Role of the CCL20/CCR6 axis in tubular epithelial cell injury: Kidney-specific translational insights from acute kidney injury to chronic kidney disease.

This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.

Effect of low sodium and high potassium diet on lowering blood pressure and cardiovascular events.

Incorporating aggressive lifestyle modifications along with antihypertensive medication therapy is a crucial treatment strategy to enhance the control rate of hypertension. Dietary modification is one of the important lifestyle interventions for hypertension, and it has been proven to have a clear effect. Among food ingredients, sodium and potassium have been found to have the strongest association with blood pressure. The blood pressure-lowering effect of a low sodium diet and a high potassium diet has been well established, especially in hypertensive population. A high intake of potassium, a key component of the Dietary Approaches to Stop Hypertension (DASH) diet, has also shown a favorable impact on the risk of cardiovascular events. Additionally, research conducted with robust measurement methods has shown cardiovascular benefits of low-sodium intake. In this review, we aim to discuss the evidence regarding the relationship between the low sodium and high potassium diet and blood pressure and cardiovascular events.

Incident dementia in kidney transplantation recipients: a matched comparative nationwide cohort study in South Korea.

BACKGROUND: 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.

Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor.

We aimed to determine the metabolomic profile of kidney cells under high glucose conditions and following sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Targeted metabolomics using the Absolute IDQ-p180 kit was applied to quantify metabolites in kidney cells stimulated with high glucose (25 and 50 mM) and treated with SGLT2 inhibitor, dapagliflozin (2 µM). Primary cultured human tubular epithelial cells and podocytes were used to identify the metabolomic profile in high glucose conditions following dapagliflozin treatment. The levels of asparagine, PC ae C34:1, and PC ae C36:2 were elevated in tubular epithelial cells stimulated with 50 mM glucose and were significantly decreased after 2 µM dapagliflozin treatment. The level of PC aa C32:0 was significantly decreased after 50 mM glucose treatment compared with the control, and its level was significantly increased after dapagliflozin treatment in podocytes. The metabolism of glutathione, asparagine and proline was significantly changed in tubular epithelial cells under high-glucose stimulation. And the pathway analysis showed that aminoacyl-tRNA biosynthesis, arginine and proline metabolism, glutathione metabolism, valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, beta-alanine metabolism, phenylalanine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism were altered in tubular epithelial cells after dapagliflozin treatment following 50 mM glucose compared to those treated with 50 mM glucose.

De novo major cardiovascular events in kidney transplant recipients: a comparative matched cohort study.

BACKGROUND: Although cardiovascular disease is known to be one of the leading causes of death after kidney transplantation (KT), evidence on the risk difference of de novo major adverse cardiovascular events (MACEs) in kidney transplant recipients (KTRs) compared with that in dialysis patients or the general population (GP) remains rare. METHODS: We identified KTRs using the nationwide health insurance database in South Korea and then 1:1 matched them with the dialysis and GP controls without a pre-existing MACE. The primary endpoint was defined as de novo MACEs consisting of myocardial infarction, coronary revascularization and ischemic stroke. The secondary endpoints were all-cause mortality and death-censored graft failure (DCGF) in KTRs. RESULTS: We included 4156 individuals in each of the three groups and followed them up for 4.7 years. De novo MACEs occurred in 3.7, 21.7 and 2.5 individuals per 1000 person-years in the KTRs, dialysis controls and GP controls, respectively. KTRs showed a lower MACE risk {adjusted hazard ratio (aHR) 0.16 [95% confidence interval (CI) 0.12-0.20], P < .001} than dialysis controls, whereas a similar MACE risk to GP controls [aHR 0.81 (95% CI 0.52-1.27), P = .365]. In addition, KTRs showed a similar MACE risk compared with the GP group, regardless of age, sex and the presence of comorbidities, including hypertension, diabetes and dyslipidemia. Among KTRs, de novo MACEs were associated with an increased risk of all-cause mortality, but not with DCGF. CONCLUSIONS: De novo MACEs in KTRs were much lower than that in dialysis patients and had a similar risk to the GP, but once it occurred it caused elevated mortality risk in KTRs.

Association of microscopic hematuria with long-term mortality in patients with hypertensive crisis.

BACKGROUND: Microscopic hematuria is associated with increased risk of developing chronic kidney function impairment and even death. However, data on the long-term mortality risk associated with microscopic hematuria among patients with hypertensive crisis are scarce. We hypothesized that microscopic hematuria at initial presentation in patients with hypertensive crisis would be associated with increased long-term mortality. METHODS: This retrospective study included patients admitted to the emergency department between 2016 and 2019 for hypertensive crisis (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg). Microscopic hematuria was defined as ≥ 3 red blood cells per high-power field on microscopic evaluation of urine. RESULTS: Among 3595 patients, 1359 (37.8%) had microscopic hematuria. The 3-year all-cause mortality in patients with and without microscopic hematuria was 25.5% and 16.3%, respectively. After adjusting for confounding variables, patients with microscopic hematuria (adjusted HR, 1.30; 95% CI 1.10-1.54) showed a significantly higher risk of 3-year all-cause mortality than patients without microscopic hematuria. In a subgroup analysis based on the presence of proteinuria, microscopic hematuria was a significant predictor of all-cause mortality in patients without proteinuria (adjusted HR, 1.61; 95% CI 1.28-2.03) but not in patients with proteinuria. CONCLUSION: Microscopic hematuria was a significant predictor of all-cause mortality in patients with hypertensive crisis. Our study suggests that microscopic hematuria can be a useful prognostic marker and may permit early detection of patients with an increased risk of death. Clinicians in the emergency department should consider screening for kidney function using urine analysis during the initial assessment of patients with hypertensive crisis.

Incidence of depression in kidney transplant recipients in South Korea: a long-term population-based study.

Depression is associated with impaired quality of life and increased morbidity and mortality in end-stage kidney disease (ESKD) patients and kidney transplantation (KT) recipients. Depression incidence after KT is unclear. We compared depression incidence among KT recipients, ESKD patients, and healthy controls (HCs). We analyzed a nationwide health insurance database in South Korea and identified patients who underwent KT during 2007-2015. Participants were matched for age, sex, and inclusion year. KT and ESKD patients were further matched for hypertension and diabetes mellitus history. The incidence rate (IR, per 1000 patients-years) of depression was compared among KT, ESKD, and HC groups. We analyzed 5,234 patients per group. Depression incidence was markedly lower in KT than ESKD patients (IR, 18.87 vs. 58.03; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.30‒0.36), but only slightly higher in KT recipients than in HCs (IR, 18.87 vs. 17.49; HR, 1.08; 95% CI, 0.96‒1.22). After adjusting for comorbidities, the depression risk was lower in KT recipients than in HCs (adjusted HR, 0.52; 95% CI, 0.44‒0.62; p < 0.001), whereas it remained higher in ESKD patients than in HCs (adjusted HR, 1.60; 95% CI, 1.36‒1.87; p < 0.001). Among KT recipients, older age, female sex, lower economic status, and more comorbidities were associated with increased depression risk. Incident depression after KT increased mortality, graft failure, and death-censored graft failure risks in KT recipients. Our data suggest a broader role of KT than previously appreciated in terms of improving quality of life by reducing depression risk.

Association of Dipstick Proteinuria with Long-Term Mortality among Patients with Hypertensive Crisis in the Emergency Department.

Proteinuria, frequently observed in hypertensive crisis, is a risk factor for cardiovascular and all-cause mortality in patients with hypertension. Here we investigated the association between proteinuria and all-cause mortality in patients with a hypertensive crisis in the emergency department (ED). This retrospective study included patients admitted to the ED of a tertiary referral center between 2016 and 2019 with hypertensive crisis (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg); 3599 patients with an assay for proteinuria were included in this study. Proteinuria was defined as a trace or more protein on a urine dipstick test. Proteinuria was present in 1964 (54.6%) of 3599 patients. At 3 years, crude all-cause mortality rates were 10.8% for patients with negative proteinuria, 21.7% for those with trace proteinuria, 29.0% for those with proteinuria (1+), 32.0% for those with proteinuria (2+), and 35.4% for those with proteinuria (≥3+). After adjusting for age, sex, blood pressure, and comorbid conditions, the hazard ratio (95% confidence interval) for dipstick proteinuria was 1.91 (1.53-2.37) for those with trace proteinuria, 2.32 (1.85-2.91) for those with proteinuria (1+), 2.40 (1.86-3.10) for those with proteinuria (2+), and 2.40 (1.78-3.24) for those with proteinuria (≥3+) compared to the reference of negative proteinuria. In patients with hypertensive crisis, dipstick proteinuria was a significant predictor of all-cause mortality, and the risk of all-cause mortality increased in a dose-dependent manner according to its degree. Moreover, even trace proteinuria was associated with an increased risk of mortality. The dipstick urine test could be used as a simple and useful method for risk assessment of all-cause mortality in patients with hypertensive crisis.

Microscopic Polyangiitis Following mRNA COVID-19 Vaccination: A Case Report.

Coronavirus disease 2019 (COVID-19) is one of the most widespread viral infections in human history. As a breakthrough against infection, vaccines have been developed to achieve herd immunity. Here, we report the first case of microscopic polyangiitis (MPA) following BNT162b2 vaccination in Korea. A 42-year-old man presented to the emergency room with general weakness, dyspnea, and edema after the second BNT162b2 vaccination. He had no medical history other than being treated for tuberculosis last year. Although his renal function was normal at last year, acute kidney injury was confirmed at the time of admission to the emergency room. His serum creatinine was 3.05 mg/dL. Routine urinalysis revealed proteinuria (3+) and hematuria. When additional tests were performed for suspected glomerulonephritis, the elevation of myeloperoxidase (MPO) antibody (38.6 IU/mL) was confirmed. Renal biopsy confirmed pauci-immune anti-neutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and MPA was diagnosed finally. As an induction therapy, a combination of glucocorticoid and rituximab was administered, and plasmapheresis was performed twice. He was discharged after the induction therapy and admitted to the outpatient clinic 34 days after induction therapy. During outpatient examination, his renal function had improved with serum creatinine 1.51 mg/dL. We suggest that MPA needs to be considered if patients have acute kidney injury, proteinuria, and hematuria after vaccination.

Impact of the estimated glomerular filtration rate on long-term mortality in patients with hypertensive crisis visiting the emergency department.

BACKGROUND: The association between renal function and all-cause mortality in patients with hypertensive crisis remains unclear. We aimed to identify the impact of estimated glomerular filtration rate (eGFR) on all-cause mortality in patients with hypertensive crisis visiting the emergency department (ED). METHODS: This retrospective study included patients aged ≥18 years admitted to the ED between 2016 and 2019 for hypertensive crisis (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg). They were classified into four groups according to the eGFR at admission to the ED: ≥90, 60-89, 30-59, and <30 mL/min/1.73 m2. RESULTS: Among the 4,821 patients, 46.7% and 5.8% had an eGFR of ≥90 and <30 mL/min/1.73 m2, respectively. Patients with lower eGFR were older and more likely to have comorbidities. The 3-year all-cause mortality rates were 7.7% and 41.9% in those with an eGFR ≥90 and <30 mL/min/1.73 m2, respectively. After adjusting for confounding variables, those with an eGFR of 30-59 (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.47-2.54) and <30 mL/min/1.73 m2 (HR, 2.35; 95% CI, 1.71-3.24) had significantly higher 3-year all-cause mortality risks than those with an eGFR of ≥90 mL/min/1.73 m2. Patients with an eGFR of 60-89 mL/min/1.73 m2 had a higher mortality (21.1%) than those with an eGFR of ≥90 mL/min/1.73 m2 (7.7%); however, the difference was not significant (HR, 1.21; 95% CI, 0.94-1.56). CONCLUSIONS: Renal impairment is common in patients with hypertensive crisis who visit the ED. A strong independent association was observed between decreased eGFR and all-cause mortality in these patients. eGFR provides useful prognostic information and permits the early identification of patients with hypertensive crisis with an increased mortality risk. Intensive treatment and follow-up strategies are needed for patients with a decreased eGFR who visit the ED.

Renoprotective Effect of KLF2 on Glomerular Endothelial Dysfunction in Hypertensive Nephropathy.

Kruppel-like factor 2 (KLF2) regulates endothelial cell metabolism; endothelial dysfunction is associated with hypertension and is a predictor of atherosclerosis development and cardiovascular events. Here, we investigated the role of KLF2 in hypertensive nephropathy by regulating KLF2 expression in human primary glomerular endothelial cells (hPGECs) and evaluating this expression in the kidney tissues of a 5/6 nephrectomy mouse model as well as patients with hypertension. Hypertension-mimicking devices and KLF2 siRNA were used to downregulate KLF2 expression, while the expression of KLF2 was upregulated by administering simvastatin. After 4 mmHg of pressure was applied on hPGECs for 48 h, KLF2 mRNA expression decreased, while alpha-smooth muscle actin (αSMA) mRNA expression increased. Apoptosis and fibrosis rates were increased under pressure, and these phenomena were aggravated following KLF2 knockdown, but were alleviated after simvastatin treatment; additionally, these changes were observed in angiotensin II, angiotensin type-1 receptor (AT1R) mRNA, and interleukin-18 (IL-18), but not in angiotensin type-2 receptor mRNA. Reduced expression of KLF2 in glomerular endothelial cells due to hypertension was found in both 5/6 nephrectomy mice and patients with hypertensive nephropathy. Thus, our study demonstrates that the pressure-induced apoptosis and fibrosis of glomerular endothelial cells result from angiotensin II, AT1R activation, and KLF2 inhibition, and are associated with IL-18.

Comparison of intradialytic neuromuscular electrical stimulation and oral nutritional supplements in hemodialysis patients: study protocol for a multicenter, parallel-group, randomized controlled trial in Korea.

BACKGROUND: The prevalence of sarcopenia increases as renal function decreases, and a considerable number of hemodialysis (HD) patients have sarcopenia. Exercise and nutritional support are established interventions to prevent and treat sarcopenia. Recently, many studies evaluating intradialytic neuromuscular electrical stimulation (NMES) showed improvement of muscular strength and mass, functional capacity, and quality of life (QOL). However, there has been no research about the effect of simultaneous nutritional support and NMES in HD patients. METHODS: This is a 12-week, randomized controlled, parallel-group, multicenter trial of intradialytic NMES and protein supplementation for HD patients. Seventy-two patients receiving HD will be randomly assigned in a 1:1:1:1 ratio to control, intradialytic NMES only, protein supplementation only, and intradialytic NMES combined with protein supplementation groups. NMES will be delivered to a total of four areas of the bilateral vastus medialis and vastus lateralis using a 4-channel NMES instrument. A total of 25 g of protein supplements will be provided at the beginning of every dialysis session or after the NMES. The primary endpoint is the difference of hand grip and leg muscle strength at 12 weeks among 4 treatment groups. Secondary endpoints include muscle mass, physical performances, and questionnaires about QOL and physical activity. DISCUSSION: In this study, we will evaluate the differential effectiveness of nutritional support and NMES during HD on muscle strength, muscle mass, physical function, and QOL. We expect that this study can provide guidelines for a new therapeutic option for HD patients who are unable or hesitant to exercise. Furthermore, this option can offer an opportunity to improve the physical function, QOL, and prognosis of HD patients. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Korea, KCT0005573 . Retrospectively registered on 03 November 2020.

Role of the IL-33/ST2 pathway in renal allograft rejection.

The interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) pathway modulates immune response and inflammation, associated with allograft dysfunction and rejection. We hypothesized that IL-33/ST2 is a marker of renal allograft rejection and IL-33/ST2 expression may differ according to rejection type. IL-33/ST2 expression was measured in sera and kidney tissues from recipients with acute antibody-mediated rejection (AAMR), acute cell-mediated rejection (ACMR), chronic antibody-mediated rejection (CAMR), and healthy controls. The soluble ST2 and IL-33/ST2 expression levels were higher in participants with all three rejection types than in controls. Although the expression levels in recipients with AAMR and ACMR were significantly higher than those with CAMR, there was no significant difference between the expression levels in AAMR and ACMR. Although IL-33, IL-8, and fibronectin expression were significantly increased after the addition of the recipients' serum in primary cultured human renal proximal tubular epithelial cells, the levels decreased after treatment with an anti-ST2 antibody. Furthermore, the anti-ST2 antibody specifically suppressed the upregulation of the mixed lymphocyte reaction. Boyden chamber assays demonstrated that anti-ST2 antibody abrogated chemotaxis induced by recombinant IL-33. Thus, IL-33 and ST2 are potent mediators of rejection. Treatment with an anti-ST2 antibody ameliorates rejection and could be a potential therapeutic strategy for renal allograft rejection.

Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study.

Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88-6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73-1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24-4.39]) and death-censored graft failure (HR 2.26 [1.39-3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.

Incident Parkinson's disease in kidney transplantation recipients: a nationwide population-based cohort study in Korea.

This nation-wide population based retrospective cohort study evaluated risk of incident Parkinson' disease in kidney transplant (KT) recipients in Korea. From Korean National Health Insurance Service database, we identified incident KT recipients aged ≥ 40 years without any history of Parkinson's disease between 2007 and 2015. We established two control cohorts without a history of Parkinson' disease: (1) General population (GP) cohort of insured subjects without a history of kidney disease, (2) end-stage renal disease (ESRD) cohort of incident ESRD subjects, with frequency matched for age, sex, and inclusion year. Parkinson's disease data were obtained from baseline until December 2017. We followed 8372 KT recipients, ESRD patients, and GP for 45,723, 38,357, and 47,476 patient-years, respectively. Their mean age was 51.2 years and 60.1% were men. During follow-up period, 19 KT recipients, 53 ESRD patients, and 15 GP developed Parkinson' disease. Risk of incident Parkinson's disease in KT recipients was similar to that in GP (adjusted hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.35 to 2.13, P = 0.75) and significantly lower than that in ESRD patients (adjusted HR 0.31, 95% CI 0.18 to 0.52, P < 0.001). Older age was the strongest predictor for incident Parkinson's disease in KT recipients.

Socioeconomic dependency and kidney transplantation accessibility and outcomes: a nationwide observational cohort study in South Korea.

BACKGROUND: Socioeconomic status is an important determinant for patients' accessibility to, and prognosis of, kidney transplantation. However, the association between socioeconomic dependency and kidney transplantation accessibility or prognosis after kidney transplantation remains unclear. METHODS: In this nationwide cohort study, based on the claims database of South Korea, we included 12,889 kidney transplant recipients from 2007 to 2015 and stratified them according to health insurance categories that reflect socioeconomic dependency: workplace-independent (employed, N = 3257), workplace-dependent (dependent to the workplace-independent, N = 3661), community-representative (heads of the household but self-employed or unemployed, N = 2479), community-member (N = 1618), aided-representative (heads of household receiving medical aid from the government, N = 1580), and aided-member (N = 294). The incidence of kidney transplantation was calculated to evaluate its accessibility. The risk of graft failure was assessed using the Cox regression analysis, adjusted for clinicodemographic variables, including financial status. RESULTS: End-stage kidney disease patients who were employed (workplace-independent group) had the highest incidence proportion of kidney transplantation. The dependent groups' prognoses were worse than those of their independent counterparts [workplace-dependent versus workplace-independent, HR 1.26 (1.11-1.43) and community-dependent versus community-independent, HR 1.46 (1.23-1.74)], although no difference was observed between the aided subgroups [aided-dependent versus aided-independent, adjusted HR 1.16 (0.90-1.50)]. CONCLUSION: Disparities in kidney transplantation accessibility were present in South Korea according to socioeconomic dependency; these differences may have an impact on prognosis.

Disparity in Accessibility to and Prognosis of Kidney Transplantation According to Economic Inequality in South Korea: A Widening Gap After Expansion of Insurance Coverage.

BACKGROUND: Nationwide studies on the effects of wealth inequality on kidney transplantation are rare, particularly in a country with an expanded National Health Insurance Service and in Asian countries. METHODS: In this nationwide, population-based cohort study, we reviewed the national claims database of Korea in which details of nationwide health insurance are provided. From 2007 to 2015, 9 annual cohorts of end-stage renal disease patients were included. The annual financial statuses were collected and stratified into 5 subgroups in each year: the aided group in which insurance fee was waived and the 4 other groups divided by quartiles of their medical insurance fee. Time trends of incidence proportion of kidney transplantation among end-stage renal disease patients in each year were initially assessed. The risk of graft failure, both including death-censored graft failure and death with a functioning graft, was analyzed as a prognostic outcome within the transplant recipients. RESULTS: Significant disparity in the accessibility of kidney transplantation was present, and it was further widening, particularly from 2009 in which the National Health Insurance Service started to cover desensitized kidney transplantation. Desensitized or preemptive transplantation was less common in the poorest group who were more frequently receiving transplantation after 5 years of dialysis in the latter years. The prognosis of kidney transplantation was significantly worse in the poorer people, and this disparity also worsened during the study period. CONCLUSIONS: Prominent disparity regarding accessibility to and prognosis of kidney transplantation was observed in Korea according to wealth inequality, and this disparity was worsening.

Late Onset Nephrogenic Systemic Fibrosis in a Patient with Stage 3 Chronic Kidney Disease: a Case Report.

Nephrogenic systemic fibrosis (NSF) is a progressive systemic fibrosing disease that may occur after gadolinium contrast exposure. It can lead to severe complications and even death. NSF is highly prevalent among patients with advanced chronic kidney disease (CKD). In this report, however, we describe the case of a patient with NSF that occurred during early CKD. A 65-year-old man with stage 3a CKD was transferred to our hospital because of lower extremity edema. The medical history revealed that he was exposed to gadolinium 185 days earlier, and the result of his tibial skin biopsy was consistent with NSF. The patient underwent a combined therapy with ultraviolet-A1 phototherapy and methotrexate and steroid therapy for 6 months. The combined therapy stopped the systemic progression of NSF.

Krüppel-like factor 15 is a key suppressor of podocyte fibrosis under rotational force-driven pressure.

Krüppel-like factor 15 (KLF15) is a well-known transcription factor associated with podocyte injury and fibrosis. Recently, hypertensive nephropathy was discovered to be closely related to podocyte injury and fibrosis. However, methods to stimulate hypertension in vitro are lacking. Here, we constructed an in vitro model mimicking hypertension using a rotational force device to identify the role of KLF15 in fibrosis due to mechanically induced hypertensive injury. First, we found that KLF15 expression was decreased in patients with hypertensive nephropathy. Then, an in vitro study of hypertension due to rotational force was conducted, and an increase in fibrosis markers and decrease in KLF15 levels were determined after application of 4 mmHg pressure in primary cultured human podocytes. KLF15 and tight junction protein levels increased with retinoic acid treatment. siRNA-mediated inhibition of KLF15 exacerbated pressure-induced fibrosis injury, and KLF15 expression after treatment with angiotensin II was similar to that observed after treatment with the blood pressure modeling device. Furthermore, the reduced KLF15 levels after mechanical pressure application were restored after the administration of an antihypertensive drug. KLF15 expression was also low in vivo. We confirmed the protective role of KLF15 in fibrosis using a mechanically induced in vitro model of hypertensive injury.

Long-term Mortality Risks Among Living Kidney Donors in Korea.

RATIONALE & OBJECTIVE: Living kidney donors may have a higher risk for death and kidney failure. This study aimed to investigate the long-term mortality experience of living kidney donors compared with members of the general public in Korea who underwent voluntary health examinations. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: We first calculated standardized mortality ratios for 1,292 Korean living kidney donors who underwent donor nephrectomy between 1982 and 2016 and 72,286 individuals who underwent voluntary health examinations between 1995 and 2016. Next we compared survival between the 1,292 living kidney donors and a subgroup of the health examination population (n=33,805) who had no evident contraindications to living kidney donation at the time of their examinations. Last, a matched comparator group was created from the health examination population without apparent contraindication to donation by matching 4,387 of them to donors (n=1,237) on age, sex, body mass index, estimated glomerular filtration rate, urine dipstick albumin excretion, previously diagnosed hypertension and diabetes, and era. EXPOSURES: Donor nephrectomy. OUTCOMES: All-cause mortality and other clinical outcomes after kidney donation. ANALYTICAL APPROACH: First, standardized mortality ratios were calculated separately for living kidney donors and the health examination population standardized to the general population. Second, we used Cox regression analysis to compare mortality between living kidney donors versus the subgroup of the health examination population without evident donation contraindications. Third, we used Cox regression analysis to compare mortality between living kidney donors and matched comparators from the health examination population without apparent contraindication to donation. RESULTS: The living kidney donors and health examination population had excellent survival rates compared with the general population. 52 (4.0%) of 1,292 kidney donors died during a mean follow-up of 12.3±8.1 years and 1,072 (3.2%) of 33,805 in the health examiner subgroup without donation contraindications died during a mean follow-up of 11.4±6.1 years. Donor nephrectomy did not elevate the hazard for mortality after multivariable adjustment in kidney donors and the 33,805 comparators (adjusted HR, 1.01; 95% CI, 0.71-1.44; P=0.9). Moreover, living donors showed a similar mortality rate compared with the group of matched healthy comparators. LIMITATIONS: Donors from a single transplantation center. Residual confounding owing to the observational study design. CONCLUSIONS: Kidney donors experienced long-term rates of death comparable to nondonor comparators with similar health status.