Sex disparity in dialysis and kidney transplantation over 20 years in Korea

( Miyeun Han ),( Jong Cheol Jeong ),( Yun Yung Cho ),( Curie Ahn ),( Yeong Hoon Kim ) 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.4

Background: Sex disparity is prevalent in organ transplantations worldwide. This study aimed to understand sex disparities in dialysis and kidney transplantation in Korea over the last 20 years. Methods: Data for incident dialysis, waiting list registration, and donors and recipients were retrospectively collected between January 2000 and December 2020 from the Korean Society of Nephrology end-stage renal disease registry and the database of the Korean Network for Organ Sharing. Data regarding the proportion of females for dialysis, waiting list, and kidney transplantation donors or recipients were analyzed using linear regression analysis. Results: The average proportion of females on dialysis over the past 20 years was 40.5%. The proportion of females on dialysis was 42.8% in 2000, and decreased to 38.2% in 2020, showing a decreasing trend. The average proportion of women on the waiting list was 38.4%, which was lower than that for dialysis. The average proportion of female recipients in living donor kidney transplantation and female living donors were 40.1% and 53.2%, respectively. The overall proportion of female donors in living donor kidney transplantation showed an increasing trend. However, there was no change in the proportion of female recipients in living donor kidney transplantation. Conclusion: Sex disparities in organ transplantation exist, including an increasing trend of female donors in living donor kidney transplantation. Further studies are needed to identify the biological and socioeconomic factors involved to resolve these disparities.

The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease

( Harin Rhee ),( Miyeun Han ),( Sang Soo Kim ),( Il Young Kim ),( Hye Won Lee ),( Sun Sik Bae ),( Hong Koo Ha ),( Eun Soon Jung ),( Min Young Lee ),( Eun Young Seong ),( Dong Won Lee ),( Soo Bong Lee 대한신장학회 2018 Kidney Research and Clinical Practice Vol.37 No.3

Background: This study was undertaken to explore the effects of aging on the kidneys in mouse models of diabetes and chronic kidney disease (CKD), and to compare the expression of two isoforms of matrix metalloproteinase-2 (MMP-2)-secretory full-length MMP-2 and intracellular N-terminal truncated MMP-2 (NTT-MMP-2)-in these models. Methods: Two experimental ICR mouse models were used: a streptozotocin (STZ)-induced type 1 diabetes mellitus model and a 5/6 nephrectomized (5/6Nx) CKD model. The abundance of each isoform of MMP-2 was determined by quantitative polymerase chain reaction (qPCR), and functional analyses were conducted. Moreover, the protein levels of the two MMP-2 isoforms were determined semi-quantitatively by immunohistochemical staining, and their association with tissue damage was assessed. Results: Both isoforms of MMP-2 were upregulated in the kidney tissues of STZ-induced diabetic mice and 5/6Nx mice, irrespective of age. Characteristically, NTT-MMP-2 protein expression was elevated in old control mice, in line with the qPCR results. NTT-MMP-2 expression was limited to the renal cortex, and to the tubulointerstitial area rather than the glomerular area. In terms of tissue damage, tubulointerstitial fibrosis was more severe in old 5/6Nx mice than in their young counterparts, whereas glomerulosclerosis was comparable in old and young 5/6Nx mice. Conclusion: The intracellular isoform of MMP-2 was induced by ageing, irrespective of the presence of diabetes or CKD, and its induction may be related to tubulointerstitial fibrosis in chronic kidney disease.

Baseline General Characteristics of the Korean Chronic Kidney Disease: Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Kang, Eunjeong,Han, Miyeun,Kim, Hyunsuk,Park, Sue Kyung,Lee, Joongyub,Hyun, Young Youl,Kim, Yong-Soo,Chung, Wookyung,Kim, Hyo Jin,Oh, Yun Kyu,Ahn, Curie,Oh, Kook-Hwan The Korean Academy of Medical Sciences 2017 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.32 No.2

<P>The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory.</P><P>As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m<SUP>2</SUP>. The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients.</P>

ST분절 비상승 심근경색증으로 오인된 호산구육아종성다발혈관염

오예슬 ( Yeseul Oh ),한미연 ( Miyeun Han ),박혜경 ( Hye-kyung Park ),조은정 ( Eun-jung Jo ) 대한천식알레르기학회(구 대한알레르기학회) 2021 Allergy Asthma & Respiratory Disease Vol.9 No.1

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic disease and a potentially life-threatening systemic necrotizing vasculitis predominantly affecting small vessels. Herein, we describe a 47-year-old man with EGPA misdiagnosed as non-ST-segment elevation myocardial infarction. He presented to the Emergency Department with indigestion and diarrhea. He had been diagnosed with asthma and chronic rhinosinusitis 3 years earlier and was taking antibiotics due to worsening sinusitis. In laboratory tests, peripheral blood eosinophils, serum creatinine, and serum troponin were elevated to 4,641 cells/μL, 13.40 ng/mL, and 1.26 ng/mL, respectively. Electrocardiography showed ST-segment depression on the inferior wall, and echocardiography indicated an ischemic insult in the right coronary artery territory. A non-ST-segment elevation myocardial infarction as well as antibiotic-associated diarrhea, eosinophilia and acute kidney injury was initially suspected. However, fever persisted and eosinophilia worsened despite cessation of antibiotics after admission. There was no significant stenosis of the coronary arteries on coronary angiography. Meanwhile, abdominal computed tomography suggested medical renal disease, and magnetic resonance imaging showed late gadolinium enhancement at the mid wall and the subepicardial area in the left ventricle of the heart. As a workup for eosinophilia, serum anti-MPO was measured and turned out to be positive. A kidney biopsy was performed, which yielded membranous nephropathy superimposed on antineutrophil cytoplasmic antibodies-mediated crescent formation. He was diagnosed as EGPA with cardiac and renal involvement, and received systemic steroid, cyclophosphamide, and plasmapheresis. Then, peripheral eosinophil counts and renal function were normalized. He is now in clinical remission even after stopping the use of steroids and immunosuppressive agents. (Allergy Asthma Respir Dis 2021;9:50-55)

Effect of Phoxilium on prognostic predictors in patients undergoing continuous venovenous hemodiafiltration

( Da Woon Kim ),( Hyo Jin Kim ),( Jin Mi Kim ),( You Hyun Jeon ),( Miyeun Han ),( Eun Young Seong ),( Sang Heon Song ) 대한신장학회 2021 Kidney Research and Clinical Practice Vol.40 No.3

Background: Phosphorus-containing dialysis solution is used to prevent hypophosphatemia in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). This study evaluated the effect of phosphorus-containing dialysis solution on mortality in pa-tients undergoing CVVHDF based on changes in phosphorus and red cell distribution width-coefficient of variation (RDW-CV) levels. Methods: We included 272 patients with acute kidney injury (AKI) who underwent CVVHDF at the medical intensive care unit from 2017 to 2019 and classified them according to Phoxilium (Baxter Healthcare Ltd.), as a phosphorus-containing dialysis solution, use within 48 hours after CVVHDF initiation. Clinical data were collected at baseline and 48 hours after CVVHDF initiation. The primary outcome was all-cause mortality during the follow-up period. Results: The non-Phoxilium (NP) group had higher phosphorus and lower RDW-CV levels than the Phoxilium (P) group (phosphorus, 7.3 ± 4.3 vs. 5.0 ± 2.8 mg/dL; RDW-CV, 14.6 ± 1.9 vs. 15.7 ± 2.6%; all p < 0.001). In the multivariable Cox proportional hazard re-gression of the NP group, an increase in phosphorus and RDW-CV at 48 hours of CVVHDF was associated with mortality (delta phos-phorus: median, >0 mg/dL vs. < -2.0 mg/dL; hazard ratio [HR], 8.62; 95% confidence interval [CI], 2.10-35.32; p = 0.003/delta RDW-CV: median, >0% vs. < -0.2%; HR, 4.34; 95% CI, 1.49-13.18; p = 0.008). Meanwhile, in the P group, an increase in delta RDW- CV was associated with mortality (delta RDW-CV: >0% vs. >-0.2% and <0%; HR, 2.65; 95% CI, 1.12-6.24; p = 0.03), while an in-crease in delta phosphorus was not. Conclusion: In patients with AKI undergoing CVVHDF, the risk factors for all-cause mortality differed according to the initial phospho-rus levels and use of Phoxilium.

Metformin treatment for patients with diabetes and chronic kidney disease: A Korean Diabetes Association and Korean Society of Nephrology consensus statement

( Kyu Yeon Hur ),( Mee Kyoung Kim ),( Seung Hyun Ko ),( Miyeun Han ),( Dong Won Lee ),( Hyuk-sang Kwon ) 대한신장학회 2020 Kidney Research and Clinical Practice Vol.39 No.1

The safety of metformin use for patients with type 2 diabetes mellitus (T2DM) and advanced kidney disease is controversial, and more recent guidelines have suggested that metformin be used cautiously in this group until more definitive evidence concerning its safety is available. The Korean Diabetes Association and the Korean Society of Nephrology have agreed on consensus statements concerning metformin use for patients with T2DM and renal dysfunction, particularly when these patients undergo imaging studies using iodinated contrast media (ICM). Metformin can be used safely when the estimated glomerular filtration rate (eGFR) is ≥ 45 mL/min/1.73 ㎡. If the eGFR is between 30 and 44 mL/min/1.73 ㎡, metformin treatment should not be started. If metformin is already in use, a daily dose of ≤ 1,000 mg is recommended. Metformin is contraindicated when the eGFR is < 30 mL/min/1.73 ㎡. Renal function should be evaluated prior to any ICM-related procedures. During procedures involving intravenous administration of ICM, metformin should be discontinued starting the day of the procedures and up to 48 hours post-procedures if the eGFR is < 60 mL/min/1.73 ㎡.

뇌동맥류 결찰술 직후 발생한 중추성 요붕증과 동반된 SIADH 1 예

고성준 ( Sung Jun Ko ),김현숙 ( Hyunsuk Kim ),신나라 ( Nara Shin ),한미연 ( Miyeun Han ),김효진 ( Hyo Jin Kim ),최홍미 ( Hong Mi Choi ),허혁 ( Hyeok Heo ),황기환 ( Kihwan Hwang ),방재승 ( Jae Seung Bang ),김세중 ( Sejoong Kim ) 전북대학교 의과학연구소 2013 全北醫大論文集 Vol.37 No.2

이상나트륨혈증은 뇌동맥류로 인한 지주막하출혈의 수술적 치료 후 나타나는 흔한 합병증 중 하나이다. 저자들은 뇌동맥류의 직접 결찰술 후 발생한 일시적인 중추성 요붕증 및 동반된 항이뇨호르몬 부적절분비증후군(SIADH)을 성공적으로 치료하였기에 보고하는 바이다. 60세 여자 환자가 오른쪽 이측의 시야 결손을 주소로 내원하였고 검사에서 발견된 상상돌기주변동맥류로 인한 것으로 생각되었다. 수술 중 동맥류의 목 부위가 파열되었으나 성공적으로 결찰되었다. 수술 직후 환자는 다뇨와 함께 고나트륨혈증이 발생하였으며 함께 시행된 검사 결과 중추성 요붕증이 의심되었다. 고나트륨혈증의 치료 후 저나트륨혈증이 발생하였고 검사 결과 SIADH가 의심되었으며 수분 제한 후 호전되었다. 이는 뇌동맥류 수술 후에 급격한 고나트륨혈증의 발생을 주의 깊게 관찰해야 하며, 회복 후에 나타날 수 있는 저나트륨혈증을 고려해야 함을 시사한다. Dysnatremia is one of common medical complications after surgical treatment of subarachnoid hemorrhage (SAH) due to cerebral aneurysm. We report a case of transient central diabetes insipidus (DI) followed by syndrome of inappropriate antidiuretic hormone secretion (SIADH), after direct clipping of ruptured cerebral aneurysm. A 60-year-old woman presented visual defect of right temporal area due to large paraclinoid aneurysm. During operation, the neck of aneurysm was ruptured, but successfully clipped. Just after the operation polyuria and hypernatremia developed and biochemical findings revealed that the patient presented central DI. A few days after recovery from hypernatremia, hyponatremia occurred and laboratory work revealed SIADH, and after free water restriction the patient was recovered from hyponatremia. Therefore, we suggest to monitor abrupt hypernatremia after operation and to implement rigorous fluid therapy, considering hyponatremia after recovery.

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.

The P2X7 receptor antagonist, oxidized adenosine triphosphate, ameliorates renal ischemia-reperfusion injury by expansion of regulatory T cells

Koo, Tai Yeon,Lee, Jae-Ghi,Yan, Ji-Jing,Jang, Joon Young,Ju, Kyung Don,Han, Miyeun,Oh, Kook-Hwan,Ahn, Curie,Yang, Jaeseok Springer-Verlag 2017 Kidney international Vol.92 No.2

<P>Extracellular adenosine triphosphate (ATP) binds to purinergic receptors and, as a danger molecule, promotes inflammatory responses. Here we tested whether periodate-oxidized ATP (oATP), a P2X7 receptor (P2X7R) antagonist can attenuate renal ischemia-reperfusion injury and clarify the related cellular mechanisms. Treatment with oATP prior to ischemia-reperfusion injury decreased blood urea nitrogen, serum creatinine, the tubular injury score, and tubular epithelial cell apoptosis after injury. The infiltration of dendritic cells, neutrophils, macrophages, CD69(+) CD4(+), and CD44(+) CD4(+) T cells was attenuated, but renal Foxp3(+) CD4(+) Treg infiltration was increased by oATP. The levels of IL-6 and CCL2 were reduced in the oATP group. Additionally, oATP treatment following injury improved renal function, decreased the infiltration of innate and adaptive effector cells, and increased the renal infiltration of Foxp3(+) CD4(+) Tregs. Post-ischemiareperfusion injury oATP treatment increased tubular cell proliferation and reduced renal fibrosis. oATP treatment attenuated renal functional deterioration after ischemiareperfusion injury in RAG-1 knockout mice; however, Treg depletion using PC61 abrogated the beneficial effects of oATP in wild-type mice. Furthermore, oATP treatment after transfer of Tregs from wild-type mice improved the beneficial effects of Tregs on ischemia-reperfusion injury, but treatment after transfer of Tregs from P2X7R knockout mice did not. Renal ischemia-reperfusion injury was also attenuated in P2X7R knockout mice. Experiments using bone marrow chimeras established that P2X7R expression on hematopoietic cells rather than nonhematopoietic cells, such as tubular epithelial cells, plays a major role in ischemia-reperfusion injury. Thus, oATP attenuated acute renal damage and facilitated renal recovery in ischemia-reperfusion injury by expansion of Tregs.</P>

High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial

Park, Jung Tak,Lee, Hajeong,Kee, Youn Kyung,Park, Seokwoo,Oh, Hyung Jung,Han, Seung Hyeok,Joo, Kwon Wook,Lim, Chun-Soo,Kim, Yon Su,Kang, Shin-Wook,Yoo, Tae-Hyun,Kim, Dong Ki,Jo, Hyung Ah,Han, Miyeun,L Elsevier 2016 American Journal of Kidney Diseases Vol.68 No.4

<P><B>Background</B></P> <P>Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear.</P> <P><B>Study Design</B></P> <P>Prospective, randomized, controlled, open-label trial.</P> <P><B>Setting & Participants</B></P> <P>Septic patients with AKI receiving CVVHDF for AKI.</P> <P><B>Intervention</B></P> <P>Conventional (40mL/kg/h) and high (80mL/kg/h) doses of CVVHDF for the duration of CRRT.</P> <P><B>Outcomes</B></P> <P>Patient and kidney survival at 28 and 90 days, circulating cytokine levels.</P> <P><B>Results</B></P> <P>212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; <I>P</I> =0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; <I>P</I> =0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups.</P> <P><B>Limitations</B></P> <P>Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled.</P> <P><B>Conclusions</B></P> <P>High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.</P>