimated glomerular filtration rates (eGFRs) < 45 or <60 mL/min/1.73 m2 and additional risk factors (age ≥ 60 years or diabetes) who were undergoing scheduled CE-CT were included from December 2016 to December 2018. INTERVENTION: An open-label intervention was performed. The study group received a balanced salt solution and the control group received 0.9% saline solution as prophylactic fluids for CE-CT. OUTCOMES: The primary outcome was CI-AKI, defined by creatinine level elevation ≥ 0.5 mg/dL or 25% from baseline within 48 to 72 hours after CE-CT. Secondary outcomes included AKI defined based on the KDIGO (Kidney Disease: Improving Global Outcomes) guideline, eGFR changes, death, or requiring dialysis within 6 months after CE-CT. RESULTS: 493 patients received the study fluids. The control and study groups included 251 and 242 patients, respectively. The occurrence of CI-AKI in the study (10 [4.2%]) and control (17 [6.8%]) groups was not significantly different (P = 0.27). No significant difference was present for the secondary outcomes; AKI by the KDIGO definition (study: 19 [7.9%], control: 27 [10.8%]; P = 0.33), death/dialysis (study: 11 [4.7%], control: 9 [3.7%]; P = 0.74), and eGFR changes (study: 0.1 ± 0.2 mg/dL, control: 0.3 ± 2.8 mg/dL; P = 0.69). LIMITATIONS: This study failed to meet target enrollment. CONCLUSIONS: The risk for CI-AKI was similar after administration of a balanced salt solution and after use of 0.9% saline solution during CE-CT in higher-risk patients. FUNDING: This study was funded by CJ Healthcare (CS2015_0046). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02799368.

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.

Predictive value of mesangial C3 and C4d deposition in IgA nephropathy.

We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value.

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.

Factors Associated With Withdrawal From Dialysis Therapy in Incident Hemodialysis Patients Aged 80 Years or Older.

OBJECTIVES: Among kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis. STUDY DESIGN: Historical cohort study. SETTING AND PARTICIPANTS: We examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011. MEASURES: We identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis. RESULTS: Among 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and <80 years, respectively. Among patients ≥80 years, minorities were much less likely than non-Hispanic whites to stop dialysis. Other factors associated with higher odds of dialysis withdrawal included having a central venous catheter compared to an arteriovenous fistula at dialysis start, dementia, living in mid-west regions, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome such as higher white blood cell counts and lower body mass index, albumin, and normalized protein catabolic rate. CONCLUSION/IMPLICATIONS: Among very-elderly incident hemodialysis patients, dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status. Further studies examining implications of withdrawal from dialysis in older patients are warranted.

Association of Ultrafiltration Rate with Mortality in Incident Hemodialysis Patients.

BACKGROUND/AIMS: Ultrafiltration rate (UFR) appears to be associated with mortality in prevalent hemodialysis (HD) patients. However, the association of UFR with mortality in incident HD patients remains unknown. METHODS: We examined a US cohort of 110,880 patients who initiated HD from 2007 to 2011. Baseline UFR was divided into 5 groups (<4, 4 to <6, 6 to <8, 8 to <10, and ≥10 mL/h/kg body weight [BW]). We examined predictors of higher baseline UFR using logistic regression and the association of baseline UFR and all-cause and cardiovascular (CV) mortality using Cox proportional hazard models with adjustments for demographics, comorbidities, and markers of malnutrition-inflammation-cachexia syndrome. RESULTS: Patients were 63 ± 15 years, with 43% women, 32% African Americans, and had a mean baseline UFR of 7.5 ± 3.1 mL/h/kg BW. In the fully adjusted logistic regression models, factors associated with higher UFR (≥7.5 mL/h/kg BW) included Hispanic ethnicity, diabetes, and higher dietary protein intake. There was a linear association between UFR and all-cause and CV mortality, where UFR ≥10 mL/h/kg BW (reference UFR 6-<8 mL/h/kg BW) conferred the highest risk in both unadjusted (HR 1.15 [95% CI 1.10-1.19]) and adjusted models (HR 1.23 [95% CI 1.16-1.31]). The linear association with all-cause mortality remained consistent across strata of age, urine volume, and treatment time. CONCLUSIONS: Higher UFR is independently associated with higher all-cause and CV mortality in incident HD patients. Clinical trials are warranted to examine the effects of lowering UFR on outcomes.

Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy.

BACKGROUND: Soluble CD89 (sCD89)-IgA complex plays a key role in the pathogenesis of IgA nephropathy (IgAN). However, there is a lack of evidence supporting this complex as a good biomarker for disease progression. This study aimed to evaluate the usefulness of sCD89-IgA complex for risk stratification of IgAN. METHODS: A total of 326 patients with biopsy-proven IgAN were included. sCD89-IgA complex was measured by sandwich-enzyme-linked immunosorbent assay. The study endpoints were a 30% decline in estimated glomerular filtration rate (eGFR). RESULTS: sCD89-IgA complex levels were inversely and weakly associated with eGFR at the time of biopsy (r=-0.12, p=0.03). However, the significance between the two factors was lost in the multivariate linear regression after adjustment of clinical factors (ß=0.35, p=0.75). In a multivariate Cox model, the highest (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.35-1.61; p=0.45) and middle (HR, 0.93; 95% CI, 0.46-1.89; p=0.84) tertiles of sCD89-IgA complex levels were not associated with an increased risk of developing a 30% decrease in eGFR. Furthermore, the decline rates in eGFR did not differ between groups and C-statistics revealed that the sCD89-IgA complex were not superior to clinical factors in predicting disease progression. CONCLUSIONS: This study found no association between sCD89-IgA complex levels and disease progression in IgAN. Although sCD89 can contribute to the formation of immune complexes, our findings suggest that the sCD89-IgA level is not a good predictor of adverse outcomes and has limited clinical utility as a biomarker for risk stratification in IgAN.