1.Genetic variants of interferon lambda-related genes and chronic kidney disease susceptibility in the Korean population
Jin Ho KWAK ; Jin Hyuk PAEK ; Gyeong Im YU ; Seungyeup HAN ; Woo Yeong PARK ; Yaerim KIM ; Dong Hoon SHIN ; Kyubok JIN
Kidney Research and Clinical Practice 2022;41(4):442-451
Chronic kidney disease (CKD) is a common condition leading to renal dysfunction and is closely related to increased cardiovascular and mortality risk. CKD is an important public health issue, and recent genetic studies have verified common CKD susceptibility variants. This research examines the interrelationship between candidate genes polymorphisms of interferon lambda (IFNL) induction, its signaling pathway, and CKD. Methods: Seventy-five patients with advanced CKD and 312 healthy subjects (as controls) participated in this research. A replication set composed of 172 patients with advanced CKD and 365 controls was used for additional analysis. The genotype of single nucleotide polymorphisms (SNPs) was determined by the Axiom Genome-Wide Human Assay and SNaPshot assay. Results: The SNP of IFNL3 was significantly associated with CKD in the codominant (p = 0.02) and dominant models (p = 0.02). In addition, the SNPs of IFNL2 were significantly associated with CKD in the dominant model (p = 0.03), and the SNP of interferon alpha receptor 2 (IFNAR2) was significantly associated with CKD in the log-additive model (p = 0.03). Concerning rs148543092, in the IFNL3 gene, a significant association was observed after pooling the original and replication sets. Conclusion: These results indicate that SNPs in the IFNL induction and signal pathway may be associated with CKD risk in the Korean population. Finally, our results also show that the IFNL3 gene variant may be associated with CKD risk.
2.Clinical significance of serum galactose-deficient immunoglobulin A1 for detection of recurrent immunoglobulin A nephropathy in kidney transplant recipients
Woo Yeong PARK ; Yaerim KIM ; Jin Hyuk PAEK ; Kyubok JIN ; Seungyeup HAN
Kidney Research and Clinical Practice 2021;40(2):317-324
Background:
Recurrent glomerulonephritis (GN) is a common cause of allograft loss in kidney transplantation (KT), the most frequent of which is immunoglobulin A (IgA) nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) plays a major role in the pathophysiology of IgAN, but the association between Gd-IgA1 and recurrent IgAN in kidney transplant recipients (KTRs) is uncertain. We aimed to evaluate the efficacy of Gd-IgA1 for prediction of recurrent IgAN and graft and patient survival according to Gd-IgA1 level.
Methods:
We enrolled 27 KTRs who underwent allograft biopsy between 2009 and 2016 and measured the serum Gd-IgA1 level of each KTR. We divided the patients into two groups: nonrecurrent IgAN (patients with IgAN prior to KT who were not diagnosed with recurrent IgAN) and recurrent IgAN (patients with IgAN prior to KT who were diagnosed with recurrent IgAN).
Results:
The mean serum Gd-IgA1 level was significantly higher in the recurrent IgAN group than in the nonrecurrent IgAN group (6,419 ± 3,675 ng/mL vs. 3,381 ± 2,844 ng/mL, p = 0.02). The cutoff value of serum Gd-IgA1 in receiver operating characteristic curve analysis was 4,338 ng/mL (area under the curve, 0.76; 95% confidence interval [CI], 0.57–0.95, p = 0.02). Serum Gd-IgA1 level was an independent factor for recurrent IgAN (odds ratio, 17.60; 95% CI, 1.33–233.03, p = 0.03). There was no significant difference in graft or patient survival between the two groups.
Conclusion
Serum Gd-IgA1 can be used as a diagnostic biomarker for recurrent IgAN in KT.
3.Clinical Implication of Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease
Semin CHO ; Jin Hyuk PAEK ; Woo Yeong PARK ; Kyubok JIN ; Dong Ki KIM ; Seungyeup HAN ; Yaerim KIM
Keimyung Medical Journal 2022;41(1):24-31
Tolvaptan, a non-peptide arginine vasopressin V2 receptor antagonist, is a newly developed drug to reduce kidney volume and preserve kidney function in autosomal dominant polycystic kidney disease (ADPKD) patients. We aimed to evaluate the descriptive characteristics of patients according to the use of tolvaptan. Also, we tried to find the efficacy of tolvaptan on kidney volume and kidney function. We included patients with ADPKD who visited a tertiary hospital in South Korea during Sep. 2018 and Apr. 2022. The data was acquired from the Electric Medical Records system. A total of 64 patients were included in the study, and there were 33 (51.6%) patients taking tolvaptan during follow-up periods. During 17.8 ± 13.1 months of follow-up periods, estimated glomerular filtration rate (eGFR) changes were 89.4% compared to the baseline eGFR. Although the latest eGFR was lower in patients with tolvaptan (55.9 ± 24.7 mL/min/1.73 m2) than without tolvaptan (68.4 ± 35.1 mL/min/1.73 m2), there was no statistical significance (p = 0.108). We found that the mean change of height-adjusted total kidney volume (HtTKV) was -2.7% based on the baseline HtTKV in patients taking tolvaptan for more than 1-year. Although there was no statistical significance, the mean change of HtTKV was the highest in patients with 1E of Mayo classification (-4.3%). To anticipate the solid data on the efficacy of tolvaptan in the Asian population, more aggressive efforts are needed to search for suitable patients accompanied by appropriate monitoring over a more extended period.
4.Clinical significance of serum galactose-deficient immunoglobulin A1 for detection of recurrent immunoglobulin A nephropathy in kidney transplant recipients
Woo Yeong PARK ; Yaerim KIM ; Jin Hyuk PAEK ; Kyubok JIN ; Seungyeup HAN
Kidney Research and Clinical Practice 2021;40(2):317-324
Background:
Recurrent glomerulonephritis (GN) is a common cause of allograft loss in kidney transplantation (KT), the most frequent of which is immunoglobulin A (IgA) nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) plays a major role in the pathophysiology of IgAN, but the association between Gd-IgA1 and recurrent IgAN in kidney transplant recipients (KTRs) is uncertain. We aimed to evaluate the efficacy of Gd-IgA1 for prediction of recurrent IgAN and graft and patient survival according to Gd-IgA1 level.
Methods:
We enrolled 27 KTRs who underwent allograft biopsy between 2009 and 2016 and measured the serum Gd-IgA1 level of each KTR. We divided the patients into two groups: nonrecurrent IgAN (patients with IgAN prior to KT who were not diagnosed with recurrent IgAN) and recurrent IgAN (patients with IgAN prior to KT who were diagnosed with recurrent IgAN).
Results:
The mean serum Gd-IgA1 level was significantly higher in the recurrent IgAN group than in the nonrecurrent IgAN group (6,419 ± 3,675 ng/mL vs. 3,381 ± 2,844 ng/mL, p = 0.02). The cutoff value of serum Gd-IgA1 in receiver operating characteristic curve analysis was 4,338 ng/mL (area under the curve, 0.76; 95% confidence interval [CI], 0.57–0.95, p = 0.02). Serum Gd-IgA1 level was an independent factor for recurrent IgAN (odds ratio, 17.60; 95% CI, 1.33–233.03, p = 0.03). There was no significant difference in graft or patient survival between the two groups.
Conclusion
Serum Gd-IgA1 can be used as a diagnostic biomarker for recurrent IgAN in KT.
5.A Case of Complete Recovery from Late Insidious Type of Acute Phosphate Nephropathy.
Choong Hwan KWAK ; Ha Yeon PARK ; Yae Rim KIM ; Jin Hyuk PAEK ; Eun Ah HWANG ; Sung Bae PARK ; Seungyeup HAN
Korean Journal of Medicine 2014;86(4):505-509
The widespread use of colonoscopy for early detection of colorectal pathology has increased the use of osmotic laxatives for colonic cleansing. Among these, oral sodium phosphate preparations can cause renal insufficiency through the development of acute phosphate nephropathy. Acute phosphate nephropathy can be distinguished as early symptomatic and late insidious patterns. Patients whose presentation is insidious are easily overlooked and can progress to chronic kidney disease. We report a case of complete recovery from the late insidious type of acute phosphate nephropathy.
Colon
;
Colonoscopy
;
Humans
;
Laxatives
;
Pathology
;
Renal Insufficiency
;
Renal Insufficiency, Chronic
;
Sodium
6.Impact of calcineurin inhibitors on rat glioma cells viability
Jeong Hun SEONG ; Woo Yeong PARK ; Jin Hyuk PAEK ; Sung Bae PARK ; Seungyeup HAN ; Kyo Cheol MUN ; Kyubok JIN
Yeungnam University Journal of Medicine 2019;36(2):105-108
BACKGROUND:
Although kidney transplantation outcomes have improved dramatically after using calcineurin inhibitors (CNIs), CNI toxicity continues to be reported and the mechanism remains uncertain. Here, we investigated the neurotoxicity of CNIs by focusing on the viability of glioma cells.
METHODS:
Glioma cells were treated with several concentrations of CNIs for 24 hours at 37℃ and their cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
RESULTS:
Exposure to 0, 0.25, 0.5, 2.5, 5.0, and 10.0 mM concentrations respectively showed 100%, 64.3%, 61.3%, 68.1%, 62.4%, and 68.6% cell viability for cyclosporine and 100%, 38.6%, 40.8%, 43.7%, 37.8%, and 43.0% for tacrolimus. The direct toxic effect of tacrolimus on glioma cell viability was stronger than that of cyclosporine at the same concentration.
CONCLUSION
CNIs can cause neurological side effects by directly exerting cytotoxic effects on brain cells. Therefore, we should carefully monitor the neurologic symptoms and level of CNIs in kidney transplant patients.
7.Impact of calcineurin inhibitors on rat glioma cells viability
Jeong Hun SEONG ; Woo Yeong PARK ; Jin Hyuk PAEK ; Sung Bae PARK ; Seungyeup HAN ; Kyo Cheol MUN ; Kyubok JIN
Yeungnam University Journal of Medicine 2019;36(2):105-108
BACKGROUND: Although kidney transplantation outcomes have improved dramatically after using calcineurin inhibitors (CNIs), CNI toxicity continues to be reported and the mechanism remains uncertain. Here, we investigated the neurotoxicity of CNIs by focusing on the viability of glioma cells.METHODS: Glioma cells were treated with several concentrations of CNIs for 24 hours at 37℃ and their cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.RESULTS: Exposure to 0, 0.25, 0.5, 2.5, 5.0, and 10.0 mM concentrations respectively showed 100%, 64.3%, 61.3%, 68.1%, 62.4%, and 68.6% cell viability for cyclosporine and 100%, 38.6%, 40.8%, 43.7%, 37.8%, and 43.0% for tacrolimus. The direct toxic effect of tacrolimus on glioma cell viability was stronger than that of cyclosporine at the same concentration.CONCLUSION: CNIs can cause neurological side effects by directly exerting cytotoxic effects on brain cells. Therefore, we should carefully monitor the neurologic symptoms and level of CNIs in kidney transplant patients.
Animals
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Brain
;
Calcineurin Inhibitors
;
Calcineurin
;
Cell Survival
;
Cyclosporine
;
Glioma
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Humans
;
Kidney
;
Kidney Transplantation
;
Neurologic Manifestations
;
Rats
;
Tacrolimus
8.Clinical Manifestations and Prognostic Factors of IgA Nephropathy with Long-Term Follow-Up.
Jin Hyuk PAEK ; Yae Rim KIM ; Ha Yeon PARK ; Eun Ah HWANG ; Seung Yeup HAN ; Sung Bae PARK
Korean Journal of Medicine 2015;88(1):46-53
BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide. Although several studies have identified IgAN prognostic factors in Korea, the follow-up period was insufficient to evaluate the natural history of IgAN. METHODS: A total of 471 patients were diagnosed with IgAN after percutaneous renal biopsy between April 1985 and March 2003. Patients with secondary IgAN and patients with a follow-up < 10 years since their diagnosis were excluded. Thus, 184 patients were enrolled. RESULTS: Among the 184 patients, 97 were males (52.7%) and 87 were females (47.3%). The mean age was 33.7 +/- 11.5 years, and the mean follow-up period was 181.3 +/- 46.3 months. During the follow up, 73 patients (36.9%) had progressed to end-stage renal disease (ESRD). The mean duration to ESRD was 98.1 +/- 55.9 months. The overall renal survival rate was 60.3%, the 10-years renal survival rate was 74.3%, and the 20-years renal survival rate was 49.3%. Univariate analyses indicated that hypertension, serum creatinine > 1.3 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, serum albumin < 3.5 g/dL, proteinuria > or = 1 g/day, and severe renal pathology by the Haas sub-classification were significantly associated with ESRD. When these factors were included in multivariate Cox regression analyses, only severe renal pathology by the Haas sub-classification was an independent prognostic factor for IgAN. CONCLUSIONS: Careful follow-up and treatment is recommended, particularly in patients with IgAN and severe renal pathology by the Haas sub-classification.
Biopsy
;
Creatinine
;
Diagnosis
;
Female
;
Follow-Up Studies*
;
Glomerular Filtration Rate
;
Glomerulonephritis
;
Glomerulonephritis, IGA*
;
Humans
;
Hypertension
;
Kidney Failure, Chronic
;
Korea
;
Male
;
Natural History
;
Pathology
;
Prognosis
;
Proteinuria
;
Serum Albumin
;
Survival Rate
9.A Brain Tumor from a Posttransplant Lymphoproliferative Disorder in a Kidney Transplant Recipient.
Jin Hyuk PAEK ; Yae Rim KIM ; Mi Hyun JANG ; Eun Ah HWANG ; Seung Yeup HAN ; Sung Bae PARK
The Journal of the Korean Society for Transplantation 2013;27(2):67-71
Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication from organ transplantation. PTLD usually manifests as a mass in the lymph node or an extranodal mass in solid organs, such as the liver, transplanted kidney, tonsil, bone marrow, or spleen. PTLD rarely involves the central nervous system (CNS); however, here we report a case of PTLD that manifested as a brain tumor after kidney transplantation. A 52-year-old man who started peritoneal dialysis due to autosomal dominant polycystic kidney disease, underwent kidney transplantation 4 years ago. After kidney transplantation, he took tacrolimus, mycophenolate mofetil, and steroids. He was admitted to our hospital, complaining of a severe headache. Brain magnetic resonance imaging showed a multifocal, irregular, and round enhancing mass in the left basal ganglia. He underwent a needle biopsy for the enhancing mass and the pathological diagnosis was diffuse large B cell lymphoma. After this mass was confirmed as PTLD by histologic diagnosis, the patient had a reduction in his immunosuppression regimen (including a change from tacrolimus to sirolimus) and was treated with chemotherapy for PTLD. After 20 days, the patient expired from sepsis. PTLD involving the CNS is a rare and serious complication associated with solid organ transplantation. PTLD should be included in the differential diagnosis of brain tumors in recipients of solid organ transplants.
Basal Ganglia
;
Biopsy, Needle
;
Bone Marrow
;
Brain
;
Brain Neoplasms
;
Central Nervous System
;
Diagnosis, Differential
;
Headache
;
Humans
;
Immunosuppression
;
Kidney
;
Kidney Transplantation
;
Liver
;
Lymph Nodes
;
Lymphoma, B-Cell
;
Lymphoproliferative Disorders
;
Magnetic Resonance Imaging
;
Mycophenolic Acid
;
Organ Transplantation
;
Palatine Tonsil
;
Peritoneal Dialysis
;
Polycystic Kidney, Autosomal Dominant
;
Sepsis
;
Spleen
;
Steroids
;
Tacrolimus
;
Transplants
10.Timing for initiation of sequential continuous renal replacement therapy in patients on extracorporeal membrane oxygenation.
Jin Hyuk PAEK ; Seohyun PARK ; Anna LEE ; Seokwoo PARK ; Ho Jun CHIN ; Ki Young NA ; Hajeong LEE ; Jung Tak PARK ; Sejoong KIM
Kidney Research and Clinical Practice 2018;37(3):239-247
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy used in critically ill patients with severe cardiopulmonary dysfunction. Continuous renal replacement therapy (CRRT) is supplemented to treat fluid overload, acute kidney injury, and electrolyte disturbances during ECMO. However, the best time to initiate CRRT is not well-defined. We performed this study to identify the optimal timing of CRRT for ECMO. METHODS: We conducted a multicenter retrospective cohort study of 296 patients over 12 years. Patients received CRRT during ECMO at Seoul National University Hospital, Seoul National University Bundang Hospital, or Yonsei University Hospital. We assigned patients to an early or late CRRT group depending on the CRRT initiation time. We considered early CRRT to be CRRT instituted within 72 hours of ECMO initiation. RESULTS: Among 296 patients, 212 patients (71.6%) received early CRRT. After using a propensity score matching method, 47 patients were included in each group. The time from ECMO initiation to CRRT initiation was 1.1 ± 0.9 days in the early CRRT group and 14.6 ± 18.6 days in the late CRRT group. No difference in patients’ mortality (P = 0.834) or hospital stay (P = 0.627) between the early and late CRRT groups was found. After adjusting all covariables, there was no significant difference in mortality between the early and late CRRT groups (hazard ratio, 0.697; 95% confidence interval, 0.410–1.184; P = 0.182). CONCLUSION: This study showed that early CRRT may not be superior to late CRRT in ECMO patients. Further clinical trials are warranted.
Acute Kidney Injury
;
Cohort Studies
;
Critical Illness
;
Extracorporeal Membrane Oxygenation*
;
Humans
;
Length of Stay
;
Methods
;
Mortality
;
Propensity Score
;
Renal Replacement Therapy*
;
Retrospective Studies
;
Seoul
;
Time-to-Treatment