Kyu-Beck Lee

Key Points: Higher urine protein-to-creatinine ratios were strongly associated with a rapid decline in kidney function in patients with CKD stages G3b–G4. The stronger association observed with time-updated urine protein-to-creatinine ratio suggests that sustained lower urine protein-to-creatinine ratio was associated with lower risk of CKD progression. In advanced CKD, patients with lower proteinuria levels exhibited slower kidney function decline and longer time to eGFR threshold for kidney failure. Background: Although urine protein-to-creatinine ratio (UPCR) is more commonly used than urine albumin-to-creatinine ratio in routine care, and particularly in low-resource settings, its association with kidney function decline and projected time to reach a kidney failure eGFR threshold in advanced CKD remains underexplored. Methods: We analyzed 2727 participants with eGFR 15–45 ml/min per 1.73 m ² without KRT from the Chronic Renal Insufficiency Cohort study and the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The main exposures were baseline and time-updated UPCR. The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of KRT. The secondary outcome was eGFR slope (ml/min per 1.73 m ² per year), whereas the exploratory outcome was projected time to reach the eGFR threshold of 10 ml/min per 1.73 m ² for kidney failure. Results: During 17,069 person-years of follow-up (median 4.9 years), the primary outcome occurred in 1474 participants (54%). Compared with UPCR 2 per year. In addition, projected time to eGFR threshold for kidney failure (95% CIs) was lower progressively with increasing proteinuria categories, estimated at 28.7 (25.6 to 32.6), 10.3 (9.3 to 11.5), 6.4 (6.0 to 6.8), and 3.8 (3.5 to 4.2) years, respectively. Conclusions: Higher UPCRs were strongly associated with accelerated CKD progression and shorter projected time to reach the eGFR threshold for kidney failure, underscoring the prognostic significance of proteinuria in patients with advanced CKD.

Background: Chronic kidney disease (CKD) substantially increases cardiovascular disease (CVD) and mortality risks, yet few models account for integrated cardio-kidney outcomes (CKOs). The American Heart Association’s PREVENT (Predicting Risk of CVD Events) score incorporates kidney-specific measures, however, its accuracy for CKOs in patients with CKD remains unclear. We aimed to evaluate PREVENT for CKOs against the Pooled Cohort Equation (PCE) and Systematic Coronary Risk Evaluation 2 (SCORE2) in two ethnically distinct CKD cohorts: KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease [KNOW-CKD] from South Korea and Chronic Renal Insufficiency Cohort [CRIC] from the United States. Methods: This study included 4,268 patients with CKD and no known CVD (CRIC: 2,530, KNOW-CKD: 1,738). We compared PREVENT (CVD and ASCVD versions) with the PCE and SCORE2. The primary outcome was CKO, a composite of major adverse kidney events (MAKE: ≥50% estimated glomerular filtration rate decline or kidney failure requiring replacement therapy) and four-point-major adverse cardiovascular events (4P-MACE). Secondary outcomes included individual components and all-cause mortality. Results: The PREVENT-CVD score showed superior predictive accuracy for CKO (Harrell’s C: 0.688; 95% confidence interval [CI]: 0.675–0.701) compared with PREVENT-ASCVD (ΔC = –0.009; 95% CI: –0.011 to –0.007), PCE (ΔC = –0.104; 95% CI: –0.113 to –0.095), and SCORE2 (ΔC = –0.106; 95% CI: –0.114 to –0.097). This superiority was driven by robust prediction for MAKE, along with significant improvements in reclassification and discrimination for 4P-MACE and all-cause mortality. Although predictive gains for 4P-MACE were attenuated in the KNOW-CKD cohort, adding albuminuria further enhanced predictive performance for primary outcome. Conclusions: The PREVENT-CVD equation outperformed traditional cardiovascular risk models in predicting integrated CKOs in patients with CKD. Its consistent discrimination across both cardiovascular and kidney events suggests that PREVENT may reflect the shared pathophysiology of cardio-kidney disease and support broader risk stratification in CKD.

Background: Mental health affects well-being and physical health. Among adults with chronic kidney disease (CKD), mental health (MH) problems are common and can induce adverse clinical outcomes. We examined the association between patient-reported MH problems and clinical outcomes in adults with non-dialysis CKD.Methods: This prospective observational study included 1,879 participants from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With CKD). Patients-reported MH problems were determined using four indicators of the Korea National Health and Nutrition Examination Survey questionnaire. We described the cross-sectional differences in health-related quality of life according to MH problems. We prospectively evaluated the hazard ratio (HR) of all-cause death and end-stage kidney disease (ESKD) according to the MH problems for a median follow-up of 6.4 years.Results: The participants (mean age 53 years; 61.6% male) had patient-reported MH problems of inadequate sleep duration (17.4%), subjective distress (27.3%), depressive symptoms (13.2%), and suicidal ideation (16.8%). In the fully adjusted Cox proportional model, poor MH (≥2 problems) was associated with a high risk of ESKD (HR, 1.46; 95% confidence interval [CI], 1.18–1.08) and death (HR, 1.55; 95% CI, 1.04–2.32) compared with good MH. Furthermore, the single indicator of suicidal ideation was associated with a high risk of ESKD (HR, 1.37; 95% CI, 1.11–1.69) and death (HR, 1.98; 95% CI, 1.34–2.92). Conclusions: Patient-reported MH problems are common in adults with CKD. Poor MH and only suicidal ideation are associated with a high risk of ESKD and early death. Age and sex modify the association between poor MH and adverse clinical outcomes in non-dialysis CKD.

Background: Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by the Korean Ministry of Food and Drug Safety in 2015 as a treatment option for autosomal dominant polycystic kidney disease (ADPKD). To prescribe tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease stages 1 to 3.Methods: A total of 117 Korean patients aged 19 to 50 years with rapidly progressing ADPKD were enrolled in the study. Tolvaptan was prescribed for 24 months with the maximum tolerable dose up to 120 mg/day. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs) including hepatic adverse events. The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR).Results: A total of 489 TEAEs occurred in 106 patients (90.6%). A total of 17 cases of hepatic adverse events (14.5%) occurred during the study period and mostly within the first 18-month period. However, liver enzymes were normalized after drug discontinuation. Although it was not statistically significant, patients with a previous history of liver disease as well as those with mild elevation of liver enzyme showed a higher frequency of hepatic adverse events. Compared with the predicted value from the calculation, tolvaptan attenuated both TKV growth and eGFR decline rate.Conclusion: Although the incidence of hepatic adverse events was higher in Korean ADPKD patients compared to the previous studies, tolvaptan can be prescribed safely and effectively using meticulous titration and 1-month interval monitoring.

The association between body mass index (BMI) and risk of kidney replacement therapy (KRT) initiation in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) remains uncertain. Furthermore, controversies remain around baseline BMI as the only exposure in the analysis. A total of 2,136 patients enrolled in the KoreaN Cohort Study for Outcome in Patients With CKD were included in this study. The exposure was baseline and time-updated BMI. The outcome was initiation of KRT including dialysis or kidney transplantation during follow-up. A multivariable Cox proportional hazards model, a time-dependent Cox model without inverse probability weights, and a marginal structural Cox model were fitted, adjusting for both time-fixed and time-varying covariates including various clinicodemographic characteristics. During the median follow-up of 8.3 years, KRT initiation occurred in 723 patients (34%). In patients with BMI ≥25.0 kg/m2, a higher time-updated BMI was significantly associated with a lower risk of KRT initiation compared to the reference group with normal BMI of 18.5-22.9 kg/m2, and a gradual decrease in risk of KRT initiation was observed with increasing BMI. The groups with BMI 25.0-29.9 kg/m2 (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.61-0.87) and BMI ≥30.0 kg/m2 (HR, 0.69; 95% CI, 0.53-0.88) exhibited a significantly lower risk of KRT initiation in the results of the marginal structural Cox model. A higher time-updated BMI has a lower risk of KRT initiation in obese patients with NDD-CKD. Therefore, aggressive reduction of body weight in patients with both obesity and CKD may not always be beneficial for adverse kidney events.

Background: The Mayo imaging classification (MIC) for polycystic kidney disease (PKD) is a crucial basis for clinical treatment decisions; however, the volumetric assessment for its evaluation remains tedious and inaccurate. While the ellipsoid method for measuring the total kidney volume (TKV) in patients with PKD provides a practical TKV estimation using computed tomography (CT), its inconsistency and inaccuracy are limitations, highlighting the need for improved, accessible techniques in real-world clinics. Methods: We compared manual ellipsoid and artificial intelligence (AI)-based kidney volumetry methods using a convolutional neural network-based segmentation model (3D Dynamic U-Net) for measuring the TKV by assessing 32 patients with PKD in a single tertiary hospital. Results: The median age and average TKV were 56 years and 1200.24 mL, respectively. Most of the patients were allocated to Mayo Clinic classifications 1B and 1C using the ellipsoid method, similar to the AI volumetry classification. AI volumetry outperformed the ellipsoid method with highly correlated scores (AI vs. nephrology professor ICC: r = 0.991, 95% confidence interval (CI) = 0.9780–0.9948, p < 0.01; AI vs. trained clinician ICC: r = 0.983, 95% CI = 0.9608–0.9907, p < 0.01). The Bland–Altman plot also showed that the mean differences between professor and AI volumetry were statistically insignificant (mean difference 159.5 mL, 95% CI = 11.8368–330.7817, p = 0.07). Conclusions: AI-based kidney volumetry demonstrates strong agreement with expert manual measurements and offers a reliable, labor-efficient alternative for TKV assessment in clinical practice. It is helpful and essential for managing PKD and optimizing therapeutic outcomes.

Background: Coronary artery calcification (CAC) is highly prevalent in patients with chronic kidney disease (CKD) and is associated with major adverse cardiovascular events and metabolic disturbances. The triglyceride-glucose index (TyGI), a novel surrogate marker of metabolic syndrome and insulin resistance, is associated with CAC in the general population and in patients with diabetes. This study investigated the association between the TyGI and CAC progression in patients with CKD, which is unknown. Methods: A total of 1,154 patients with CKD (grades 1–5; age, 52.8 ± 11.9 years; male, 688 [59.6%]) were enrolled from the KNOWCKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The TyGI was calculated as follows: ln (fasting triglycerides × fasting glucose/2). Patients were classified into tertiles (low, intermediate, high) based on the TyGI. The primary outcome was annualized percentage change in CAC score [(percent change in CAC score + 1)12/follow-up months – 1] of ≥15%, defined as CAC progression. Results: During the 4-year follow-up, the percentage of patients with CAC progression increased across TyGI groups (28.6%, 37.5%, and 46.2% in low, intermediate, and high groups, respectively; p < 0.001). A high TyGI was associated with an increased risk of CAC progression (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.14–3.88; p = 0.02) compared to the low group. Moreover, a 1-point increase in the TyGI was related to increased risk of CAC progression (OR, 1.55; 95% CI, 1.06–1.76; p = 0.02) after adjustment. Conclusion: A high TyGI may be a useful predictor of CAC progression in CKD.

While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9 years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan–Meier curve analysis (P < 0.001, log-rank test), with the highest incidence observed in the 4th quartile. Cox regression analysis indicated that, relative to the 1st quartile, the risk of 3-point MACE was significantly higher in the 3rd (adjusted hazard ratio 2.901, 95% confidence interval 1.009 to 8.341) and the 4th quartiles (adjusted hazard ratio 4.347, 95% confidence interval 1.410 to 13.395). In conclusion, elevated circulating OPG levels are associated with adverse cardiovascular outcomes in pre-dialysis CKD patients.

Background: Identifying genetic mutations in individuals with inherited cystic kidney disease is necessary for precise treatment. We aimed to elucidate the genetic characteristics of cystic kidney disease in the Korean population.Methods: We conducted a 3-year prospective, multicenter cohort study at eight hospitals from May 2019 to May 2022. Patients with more than three renal cysts were enrolled and classified into two categories, typical autosomal dominant polycystic kidney disease (ADPKD) and atypical PKD. We identified the clinical characteristics and performed a genetic analysis using a targeted gene panel. Results: A total of 725 adult patients were included in the study, of which 560 (77.2%) were diagnosed with typical ADPKD and 165 (22.8%) had atypical PKD. Among the typical ADPKD cases, the Mayo imaging classification was as follows: 1A (55, 9.9%), 1B (149, 26.6%), 1C (198, 35.8%), 1D (90, 16.3%), and 1E (61, 11.0%). The atypical PKD cases were classified as bilateral cystic with bilateral atrophic (31, 37.3%), lopsided (27, 32.5%), unilateral (nine, 10.8%), segmental (eight, 9.6%), bilateral cystic with unilateral atrophic (seven, 8.4%), and asymmetric (one, 1.2%). Pathogenic variants were found in 64.3% of the patients using the ciliopathy-related targeted gene panel. The typical ADPKD group demonstrated a higher discovery rate (62.3%) than the atypical PKD group (41.8%).Conclusion: We present a nationwide genetic cohort’s baseline clinical and genetic characteristics for Korean cystic kidney disease.

Background: Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.