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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Optimal blood pressure (BP) control is a major therapeutic strategy to reduce adverse cardiovascular events (CVEs) and mortality in patients with chronic kidney disease (CKD). We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD. Methods Among 2238 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD), 2226 patients with baseline BP measurements were enrolled. The main predictor was systolic BP (SBP) categorized by five levels: <110, 110–119, 120–129, 130–139 and ≥140 mmHg. The primary endpoint was a composite outcome of all-cause death or incident CVEs. We primarily used marginal structural models (MSMs) using averaged and the most recent time-updated SBPs. Results During the follow-up of 10 233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 [95% confidence interval (CI) 20.7–26.6]/1000 patient-years. MSMs with averaged SBP showed a U-shaped relationship with the primary outcome. Compared with time-updated SBP of 110–119 mmHg, hazard ratios (95% CI) for <110, 120–129, 130–139 and ≥140 mmHg were 2.47 (1.48–4.11), 1.29 (0.80–2.08), 2.15 (1.26–3.69) and 2.19 (1.19–4.01), respectively. MSMs with the most recent SBP also showed similar findings. Conclusions In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcomes. Our findings highlight the importance of BP control and suggest a potential hazard of SBP <110 mmHg. [ABSTRACT FROM AUTHOR]

Background Increased body mass index (BMI) has been associated with a higher risk of severe coronavirus disease 2019 (COVID-19) infections. However, whether obesity is a risk factor for contracting COVID-19 has hardly been investigated so far. Methods We examined the association between BMI level and the risk of COVID-19 infection in a nationwide case-control study comprised of 3788 case patients confirmed to have COVID-19 between 24 January and 9 April 2020 and 15 152 controls matched by age and sex, who were aged 20 years or more and underwent National Health Insurance Service (NHIS) health examinations between 2015−2017, using data from the Korean NHIS with linkage to the Korea Centers for Disease Control and Prevention data. Our primary exposure of interest was BMI level, categorized into 4 groups: <18.5 (underweight), 18.5–22.9 (normal weight), 23–24.9 (overweight), and ≥25 kg/m2 (obese). Results Of the entire 18 940 study participants, 11 755 (62.1%) were women, and the mean age of the study participants was 53.7 years (standard deviation, 13.8). In multivariable logistic regression models adjusted for sociodemographic, comorbidity, laboratory, and medication data, there was a graded association between higher BMI levels and higher risk of COVID-19 infection. Compared to normal-weight individuals, the adjusted odds ratios in the overweight and obese individuals were 1.13 (95% confidence interval [CI], 1.03–1.25) and 1.26 (95% CI, 1.15–1.39), respectively. This association was robust across age and sex subgroups. Conclusions Higher BMI levels were associated with a higher risk of contracting COVID-19. [ABSTRACT FROM AUTHOR]

Background Urinary chloride is regulated by kidney transport channels, and high urinary chloride concentration in the distal tubules can trigger tubuloglomerular feedback. However, little attention has been paid to urinary chloride as a biomarker of clinical outcomes. Here, we studied the relationship between urinary chloride concentration and chronic kidney disease (CKD) progression. Methods We included 2086 participants with CKD from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease. Patients were categorized into three groups, according to baseline urinary chloride concentration tertiles. The study endpoint was a composite of ≥50% decrease in estimated glomerular filtration rate from baseline values, or end-stage kidney disease. Results During a median follow-up period of 3.4 years (7452 person-years), 565 participants reached the primary endpoint. There was a higher rate of CKD progression events in the lowest and middle tertiles than in the highest tertile. Compared with the lowest tertile, the highest tertile was associated with 33% [95% confidence interval (CI) 0.49–0.90] lower risk for the primary outcome in a cause-specific hazard model after adjustment for confounding variables. In addition, for every 25 mEq/L increase in urinary chloride concentration, there was 11% (95% CI 0.83–0.96) lower risk for CKD progression. This association was consistent in a time-varying model. Urinary chloride concentration correlated well with tubule function and kidney injury markers, and its predictive performance for CKD progression was comparable to that of these markers. Conclusions In this hypothesis-generating study, low urinary chloride concentration was associated with a higher risk for CKD progression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: This study utilized the method of medical record review to determine characteristics of adverse events that occurred in the inpatient units of hospitals in Korea as well as the variations in adverse events between institutions.Design: A two-stage retrospective medical record review was conducted. The first stage was a nurse review, where two nurses reviewed medical records of discharged patients to determine if screening criteria had been met. In the second stage, two physicians independently reviewed medical records of patients identified in the first stage, to determine whether an adverse event had occurred.Setting: Inpatient units of six hospitals.Participants: Medical records of 2 596 patients randomly selected were reviewed in the first stage review.Intervention(s): N/A.Main Outcome Measure(s): Adverse events.Results: A total of 277 patients (10.7%) were confirmed to have had one or more adverse event(s), and a total of 336 adverse events were identified. Physician reviewers agreed about whether an adverse event had occurred for 141 patients (5.4%). The incidence rate of adverse events was at least 1.3% and a maximum of 19.4% for each hospital. Most preventability scores were less than four points (non-preventable), and there were large variations between reviewers and institutions.Conclusions: Given the level of variation in the identified adverse events, further studies that include more medical institutions in their investigations are needed, and a third-party committee should be involved to address the reliability issues regarding the occurrence and characteristics of the adverse events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Apoptosis, which is involved in the process of mesangial cell and podocyte loss in diabetic nephropathy, is known to be regulated by protein kinase B/Akt (Akt). A number of studies have therefore investigated the activity of Akt under diabetic conditions, but the results have not been consistent. In this study, we hypothesized that apoptosis may occur differentially and that Akt may be differentially activated according to glomerular size in diabetic kidney disease. Methods. Fifty male Sprague–Dawley rats were injected intraperitoneally with diluent (C, n = 25) or streptozotocin (DM, n = 25). After 3 months, glomeruli were isolated using sieves with pore sizes of 250, 150, 125 and 75 μm and then classified into large glomeruli (on the 125-μm sieve, LG) and small glomeruli (on the 75-μm sieve, SG) groups. Western blot analyses for phospho-Akt, apoptosis-related molecules (Bax, Bcl-2, active fragments of Caspase-3 and phospho-p53) and cyclin-dependent kinase inhibitors were performed. Conclusions. The numbers of total cells and podocytes in isolated glomeruli were determined using transmission electron microscopy. Akt phosphorylation was significantly decreased in DM-LG, while it was significantly increased in DM-SG (P < 0.05). The ratio of Bax/Bcl-2 protein expression and active fragments of Caspase-3 and phospho-p53 protein expression were significantly increased in DM-LG compared to DM-SG and C-SG (P < 0.001 and P < 0.01, respectively). In contrast, the expression of p27Kip1 and p21Cip1 was significantly increased in DM-SG compared to DM-LG and C-SG (P < 0.05). The numbers of total glomerular cells and podocytes were significantly decreased in DM-LG (P < 0.05). In conclusion, these data show differential expression of Akt activity and apoptosis-related molecules according to glomerular size in diabetic nephropathy, suggesting that apoptosis may be more operative in more hypertrophic glomeruli, resulting in fewer glomerular cells and podocytes in diabetic nephropathy. [ABSTRACT FROM PUBLISHER]