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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.
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Despite efforts to treat critically ill patients who require continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI), their mortality risk remains high. This condition may be attributable to complications of CRRT, such as arrhythmias. Here, we addressed the occurrence of ventricular tachycardia (VT) during CRRT and its relationship with patient outcomes. Methods: This study retrospectively enrolled 2,397 patients who started CRRT due to AKI from 2010 to 2020 at Seoul National University Hospital in Korea. The occurrence of VT was evaluated from the initiation of CRRT until weaning from CRRT. The odds ratios (ORs) of mortality outcomes were measured using logistic regression models after adjustment for multiple variables. Results: VT occurred in 150 patients (6.3%) after starting CRRT. Among them, 95 cases were defined as sustained VT (i.e., lasting ≥30 seconds), and the other 55 cases were defined as non-sustained VT (i.e., lasting <30 seconds). The occurrence of sustained VT was associated with a higher mortality rate than a nonoccurrence (OR, 2.04 and 95% confidence interval [CI], 1.23–3.39 for the 30- day mortality; OR, 4.06 and 95% CI, 2.04–8.08 for the 90-day mortality). The mortality risk did not differ between patients with non-sustained VT and nonoccurrence. A history of myocardial infarction, vasopressor use, and certain trends of blood laboratory findings (such as acidosis and hyperkalemia) were associated with the subsequent risk of sustained VT. Conclusion: Sustained VT occurrence after starting CRRT is associated with increased patient mortality. The monitoring of electrolytes and acid-base status during CRRT is essential because of its relationship with the risk of VT.
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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.
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Background@#The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function. @*Methods@#Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed. @*Results@#Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to –1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated. @*Conclusion@#Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.
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As a leading cause of chronic kidney disease, clinical demand for noninvasive biomarkers of diabetic kidney disease (DKD) beyond proteinuria is increasing. Metabolomics is a popular method to identify mechanisms and biomarkers. We investigated urinary targeted metabolomics in DKD patients. Methods: We conducted a targeted metabolomics study of 26 urinary metabolites in consecutive patients with DKD stage 1 to 5 (n = 208) and healthy controls (n = 26). The relationships between estimated glomerular filtration rate (eGFR) or urine protein-creatinine ratio (UPCR) and metabolites were evaluated. Multivariate Cox analysis was used to estimate relationships between urinary metabolites and the target outcome, end-stage renal disease (ESRD). C statistics and time-dependent receiver operating characteristics (ROC) were used to assess diagnostic validity. Results: During a median 4.5 years of follow-up, 103 patients (44.0%) progressed to ESRD and 65 (27.8%) died. The median fold changes of nine metabolites belonged to monosaccharide and tricarboxylic acid (TCA) cycle metabolites tended to increase with DKD stage. Myo-inositol, choline, and citrates were correlated with eGFR and choline, while mannose and myo-inositol were correlated with UPCR. Elevated urinary monosaccharide and TCA cycle metabolites showed associations with increased morality and ESRD progression. The predictive power of ESRD progression was high, in the order of choline, myo-inositol, and citrate. Although urinary metabolites alone were less predictive than serum creatinine or UPCR, myo-inositol had additive effect with serum creatinine and UPCR. In time-dependent ROC, myo-inositol was more predictive than UPCR of 1-year ESRD progression prediction. Conclusion: Myo-inositol can be used as an additive biomarker of ESRD progression in DKD.
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Recent studies have shown that patients with end-stage renal disease (ESRD) are at elevated risk of dementia. However, whether kidney transplantation (KT) lowers the risk for incident dementia remains unclear. Methods: From the Korean National Health Insurance Service database, we identified incident KT recipients aged ≥40 years without any history of dementia between 2007 and 2015. We also established a pair of age-, sex-, and inclusion year-matched control cohorts of patients with incident dialysis-dependent ESRD and members of the general population (GP) without a history of dementia, respectively. Cases of incident all-cause dementia, including Alzheimer disease (AD), vascular dementia (VD), and other kinds of dementia, were obtained from baseline until December 31, 2017. Results: We followed 8,841 KT recipients, dialysis-dependent ESRD patients, and GP individuals for 48,371, 28,649, and 49,149 patient- years, respectively. Their mean age was 52.5 years, and 60.6% were male. Over the observation period, 55/43/19 KT recipients, 230/188/75 dialysis-dependent ESRD patients, and 38/32/14 GP individuals developed all-cause dementia/AD/VD. The risks of incident all-cause dementia, AD, and VD in KT recipients were similar to those in GP (hazard ratio: 0.74 [p = 0.20], 0.74 [p = 0.24], and 0.59 [p = 0.18], respectively) and significantly lower than those in dialysis-dependent ESRD patients (hazard ratio: 0.17 [p < 0.001], 0.16 [p < 0.001], and 0.16 [p < 0.001], respectively). Older age and diabetes mellitus at the time of KT were risk factors for incident all-cause dementia and AD in KT recipients. Conclusion: This is the first study to show a beneficial impact of KT on incident dementia compared to dialysis dependency.
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Background@#Factors related to the development and severity of polycystic liver disease (PLD) have not been well established. We aimed to evaluate the genetic and epidemiologic risk factors of PLD in patients with autosomal dominant polycystic kidney disease (ADPKD). @*Methods@#Adult patients with inherited cystic kidney disease were enrolled from May 2019 to May 2021. Demographic, clinical, and laboratory data were collected at the initial study visit. The severity of PLD was graded based on the height-adjusted total liver volume: 1,800 mL/m (Gr3). Targeted exome sequencing was done by a gene panel including 89 ciliopathy-related genes. We searched out the relative factors to the presence and the severity of PLD using logistic regression analysis. @*Results@#Of 602 patients with typical ADPKD, 461 (76.6%) patients had PLD. The patients with PLD showed female predominance and a higher frequency of other ADPKD-related complications. The genetic variants with truncating mutation of PKD1 (PKD1-proteintruncating [PT]) or PKD2 commonly affected the development and severity of PLD. An older age, female sex, and higher kidney volume with Mayo classification 1C-1E was significantly associated with the development of PLD, but not with the severity of PLD. On the other hand, higher body mass index, lower hemoglobin, and higher alkaline phosphatase (ALP) were the significant risk factors of severe PLD (≥ Gr2). @*Conclusion@#Hepatic involvement in ADPKD could be related to kidney manifestations and genetic variants including PKD1-PT or PKD2. Monitoring hemoglobin and ALP and evaluating the genetic variants might help predict severe PLD.
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Background@#Due to impaired cell-mediated immunity, solid organ transplantation (SOT) recipients are at increased risk of developing nontuberculous mycobacterial pulmonary disease (NTM-PD). However, the clinical course of NTM-PD in SOT patients and the impact of SOT on the prognosis of NTM-PD remain unclear. @*Methods@#We analyzed patients who developed NTM-PD after receiving SOT between January 2001 and December 2020, at a tertiary referral hospital in South Korea. Baseline characteristics, clinical course, and prognosis were evaluated. Propensity score-matched analysis was performed to assess the impact of SOT on long-term survival in patients with NTM-PD. @*Results@#Among 4,685 SOT recipients over 20 years, 12 patients (median age, 64 years;interquartile range [IQR], 59–67 years; men, 66.7%) developed NTM-PD. Seven (58.3%) and five (41.7%) patients underwent kidney and liver transplantation, respectively, before the diagnosis of NTM-PD. The incidence of NTM-PD was 35.6 cases per 100,000 person-years among kidney transplant recipients and 28.7 cases per 100,000 person-years among liver transplant recipients. The median time between transplantation and the diagnosis of NTMPD was 3.3 (IQR, 1.5–10.8) years. The most common mycobacterial species was Mycobacterium avium (50.0%). Antibiotic treatment was initiated in five (41.7%) patients, and two patients (40.0%) achieved microbiological cure. Two patients died during a median follow-up of 4.2 (IQR, 2.3–8.8) years and NTM-PD was assumed to be the cause of death in one patient. When matched to patients without a history of SOT, patients with a history of SOT did not show worse survival (P value for log-rank test = 0.62). @*Conclusion@#The clinical course of NTM-PD in SOT recipients was comparable to that of patients without SOT, and SOT did not increase the risk of all-cause mortality in patients with NTM-PD.
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Comorbid conditions impact the survival of patients with severe acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT). The weights assigned to comorbidities in predicting survival vary based on type of index, disease, and advances in management of comorbidities. We developed a modified Charlson Comorbidity Index (CCI) for use in patients with AKI requiring CRRT (mCCI-CRRT) and improved the accuracy of risk stratification for mortality. Methods: A total of 828 patients who received CRRT between 2008 and 2013, from three university hospital cohorts was included to develop the comorbidity score. The weights of the comorbidities were recalibrated using a Cox proportional hazards model adjusted for demographic and clinical information. The modified index was validated in a university hospital cohort (n = 919) using the data of patients treated from 2009 to 2015. Results: Weights for dementia, peptic ulcer disease, any tumor, and metastatic solid tumor were used to recalibrate the mCCI-CRRT. Use of these calibrated weights achieved a 35.4% (95% confidence interval [CI], 22.1%–48.1%) higher performance than unadjusted CCI in reclassification based on continuous net reclassification improvement in logistic regression adjusted for age and sex. After additionally adjusting for hemoglobin and albumin, consistent results were found in risk reclassification, which improved by 35.9% (95% CI, 23.3%–48.5%). Conclusion: The mCCI-CRRT stratifies risk of mortality in AKI patients who require CRRT more accurately than does the original CCI, suggesting that it could serve as a preferred index for use in clinical practice.
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Appropriate monitoring of intradialytic biosignals is essential to minimize adverse outcomes because intradialytic hypotension and arrhythmia are associated with cardiovascular risk in hemodialysis patients. However, a continuous monitoring system for intradialytic biosignals has not yet been developed. Methods: This study investigated a cloud system that hosted a prospective, open-source registry to monitor and collect intradialytic biosignals, which was named the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry. This registry was based on real-time multimodal data acquisition, such as blood pressure, heart rate, electrocardiogram, and photoplethysmogram results. Results: We analyzed session information from this system for the initial 8 months, including data for some cases with hemodynamic complications such as intradialytic hypotension and arrhythmia. Conclusion: This biosignal registry provides valuable data that can be applied to conduct epidemiological surveys on hemodynamic complications during hemodialysis and develop artificial intelligence models that predict biosignal changes which can improve patient outcomes.
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The recent novel coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented changes in behavior. We evaluated the current status of precautionary behavior and physical activity in chronic kidney disease (CKD) patients during the COVID-19 pandemic. Methods: A population of CKD patients (n = 306) registered in the Study on Kidney Disease and Environmental Chemicals (SKETCH, Clinical Trial No. NCT04679168) cohort recruited from June 2020 to October 2020 was included in the study. We conducted a questionnaire survey related to risk perception of COVID-19, precautionary behavior, and physical activity. Results: There were 187 patients (61.1%) with estimated glomerular filtration rate of <45 mL/min/1.73 m2 . This population showed a higher degree of risk perception for COVID-19 than the general population. Age was the most significant determinant of risk perception among CKD patients. During the pandemic, social distancing and hygiene-related behavior were significantly increased (p < 0.001). The frequency of exercise was decreased only in those who took regular exercise, without diabetes, or with a lower Charlson comorbidity index (CCI) (p < 0.001), with no change among the other groups. Socioeconomic status and comorbidities significantly affected behavioral characteristics regardless of the category. Education and income were significantly associated with precautionary behaviors such as staying at home and hand sanitizer use. Patients with higher CCI status significantly increased frequency of exercise (adjusted odds ratio, 2.10; 95% confidence interval, 1.01–4.38). Conclusion: CKD patients showed higher risk perception with active precautionary behavioral changes than the general population. Healthcare providers should be aware of the characteristics to comprise precautionary behavior without reducing physical activity.
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Long-term outcomes of live kidney donors remain controversial, although this information is crucial for selecting potential donors. Thus, this study compared the long-term risk of all-cause mortality between live kidney donors and healthy control. Methods: We performed a retrospective cohort study including donors from seven tertiary hospitals in South Korea. Persons who underwent voluntary health screening were included as controls. We created a matched control group considering age, sex, era, body mass index, baseline hypertension, diabetes, estimated glomerular filtration rate, and dipstick albuminuria. The study outcome was progression to end-stage kidney disease (ESKD), and all-cause mortality as identified in the linked claims database. Results: We screened 1,878 kidney donors and 78,115 health screening examinees from 2003 to 2016. After matching, 1,701 persons remained in each group. The median age of the matched study subjects was 44 years, and 46.6% were male. Among the study subjects, 2.7% and 16.6% had underlying diabetes and hypertension, respectively. There were no ESKD events in the matched donor and control groups. There were 24 (1.4%) and 12 mortality cases (0.7%) in the matched donor and control groups, respectively. In the age-sex adjusted model, the risk for all-cause mortality was significantly higher in the donor group than in the control group. However, the significance was not retained after socioeconomic status was included as a covariate (adjusted hazard ratio, 1.82; 95% confidence interval, 0.87–3.80). Conclusion: All-cause mortality was similar in live kidney donors and matched non-donor healthy controls with similar health status and socioeconomic status in the Korean population.
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Background@#Peritoneal dialysis (PD) is improving as a renal replacement therapy for end-stage renal disease (ESRD) patients. We analyzed the main outcomes of PD over the last three decades at a single large-scale PD center with an established high-quality care system. @*Methods@#As a retrospective cohort study, we included participants (n = 1,203) who began PD between 1990 and 2019. Major PD-related outcomes were compared among the three 10-year cohorts. @*Results@#The 1,203 participants were 58.3% male with a mean age of 47.9 ± 13.8 years. The median PD treatment duration was 45 months (interquartile range, 19–77 months); 362 patients (30.1%) transferred to hemodialysis, 289 (24.0%) received kidney transplants, and 224 (18.6%) died. Overall, the 5- and 8-year adjust patient survival rates were 64% and 49%, respectively. Common causes of death included infection (n = 55), cardiac (n = 38), and cerebrovascular (n = 17) events. The 5- and 8-year technique survival rates were 77% and 62%, respectively, with common causes of technique failure being infection (42.3%) and solute/water clearance problems (22.7%). The 5-year patient survival significantly improved over time (64% for the 1990–1999 cohort vs. 93% for the 2010–2019 cohort). The peritonitis rate also substantially decreased over time, from 0.278 episodes/patient-year (2000–2004) to 0.162 episodes/patient-year (2015–2019). @*Conclusion@#PD is an effective treatment option for ESRD patients. There was a substantial improvement in the patient survival and peritonitis rates over time. Establishing adequate infrastructure and an effective system for high-quality PD therapy may be warranted to improve PD outcomes.
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Background@#Considering the growing prevalence of Western lifestyles and related chronic diseases occurring in South Korea, this study aimed to explore the progression of metabolic risk factors in living kidney donors compared to a control group. @*Methods@#This study enrolled living kidney donors from seven hospitals from 1982 to 2016. The controls were individuals that voluntarily received health check-ups from 1995 to 2016 that were matched with donors according to age, sex, diabetes status, baseline estimated glomerular filtration rate, and date of the medical record. Data on hyperuricemia, hypertension, hypercholesterolemia, and overweight/obesity were collected to determine metabolic risks. The proportion of individuals with three or more metabolic risk factors was evaluated. Logistic regressions with interaction terms between the medical record date and donor status were used to compare the trends in metabolic risks over time in the two groups. @*Results@#A total of 2,018 living kidney donors and matched non-donors were included. The median age was 44.0 years (interquartile range, 34.0–51.0 years) and 54% were women. The living kidney donors showed a lower absolute prevalence for all metabolic risk factors, except for those that were overweight/obese, than the non-donors. The proportion of subjects that were overweight/obese was consistently higher over time in the donor group. The changes over time in the prevalence of each metabolic risk were not significantly different between groups, except for a lower prevalence of metabolic risk factors ≥ 3 in donors. @*Conclusion@#Over time, metabolic risks in living kidney donors are generally the same as in non-donors, except for a lower prevalence of metabolic risk factors ≥ 3 in donors.
ABSTRACT
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by cyst growth in the kidneys, resulting in kidney enlargement and end-stage kidney disease. The polycystic kidney disease 1 (PKD1) and PKD2 have been identified as genes related to ADPKD and their significance in the molecular pathology of the disease has been studied. A disease-modifying drug has been approved; therefore, it has become important to identify patients at a high risk of kidney disease progression. Genetic tests, image analysis methods, and clinical factors for kidney disease progression prediction have been established. This review describes genetic and clinical characteristics, and discusses ongoing studies in Korean ADPKD patients.
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Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.
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Background@#As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). @*Methods@#Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. @*Results@#During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. @*Conclusion@#Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.
ABSTRACT
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by cyst growth in the kidneys, resulting in kidney enlargement and end-stage kidney disease. The polycystic kidney disease 1 (PKD1) and PKD2 have been identified as genes related to ADPKD and their significance in the molecular pathology of the disease has been studied. A disease-modifying drug has been approved; therefore, it has become important to identify patients at a high risk of kidney disease progression. Genetic tests, image analysis methods, and clinical factors for kidney disease progression prediction have been established. This review describes genetic and clinical characteristics, and discusses ongoing studies in Korean ADPKD patients.
ABSTRACT
Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.
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Background@#As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). @*Methods@#Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. @*Results@#During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. @*Conclusion@#Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.