Insufficient early renal recovery and progression to subsequent chronic kidney disease in living kidney donors

Yaerim Kim,Eunjeong Kang,Dong-Wan Chae,Jung Pyo Lee,Sik Lee,Soo Wan Kim,Jang-Hee Cho,Miyeun Han,Seungyeup Han,Yong Chul Kim,Dong Ki Kim,Kwon Wook Joo,Yon Su Kim,Hajeong Lee 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.5

Background/Aims: Renal recovery of a kidney donor after undergoing nephrectomy though challenging is essential. We aimed to examine the effect of estimated glomerular filtration rate (eGFR) percent change at 1-month post-donation on insufficient kidney function after kidney donation. Methods: A total of 3,952 living kidney donors who underwent donor nephrectomy from 1982 to 2019 from eight different tertiary hospitals in Korea were initially screened. Percent changes in the eGFR from baseline to 1-month post-donation were calculated. The degree of percent changes was categorized by quartile, and the 1st quartile was regarded as the group with the lowest decreased eGFR at 1-month after donation. The remaining eGFR less than 60 mL/min/1.73 m2 was the endpoint. The Cox proportional hazard model was used for evaluating the impact of initial eGFR and eGFR percent change at 1-month post-donation on the condition with remaining eGFR < 60 mL/min/1.73 m2. In the multivariate analysis, we used variables with a p < 0.1 in the univariate analysis. Results: A total of 1,585 donors were included in the analysis. During 62.2 ± 49.3 months, 13.7% of donors showed renal insufficiency. The 4th (adjusted hazard ratio [aHR], 10.41; 95% confidence interval [CI], 5.15 to 21.04) and the 3rd (aHR, 4.29; 95% CI, 2.15 to 8.56) quartiles of percent change in eGFR and the pre-donation eGFR (aHR, 0.90; 95% CI, 0.88 to 0.92) were associated with the development of renal insufficiency. Conclusions: The impact of worse initial renal recovery on renal insufficiency was pronounced in donors with lower pre-donation eGFRs. Additionally, worse initial renal recovery of remaining kidney affected the long-term development of renal insufficiency in kidney donors.

Factors Associated With the Development and Severity of Polycystic Liver in Patients With Autosomal Dominant Polycystic Kidney Disease

Kim Yaerim,Park Hayne Cho,Ryu Hyunjin,Kim Yong Chul,Ahn Curie,Lee Kyu-Beck,Kim Yeong Hoon,Han Seungyeup,Bae Eun Hui,Jeong Kyungjo,Choi Jungmin,Oh Kook-Hwan,Oh Yun Kyu 대한의학회 2023 Journal of Korean medical science Vol.38 No.38

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: < 1,000 mL/m (Gr1), 1,000–1,800 mL/m (Gr2), and > 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.

A Pedigree with c.179 Cytosine to Threonine Missense Mutation of SLC12A3 Gene Presenting Gitelman`s Syndrome

( Yaerim Kim ),( Seong Sik Kang ),( Woo Yeong Park ),( Kyubok Jin ),( Dae Kwang Kim ),( Seungyeup Han ) 대한전해질학회 2016 Electrolytes & Blood Pressure Vol.14 No.1

A 42-year-old man came to the hospital presenting chest discomfort and general weakness. He had come to the hospital with the same symptoms 3 months ago and 12 years prior. His laboratory test showed hypokalemia, hypomagnesemia and hypocalciuria. The arterial blood gas analysis showed hypochloremic metabolic alkalosis. He had an ultrasonography guided renal biopsy, the result was normal at light microscopy and immunofluorescence microscopy. However, a special stain for Na-Cl cotransporter was weakly expressed compared with the control. The patient and his family underwent genetic sequencing about the SLC12A3 gene. He had a homozygous mutation in the 179th nucleotide of Exon 1 on the SLC12A3 gene (p.Thr60Met) and his parents and sisters were diagnosed as carrier state of Gitelman’s syndrome (GS). GS is an inherited tubular disorder which presents mild hypokalemia, hypomagnesemia and hypocalciuria. Since the symptoms and laboratory results are not severe, it can go unnoticed by physicians. Herein we present a family with GS, diagnosed by genetic sequencing.

Relapsing lupus enteritis in systemic lupus erythematosus

( Yaerim Kim ),( Seungyeup Han ) 대한신장학회 2016 Kidney Research and Clinical Practice Vol.35 No.2

Recent updates in therapeutic approach using tolvaptan for autosomal dominant polycystic kidney disease

Yaerim Kim,한승엽 대한내과학회 2023 The Korean Journal of Internal Medicine Vol.38 No.3

As a genetic disease, there has been a long-standing effort to identify therapeutic options for autosomal dominant polycystic kidney disease (ADPKD). Following the development of tolvaptan, a vasopressin 2 receptor antagonist, the treatment strategy for ADPKD patients with rapid disease progression has been changed with a disease-targeted approach. Tolvaptan showed significant efficacy in preserving kidney function and reducing the total kidney volume (TKV) growth rate. These effects were especially pronounced in patients with more severe clinical phenotypes, such as higher TKV and rapidly declining kidney function. Despite the therapeutic effects of tolvaptan, aquaretic symptoms are unavoidable side effects related to the mechanism of the drug and are also directly related to the quality of life. A shared decision-making process could be a valuable strategy for reducing the incidence of side effects and improving medication adherence. Herein, we aimed to review overall clinical trials for applying tolvaptan and suggest important factors during the shared decision-making process.

Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management of autosomal domInAnt poLycystic kidney disease (ESSENTIAL): short-term outcomes during the titration period

( Hyuk Huh ),( Yong Soo Kim ),( Wookyung Chung ),( Yong Lim Kim ),( Yaerim Kim ),( Seungyeup Han ),( Yeonsoon Jung ),( Ki Young Na ),( Kyu Beck Lee ),( Yun Kyu Oh ),( Hyeong Cheon Park ),( Seung Hyeok 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.2

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 ㎡ 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 ㎡ 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.

Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea

( Sehyun Jung ),( Soojin Lee ),( Yaerim Kim ),( Semin Cho ),( Hyuk Huh ),( Yong Chul Kim ),( Seung Seok Han ),( Hajeong Lee ),( Jung Pyo Lee ),( Kwon Wook Joo ),( Chun Soo Lim ),( Yon Su Kim ),( Dong 대한신장학회 2024 Kidney Research and Clinical Practice Vol.43 No.2

Background: Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. Methods: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. Results: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m² and in the eGFR ≥120 mL/min/1.73 m² groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90-120 mL/min/1.73 m²). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. Conclusion: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.

Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study

( Sehoon Park ),( Seong Geun Kim ),( Soojin Lee ),( Yaerim Kim ),( Semin Cho ),( Kwangsoo Kim ),( Yong Chul Kim ),( Seung Seok Han ),( Hajeong Lee ),( Jung Pyo Lee ),( Kwon Wook Joo ),( Chun Soo Lim ) 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.4

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.

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study

( Sehoon Park ),( Soojin Lee ),( Yaerim Kim ),( Yeonhee Lee ),( Min Woo Kang ),( Kwangsoo Kim ),( Yong Chul Kim ),( Seung Seok Han ),( Hajeong Lee ),( Jung Pyo Lee ),( Kwon Wook Joo ),( Chun Soo Lim ) 대한신장학회 2021 Kidney Research and Clinical Practice Vol.40 No.2

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.

Reduced risk for chronic kidney disease after recovery from metabolic syndrome: A nationwide populationbased study

( Sehoon Park ),( Soojin Lee ),( Yaerim Kim ),( Yeonhee Lee ),( Min Woo Kang ),( Kyungdo Han ),( Hajeong Lee ),( Jung Pyo Lee ),( Kwon Wook Joo ),( Chun Soo Lim ),( Yon Su Kim ),( Dong Ki Kim ) 대한신장학회 2020 Kidney Research and Clinical Practice Vol.39 No.2

Background: Metabolic syndrome (MetS) is linked to various chronic comorbidities, including chronic kidney disease (CKD). However, few large studies have addressed whether recovery from MetS is associated with reduction in the risks of such comorbidities. Methods: This nationwide population-based study in Korea screened 10,664,268 people who received national health screening ≥ 3 times between 2012 and 2016. Those with a history of major cardiovascular events or preexisting CKD were excluded. We classified study groups into four, according to the course of MetS state, as defined by the harmonizing criteria. The main study outcome was incidental CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m² which was persistent until the last health exams). The study outcomes were investigated using multivariable logistic regression analysis, which was adjusted for clinical variables and the previous severity of MetS. Results: Four study groups included 6,315,301 subjects: 4,537,869 people without MetS, 1,034,605 with chronic MetS, 438,287 who developed MetS, and 304,540 who recovered from preexisting MetS. Those who developed MetS demonstrated higher risk of CKD (adjusted odds ratio [OR], 1.26 [1.23-1.29]) than did those who did not develop MetS. In contrast, MetSrecovery was associated with decreased risk of CKD (adjusted OR, 0.84 [0.82-0.86]) than that in people with chronic MetS. Among the MetS components, change in hypertension was associated with the largest difference in CKD risk. Conclusion: Reducing or preventing MetS may reduce the burden of CKD on a population-scale. Clinicians should consider the clinical importance of altering MetS status for risk of CKD.