Kidney Research and Clinical Practice最新文献

Background: Digital therapeutics are emerging as treatments for diseases and disabilities. In chronic kidney disease (CKD), gait is a potential biomarker for health status and intervention effectiveness. This study aims to analyze gait characteristics in CKD patients, providing baseline data for digital therapeutics development.

Methods: At baseline and after an 8-week intervention, we performed bioimpedance analysis measurements, the Timed Up and Go, Tinetti, and grip strength tests, and gait analysis in 217 healthy individuals and 276 patients with CKD. Demographic and clinical information was collected, including underlying diseases and medications, laboratory tests, and quality of life satisfaction surveys. Gait analysis was performed using skeleton data, which involved acquiring three-dimensional skeleton data of a walker using a single Kinect sensor. The performance of an artificial intelligence-based classification model in distinguishing between healthy individuals and those with CKD was then investigated. Simultaneously, inertia measurement unit analysis was conducted using measurements taken from the wrist and waist.

Results: Most subjects received a health intervention via an app, and their gait was assessed for improvements after an 8-week period. Incidents such as falls, fractures, hospitalizations, and deaths will be investigated in years 1 and 3.

Conclusion: This study confirmed that the gaits of healthy individuals and CKD patients were different, and the effect of the 8-week app-based health intervention will be analyzed. The study will yield important baseline data for creating digital therapeutics for CKD patients' diet/exercise in the future.

Background: Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage kidney disease (ESKD). The International IgA Nephropathy Prediction Tool (IIgAN-PT) predicts IgAN prognosis, but improvement in the prediction performance using machine learning (ML)-based methods is needed.

Methods: We analyzed 4,425 biopsy-confirmed patients with IgAN and ≥6 months of follow-up from nine tertiary university hospitals in Korea. The study population was divided into development and validation cohorts. Using the collected 87 clinicodemographic and pathological variables, ML-based prediction models for ESKD or estimated glomerular filtration rate decline (50% reduction or <15 mL/min/1.73 m2 ) were constructed: 1) the conventional CatBoost model, 2) the optimized CatBoost model with Cox proportional hazards, 3) the deep Cox proportional hazards model, and 4) the deep Cox mixture model. The area under the curve (AUC) and calibration plots were used to investigate the discriminative and calibration performance of the models, which were then compared with those of the IIgAN-PT full model.

Results: The full model showed excellent performance (AUC [95% confidence interval] for 5-year outcome, 0.896 [0.853-0.940]), with acceptable calibration results. The ML-based models showed good performance in predicting adverse kidney outcomes and revealed acceptable discrimination performance in the external validation (AUC [95% confidence interval] for the 5-year outcome: 1) 0.829 [0.791-0.866]; 2) 0.847 [0.804-0.890]; 3) 0.823 [0.784-0.862]; and 4) 0.832 [0.794-0.870]), although the models showed underestimation in calibration analysis of the external validation cohort. With the validation data, the overall performance of the IIgAN-PT was non-inferior to that of the ML-based model.

Conclusions: Our ML-based models showed good performance in predicting adverse kidney outcomes in patients with IgAN but they did not outperform the IIgAN-PT.

Background: The association between abnormal left ventricular geometry (LVG) patterns and the presence of coronary artery calcification is unclear in patients with CKD.

Methods: A total of 2,038 patients with pre-dialysis CKD at stages 1 to 5 were categorized by LVG patterns, which were echocardiographically determined by the presence or absence of left ventricular hypertrophy (LVH) and relative wall thickness (RWT): normal, concentric remodeling, eccentric LVH, and concentric LVH. The study outcome was the presence of heavy coronary artery calcification, which is defined as coronary artery calcium score >1,000 Agatston units.

Results: Logistic regression analyses demonstrated that concentric remodeling (adjusted odds ratio [OR], 2.53; 95% confidence interval [95% CI], 1.32-4.85) and concentric LVH (adjusted OR, 2.89; 95% CI, 1.49-5.62), but not eccentric LVH (adjusted OR, 1.58; 95% CI, 0.71-3.51), were significantly associated with the risk of heavy coronary artery calcification. The presence of LVH alone was not significantly associated with the risk of heavy coronary artery calcification (adjusted OR, 1.65; 95% CI, 0.97-2.81), while the increase in RWT independently increased the risk of heavy coronary artery calcification (adjusted OR, 2.423; 95% CI, 1.48-4.00).

Conclusion: Abnormal LVG patterns, such as concentric remodeling and concentric LVH, but not eccentric LVH, are significantly associated with the risk of heavy coronary artery calcification in patients with CKD. It is expected that the determination of LVG patterns may facilitate risk stratification in relation to the coronary evaluation strategy.

Background: Since the glomerular filtration rate (GFR) naturally declines with age, age-adjusted chronic kidney disease diagnostic criteria have been proposed. This study aimed to investigate the prognostic impact of estimated GFR (eGFR) on mortality and progression to end-stage kidney disease (ESKD) in normoalbuminuric older adults with type 2 diabetes mellitus.

Methods: We categorized patients aged ≥65 years without albuminuria who visited our diabetes center by their baseline eGFR levels. Primary outcomes were composite events encompassing all-cause mortality and ESKD.

Results: Among 1,997 participants, 8%, 71%, 16%, and 5% had an eGFR of ≥90, 60-89, 45-59, and 15-44 mL/min/1.73 m2, respectively. Adjusted hazard ratios for composite outcomes were 1.30 (95% confidence interval, 1.01-1.76) for those with an eGFR of 45-59 mL/min/1.73 m2, compared to those with an eGFR of 60-90 mL/min/1.73 m2. Subgroup analyses revealed consistently increased risk associated with eGFR 45-59 mL/min/1.73 m2 across individuals with body mass index <25 kg/m2 and those with urine albumin-to-creatinine ratio <10 µg/mgCr.

Conclusion: This study indicated that an eGFR of 45-59 mL/min/1.73 m2 possesses an elevated risk of composite events, which suggests that the current traditional eGFR criteria could be applicable to older patients with diabetes mellitus.

Background: A paucity of literature exists on the development of predictive tools for the decline of kidney function in pediatric chronic kidney disease (CKD). The objective of this study is to develop and internally validate a tool for the short-term prediction of a kidney function decline in pediatric patients with CKD.

Methods: A total of 539 patients participating in the KNOW-PedCKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease) were evaluated for 48 variables related to sociodemographic characteristics, laboratory data, and treatment use. These variables were assessed as potential predictors of a kidney function decline in pediatric patients with CKD using a range of machine learning algorithms.

Results: The models demonstrated strong predictive performances in identifying kidney function decline, defined as an estimated glomerular filtration rate (eGFR) decline of ≥20%, which includes progression to kidney replacement therapy or death. The random forest and XGBoost models demonstrated the best performance in predicting eGFR outcomes at 1 year compared with 2 and 3 years, respectively. The spot urine protein-to-creatinine ratio was the most influential variable in the prediction model, followed by baseline eGFR and serum albumin, chloride, and hemoglobin levels.

Conclusion: A tool for predicting kidney function decline in children with CKD over a short period of time was developed using potential predictors and machine learning methods in a large Korean pediatric CKD cohort.

Background: Receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of numerous inflammatory conditions including sepsis. We investigated the possible therapeutic role of soluble RAGE (sRAGE) in septic acute kidney injury (AKI) models.

Methods: sRAGE level was measured in healthy controls and patients with septic AKI. C57/BL6 mice with cecal ligation and puncture (CLP) were injected with sRAGE (CLP + sRAGE) 1 hour before the operation. NRK-52E cells were treated with lipopolysaccharide (LPS, 1 μg/mL) and sRAGE (1 μg/mL) or RAGE small interfering RNA. RAGE-associated signaling molecule and apoptosis-related protein (ARP) expression levels were analyzed.

Results: Serum sRAGE level was significantly higher in septic AKI patients than in healthy controls, and higher sRAGE level was associated with better survival rates. Blood urea nitrogen and creatinine levels were significantly higher in CLP mice than controls, and these increases were significantly abrogated in CLP + sRAGE mice. Renal MyD88 and phospho-ERK, -p38, and -JNK proteins and ARP expression levels in the CLP group were also significantly increased compared to controls, and these changes were significantly ameliorated by sRAGE treatment in CLP mice. In vitro, RAGE-associated activation of mitogen-activated protein kinase and ARP expression in LPS-stimulated cells were significantly ameliorated by sRAGE. Furthermore, the increases in nuclear factor kappa B nuclear translocation and intercellular adhesion molecule 1 protein expression by LPS were significantly attenuated by sRAGE in these cells.

Conclusion: These findings suggest that RAGE plays an important role in septic AKI, and its inhibition by sRAGE may be a potential therapeutic target for AKI in severe sepsis.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. The glomerulus is the primary site of injury in DKD progression. Pathologically, the integrity of the glomerular filtration barrier is disrupted, characterized by podocyte process fusion and detachment, glomerular basement membrane thickening, and reduction of the endothelial cell glycocalyx. These disruptions result in albuminuria due to impaired function of glomerular selective filtration. Additionally, mesangial expansion driven by mesangial cell proliferation and excessive mesangial matrix accumulation in glomeruli is a hallmark of the disease, leading to nodular sclerosis and glomerulosclerosis eventually. Multiple molecular mechanisms involving abnormal metabolism of nutrients, oxidative stress, inflammation, and hyperactivity of the renin-angiotensin system contribute to glomerular pathophysiological changes and renal function deterioration in diabetes mellitus. This review focuses on disturbances in nutrient metabolism and their roles in the pathophysiology of glomerular impairments. Blood glucose control, cardiovascular risk factors intervention, blood pressure management, and renin-angiotensin system blockade are pivotal in preventing the development and progression of DKD. Future research is urgently needed to identify innovative therapeutic targets based on advances in molecular mechanisms.

Background: This study aimed to investigate the relationship between the creatinine-to-cystatin C ratio (CCR) and handgrip strength in individuals with prediabetes, to identify patients with reduced handgrip strength.

Methods: This study used a nationally representative sample from the Chinese middle-aged and elderly population. The cross-sectional portion utilized data from the first wave of the 2011 China Health and Retirement Longitudinal Study (CHARLS), while the longitudinal portion used data from the fourth wave of the 2015 CHARLS. Data on CCR, handgrip strength, and other relevant variables were collected and analyzed using univariate and multivariate regression.

Results: A total of 2,704 participants were included, with 1,276 males (47.2%) and 1,428 females (52.8%), and the mean age was 60.5 ± 9.5 years. Univariate analysis showed a positive correlation between CCR and handgrip strength (β = 18.3; 95% confidence interval [CI], 16.46-20.14; p < 0.001). After adjusting for confounding variables, the β value was 3.52 (95% CI, 1.95-5.09; p < 0.001). Compared to the lowest CCR group (Q1, 0.27 to 0.67), the adjusted β values for Q2 (0.67 to 0.77), Q3 (0.77 to 0.89), and Q4 (0.89 to 2.39) were 0.37 (95% CI, -0.46 to 1.2; p = 0.38), 1.6 (95% CI, 0.73-2.47; p < 0.001), and 2.16 (95% CI, 1.24-3.09; p < 0.001), respectively. Subgroup and stratified analyses further supported these results.

Conclusion: This study suggests that in individuals with prediabetes, there is a positive correlation between the CCR and handgrip strength.

Background: Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed.

Methods: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria.

Results: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50-1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06-4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05-4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10-2.85), without a substantial increase in the risk of decreased renal function.

Conclusion: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation.

Background: Cardiovascular disease is an important risk factor for mortality among kidney transplant recipients. In this study, we aimed to investigate the association between cardiovascular risk score at kidney transplantation and long-term outcomes of patients.

Methods: In this prospective, observational cohort study, we enrolled kidney transplant recipients who participated in the Korean Organ Transplantation Registry and underwent transplantation between April 2014 and December 2019. The cardiovascular risk status of kidney transplant recipients was assessed using the Framingham risk score. All-cause mortality, major adverse cardiovascular events, allograft failure, estimated glomerular filtration rates (eGFRs), and composite outcomes were evaluated after kidney transplantation.

Results: Of the 4,682 kidney transplant recipients, 96 died during 30.7 ± 19.1 months of follow-up. The Kaplan-Meier survival analysis results showed that high Framingham risk scores were associated with all-cause mortality, major adverse cardiovascular events, and composite outcomes. According to the multivariable Cox analysis, high Framingham risk scores were associated with an increased risk of mortality (hazard ratio [HR], 3.20; 95% confidence interval [CI], 1.30-7.91), major adverse cardiovascular events (HR, 8.43; 95% CI, 2.41-29.52), and composite outcomes (HR, 2.05; 95% CI, 1.19-3.46). The eGFRs after transplantation were significantly higher among patients in the low Framingham risk score group (p < 0.001). However, Framingham risk scores were not associated with graft loss or rapid decline in eGFRs.

Conclusion: The Framingham risk score is a useful indicator of cardiovascular events, mortality, and kidney function after kidney transplantation.