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To overcome organ shortage, expanded criteria donors, including elderly deceased donors (DDs), should be considered. We analyzed outcomes of kidney transplantation (KT) from elderly DDs in a nationwide study. In total, data of 1049 KTs from DDs using the database of Korean Organ Transplantation Registry (KOTRY) were retrospectively analyzed based on the age of DDs: age ≥60 years vs. <60 years. Clinical information, graft status, and adverse events were reviewed in DDs and recipients. The mean age of the 1006 DDs was 51.04±10.54 years, and 21.5% of donors were aged ≥60 years. Elderly DDs had a significantly higher prevalence of diabetes and hypertension and higher Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI). The mean age of the recipients was 47.45±14.87 years. Patients who received KT from elderly DDs were significantly older (53.12±15.14 vs. 45.88±14.41, P<0.001) and had a higher rate of diabetes (41.9 vs. 24.4%, P<0.001). Graft outcomes were not significantly different. Renal function was similar between the groups at the time of discharge and at 6 months, 1 year, and 2 years after KT. The rate of delayed graft function (DGF) was not significantly different. Risk factors of DGF were significantly different in DDs aged ≥60 years and <60 years. In the multivariable model, male sex (odds ratio: 3.99, 95% confidence interval: 1.42–11.22; P = 0.009) and KDRI (12.17, 2.23–66.34; P = 0.004) were significant risk factors for DGF in DDs aged ≥60 years. In DDs aged <60 years, thymoglobulin induction (2.62, 1.53–4.48; P<0.001) and continuous renal replacement therapy (3.47, 1.52–7.96; P = 0.003) were significant factors. Our data indicated that graft outcomes, including renal function and DGF, were similar for elderly DDs and DDs aged <60 years. Elderly DDs might be considered tolerable donors for KT, with active preoperative surveillance. [ABSTRACT FROM AUTHOR]

Background/Aims: No studies have examined the association among serum hepcidin, iron indices, or anemia status based on the kidney function of non-dialysis chronic kidney disease (CKD) patients. Methods: We reviewed data of 2238 patients from a large-scale multicenter prospective Korean study (2011-2016) and excluded 198 patients with missing data regarding serum hepcidin, hemoglobin, transferrin saturation (TSAT), ferritin, and usage of erythropoiesisstimulating agents (ESA) or supplemental iron and 363 patients using ESA or supplemental iron. Finally, 1677 patients were included. Results: The mean patient age was 53.5 years, and 65.4% were men. TSAT and serum hepcidin were significantly associated with anemia status, whereas serum ferritin was not, regardless of anemia severity. For patients with an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m², a 10% increase of TSAT was associated with hemoglobin <13 g/dL (odds ratio [OR], 0.628; 95% confidence interval [CI], 0.515-0.765; P<0.001) and hemoglobin <11.5 g/dL (OR, 0.672; 95% CI, 0.476-0.950; P=0.024), whereas a 10-ng/mL increase of serum hepcidin was associated with hemoglobin <11.5 g/dL (OR, 1.379; 95% CI, 1.173-1.620; P<0.001) and hemoglobin <10.0 g/dL (OR, 1.360; 95% CI, 1.115-1.659; P=0.002) for patients with eGFR <45 mL/min/1.73 m² according to multivariate logistic analysis. Conclusions: TSAT was associated with less severe anemia in early CKD patients. Serum hepcidin was associated with more severe anemia in advanced CKD patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of surgical wide excision and amniotic membrane transplantation with adjuvant mitomycin C 0.04% eye drops on recurrent conjunctival-corneal intraepithelial neoplasia (CCIN). Methods: The authors applied amniotic membrane transplantation after total surgical excision of a tumor to a patient with recurrent conjunctival-corneal intraepithelial neoplasia. The tumor co-existed as a conjunctival lesion and corneal opacity. After one week, the patient received mitomycin C 0.04% eye drops four times a day for one month to prevent recurrence. Ocular complications and recurrence were evaluated under slit lamp microscopy for one year. Results: Corneal epithelium completely healed within one week after the surgery. Both conjunctival and corneal lesions were completely regressed and no recurrence has been found with follow-up to 24 months. Conclusions: Surgical wide excision and amniotic membrane transplantation with adjuvant topical MMC would be an effective treatment modality for treatment of recurrent CCIN. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association and interaction of single nucleotide polymorphisms in CFH and LOC387715/ARMS2 with age-related macular degeneration (AMD) in a Korean population. Methods: A total of 114 exudative AMD patients and 240 normal subjects participated in the study. PCR and direct sequencing were used to screen SNPs in the CFH and in the LOC387715/ARMS2. Genotype and haplotype analyses were performed. Two-locus gene-gene interactions were evaluated by the data mining approach multifactor-dimensionality reduction method. Results: The *C/*T genotype frequency of rs1061170 in CFH showed a significant difference (OR = 1.79). Genotype and allele frequencies of rs551397 (*C/*C, OR = 2.84; *C, OR = 1.67) and rs800292 (*G/*G, OR = 2.198; *G, OR = 1.676) in CFH, and rs10490924 (T/*T, OR = 12.45; *T, OR = 4.45) and rs2736911 (*C/*C, OR = 3.21; *C, OR = 2.71) in LOC387715/ARMS2 were significantly higher in patients. In the haplotype analysis, C-T of rs2736911-rs10490924 in LOC387715/ARMS2 (OR = 4.85) and C-G of rs551397-rs800292 in CFH (OR = 2.22) predisposed significantly to AMD. After cross-validation consistency (CVC) and permutation tests, we identified the 1 marker model (rs10490924), which has a prediction accuracy of 73.5%, and the two locus model, rs10490924_ rs800292, with 75.3% balanced accuracy in predicting AMD disease risk. Conclusions: Korean individuals with the LOC387715/ARMS2 rs10490924, and to a lesser extent, CFH rs800292 variants might be at a greater risk for the development of exudative AMD. Furthermore, the risk of exudative AMD may increase significantly if these variants are both present in the two genes. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β) signaling transduction initiates TGF-β activation, resulting in activation of TGF-β receptor II (TGFBR2). Any quantitative and qualitative changes in TGFBR2 are expected to affect the TGF-β signaling pathway, which occupies a central position with respect to the regulation of cell growth, differentiation, apoptosis, immune reaction, angiogenesis and extracellular matrix formation. Recent studies have shown that TGF-β1 gene polymorphisms may confer susceptibility to early acute and chronic allograft rejection in kidney transplantation recipients. In this study, we assessed whether polymorphisms of the TGFBR2 gene were associated with susceptibility to kidney transplantation rejection. A total of 347 renal allograft recipients transplanted at three centers in Korea were analyzed. Three SNPs (rs764522, rs3087465, rs2228048) of the TGFBR2 gene were genotyped from genomic DNA with direct sequencing. Multiple logistic regression models (codominant, dominant, recessive, and log-additive) were performed to evaluate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. A total of 63 patients (18%) developed acute rejection (AR). There were no significant differences in age, sex, number of HLA mismatches, cause of renal failure, or immunosuppressant regimen between the AR and non-AR group. The synonymous SNP rs2228048 was significantly associated with AR (p = 0.020 in recessive model, and p = 0.036 in log-additive model. The allele frequencies of rs2228048 were different between the AR and non-AR group (p = 0.026). These results suggest that the synonymous TGFBR2 gene SNP rs2228048 may be associated with the development of AR in Korean kidney transplantation recipients. [ABSTRACT FROM AUTHOR]

Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Background. Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the puromycin aminonucleoside (PAN)-treated rat could be attributed to podocyte depletion. Methods. PAN was injected in Sprague-Dawley rats once, twice, or three times at 30-day intervals. Podocytes were counted in glomeruli using immunoperoxidase histochemistry and antibodies to both GLEPP1 (PTPRO) and WT-1. Podocytes were assayed in urine using reverse transcription-quantitative polymerase chain reaction (RT-QPCR). Glomerular areas were measured by computerized morphometry. Results. In a preliminary experiment, a single injection of PAN caused a reduction in the glomerular podocyte count by 25%. Additional independent confirmation that podocytes were lost from glomeruli after PAN injection was obtained identifying detached podocytes in Bowman's space, measurement of nephrin and GLEPP1 mRNAs in urine, ultrastructural analysis of glomeruli, and identification of TUNEL-positive apoptotic podocytes in glomeruli. In a second experiment, sequential podocyte depletion by 15, 31, and 53% was achieved by the administration of one, two, or three injections of PAN at 30-day intervals. The region of the glomerulus devoid of podocytes developed glomerulosclerosis, and this area progressively increased as podocytes were progressively depleted. The correlation coefficient (r2) value for the relationship between percent podocyte depletion and glomerulosclerotic area was 0.99. The Y intercept of this plot showed that glomerulosclerosis was initiated when only 10 to 20% of podocytes were lost. Conclusion. This report supports the growing body of data linking... [ABSTRACT FROM AUTHOR]

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs. [ABSTRACT FROM AUTHOR]

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy. [ABSTRACT FROM AUTHOR]

Introduction: End-stage renal disease (ESRD) is a growing disease worldwide, including Korea. This is an important condition that affects patient outcome. To provide optimal management for mineral disturbance, vascular calcification, and bone disease in ESRD patients, the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) study was conducted by enrolling Korean dialysis patients. Methods: Sixteen university-affiliated hospitals and one Veterans' Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive patients on dialysis between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of the patients were performed, and their biospecimens were collected according to the study protocol. The primary outcomes were the occurrence of major adverse cardiovascular events, invasive treatment for peripheral artery disease, and osteoporotic fractures. The secondary outcomes were hospitalization for cerebrovascular disease or progression of abdominal aortic calcification. Participants will be assessed for up to 3 years to determine whether primary or secondary outcomes occur. Results: Between May 2019 and January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of the subjects was 60.4 ± 12.3 years. Males accounted for 57.7% of the total population. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. Conclusion: This nationwide, multicenter, prospective cohort study focused on chronic kidney disease-mineral and bone disorder and aimed to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients. [ABSTRACT FROM AUTHOR]

Anti-thymocyte globulin (ATG) is currently the most widely prescribed induction regimen for preventing acute rejection after solid organ transplantation. However, the optimal dose of ATG induction regimen in Asian kidney recipients is unclear. Using the Korean Organ Transplantation Registry, we performed a retrospective cohort study of 4579 adult patients who received renal transplantation in South Korea and divided them into three groups according to the induction regimen: basiliximab group (n = 3655), low-dose ATG group (≤ 4.5 mg/kg; n = 467), and high-dose ATG group (> 4.5 mg/kg; n = 457). We applied the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) package to generate high-quality propensity score weights for intergroup comparisons. During four-year follow-ups, the high-dose ATG group had the highest biopsy-proven acute rejection rate (basiliximab 20.8% vs. low-dose ATG 22.4% vs. high-dose ATG 25.6%; P < 0.001). However, the rates of overall graft failure (4.0% vs. 5.0% vs. 2.6%; P < 0.001) and mortality (1.7% vs. 2.8% vs. 1.0%; P < 0.001) were the lowest in the high-dose ATG group. Our results show that high-dose ATG induction (> 4.5 mg/kg) was superior to basiliximab and low-dose ATG induction in terms of graft and patient survival in Asian patients undergoing kidney transplant. [ABSTRACT FROM AUTHOR]

Background: Urine exosomal bkv-miR-B1-5p is associated with BK virus (BKV) nephropathy (BKVN); however, its post-transplantation changes and predictability for BKVN have not been determined in kidney transplant recipients (KTRs).Methods: Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA were measured at 2 weeks and 3, 6, and 12 months post-transplant in 83 KTRs stratified into biopsy-proven or presumptive BKVN, BKV viruria, and no evidence of BKV reactivation. Joint model, multivariable Cox model, and receiver operating characteristic curve (ROC) were used to investigate the association of each assay with the following events: a composite of biopsy-proven or presumptive BKVN, and biopsy-proven BKVN.Results: Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA showed similar post-transplant time-course changes. Joint models incorporating serial values demonstrated significant associations of all assays with the events, and Cox analyses using single time point values at 2 weeks post-transplant showed that only urine exosomal bkv-miR-B1-5p was significantly associated with the events although it did not outperform urine BKV DNA in ROC analyses.Conclusions: Urine exosomal bkv-miR-B1-5p was associated with BKVN as were urine and plasma BKV DNA loads on serial follow-up, and might have potential as a predictive marker for BKVN during the early post-transplant period.Clinical Trials Registration: Clinical Research Information Service (https://cris.nih.go.kr/cris/), KCT0001010. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate changes in health-related quality of life (HRQOL) in patients with chronic kidney disease (CKD) according to decline in kidney function. HRQOL was assessed using the Short Form-36 questionnaire composed of a physical component summary (PCS) and mental component summary (MCS). Rapid decline in kidney function was defined as a decline in the estimated glomerular filtration rate (eGFR) of > 3 mL/min/1.73 m2/year. Rapid deterioration of HRQOL was defined a change in the HRQOL value greater than the median. Among 970 patients, 360 (37.1%) were in the rapid kidney function decline group. In 720 patients who were 1:1 propensity score-matched, the baseline eGFR was not significantly different between the non-rapid and rapid kidney function decline groups. Compared with the baseline PCS score, the 5-year PCS score decreased in the non-rapid and rapid kidney function decline groups. The 5-year MCS score significantly decreased in the rapid kidney function decline group alone. Rapid decline in kidney function was significantly associated with rapid deterioration of the PCS (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07–2.05; P = 0.018) and MCS (OR: 1.89; 95% CI 1.36–2.62; P < 0.001) scores. Rapid decline in kidney function was associated with rapid deterioration of HRQOL in patients with CKD. [ABSTRACT FROM AUTHOR]

The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69–7.63; P < 0.001; aHR 2.37; 95% CI 1.06–5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94–25.00; P < 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT. [ABSTRACT FROM AUTHOR]

Background Optimal blood pressure (BP) control is a major therapeutic strategy to reduce adverse cardiovascular events (CVEs) and mortality in patients with chronic kidney disease (CKD). We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD. Methods Among 2238 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD), 2226 patients with baseline BP measurements were enrolled. The main predictor was systolic BP (SBP) categorized by five levels: <110, 110–119, 120–129, 130–139 and ≥140 mmHg. The primary endpoint was a composite outcome of all-cause death or incident CVEs. We primarily used marginal structural models (MSMs) using averaged and the most recent time-updated SBPs. Results During the follow-up of 10 233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 [95% confidence interval (CI) 20.7–26.6]/1000 patient-years. MSMs with averaged SBP showed a U-shaped relationship with the primary outcome. Compared with time-updated SBP of 110–119 mmHg, hazard ratios (95% CI) for <110, 120–129, 130–139 and ≥140 mmHg were 2.47 (1.48–4.11), 1.29 (0.80–2.08), 2.15 (1.26–3.69) and 2.19 (1.19–4.01), respectively. MSMs with the most recent SBP also showed similar findings. Conclusions In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcomes. Our findings highlight the importance of BP control and suggest a potential hazard of SBP <110 mmHg. [ABSTRACT FROM AUTHOR]

Late Pneumocystis jirovecii pneumonia (PJP) is not rare in the era of universal prophylaxis after kidney transplantation. We aimed to determine the nationwide status of PJP prophylaxis in Korea and compare the incidence, risk factors, and outcomes of early and late PJP using data from the Korean Organ Transplantation Registry (KOTRY), a nationwide Korean transplant cohort. We conducted a retrospective analysis using data of 4,839 kidney transplant patients from KOTRY between 2014 and 2018, excluding patients who received multi-organ transplantation or were under 18 years old. Cox regression analysis was performed to determine risk factors for early and late PJP. A total of 50 patients developed PJP. The number of patients who developed PJP was same between onset before 6 months and onsets after 6 months. There were no differences in the rate, duration, or dose of PJP prophylaxis between early and late PJP. Desensitization, higher tacrolimus dose at discharge, and acute rejection were associated with early PJP. In late PJP, old age as well as acute rejection were significant risk factors. In conclusion late PJP is as common and risky as early PJP and requires individualized risk-based prophylaxis, such as prolonged prophylaxis for old patients with a history of rejection. [ABSTRACT FROM AUTHOR]

Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin β (CERA) in pre-dialysis chronic kidney disease (CKD) patients. Methods: Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-β, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. Results: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S). Conclusion: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Although it is well known that low bone mineral density (BMD) is associated with an increased risk of cardiovascular disease (CVD) and mortality in the general population, the prognostic role of bone mineral density (BMD) has not been established in the chronic kidney disease (CKD) population. Therefore we aimed to evaluate the association between BMD and the risk of CVD and cardiovascular mortality in patients with predialysis CKD. Methods This prospective cohort study was conducted with 1957 patients with predialysis CKD Stages 1–5. BMD was measured using dual-energy X-ray absorptiometry and coronary arterial calcification (CAC) scores were evaluated using coronary computed tomography. The primary outcome was a major adverse cardiovascular event (MACE). Results When patients were classified based on total hip BMD T -score tertiles stratified by sex, the lowest BMD tertile was significantly associated with an increased risk of MACE {hazard ratio 2.16 [95% confidence interval (CI) 1.25–3.74]; P = 0.006}. This association was also shown with BMD at the femur neck but not with BMD at lumbar spine. In the subgroup of 977 patients with follow-up CACs at their fourth year, 97 (9.9%) showed accelerated CAC progression (>50/year), and BMD was inversely associated with accelerated CAC progression even after adjusting for the baseline CAC score [odds ratio 0.75 (95% CI 0.58–0.99); P = 0.039]. In addition, baseline CAC was associated with an increased risk of MACEs after adjusting for total hip T -score. Conclusions Low BMD was significantly associated with CAC progression and MACEs in patients with predialysis CKD. [ABSTRACT FROM AUTHOR]

Background. The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients. Methods. This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables. Results. Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups. Conclusion. Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients. [ABSTRACT FROM PUBLISHER]

Background. Impaired urinary concentration is uniformly present with advanced disease in chronic renal failure. Aquaporin-2 (AQP-2) is known to be expressed in the renal collecting duct cells and participates in urinary concentration in response to vasopressin. Recently, the study of AQP expression in various forms of chronic kidney disease (CKD) demonstrated a reduction in AQP-2 expression associated with a loss of nephrons and the presence of chronic interstitial fibrosis. No information on aquaporin genetic variations in CKD is available to date. The aim of our study was to evaluate the possible impact of aquaporin-2 genotype on the development and clinical course of CKD. Methods. Blood samples from 259 patients with CKD and 106 ethnicity-, age-, and sex-matched healthy controls were collected, and genomic DNA was extracted. AQP-2 -667 genotype was assessed by PCR, followed by restriction fragment length polymorphism analysis. Results. There were no significant differences in genotype and allele frequencies between the patients and healthy controls (p = 0.3936, p = 0.2941, respectively). In all, 79 (30.5%) patients had the AQP-2 -667 wild-type A/A, 123 (47.5%) were heterozygous for the G allele, and 57 (22.0%) patients showed homozygosity. After subclassification of CKD according to underlying disease, no significant differences were observed between those patients and controls (p = 0.72 for diabetic nephropathy, p = 0.52 for hypertensive nephropathy, p = 0.27 for chronic glomerulonephritis, and p = 0.80 for unknown etiology). Genotype and allele frequencies of the AQP-2 gene polymorphism (rs3759126) of hypertensive patients in pre-ESRD did not show a noticeable difference compared with normal blood pressure patients in pre-ESRD (p = 0.50). No correlation was found to exist between the AQP-2 gene polymorphism (rs3759126) and serum electrolyte levels in pre-ESRD patients (p = 0.38 for serum sodium level and p = 0.44 for serum potassium level). Conclusion. Our data indicate that no association exists between the -667 AQP-2 A/G polymorphism and susceptibility to CKD or its clinical course. [ABSTRACT FROM AUTHOR]

Decreased kidney function is an important risk factor for cardiovascular disease (CVD). However, assessing risk of CVD may be difficult when there is a gap between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR). We studied the association of the difference in eGFRs with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD). This prospective cohort study was conducted in 2076 patients with CKD stages based on the KDIGO guideline (eGFR categories of G1: ≥90; G 2: 60–89; G3: 30–59; G4: 15–29; G5: <15 mL/min/1.73 m2 without kidney replacement therapy). The difference in eGFR (eGFR diff) was calculated by subtracting the cystatin C-based eGFR (eGFR cys) from the creatinine-based eGFR (eGFR creat). The primary outcome was MACE, defined as non-fatal acute myocardial infarction and unstable angina, stroke, congestive heart failure, symptomatic arrhythmia, and cardiac death. During a median follow-up of 4.1 years, MACE occurred in 147 patients (incidence rate, 15.0 per 1000 patient-years). When patients were categorized into baseline eGFR diff tertiles, the highest tertile was associated with a significantly higher risk of MACE (hazard ratio, 2.12; 95% confidence interval [CI], 1.28–3.51) than the lowest tertile when adjusted for eGFR creat , eGFR cys , or eGFR based on both creatinine and cystatin C. Patients in the highest tertile had more baseline coronary artery calcification (CAC) than those in the lowest tertile (odds ratio [OR], 1.38; 95% CI, 1.03–1.86). In addition, 978 patients had data for both baseline and follow-up CAC at year 4. In this subgroup, baseline eGFR diff was significantly associated with accelerated CAC progression (≥50/year) (OR, 1.03; 95% CI, 1.01–1.05). A large positive difference between eGFR creat and eGFR cys was associated with a higher risk of MACE and faster CAC progression in patients with CKD. Therefore, careful monitoring of CVD is needed for patients with a higher eGFR diff. [Display omitted] • Cardiovascular disease is a leading cause of death in patients with chronic kidney disease. • Assessing risk of cardiovascular disease may be difficult when there is a gap between creatinine- and cystatin C-based eGFR. • Risk of major adverse cardiovascular events was high in patients with high eGFR difference between creatinine and cystatin C. • Patients with high eGFR difference also had high risk of coronary artery calcification progression. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate whether or not delayed graft function (DGF) and pre-transplant sensitization have synergistic adverse effects on allograft outcome after deceased donor kidney transplantation (DDKT) using the Korean Organ Transplantation Registry (KOTRY) database, the nationwide prospective cohort. The study included 1359 cases between May 2014 and June 2019. The cases were divided into 4 subgroups according to pre-sensitization and the development of DGF post-transplant [non-pre-sensitized-DGF(−) (n = 1097), non-pre-sensitized-DGF(+) (n = 127), pre-sensitized-DGF(−) (n = 116), and pre-sensitized-DGF(+) (n = 19)]. We compared the incidence of biopsy-proven allograft rejection (BPAR), time-related change in allograft function, allograft or patient survival, and post-transplant complications across 4 subgroups. The incidence of acute antibody-mediated rejection (ABMR) was significantly higher in the pre-sensitized-DGF(+) subgroup than in other 3 subgroups. In addition, multivariable cox regression analysis demonstrated that pre-sensitization combined with DGF is an independent risk factor for the development of acute ABMR (hazard ratio 4.855, 95% confidence interval 1.499–15.727). Moreover, DGF and pre-sensitization showed significant interaction (p-value for interaction = 0.008). Pre-sensitization combined with DGF did not show significant impact on allograft function, and allograft or patient survival. In conclusion, the combination of pre-sensitization and DGF showed significant synergistic interaction on the development of allograft rejection after DDKT. [ABSTRACT FROM AUTHOR]

Introduction: The renal hazard of polypharmacy has never been evaluated in predialysis chronic kidney disease (CKD) patients. Objective: We aimed to analyze the renal hazard of polypharmacy in predialysis CKD patients with stage 1–5. Method: The data of 2,238 patients from a large-scale multicenter prospective Korean study (2011–2016), excluding 325 patients with various missing data, were reviewed. Polypharmacy was defined as taking 6 or more medications at the time of enrollment; renal events were defined as a ≥50% decrease in kidney function from baseline values, doubling of the serum creatinine levels, or initiation of renal replacement treatment. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox proportional-hazard regression analysis. Results: Of the 1,913 patients, the mean estimated glomerular filtration rate was 53.6 mL/min/1.73 m2. The mean medication count was 4.1, and the prevalence of polypharmacy was 27.1%. During the average period of 3.6 years, 520 patients developed renal events (27.2%). Although increased medication counts were associated with increased renal hazard with HR (95% CI) of 1.056 (1.007–1.107, p = 0.025), even after adjusting for various confounders, adding comorbidity score and kidney function nullified the statistical significance. In mediation analysis, 55.6% (p = 0.016) of renal hazard in increased medication counts was mediated by the kidney function, and there was no direct effect of medication counts on renal event development. In subgroup analysis, the renal hazard of the medication counts was evident only in stage 1–3 of CKD patients (p for interaction = 0.014). Conclusions: We cannot identify the direct renal hazard of multiple medications, and most of the potential renal hazard was derived from intimate relationship with disease burden and kidney function. [ABSTRACT FROM AUTHOR]

Aim: The safety of donors is an important issue in living donor kidney transplantation. We investigated serial changes in renal function and predictors affecting the renal outcome of living kidney donors. Methods: We obtained the data of 456 kidney donors registered to the Korean Organ Transplantation Registry from 2014 to 2016. The estimated glomerular filtration rate (eGFR) changes according to the development of incident chronic kidney disease (CKD) and factors related to CKD were analysed. CKD was defined as an eGFR <60 ml/min/1.73 m2 or the presence of proteinuria or albuminuria. The change in eGFR over time was analysed using a linear mixed model. Results: At 2 years after kidney donation, 21.7% of the donors (99/456) developed CKD. Annual eGFR changes after nephrectomy were 2.2 ml/min/1.73 m2/year in donors without CKD, and − 0.4 ml/min/1.73 m2/year in donors with CKD. Higher systolic blood pressure was associated with higher risk of CKD (odds ratio [OR] 1.322 per 10 mmHg increment, 95% confidence interval [CI] 1.036–1.686, p =.025). Higher pre‐donation eGFR (OR 0.906 per 1 ml/min/1.73 m2 increment, 95% CI 0.876–0.936, p <.001) and higher ratio of eGFR at discharge to pre‐donation (OR 0.603 per 0.1 increment, 95% CI 0.426–0.849, p =.004) were related to lower risk of CKD. Conclusion: Kidney donors without incident CKD at 2 years after donation showed gradual increases in eGFR, whereas donors with CKD had relatively constant eGFR. A low ratio of eGFR at discharge after nephrectomy to baseline was a risk factor of CKD. SUMMARY AT A GLANCE: A population cohort study of live donors registered in the Korean Organ Transplant Registry showing that over 1 in 5 live‐donors developed chronic kidney disease at 2‐years post‐donation, and had exhibited decline in eGFR over time. The authors also showed that higher systolic blood pressure was associated with the development of chronic kidney disease suggesting that close long‐term follow‐up of these donors are required. [ABSTRACT FROM AUTHOR]

The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1 < 60.0 kg). Secondary outcomes were not significantly different between aspirin users and non-users. It needs to be individualized of prescribing low-dose aspirin for the prevention of cardiovascular events in patients with chronic kidney disease, particularly patients with low bodyweight (< 60 kg). [ABSTRACT FROM AUTHOR]

Few studies have investigated the incidence of cardiovascular disease (CVD) in the Asian chronic kidney disease (CKD) population. This study assessed the incidence of CVD, death, and a composite outcome of CVD and death in a prospective Korean predialysis CKD cohort. From a total of 2179 patients, incidence rates were analyzed, and competing risk analyses were conducted according to CKD stage. Additionally, incidence was compared to the general population. During a median 4.1 years of follow-up, the incidence of CVD, all-cause death, and the composite outcome was 17.2, 9.6, and 24.5 per 1000 person-years, respectively. These values were higher in diabetic vs. non-diabetic subjects (P < 0.001). For all outcomes, incidence rates increased with increasing CKD stage (CVD, P = 0.001; death, P < 0.001; and composite, P < 0.001). Additionally, CKD stage G4 [hazard ratio (HR) 2.8, P = 0.008] and G5 (HR 5.0, P < 0.001) were significant risk factors for the composite outcome compared to stage G1 after adjustment. Compared to the general population, the total cohort population (stages G1–G5) showed significantly higher risk of CVD (HR 2.4, P < 0.001) and the composite outcome (HR 1.7, P < 0.001). The results clearly demonstrate that CKD is a risk factor for CVD in an Asian population. [ABSTRACT FROM AUTHOR]

Introduction: In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce.Aims and Methods: We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation.Results: There were 967 never-smokers and 369, 276, and 339 smokers who smoked <15, 15 to 29, ≥30 pack-years, respectively. During a mean follow-up of 3.0 years, the incidence rates (95% confidence interval [CI]) of the primary outcome were 54.3 (46.4-63.5), 46.9 (35.9-61.4), 69.2 (52.9-90.6), and 76.3 (60.7-96.0) events per 1,000 person-yr in never-, <15, 15 to 29, and ≥30 pack-year smokers. In cause-specific hazard model after adjustment of confounding factors, smokers were associated with 1.09 (0.73-1.63), 1.48 (1.00-2.18), and 1.94 (1.35-2.77) fold increased risk (95% CI) of primary outcome in <15, 15-29, and ≥30 pack-year smokers compared with never-smokers. The association of longer smoking duration with higher risk of CKD progression was evident particularly in patients with eGFR < 45 mL/min/1.73 m2 and proteinuria ≥ 1.0 g/g. In contrast, the risk of adverse kidney outcome decreased with longer smoking-free periods among former-smokers.Conclusions: These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD.Implications: Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the relationship between pre-operative donor split renal function (SRF) and the renal function outcome of donors and recipients after kidney transplantation (KT). A total of 217 living KT cases were investigated. The estimated glomerular filtration rate (eGFR) change of recipients and donors, as well as graft survival, were analyzed based on the donor SRF. The difference in SRF (dSRF) in a donor was defined as follows: the SRF of the donated kidney minus the SRF of the remaining kidney determined by pre-operative 99mTc-diethylenetriaminepentaacetic acid in the donors. The dSRF was categorized into tertiles. The dSRF was not associated with the eGFR in recipients in any tertile at 6 or 12 months post-KT. The overall graft and patient survival did not differ significantly among tertiles. Donors in the high tertile, who donated kidneys with a higher SRF, showed a greater reduction in eGFR than did donors in the low and middle tertile after adjustment for function of the not-donated kidney (−34 ± 1.9 vs −28 ± 2.2, and −27 ± 1.3 mL/min/1.73 m2, P <.05). The dSRF did not affect the post-KT renal function or graft survival in recipients. However, the donors who donated the better functioning kidney had a poorer renal function after donation. • This retrospective study was conducted in a single transplantation center in South Korea. • Renal function as determined by 99mTc-DTPA in the donors prior to transplantation did not affect the post-transplant renal function or graft survival in recipients. However, the donors who donated the better-functioning kidney had poorer renal function after donation. [ABSTRACT FROM AUTHOR]

Epidermal growth factor (EGF) has been found to be associated with the development and repair mechanisms of several renal diseases. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in EGF or its receptor genes might have an association with end-stage renal disease (ESRD) or acute renal allograft rejection (AR) in a Korean population. Three-hundred and forty seven recipients of the first renal transplants for ESRD, including 63 AR patients along with 289 healthy adults were included in the study. Five EGF gene SNPs (rs11568835, rs11568943, rs2237051, rs11569017, and rs3756261) and four EGFR gene SNPs (rs1140475, rs2293347, rs1050171, and rs6965469) were analyzed. The genotypes of these SNPs were analyzed using the AxiomTM genome-wide human assay. Statistical analysis was performed using SNPStats and Haploview version 4.2 software. Multiple logistic regression models (codominant, dominant, recessive, and Log-additive) were used to estimate the odds ratio (OR), 95% confidence interval (CI), and P value. One SNP (rs11569017) in the EGF gene showed significant association with ESRD but not with AR. Another SNP (rs11568835) in the EGF gene showed significant association with susceptibility to AR but not with ESRD. One SNP (rs1050171) in the EGFR gene showed significant association with susceptibility to AR but not with ESRD. Our findings suggest that SNPs in the EGF and EGFR gene may be associated with the risk of ESRD and AR development in the Korean population. [ABSTRACT FROM AUTHOR]

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen. [ABSTRACT FROM AUTHOR]

Background Few s tudies have examined the association between hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease (CKD) patients. Methods We reviewed the data of 2238 patients from a large-scale multicenter prospective Korean study (2011–16) and excluded 214 patients with missing data on markers and related medications of iron and bone mineral metabolism, hemoglobin, blood pressure and causes of CKD. Multivariate linear regression analysis was used to identify the association between iron and bone mineral metabolism. Results The proportion of CKD Stages 1–5 were 16.2, 18.7, 37.1, 21.6 and 6.4%, respectively. Per each 10% increase in transferrin saturation (TSAT), there was a 0.013 mmol/L decrease in phosphorus [95% confidence interval (CI) −0.021 to −0.004; P   =   0.003] and a 0.022 nmol/L increase in logarithmic 25-hydroxyvitamin D (Ln-25OHD) levels (95% CI 0.005–0.040; P   =   0.019). A 1 pmol/L increase in Ln-ferritin was associated with a 0.080 ng/L decrease in Ln-intact parathyroid hormone (Ln-iPTH; 95% CI −0.122 to −0.039; P   <   0.001). Meanwhile, beta (95% CI) per 1 unit increase in phosphorus, Ln-25OHD and Ln-iPTH for the square root of the serum hepcidin were 0.594 (0.257–0.932; P   =   0.001), −0.270 (−0.431 to −0.108; P   =   0.001) and 0.115 (0.004–0.226; P   =   0.042), respectively. In subgroup analysis, the relationship between phosphorus, 25OHD and hepcidin was strongest in the positive-inflammation group. Conclusions Markers of bone mineral metabolism and iron status, including hepcidin, were closely correlated to each other. Potential mechanisms of the relationship warrant further studies. [ABSTRACT FROM AUTHOR]

Graft biopsy is the gold standard for the differential diagnosis of graft dysfunction. The time interval between transplant surgery and biopsy often provides clinicians with diagnostic clues. However, the clinicopathologic features of late graft biopsy, especially those obtained at more than 5 years after kidney transplant, are not well understood. We retrospectively collected graft biopsy tissues obtained from kidney transplant recipients who underwent indication biopsy between February 2012 and March 2017. Patients were divided according to their post-transplant period, and their clinical characteristics, pathologic diagnosis, and Banff scores were compared across groups. A total of 410 indication biopsy specimens obtained from 321 kidney transplant recipients were analyzed in this study. Overall, the incidence of T cell–mediated rejection, borderline rejection, and BK virus–associated nephropathy decreased while that of antibody-mediated rejection, nonspecific interstitial fibrosis and tubular atrophy, and glomerulonephritis increased over time. Most samples obtained over 5 years after kidney transplant exhibited chronic glomerular and tubulointerstitial injuries irrespective of their pathologic diagnosis. In patients whose post-transplant period was less than 5 years, urine protein-to-creatinine ratio was significantly elevated in the glomerulonephritis and chronic active antibody-mediated rejection groups only. In contrast, patients who underwent graft biopsy more than 5 years after kidney transplant showed significantly high levels of proteinuria irrespective of the pathologic diagnosis, and there was no statistical difference between groups. We demonstrated that the etiology of graft dysfunction is largely influenced by the biopsy time point. • The etiology of graft dysfunction is largely influenced by the biopsy time point. • Most patients more than 5 years post transplant exhibited evidences of chronic allograft fibrosis. • Early proteinuria indicates specific etiology, while late proteinuria may be nonspecific. [ABSTRACT FROM AUTHOR]

Background: Urine osmolality indicates the ability of the kidney to concentrate the urine and reflects the antidiuretic action of vasopressin. However, results about the association between urine osmolality and adverse renal outcomes in chronic kidney disease (CKD) are conflicting. We investigated the association between urine osmolality and adverse renal outcomes in a nationwide prospective CKD cohort. Methods: A total of 1,999 CKD patients were categorized into 3 groups according to their urine osmolality tertiles. Primary outcome was a composite of 50% decline in the estimated glomerular filtration rate (eGFR), initiation of dialysis, or kidney transplantation. Results: During a mean follow-up of 35.2 ± 19.0 months, primary outcome occurred in 432 (21.6%) patients; 240 (36.4%), 162 (24.3%), and 30 (4.5%) in the lowest, middle, and highest tertiles, respectively. Low urine osmolality was independently associated with a greater risk of CKD progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12–2.59). This association was particularly evident in patients with CKD stages 3–4 (per 10 mosm/kg decrease; HR, 1.02; 95% CI, 1.00–1.03). Adding urine osmolality to a base model with conventional factors significantly increased the ability to predict CKD progression (C-statistics, 0.86; integrated discrimination improvement [IDI], 0.021; both p < 0.001). However, adding both urine osmolality and eGFR did not further improve the predictive ability compared with the addition of eGFR only (C-statistics, p = 0.29; IDI, p = 0.09). Conclusions: Low urine osmolality was an independent risk factor for adverse renal outcomes in CKD patients, but its predictive ability did not surpass eGFR. Thus, kidney function should be considered while interpreting the clinical significance of urine osmolality. [ABSTRACT FROM AUTHOR]

The incidence rate of breast fibroadenomas is higher among female kidney transplant (KT) patients treated using cyclosporine (CsA) for immunosuppression than in the general population. As such, there is an effort to convert immunosuppression from CsA or tacrolimus to sirolimus. Our aim was to assess the reversibility of a breast fibroadenoma after conversion in a small cohort of female KT recipients. This was an open-label, single-arm study including 128 female KT recipients, with a positive finding of a breast fibroadenoma in 15. Lesions were classified according to the Breast Imaging Reporting and Data System (BIRADS). Among these 15, a total of 7 converted from tacrolimus to sirolimus and 8 converted from CsA. We measured the change in BIRADS category and hormone and cytokine levels from baseline to 12 months after conversion. The primary outcome was progression or reversal of existing fibroadenomas at 12 months after conversion. Secondary outcomes were differences in hormone and cytokine levels. Conversion from CsA or tacrolimus to sirolimus had no significant effect on the BIRADS classification. However, conversion to sirolimus did produce a significant decrease in the level of transforming growth factor β cytokine, this level being closely associated with fibroadenomas. Conversion from a calcineurin inhibitor to sirolimus can block the progression of fibroadenomas. Further research is needed to confirm our results. • Cyclosporine after kidney transplant increases the risk of breast fibroadenoma. • Conversion from cyclosporine or tacrolimus to sirolimus can lower this risk. • Among 15 women with breast fibroadenoma, conversion did not change the Breast Imaging Reporting and Data System class. • Conversion did lower transforming growth factor βl level, which is associated with breast fibroadenoma. [ABSTRACT FROM AUTHOR]

To improve early renal allograft function, it is important to develop a noninvasive diagnostic method for acute T cell-mediated rejection (TCMR). This study aims to explore potential noninvasive urinary biomarkers to screen for acute TCMR in kidney transplant recipients (KTRs) using untargeted metabolomic profiling. Urinary metabolites, collected from KTRs with stable graft function (STA) or acute TCMR episodes, were analyzed using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses were performed to discriminate differences in urinary metabolites between the two groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of potential urinary biomarkers. Statistical analysis revealed the differences in urinary metabolites between the two groups and indicated several statistically significant metabolic features suitable for potential biomarkers. By comparing the retention times and mass fragmentation patterns of the chemicals in metabolite databases, samples, and standards, six of these features were clearly identified. ROC curve analysis showed the best performance of the training set (area under the curve value, 0.926; sensitivity, 90.0%; specificity, 84.6%) using a panel of five potential biomarkers: guanidoacetic acid, methylimidazoleacetic acid, dopamine, 4-guanidinobutyric acid, and L -tryptophan. The diagnostic accuracy of this model was 62.5% for an independent test dataset. LC-MS-based untargeted metabolomic profiling is a promising method to discriminate between acute TCMR and STA groups. Our model, based on a panel of five potential biomarkers, needs to be further validated in larger scale studies. • We explored urinary biomarkers for acute TCMR using LC-MS-based metabolomics. • OPLS-DA well distinguished between acute TCMR and STA groups. • Multivariate statistical analyses revealed differences in urinary metabolites. • ROC curve analysis evaluated the performance of potential urinary biomarkers. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate the clinical outcomes of kidney transplantation (KT) in elderly recipients compared with those in young recipients. Methods: We compared the incidence of biopsy‐proven acute rejection, death‐censored allograft survival and all‐cause mortality, and also compared the impact of high sensitization or desensitization on the clinical outcomes of elderly and young recipients. Results: A total of 4966 KT recipients from the Korean Organ Transplantation Registry were included. The definition of elderly recipients was based on age >60 years (n = 356), and recipients aged <60 years were defined as young recipients (n = 4610). The incidence of biopsy‐proven acute rejection did not differ between the two groups irrespective of the donor type; however, the impact of high sensitization was significant only in young recipients. Being an elderly recipient was an independent risk factor for death‐censored allograft failure in terms of overall and living donor KT, but not with deceased donor KT. In regard to patient death, being an elderly recipient was a significant predictor in general and in the two subgroups, and desensitization showed a significant interaction with death in the elderly recipients in the living donor KT group. Conclusions: In conclusion, KT in elderly recipients might be associated with poor allograft or patient survival in general, and especially, desensitization therapy carried out in these patients might increase the risk of patient mortality. Geriatr Gerontol Int 2019; 19: 392–398. [ABSTRACT FROM AUTHOR]

Background Adiponectin is an adipokine secreted by adipocytes. A low adiponectin level is a significant risk factor of diabetes mellitus and cardiovascular disease. Recent studies have shown that adiponectin is negatively associated with hematopoiesis and predicts the development of anemia in the general population. In chronic kidney disease (CKD) patients, circulating adiponectin level is paradoxically elevated and the role of adiponectin is complex. Therefore, we evaluated the relationship between adiponectin and anemia in these patients. Methods This prospective longitudinal study included 2113 patients from the KNOW-CKD study (KoreaN cohort study for Outcome in patients With CKD), after excluding 125 without data on adiponectin levels. Hemoglobin levels were measured yearly during a mean follow-up period of 23.7 months. Anemia was defined as hemoglobin levels of <13.0 and 12.0 g/dL for men and women, respectively. Results Mean patient age was 53.6 ± 12.2 years, and 1289 (61%) were men. The mean estimated glomerular filtration rate (eGFR) was 50.4 ± 30.2 mL min −1  1.73 m −2 . Serum adiponectin level was inversely associated with body mass index, eGFR, log-transformed C-reactive protein, and positively with Charlson comorbidity index, urine protein to creatinine ratio, and high density lipoprotein cholesterol. In addition, serum adiponectin level was also negatively correlated with hemoglobin level and reticulocyte production index in both men and women. In multivariable linear regression analysis after adjustment of multiple confounders, adiponectin was negatively associated with hemoglobin (men, β  = −0.219, P  < .001; women, β  = −0.09, P  = .025). Among 1227 patients without anemia at baseline, 307 newly developed anemia during the follow-up period. In multivariable Cox regression analysis after adjustment of confounders, high adiponectin level was significantly associated with an increased risk of incident anemia (per 1 µg/mL increase, hazard ratio, 1.02; 95% confidence interval 1.01–1.04; P  = .001). Conclusions A high serum adiponectin level is independently associated with a low hemoglobin level and predicts the development of anemia in patients with CKD. These findings reveal the potential role of adiponectin in CKD-related anemia. [ABSTRACT FROM AUTHOR]

This was a nationwide cohort study to investigate the impact of anti-A/B and donor-specific anti- HLA ( HLA- DSA) antibodies on the clinical outcomes in kidney transplant recipients ( KTRs). We classified a total of 1964 KTRs into four groups: transplants from ABO-incompatible donors ( ABOi, n = 248); transplants in recipients with HLA- DSA ( HLAi, n = 144); transplants from combined ABOi and HLAi donors ( ABOi + HLAi, n = 31); and a control group for whom neither ABOi nor HLAi was applicable ( CONT, n = 1541). We compared the incidence of biopsy-proven acute rejection ( BPAR), allograft and patient survival rates. The incidence of BPAR was higher in the HLAi and ABOi + HLAi groups relative to the CONT group; in contrast, it was not higher in the ABOi group. Death-censored graft survival rates did not differ across the four groups. However, relative to the CONT group, patient survival rate was reduced in the ABOi and ABOi + HLAi groups, and with infection being the most common cause of death. Further, multivariable analysis revealed that desensitization therapy because of ABOi or HLAi was independent risk factors for patient mortality. HLAi was a more important risk factor for BPAR compared with ABOi. However, pretransplant desensitization therapy for either ABOi or HLAi significantly increased the risk of infection-related mortality. [ABSTRACT FROM AUTHOR]

Urinary mRNA analysis with three-gene set (18S rRNA, CD3ε, and IP-10) has been suggested as a non-invasive biomarker of acute rejection (AR) in kidney transplant recipients using quantitative real-time PCR (qPCR). Application of droplet digital PCR (ddPCR), which has been suggested to provide higher sensitivity, accuracy, and absolute quantification without standard curves, could be a useful method for the quantifying low concentration of urinary mRNA. We investigated the urinary expression of these three genes in Korean patients with kidney transplantation and also evaluated the usefulness of ddPCR. 90 urine samples were collected at time of allograft biopsy in kidney recipients (n = 67) and from patients with stable renal function more than 10 years (n = 23). Absolute quantification with both PCR system showed significant higher mRNA levels of CD3ε and IP-10 in AR patients compared with stable transplants (STA), but there was no difference in 18S rRNA expression across the patient groups. To evaluate discrimination between AR and STA, ROC curve analyses of CTOT-4 formula yielded area under the curve values of 0.72 (95% CI 0.60–0.83) and 0.77 (95% CI 0.66–0.88) for qPCR and ddPCR, respectively. However, 18S normalization of absolute quantification and relative quantification with 18S showed better discrimination of AR from STA than those of the absolute method. Our data indicate that ddPCR system without standard curve would be useful to determine the absolute quantification of urinary mRNA from kidney transplant recipients. However, comparative method also could be useful and convenient in both qPCR and ddPCR analysis. [ABSTRACT FROM AUTHOR]

Fibrosis is the final pathological outcome of many chronic kidney diseases and is quite common. Thus, development of effective anti-fibrotic agents is urgently needed. Although histone deacetylases (HDACs) have been reported to be involved in renal fibrosis, current HDAC inhibitors are unsatisfactory anti-fibrosis drugs. Therefore, more potentially relevant anti-renal fibrosis HDAC inhibitors are needed. We initially found that non-cytotoxic concentrations of SB939 (pracinostat) had strong anti-fibrotic activity, drastically decreasing TGF-β1-induced alpha smooth muscle actin (α-SMA) expression in the NRK renal fibroblast cell line. Similar anti-fibrotic activity of SB939 on epithelial-to-mesenchymal transition (EMT) was confirmed using the HK-2 human renal proximal tubular epithelial cell line. SB939 inhibited Smad-independent TGF-β signaling involving the MAPK and PI3K/AKT pathways. To evaluate in vivo anti-fibrotic activity, we administered SB939 in a unilateral ureteric obstruction (UUO) model. SB939 treatment markedly inhibited the accumulation of α-SMA and tissue injury. Inflammatory and pro-fibrotic cytokines in the obstructed kidney were also significantly decreased by SB939 treatment. Our results suggest that SB939 might be a promising therapeutic drug for preventing renal fibrosis. [ABSTRACT FROM AUTHOR]

Background: Anemia is a common complication among patients with chronic kidney disease (CKD), and it is associated with unfavorable clinical outcomes in patients with CKD independent of the estimated glomerular filtration rate (eGFR). We assessed the association of the urinary albumin-to-creatinine ratio (ACR) and eGFR with anemia in CKD patients. Methods: We conducted a cross-sectional study using baseline data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). Multiple regression analysis was performed to identify the independent association of albuminuria with anemia. Furthermore, odds ratios for anemia were calculated by cross-categorization of ACR and eGFR. Results: Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and the mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 m2 and 853.2 ± 1,330.3 mg/g, respectively. Anemia was present in 644 patients (40.5%). Multivariate analysis showed that the odds ratio of anemia increased according to ACR levels, after adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use of erythropoiesis stimulating agents, serum calcium and ferritin (ACR < 30 mg/g as a reference group; 30–299 mg/g, adjusted odds ratio (OR) = 1.43, 95% confidence interval (CI) = 0.88–2.33; ≥300 mg/g, adjusted OR = 1.86, 95% CI = 1.12–3.10). In addition, graded associations were observed in cross-categorized groups of a higher ACR and eGFR compared to the reference group with an ACR <30 mg/g and eGFR ≥60 mL/min per 1.73 m2. Conclusion: The present study demonstrated that albuminuria was a significant risk factor for anemia in CKD patients independent of the eGFR. [ABSTRACT FROM AUTHOR]

Background: Serial interferon-gamma-release-assay (IGRA) result can show variance due to within-subject variation and difference in host immune status, and may be affected by latent tuberculosis infection (LTBI) treatment. We aimed to know the changes in QFT-IT (QuantiFERON-TB Gold In-Tube) results measured at a 4 month interval in end stage renal disease patients and whether these changes were influenced by dialysis method or LTBI treatment.Methods: We prospectively performed serial QFT-IT tests at 4 month interval in 93 end stage renal disease (ESRD) patients on HD (hemodialysis) or PD (peritoneal dialysis). LTBI treatment was given to 18 of 39 patients with initial positive QFT-IT result. Agreement between the two results was estimated for all 93 patients and reversion rates were estimated among the 39 patients with initial positive QFT-IT.Results: Positive QFT-IT at the first and 2(nd) tests were 41.9 and 34.4 %, respectively. The concordance rate between baseline QFT-IT and 2(nd) QFT in 93 ESRD patients was excellent (90.3 %, kappa = 0.80, p < 0.001). Agreement between the first QFT-IT and 2(nd) QFT-IT in HD (95.3 %, kappa = 0.91, p < 0.001) was higher than in PD patients (86.0 %, kappa = 0.69, p < 0.001). Among all ESRD patients, the odds of reversion of QFT-IT was not different in those who were, or were not treated for LTBI [odds ratio = 2.3 (0.5-11.4), p = 0.43].Conclusions: In a group of 93 dialyzed ESRD patients 8.6 % showed reversion of initial positive QFT to negative within 4 months. Reversion seemed not to be associated with LTBI treatment. Further study with larger numbers of patients is needed to investigate the variation of QFT-IT tests in dialyzed ESRD patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Retinal degeneration is caused by neovascularization and persistent inflammation in the retinal pigment epithelium (RPE) and choroid, and causes serious eye disease including age-related macular degeneration (AMD). Thus, inhibiting inflammation and neovascularization may be a primary approach to protect the retina from degeneration. The purpose of this study was to determine whether substance P (SP), which can suppress inflammation and mobilize stem cells, can protect the RPE from degeneration. The effect of SP was evaluated by analyzing systemic inflammation, cell survival, and neovascularization within the argon laser-injured retina of mice. At 1 week postinjury, the SP-treated group had lower tumor necrosis factor-alpha and higher interleukin-10 serum concentrations, and a more intact retinal structure compared to the vehicle-treated group. In mice administered SP repeatedly for 4 weeks, the retinal structure appeared normal and showed sparse neovascularization, whereas the vehicle-treated group showed severe retinal destruction and dense neovascularization. Moreover, the efficacy of SP was identical to that of mesenchymal stem cells that were transplanted into the vitreous after retinal injury. This study highlights the potential for the endogenous neuropeptide SP as a treatment for retinal damage to prevent conditions such as AMD. [ABSTRACT FROM AUTHOR]

Recent studies have shown that single-nucleotide polymorphisms ( SNPs) are associated with allograft rejection in kidney transplantation recipients. We evaluated the possible association between SNPs of the cytochrome P450, family 2, subfamily E, polypeptide 1 ( CYP2E1) gene, and acute rejection ( AR) among renal transplant patients in a Korean population. We conducted a case-control association study in 63 AR and 284 non- AR kidney transplant recipients. The SNPs of CYP2E1 were genotyped by direct sequencing. Recipient sex (p = 0.023) and the use of tacrolimus (p = 0.017) were significantly different between the two groups. The use of mycophenolate mofetil ( MMF) and antibody induction therapy was significantly lower in the AR group. Multiple logistic regression models (codominant, dominant, recessive, and log-additive models) adjusted by sex and type of immunosuppressive regimens were applied to determine the odds ratios ( ORs), 95% confidence intervals ( CIs), and p-values. The rs2515641 of CYP2E1 showed significant differences between the AR patient group and non- AR group (p = 0.003, OR = 2.55, 95% CI = 1.37-4.75 in the codominant 1 model; p = 0.002, OR = 2.61, 95% CI = 1.43-4.77 in the dominant model; p = 0.0035, OR = 2.13, 95% CI = 1.29-3.50 in the log-additive model). The allele of the rs2515641 SNP also showed a significant association (p = 0.004, OR = 1.99, 95% CI = 1.24-3.21). This study suggests that the CYP2E1 polymorphism may be related to the development of AR in Korean kidney transplantation recipients. [ABSTRACT FROM AUTHOR]

Background: Post-transplant diabetes mellitus (PTDM) is a common and serious metabolic complication. Genetic polymorphisms of angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) genes have been reported to be related to diabetes mellitus and insulin sensitivity; however, the role of these genes in the development of PTDM is not known. For this purpose, we investigated the association of ACE and AGT genetic polymorphisms with PTDM. Methods: A total of 302 subjects without previously diagnosed diabetes who had received kidney transplants were included. One ACE single nucleotide polymorphism (SNP) (rs4291) and two AGT SNPs (rs 699 and rs 4762) were genotyped from genomic DNA with direct sequencing. Results: PTDM developed in 49 (16.2%) of 302 subjects. Subjects in the PTDM were older than those in the non-PTDM. There was a significant difference between the two groups in tacrolimus use (p=0.03). Of the three SNPs, the rs4762 of the AGT gene was significantly associated with the development of PTDM in the dominant models (p = 0.03) after adjusting for age and tacrolimus usage. Conclusions: AGT gene rs4762 polymorphisms may serve as genetic markers for the development of PTDM. The exact molecular mechanisms still need to be clarified. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Fibrillary glomerulonephritis (FGN) is a rare cause of progressive renal dysfunction resulting in fibrillary deposits in the mesangium and/or glomerular basement membrane (GBM). Some case reports have shown FGN in patients with rheumatoid arthritis and other autoimmune diseases. This is the first case report of FGN in a patient with Behçet's syndrome. The most common renal histological finding in Behçet's syndrome is secondary amyloidosis. A 46-year-old woman with a 4-year history of Behçet's syndrome was referred to the nephrology clinic with foamy urine with non-selective proteinuria (urine protein-to-creatinine ratio was 1400 mg protein/g creatinine) and microscopic hematuria. Serum and urine protein electrophoresis showed no evidence of monoclonal gammopathy. A renal biopsy was performed. Light microscopy showed mesangial widening and nodular expansion with hyaline deposits. Immunofluorescence microscopy revealed immunoglobulin M deposits in the mesangium. Congo red staining was negative. Electron microscopy showed fibrillary deposits on the GBM. Pathological findings were consistent with FGN. She had been taking 50 mg azathioprine and 3000 mg mesalazine per day for 4 years due to Behçet's syndrome, so we did not add any other immunosuppressive agents or corticosteroids. Treatment of this glomerulopathy is not promising. It has been noted that none of the various approaches, including corticosteroid, plasmapheresis, and cytotoxic therapy, improves prognosis. [ABSTRACT FROM AUTHOR]

ABO-incompatible (ABOi) and positive crossmatch (XM) kidney transplantation (KT) have been considered immunologically challenging. The present study analyzed the clinical outcomes in XM positive KT based on ABO incompatibility. We used data from the Korea Organ Transplantation Registry, a nationwide database, and a single-center registry. A total of 263 patients with positive XM were divided into an ABO compatible (ABOc) & XM positive (ABOc/XM+, n = 176) group and an ABOi & XM positive (ABOi/XM+, n = 87) group. The overall rejection rate one year after KT was significantly higher in the ABOi/XM+ group than in the ABOc/XM+ group (P < 0.01). A total of four mortalities occurred, all in the ABOi/XM+ patients (P < 0.01). There were no differences in surgical complications or the occurrence of infection-related complications, including BK virus nephropathy. Multivariate analysis indicated that female vs. male (odds ratio (OR), 2.27; P = 0.03), DSA class I (MFI/1000) (OR, 1.10; P = 0.03), DSA class II (MFI/1000) (OR, 1.10; P < 0.01), and ABOi & XM+ status (OR, 2.38; P < 0.01) were significant risk factors for acute rejection during the year after transplantation. Overall graft survival was inferior in ABOi/XM+ patients than in ABOc/XM+ patients (P = 0.02). ABO incompatibility in XM-positive KT patients was found to be a significant risk factor for the development of rejection within one year after transplantation as well as for long-term graft survival. The anti-blood group A, B and anti-HLA antibodies may show synergistic activity. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent evidence suggests that genetic factors are related to the pathogenesis of IgAN. We conducted a genome-wide association study (GWAS) to identify novel genetic susceptibility loci for IgAN in a Korean population. Methods: We enrolled 188 biopsy-confirmed IgAN cases and 455 healthy controls for the discovery stage and explored associations between IgAN and single nucleotide polymorphisms (SNPs) using a customized DNA chip. The significant SNPs from the discovery samples were then selected for replication in an independent cohort with 310 biopsy-confirmed IgAN cases and 438 healthy controls. Results: In the first stage, two SNPs (rs10172700 in LOC105373592 and rs2296136 in ANKRD16) were selected for further association analysis in the next stage. In the replication cohort, rs2296136 in ANKRD16 was significantly associated with IgAN (odds ratio [OR] = 1.40, 95% confidence interval [CI] 0.99–1.98, p = 0.05 in log-additive model, OR = 1.55, 95% CI = 1.06–−2.27, p = 0.02 in dominant model, and OR = 0.70, 95% CI = 0.17–−2.84, p = 0.62 in recessive model). rs2296136 in ANKRD16 also showed a significant association with IgAN in the entire study population combining GWAS and replication study (p = 0.0045 in log-additive model, p = 0.0027 in dominant model, and p = 0.76 in recessive model). Conclusions: The SNPs identified in the present study could be good candidate markers for predicting IgAN in Koreans, although further experimental validation is needed. [ABSTRACT FROM AUTHOR]

Background: The independent association between eGFR and coronary artery calcification (CAC) is complex and not clear. The aim of this study was to investigate the relationship between eGFR calculated from different equations and CAC in predialysis CKD patients in Korea. Methods: In this cross‐sectional study, we analysed 1533 patients from the KNOW‐CKD cohort. eGFR was calculated by a four‐variable MDRD equation (eGFRMDRD), CKD‐EPI creatinine equations (eGFRCr), CKD‐EPI cystatin C equation (eGFRCys) and CKD‐EPI creatinine‐cystatin equation (eGFRCrCys). Participants were divided into eGFR categories (<30, 30‐59, 60‐89, ≥90 mL/min/1.73 m2). CACS (coronary artery calcium score) was measured using cardiac computed tomography. CAC was defined as CACS >100. Results: Coronary artery calcification was found in 334 (21.8%) patients and was more prevalent in the lower eGFR groups (P < 0.001). In multivariate Tobit regression, CACS increased gradually as eGFRCrCys decreased (P for trend = 0.034). In multivariate logistic regression, there were gradual associations between lower eGFR and CAC when an eGFRCys or eGFRCrCys was used. The adjusted OR for CAC in the group with eGFR <30 mL/min/1.73 m2 compared to the group with eGFR ≥90 mL/min/1.73 m2 was 2.64 (95% CI, 1.09‐3.60) when eGFRCrCys was used. Of the four eGFR formulas, only adding eGFRCrCys significantly improved CAC prediction models without eGFR (P = 0.046). Conclusions: There was a gradual and independent association between low eGFR and CAC in a predialysis CKD cohort in Korea. eGFRCrCys predicted CAC better than other equations in this population. [ABSTRACT FROM AUTHOR]