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Background Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning–based artificial intelligence (AI) model to predict IDH using pre-dialysis features. Methods Data from 2,007 patients with 943,220 HD sessions at seven university hospitals were used. The performance of deep learning model was compared with 3 machine learning models (logistic regression, random forest, and XGBoost). Results IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared to non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared to non-IDH sessions. Matthews correlation coefficient (MCC) and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost, and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. Conclusions Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Immune check point inhibitors (ICI) have secured regulatory approvals across the world for the treatment of various types of cancers. Though not as frequent as immune-related adverse events (AEs) involving other organs, a considerable number of ICI-related renal AE have also been reported and predicting such events has become important. We provide an updated review on possible mechanisms of ICI-related acute kidney injury (AKI), related risk factors, and the use of ICIs in patients with chronic kidney diseases (CKD). A systematic search for related articles was conducted. Acute tubulointerstitial nephritis (ATIN) is known to be the main cause of ICI-related AKI, with glomerulonephritis also a significant cause. Factors including use of concurrent medications, extra-renal immune related AEs, and combination of two or more immunotherapy drugs are possible risk factors. Use of ICI in patients with CKD may be related to increased occurrence of overall immune related AEs. If the diagnosis of ICI related renal AEs is confirmed, prompt use of steroids is recommended, and in severe cases of AKI, discontinuation of ICI should be considered.

IntroductionTacrolimus (TAC) has been widely used as an immunosuppressant after kidney transplantation (KT); however, the combined effects of intra-patient variability (IPV) and inter-patient variability of TAC-trough level (C0) in blood remain controversial. This study aimed to determine the combined impact of TAC-IPV and TAC inter-patient variability on allograft outcomes of KT.MethodsIn total, 1,080 immunologically low-risk patients who were not sensitized to donor human leukocyte antigen (HLA) were enrolled. TAC-IPV was calculated using the time-weighted coefficient variation (TWCV) of TAC-C0, and values > 30% were classified as high IPV. Concentration-to-dose ratio (CDR) was used for calculating TAC inter-patient variability, and CDR < 1.05 ng•mg/mL was classified as rapid metabolizers (RM). TWCV was calculated based on TAC-C0 up to 1 year after KT, and CDR was calculated based on TAC-C0 up to 3 months after KT. Patients were classified into four groups according to TWCV and CDR: low IPV/non-rapid metabolizer (NRM), high IPV/NRM, low IPV/RM, and high IPV/RM. Subgroup analysis was performed for pre-transplant panel reactive antibody (PRA)-positive and -negative patients (presence or absence of non-donor-specific HLA-antibodies). Allograft outcomes, including deathcensored graft loss (DCGL) and biopsy-proven allograft rejection (BPAR), were compared.ResultsThe incidences of DCGL, BPAR, and overall graft loss were the highest in the high-IPV/RM group. In addition, a high IPV/RM was identified as an independent risk factor for DCGL. The hazard ratio of high IPV/RM for DCGL and the incidence of active antibody-mediated rejection were considerably increased in the PRA-positive subgroup.DiscussionHigh IPV combined with RM (inter-patient variability) was closely related to adverse allograft outcomes, and hence, more attention must be given to pre-transplant PRA-positive patients.

We investigated whether HLA class II eplet mismatch was related to dnDSA development and analyzed its combined impact with tacrolimus levels for kidney transplantation outcomes. A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, antibody (Ab)-verified eplet mismatch analyses, and Ab-verified single molecular analysis to identify HLA-DR/DQ molecular thresholds for the risk of dnDSA development. A time-weighted tacrolimus trough level (TAC-C0) of 5 ng/mL and a TAC-C0 time-weighted coefficient variability (TWCV) of 20% were applied to find the combined effects on dnDSA development. A high level of mismatch for single molecular eplet (DQ ≥ 10), total eplet (DQ ≥ 12), Ab-verified eplet (DQ ≥ 4), and Ab-verified single molecular eplet (DQ ≥ 4) significantly correlated with HLA class II dnDSA development. Class II dnDSA developed mostly in patients with low TAC-C0 and high eplet mismatch. In the multivariable analyses, low TAC-C0 and high eplet mismatch showed the highest hazard ratio for the development of dnDSA. No significant combined effect was observed in dnDSA development according to TWCV. In conclusion, the determination of HLA class II eplet mismatch may improve the risk stratification for dnDSA development, especially in conjunction with tacrolimus trough levels.

Background This study aimed to investigate whether high body mass index (BMI) and presensitization to human leukocyte antigen (HLA) in kidney transplant recipients (KTRs) affected allograft outcomes. Methods From January 2010 to December 2018, 1,290 kidney transplantations (KTs) were performed at the Seoul St Mary's Hospital. Of these, 682 cases of ABO-compatible living donor KT patients were enrolled. They were divided into four groups (low BMI-non-sensitized, high BMI-non-sensitized, low BMI-sensitized, and high BMI-sensitized) according to the median BMI value (22.7 kg/m2) and HLA presensitization status (anti-HLA antibody mean fluorescence intensity > 3,000). Short-term and long-term allograft outcomes were compared between groups. Results In the high BMI-sensitized group, the decline in allograft function was higher than that in the other three groups. Death-censored graft loss (DCGL) rates were highest in the high BMI-sensitized group (4 of 21 [19.0%], p = 0.04). In the multivariable Cox regression hazard regression model analysis, the hazard ratio (HR) for DCGL was intensified when high BMI and presensitization statuses were combined (HR, 3.75; p = 0.03); these statuses significantly interacted with each other (p-value for interaction = 0.008). Conclusion Our results suggest that presensitization to HLA and high BMI might have an interactive adverse impact on allograft outcomes in KTRs.

This study aimed to investigate the impact of low-level donor-specific HLA antibody (low-DSA) on post-transplant clinical outcomes of kidney transplantation (KT) recipients. We retrospectively reviewed 1,027 cases of KT, including 629 living donor kidney transplantations (LDKTs) and 398 deceased donor kidney transplantations (DDKTs) between 2010 and 2018 in our center. Low-DSA was confirmed by positive Luminex assay and negative crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and post-transplant infections between subgroups according to pre-transplant low-DSA. The incidence of overall BPAR and T-cell mediated rejection did not differ between subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort, LDKT, and DDKT. In multivariate analysis, low-DSA was an independent risk factor for ABMR. Its impact was more pronounced in DDKT (Odds ratio [OR]: 10.000, 95% confidence interval [CI]: 2.781–35.960) than in LDKT (OR: 5.210, 95% CI: 2.100-12.924). There were no significant differences in other outcomes according to low-DSA. In conclusion, pre-transplant low-DSA had a significant impact on the development of AMBR, which was more pronounced in DDKT than in LDKT. However, its impact on long-term outcome was not significant.

Tacrolimus is a key drug in kidney transplantation (KT) with a narrow therapeutic index. The association between the tacrolimus metabolism rate and KT outcomes have not been investigated in large-scale multi-center studies. The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C0 ) divided by the daily dose (D). The patients were grouped into fast, intermediate, or slow metabolizers by the C0 /D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m2 higher adjusted estimated glomerular filtration rate (eGFR) at 6 months [95% confidence interval (C.I.) 1.2-4.3, P = 0.001], less acute rejection (AR) within 6 months [Odds ratio (OR) 0.744, 95% C.I. 0.585-0.947, P = 0.016], and less interstitial fibrosis and tubular atrophy [OR 0.606, 95% C.I. 0.390-0.940, P = 0.025]. Fast tacrolimus metabolism affected the 6-month post-KT eGFR through mediation of AR [natural indirect effect (NIE) -0.434, 95% C.I. -0.856 to -0.012, P = 0.044) and delayed graft function (DGF; NIE -0.119, 95% C.I. -0.231 to -0.007, P = 0.038). Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.

We investigated the impact of acute kidney injury (AKI) in elderly deceased-donors (DDs) vs. AKI in young DDs on post-transplant clinical outcomes. A total of 709 kidney transplant recipients (KTRs) from 602 DDs at four transplant centers were enrolled. KTRs were divided into young-DDKT and elderly-DDKT groups according to the age of DD of 60 years. Both groups were subdivided into non-AKI-KT and AKI-KT subgroups according to AKI in DDs. We investigated short-term and long-term clinical outcomes of non-AKI-DDKT and AKI-DDKT subgroups within young-DDKT and elderly-DDKT groups. The incidence of DGF in the AKI-DDKT subgroup was higher and the allograft function within 12 months after KT in the AKI-DDKT subgroup was lower than those in the non-AKI-DDKT subgroup in both young-DDKT and elderly-DDKT groups. Death-censored allograft survival rate was significantly lower in the AKI-elderly-DDKT subgroup than that in the non-AKI-elderly-DDKT subgroup, but it did not differ between AKI-young-DDKT and non-AKI-young-DDKT subgroup. In multivariable analysis, AKI-elderly-DDKT was an independent risk factor for allograft failure (hazard ratio: 2.648, 95% CI: 1.170–5.994, p = 0.019) and a significant interaction between AKI and old age in DDs on allograft failure was observed (p = 0.001). AKI in elderly DDs, but not in young DDs, can significantly affect long-term allograft outcomes of KTRs.

We sought to analyze the visual outcome and systemic prognostic factors for diabetic vitrectomy and predicted outcomes using these factors.This was a multicenter electronic medical records (EMRs) review study of 1504 eyes with type 2 diabetes that underwent vitrectomy for proliferative diabetic retinopathy at 6 university hospitals. Demographics, laboratory results, intra-operative findings, and visual acuity (VA) values were analyzed and correlated with visual outcomes at 1 year after the vitrectomy. Prediction models for visual outcomes were obtained using machine learning.At 1 year, VA was 1.0 logarithm of minimal angle resolution (logMAR) or greater (poor visual outcome group) in 456 eyes (30%). Baseline visual acuity, duration of diabetes treatment, tractional membrane, silicone oil tamponade, smoking, and vitreous hemorrhage correlated with logMAR VA at 1 year (r = 0.450, -0.159, 0.221, 0.280, 0.067, and -0.105; all P ≤ 0.036). An ensemble decision tree model trained using all variables generated accuracy, specificity, F1 score (the harmonic means of which precision and sensitivity), and receiver-operating characteristic curve area under curve values of 0.77, 0.66, 0.85, and 0.84 for the prediction of poor visual outcomes at 1 year after vitrectomy.Visual outcome after diabetic vitrectomy is associated with pre- and intra-operative findings and systemic factors. Poor visual outcome after diabetic vitrectomy was predictable using clinical factors. Intensive care in patients who are predicted to result in poor vision may limit vision loss resulting from type 2 diabetes.This study demonstrates that a real world EMR big data could predict outcome after diabetic vitrectomy using clinical factors.

Background The aim of this study was to investigate whether high body mass index (BMI) and pre-sensitization to human leukocyte antigen (HLA) in kidney transplant recipients (KTR) had a synergistic impact on the allograft outcomes.Methods From January 2010 to December 2018, 1,290 KTs were performed in Seoul St Mary's Hospital. Of these, 682 cases of ABO compatible KT were enrolled. They were divided into 4 groups (low BMI-non-sensitized, high BMI-non-sensitized, low BMI sensitized, high BMI-sensitized) according to the median BMI value (22.7 kg/m2) and HLA pre-sensitization status (HLA-DSA MFI >3,000). Short-term and long-term allograft outcomes were compared between the groups.Results The rate of late antibody mediated rejection tended to be the highest in the high BMI-sensitized group, and the decline in allograft function in the high BMI-sensitized group was higher than in the other 3 groups. Death-censored graft loss (DCGL) rates and the hazard ratio (HR) for DCGL were the highest in the high BMI-sensitized group (4/21 (19.0%), HR 4.648, P = 0.022) and a significant interaction was detected between high BMI and HLA pre-sensitization status (P value for interaction = 0.008). Conclusions Our results suggest that pre-sensitization to HLA and high BMI in KTRs might have a synergistic adverse impact on the allograft outcomes.

We investigated if clinical outcomes after kidney transplantation (KT) from deceased donors (DDs) with high Kidney Donor Profile Index (KDPI) can be different according to the age of KT recipients (KTRs). Six-hundred fifty-seven KTRs from 526 DDs were included from four transplant centers. We divided KTRs into elderly-KTR and young-KTR groups based on age 60 and each group was subdivided into high- or low-KDPI subgroup based on KDPI score of 65%. We compared short-term and long-term clinical outcomes among those four subgroups (low KDPI-young KTR, low KDPI-elderly-KTR, high KDPI-young-KTR, high KDPI-elderly-KTR). In short-term outcomes including acute rejection, BK virus and CMV infection, there was no significant difference among the four subgroups. In the long-term outcomes, the development of cardiovascular disease was higher in the high KDPI-elderly-KTR group than the other groups. In comparison of allograft survival rate, the high KDPI-young KTR subgroup showed highest risk for allograft failure and there was significant interaction between high-KDPI donors and young-KTR on allograft survival rate (P = 0.002). However, there was no significant difference in comparison of the patient survival rate. In conclusion, clinical impact of high-KDPI in DDs on post-transplant allograft survival may be less significant in elderly-KTR than in young-KTR.

Background/Aims To investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). Methods We included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller (< 3 months) and noncontroller (> 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). Results BKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). Conclusions BKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

Background Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients. Methods Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics. Results Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti-AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (-) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017-24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti-AT1R. Conclusions Pre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue.

Background Favorable long-term and short-term graft survival and patient survival after kidney transplantation (KT) from deceased donors with acute kidney injury (AKI) have been reported. However, few studies have evaluated effects of donor AKI status on graft outcomes after KT in Asian population. Thus, the purpose of this study was to evaluate graft function after KTs from donors with AKI compared to matched KTs from donors without AKI using a multicenter cohort in Korea. Methods We analyzed a total of 1,466 KTs collected in Korean Organ Transplant Registry between April 2014 and December 2017. KTs from AKI donors (defined as donors with serum creatinine level ≥ 2 mg/dL) and non-AKI donors (275 cases for each group) were enrolled using a 1:1 propensity score matching. Graft outcomes including graft and patient survival, delayed graft function (DGF), rejection rate, and serially measured estimated glomerular filtration rate (eGFR) were evaluated. Results After propensity matching, KTs from AKI donors showed higher rate of DGF (44.7% vs. 24.0%, p < 0.001). However, the rejection rate was not significantly different between the two groups (KTs from AKI donors vs. KTs from non-AKI donors). eGFRs measured after 6 months, 1 year, 2 years and 3 years were not significantly different by donor AKI status. With median follow-up duration of 3.52 years, cox proportional hazards models revealed hazard ratio of 0.973 (95% confidence interval [CI], 0.584 to 1.621), 1.004 (95% CI, 0.491 to 2.054) and 0.808 (95% confidence interval [CI], 0.426 to 1.532) for overall graft failure, death-censored graft failure and patient mortality, respectively, in KTs from AKI donors compared to KTs from non-AKI donors as a reference. Conclusions KTs from AKI donors showed comparable outcomes to KTs from non-AKI donors, despite a higher incidence of DGF. Results of this study supports the validity of using kidneys from deceased AKI donors in Asian population.

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males, higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio, and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients, 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level &gt, 7.0 mg/dL for males and &gt, 5.6 mg/dL for females, 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.

BackgroundThe aim of this study was to investigate whether 1α,25-dihydroxyvitamin D3 can regulate Th17-related immune responses in kidney transplant recipients (KTRs) being treated with tacrolimus (Tac)-based immunosuppression.MethodsFirst, we evaluated the effect of 1α,25-dihydroxyvitamin D3 (1,25(

Spontaneous renal artery dissection is a rare disease and an uncommon cause of renal infarction. The patient was a man who presented to the emergency room with sudden-onset right flank pain. Computed tomography revealed right renal infarction; thus, anticoagulation was initiated. Renal angiography revealed luminal narrowing of the segmental artery to the superior pole of right kidney without a dissection flap or false lumen. We stopped anticoagulation due to a lack of evidence of thrombi or luminal narrowing of the dissected vessels. When patients present with acute flank pain, it is important to suspect renal infarction and to perform a correct diagnostic workup, even when the patient shows normal urinalysis results and a normal LDH value.

B cell activating factor (BAFF) is a cytokine that plays a role in the survival, proliferation and differentiation of B cells. We proposed to observe the effects of BAFF inhibition on the humoral immune responses of an allosensitized mouse model using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and were treated with anti-BAFF monoclonal antibody (mAb) (named Sandy-2) or control IgG1 antibody. HLA.A2-specific IgG was reduced in BAFF-inhibited mice compared to the control group (&Delta, 13.62 vs. &Delta, 27.07, p &lt, 0.05). BAFF inhibition also resulted in increased pre-pro and immature B cell proportions and decreased mature B cells in the bone marrow (p &lt, 0.05 vs. control). In the spleen, an increase in transitional B cells was observed with a significant decrease in marginal and follicular B cells (p &lt, 0.05 vs. control). There was no significant difference in the proportions of long-lived plasma and memory B cells. Microarray analysis showed that 19 gene probes were significantly up- (&gt, 2-fold, p &lt, 0.05) or down-regulated (&le, 0.05) in the BAFF-inhibited group. BAFF inhibition successfully reduced alloimmune responses through the reduction in alloantibody production and suppression of B cell differentiation and maturation. Our data suggest that BAFF suppression may serve as a useful target in desensitization therapy.

Purpose We sought to assess the relationship between retinal nonperfusion area (NPA) on ultra-widefield fluorescein angiography (UWFA) and renal function in type 2 diabetes mellitus (DM) patients with diabetic retinopathy (DR) and nephropathy. Methods UWFA was performed in 248 eyes (124 patients) with DR, comprising 94 eyes from patients with chronic kidney disease (CKD) caused by diabetes and 154 eyes without CKD (non-CKD). Serum creatinine level (Cr), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio (UACR), and urine protein/creatinine ratio (UPCR) were collected. On UWFA, retinal NPA was measured in an automated manner. The correlation between NPA and renal function was analyzed. Results The mean NPA value of the total eye was 33.11 ± 45.77-disc diameter (DA) in non-CKD and 100.57 ± 69.52 in CKD (P < 0.001). NPA of posterior pole was 1.21 ± 3.28 DA in non-CKD and 7.99 ± 6.75 in CKD group (P < 0.001). The NPA values of both the total eye and posterior pole were significantly correlated with Cr (r = 0.585 and 0.483), eGFR (r = −0.572 and −0.524), UACR (r = 0.541 and 0.482), and UPCR (r = 0.509 and 0.529, respectively) (all P ≤ 0.001). Linear modeling encompassing all clinical factors and relative clinical factors suggested eGFR as the most important predictor for NPAs of the total eye and posterior pole. Conclusions Larger retinal NPA on UWFA is associated with worse renal function in DM patients. Renal function can be used to predict retinal NPA in type 2 DM patients with nephropathy and DR.

Background: Human leukocyte antigen (HLA) analysis has been suggested as a predictive tool for alloimmune risk stratification in kidney transplantation (KT). We investigated whether the whole or single molecule HLA class II eplet mismatch was related to the de-novo donor-specific-antibody (dnDSA) development or antibody-mediated rejection (AMR). Methods: Total 300 kidney transplants performed at Seoul St. Mary’s Hospital between 2016 December and 2020 January with out preformed DSA have been analyzed. HLA class II eplet mismatches were determined by high resolution HLA DRB1/DQB1 typing results and HLA Matchmaker program. Results: During the 22.6 months (median) follow-up period, 24 recipients developed HLA class II dnDSA and 20 patients diag nosed as AMR. Using receiver operating characteristic analysis, we identified eplet mismatch thresholds associated with dnDSA development and stratified recipients into low-, intermediate-, and high-risk categories. In whole eplet mismatch analysis, risk categories were significantly correlated with dnDSA development (log-rank P-value 8 predicted dnDSA development with 75% sensitivity and 63.4% specificity. Risk categories by single molecular eplet mis match also had significant correlation with dnDSA development (log-rank P-value= 0.001) with significant difference between low (HLA-DR ≤7 and HLA-DQ ≤4) (n=78) and intermediate (HLA-DR ≥8 and HLA-DQ ≤6 or HLA-DR 0-7 and HLA-DQ 5-6) (n=95) group (P=0.026). High-risk group (HLA-DR 0-20 and HLA DQ 7-17) predicted dnDSA development with 75% sensitivity and 60.5% specificity. Both eplet mismatch risk categories were significantly associated with AMR, but no differences were found among risk groups. Conclusions: HLA class II eplet mismatches showed the possibility of being used as a clinically relevant parameter in alloim mune risk assessments of KT.

Background: Uremic pruritus is a common, but unpleasant, complication of end-stage renal disease. The uremic burden may differ between hemodialysis (HD) and peritoneal dialysis (PD) patients. This difference may also change the clinical characteristics of uremic pruritus between the 2 modalities. In this study, we investigated the uremic pruritus between patients on HD and PD. Methods: A total of 425 HD and 223 PD patients from the Clinical Research Center registry in Korea were included. Patients were assessed for pruritus intensity, scratching activity, pruritus distribution, and frequency of pruritus-related sleep disturbance using the visual analog scale and questionnaire. Results: The prevalence of uremic pruritus was higher in PD patients than that in HD patients (62.6% vs. 48.3%, P = 0.001). In the multivariable logistic analysis, PD treatment was significantly associated with the prevalence of uremic pruritus (odds ratio, 1.76; 95% confidence interval, 1.20-2.57, P = 0.004) after adjustment for clinical variables. The visual analog scale score, representing a subjective intensity of itchiness, was significantly higher in PD patients (PD 2.11 +/- 2.32 vs. HD 1.65 +/- 2.28, P = 0.013) compared with HD patients. The intensity of uremic pruritus was independently related with serum albumin levels (beta = -0.143, P = 0.006) in HD patients and total weekly Kt/V (beta = -0.176, P = 0.028) in PD patients. Conclusion: Our data demonstrate the difference in prevalence, intensity, and risk factors of uremic pruritus between HD and PD patients. These findings suggest that careful consideration for uremic pruritus might be needed in end-stage renal disease patients according to the dialysis modality. Copyright (C) 2016. The Korean Society of Nephrology. Published by Elsevier.

The increasing interest in healthcare and health screening events is revealing additional cases of asymptomatic isolated microscopic hematuria (IMH). However, a consensus of the evaluation and explanation of the IMH prognosis is controversial among physicians. Here, we present the natural course of IMH together with the pathological diagnosis and features to provide supportive data when approaching patients with IMH. We retrospectively evaluated 350 patients with IMH who underwent a renal biopsy between 2002 and 2011, and the pathological diagnosis and chronic histopathological features (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) were reviewed. Deterioration of renal function was examined during follow up. The patients with IMH were evaluated for a mean of 86 months. IgA nephropathy was the most common diagnosis in 164 patients (46.9%). Chronic histopathological changes were observed in 166 (47.4%) but was not correlated with proteinuria or a decline in renal function. Ten patients developed proteinuria, and all of them had IgA nephropathy. Three patients progressed to chronic kidney disease with an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) but none progressed to end stage renal disease. In conclusion, IMH had a generally benign course during 7-years of observation, although IgA nephropathy should be monitored if it progresses to proteinuria. Future prospective randomized studies may help conclude the long-term prognosis and lead to a consensus for managing IMH.

Eosinophils are bone-marrow–derived granulocytes present in peripheral blood and tissue that are primarily involved as effector cells in various conditions, including inflammatory diseases, allergic diseases, and parasitic infections [1,2]. Researchers have long thought that the main role of eosinophils was to act as effector cells in allergic reactions and helminth infections, but their role as antitumor effectors has recently been revealed [3-6]. Eosinophils function as antitumor effector cells in neoplastic lesions through a variety of eosinophil-derived mediators, including tumor necrosis factor alpha and granzyme-A [3,7]. Changes in the number of tissue eosinophils have been reported in several types of cancer and premalignant lesions from a wide range of organs, including the head and neck and the gastrointestinal tract [5,8-12]. Some studies have shown that the degree of tissue eosinophilia correlates with cancer prognosis because of its significant association with response to chemoradiation therapy, operability, and even lymph node metastasis [5,11,13-16]. These findings suggest that the degree of eosinophilia could be used as a prognostic marker. Among the studies on eosinophils and neoplastic conditions, both increasing and decreasing trends in the number of eosinophils in colorectal neoplasms have been reported with regards to tumor progression. A histopathological study on tissue eosinophilia in colorectal neoplasms has revealed that the degree of eosinophilia differs according to the malignant potential of the lesion; the number of tissue-infiltrating eosinophils increases in low-grade dysplasia, decreases in high-grade lesions, and decreases even more in cancer cases, showing significant and rapid change compared to the surrounding normal tissues [17-19]. As mentioned earlier, more prominent eosinophilia in colorectal cancer is associated with a better prognosis, including significant improvement in the 5-year survival rate. As the association between the infiltration of eosinophils and neoplasms is better understood, interest in how chemokines affect the differentiation and migration of eosinophils is increasing. Many kinds of chemokines are involved in the production, differentiation, and migration of eosinophils. Among the interleukins, interleukin (IL)-3 and IL-5 play major roles in the production and differentiation of eosinophils, and IL-4, IL-6, IL-11, and IL-12 are involved in their differentiation. A variety of C-C chemokines (named after the cysteine terminus residue near the C-terminus in the amino acid sequence), including C-C chemokine ligands-5 (CCL5, RANTES), CCL11 (eotaxin-1), CCL24 (eotaxin-2), and CCL26 (eotaxin-3), are involved in the differentiation and, in particular, the migration of eosinophils from the bone marrow to tissue stroma through enhancement and regulation of tethering, rolling, and endothelial adhesion of the eosinophils [1,2]. Expression of CCL11 and CCL24 in the human gastrointestinal tract is higher than in other tissues in the normal state, and increases during inflammatory disease, allergic reaction, and helminth infections, in which eosinophils function as effector cells [1,20-22]. The concentration of CCL24 is shown to be elevated in tumor tissue, and is also elevated in the stromal cells of colorectal tumors [23]. As mentioned earlier, a decrease in tissue eosinophils was observed in colorectal adenocarcinoma, but tissue levels of CCL11 were found to be elevated. Therefore, there is a discrepancy between decreased tissue eosinophilia and the tissue levels of chemokines such as CCL11 and CCL24, which enhance the recruitment of eosinophils. Serum chemokine levels appear to be elevated in prostate and colorectal adenocarcinoma, and they have been proposed as serum tumor markers [24-28]. In this study, we aimed to (1) evaluate the number of tissue-infiltrating eosinophils in colorectal tubular adenoma with low-grade dysplasia, tubular adenoma with high-grade dysplasia, and adenocarcinoma, and (2) evaluate the expression of CCL11 and CCL24 in colorectal neoplastic lesions by immunohistochemical staining to determine the correlation between the expression of cytokines, eosinophilia, and progression of neoplastic lesions. Even though much is known about the correlation between the prognosis and progression of colorectal neoplasms and eosinophilia, little is known about local expression of the chemokines associated with eosinophils. This study may provide insight into the relationship between tumor eosinophilia and local expression of chemokines, and thus explain the observed discrepancy between chemokine levels and tissue eosinophilia.

Background: BK virus-associated nephropathy (BKVAN) is a known risk factor for allograft dysfunction and graft failure in kidney transplant recipients. The mainstay of treatment for BKVAN is reduction of immunosuppression and this may increase risk for acute rejection. We proposed to observe the effects of acute rejection on patients with BKVAN. Methods: Using data from the Korean Organ Transplantation Registry, a nationwide organ transplantation database, we com pared graft function, and allograft survival in BKVAN patients with or without biopsy proven acute rejection (BPAR). Results: Among the 5,403 patients who received kidney transplantation between 2014 and June 2019, a total of 97 patients were diagnosed with BKVAN. Twenty-six patients (27%) developed BPAR within 6 months of BKVAN diagnosis, 71 patients did not. There were no differences in baseline characteristics, immunosuppression or BKVAN treatment methods between the BPAR and no BPAR groups. There was a significant decrease in allograft function in the BPAR group compared to the no BPAR group in both the 1-year (BPAR creatinine [Cr], 2.5±1.9 mg/dL vs. no BPAR Cr, 1.9±0.9 mg/dL; P=0.044) and 2-year follow-up period (BPAR Cr, 3.8±3.6 mg/dL vs. no BPAR Cr, 2.2±1.0 mg/dL; P=0.015). The BPAR group had lower allograft survival rates compared to the no BPAR group, although not statistically significant (P=0.474). On multivariate Cox regression analysis, MMF discontinuation was observed as a significant risk factor for rejection in BKVAN patients (hazard ratio, 4.000; 95% confidence interval [CI], 1.014- 15.775; P=0.048). Conclusions: Acute rejection with BKVAN is associated with poorer allograft function and survival. Also, discontinuation of MMF as treatment for BKVAN increases risk for acute rejection.

Several studies reported the effect of obesity on the progression of IgA nephropathy (IgAN). However, the impact of obesity on the clinicopathologic presentation of IgAN remains uncertain. This is a retrospective cross-sectional study from eight university hospitals in South Korea. Patients were categorized into three groups using the Asia-Pacific obesity classification based on body mass index (BMI). Clinical and histopathologic data at the time of renal biopsy were analyzed. Among 537 patients with IgAN, the obese group was more hypertensive and had lower estimated glomerular filtration rate and more proteinuria than other groups. The histologic scores for mesangial matrix expansion (MME), interstitial fibrosis, tubular atrophy, and mesangial C3 deposition differed significantly between the three groups. Among these histopathologic parameters, BMI was independently positively associated with MME score on multivariable linear regression analysis (p = 0.028). Using multivariable logistic regression analysis, the obese group was independently associated with higher MME scores compared to the normal weight/overweight group (p = 0.020). However, BMI was not independently associated with estimated glomerular filtration rate or proteinuria on multivariable analysis. Obesity was independently associated with severe MME in patients with IgAN. Obesity may play an important pathogenetic role in mesangial lesions seen in IgAN.

Background Many women with endometriosis have become pregnant through assisted reproductive technology (ART), and have often experienced placenta previa (PP) during pregnancy. The objective of this study was to assess the association between women with endometriosis, especially those who conceived with ART, and the risk of PP. Methods Two reviewers independently determined studies that were considered suitable for meta-analyses published in various medicine-related databases from March 1, 2004 through July 31, 2017 without language restrictions. Eight studies met the inclusion criteria, with a combined sample size of 21,930 women. Of these 21,930 pregnancies, 6,256 had endometriosis (endometriosis) and 15,674 had no endometriosis. Four of these studies included 8,161 women who conceived with ART, 1,640 of whom had endometriosis (endometriosis + ART), and 6,521 of whom did not have endometriosis. Meta-analyses were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using random effect analysis according to heterogeneity of studies. Results These meta-analyses showed women with endometriosis (endometriosis) have an increased risk of PP (OR, 4.038; 95% CI, 2.291–7.116; P = 0.000). These results showed women who conceived with ART (endometriosis + ART), have a substantially increased risk of PP (OR, 5.543; 95% CI, 1.659–18.523; P = 0.005). Conclusion These meta-analyses demonstrate women with endometriosis have an increased risk of PP., Graphical Abstract

Emphysematous pyelonephritis (EPN) is a life-threatening infection characterized by the formation of gas. Complications of EPN include septic shock, acute renal failure, and disseminated intravascular coagulation. Spontaneous subcapsular hematoma (SCH) has also been reported as a rare complication of EPN, although there have been no reports to date of this occurring prior to the presentation of EPN. We report a case of EPN that initially presented as spontaneous SCH. The patient was admitted for left flank pain, and initial computed tomography revealed SCH without any air shadows. Laboratory findings and clinical symptoms suggested the presence of urinary tract infection and the patient was started on antibiotics. Fever developed 24 hours after admission. On follow-up computed tomography 7 days later, EPN was newly observed, and a percutaneous drain was inserted. Blood, urine, and drainage fluid cultures all revealed growth of extended-spectrum β-lactamase-negative Escherichia coli.

Li-rich Li1.2Ni0.17Co0.17Mn0.5O2 cathode materials were synthesized by electrospinning technique with different polymers, and their structural, morphological, and electrochemical performances were investigated. It was found that the electrospinning process leads to the formation of a fiber and flower-like morphology, by using different polymers and heat treatment conditions. The nanostructured morphology provided these materials with high initial discharge capacity. The cycling stability was improved with agglomerated nano-particles, as compared with porous materials.

Flower-like Li 1.2 Ni 0.17 Co 0.17 Mn 0.5 O 2 microstructures were prepared by a simple one step low-temperature electrospinning method. The morphological changes occurred with temperature increase from 500 °C to 700 °C. Scanning electron microscopy showed that flower-like Li 1.2 Ni 0.17 Co 0.17 Mn 0.5 O 2 after heat treatment at 600 °C was composed of nanoplates with an open porous structure. Flower-like electrode with well-organized porous structure can be attributed to the favorable shape to facilitate the diffusion of lithium ions. Flower-like Li 1.2 Ni 0.17 Co 0.17 Mn 0.5 O 2 microstructures showed a high discharge capacity of 235 mA h g −1 during the first cycle compared to other electrode materials.