To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a ...proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin‐digested using a gel‐assisted protocol, and quantified by label‐free LC‐MS/MS, using an MSE mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α‐1‐antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi‐quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level.
Bkv-miR-B1-5p, one of the microRNAs encoded by BK virus, was recently reported to be elevated in the blood among the patients with BK virus nephropathy (BKVN). Urinary exosome was suggested to be a ...possible source of biomarker for kidney diseases, but it was unknown whether it could contain viral microRNA as well as human microRNAs. The aim of this study was to evaluate whether urinary exosomal BK viral microRNA were expressed during replication and could be used to diagnose BKVN in kidney transplant recipients.
In a cross-sectional multicenter study, we collected and analyzed 458 graft biopsies from 385 kidney transplant recipients. Urine samples were collected at the time of graft biopsy, and microRNAs in urinary exosome were measured once. For 13 patients with BKVN and 67 age, sex-matched kidney transplant recipients, we measured BK viral microRNA B1-5p, 3p and human microRNA-16 in urinary exosomal fraction and compared the diagnostic value with BK viral load in plasma and urine.
Pathology proven BKVN was diagnosed in 13 patients (2.8%). High levels of bkv-miR-B1-5p and bkv-miR-B1-3p were shown in all patients with BKVN. Meanwhile, plasma BK viral load assay (cut-off value of ≥ 4.0 log10 copies/mL) showed false negative in 3 cases and urinary BK viral load assay (cut-off value of ≥ 7.0 log10 copies/mL) showed false negative in 1 case among these 13 patients. The receiver operator characteristics curve analysis for bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 showed excellent discriminative power for the diagnosis of BKVN, with area under the curve values of 0.989 and 0.985, respectively.
This study suggests that urinary exosomal bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 could be surrogate markers for the diagnosis of BKVN.
Medium cut-off (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on ...the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2 ± 20.8 vs. 59.8 ± 30.1, P = 0.042; 61.5 ± 37.6 vs. 39.0 ± 39.6, P = 0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29 ± 0.46 vs. 1.64 ± 0.64, P = 0.034; 0.25 ± 0.53 vs. 1.00 ± 1.47, P = 0.023, respectively). MCO dialyzers may improve patient-reported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers.
Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary ...exosomes of KTRs.
Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis.
A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively).
Tetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR.
HLA-incompatible (HLAi) and ABO-incompatible (ABOi) kidney transplantation (KT) has been on the increase over the last decade. However, there are wide variations in outcomes from these procedures. In ...this study we evaluated the graft and patient outcomes in incompatible KT and non-sensitized KT.
Patients who underwent KT between January 2012 and April 2018 were enrolled and reviewed. We divided kidney transplant recipients (KTRs) into five groups as follows: HLAi (n = 50); ABOi (n = 65); HLAi+ABOi (n = 5); control (n = 428); and living-donor control (LD control, n = 218). We compared the risk of rejection, graft function, graft survival, and patient survival between incompatible KTRs and control/LD control KTRs.
Although the incidence of active antibody-mediated rejection in HLAi group tends to be higher than in control and LD control groups (6.0% vs. 2.8%, P = 0.20; 6.0% vs. 3.7%, P = 0.44, respectively), the rejection-free survival, graft survival, and patient survival were not significantly different from those of the control and LD control groups in all three incompatible KT groups (all P>0.05). Graft function during the study period was also not different between incompatible KTRs and control/LD control groups (both P>0.05). Using Cox regression analysis, neither HLAi nor ABOi were risk factors for graft failure. Some infectious diseases such as urinary tract infection and cytomegalovirus infection were more common in the HLAi group than in the control/LD control group (both P<0.05), but only one infection-related death occurred in HLAi KTRs. Infection risks were similar in the ABOi and HLAi+ABOi groups compared to controls.
Our results showed favorable outcomes for incompatible KT after desensitization. Although desensitization therapy for incompatible KT has improved access to transplantation for KT candidates with high immunological risk, more clinical data are clearly needed.
This study aimed to compare health-related quality of life (HRQOL) over time in patients initiating hemodialysis (HD) or peritoneal dialysis (PD). A total of 989 incident patients starting HD or PD ...were included from a prospective nationwide cohort study. HRQOL was assessed 3, 12, and 24 months after the start of dialysis. The scores of questionnaires were adjusted for clinical and socioeconomic parameters. The adjusted three months scores of patients on PD showed better HRQOL in eight end-stage renal disease (ESRD), three physical component summary and one mental component summary domains compared with patients on HD. Both patients on HD and PD experienced significant decreases in different HRQOL domains over two years and the degree of changes in HRQOL over time was not different between dialysis modality. However, the scores of three (effects of kidney disease, burden of kidney disease, and dialysis staff encouragement, all P < 0.05) and two (sexual function and dialysis staff encouragement, all P < 0.05) ESRD domains were still higher in patients on PD compared with patients on HD at one and two years after initiation of dialysis, respectively. PD shows better HRQOL during the initial period after dialysis even after adjusting for clinical and socioeconomic characteristics, and the effect lasts up to two years. It was similar in terms of changes in HRQOL over time between HD and PD.
Various coronavirus disease 2019 (COVID-19) vaccines are being developed, which show practical preventive effects. Here, we report a 51-year-old healthy man with nephrotic syndrome secondary to ...minimal change disease (MCD) after Ad26.COV.2 (Janssen) vaccination. He had no comorbid disease and received Ad26.COV.2 on April 13, 2021. Seven days after vaccination, he developed edema and foamy urine. Edema rapidly aggravated with decreased urine volume. He was admitted to the hospital 28 days after vaccination, and his body weight increased by 21 kg after vaccination. His serum creatinine level was 1.54 mg/dL, and 24-h urinary protein excretion was 8.6 g/day. Kidney biopsy revealed no abnormality in the glomeruli and interstitium of the cortex and medulla under the light microscope. Electron microscopy revealed diffuse effacement of the podocyte foot processes, thus, he was diagnosed with MCD. High-dose steroid therapy was applied, and his kidney function improved three days after steroid therapy. Three weeks after steroid use, his serum creatinine decreased to 0.95 mg/dL, and spot urine protein-to-creatine decreased to 0.2 g/g. This case highlights the risk of new-onset nephrotic syndrome secondary to MCD after vectored COVID-19 vaccination. Although the pathogenesis is uncertain, clinicians need to be careful about adverse renal effects of COVID-19 vaccines.
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 (
= 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 (
= 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.
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.
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.
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.
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.
Diabetic nephropathy is the leading cause of end stage renal disease. The number of kidney transplantation (KT) due to diabetic nephropathy is increasing and there is debate on glycemic control after ...KT. In this study, we used a multi-center database to determine the relationship between post-transplant glycemic control and the outcomes of KT in patients with diabetic nephropathy.
We conducted a retrospective chart review of kidney transplant recipients (KTRs) with diabetic nephropathy from three tertiary hospitals to analyze the association between post-transplant glycemic control and the clinical outcomes of graft failure, including patient death and biopsy-proven acute rejection (BPAR). We assessed time-averaged glucose level and hemoglobin A1c (HbA1c) for 36 months after KT.
Among 3,538 KTRs, a total of 476 patients received kidney transplantation because of diabetic nephropathy. Mean time-averaged glucose and HbA1c levels were 147 ± 46 mg/dl and 7.7 ± 1.5%, respectively. Patients with diabetic nephropathy had poor graft and patient survival rate compared with non-diabetic nephropathy. Among KTRs with diabetic nephropathy, the highest quartile of time-averaged glucose was related to poor graft outcomes and the 3rd quartile of time-averaged HbA1c was associated with significantly better graft outcomes than the 1st, 2nd or 4th quartiles. There were no significant differences in the risk of BPAR across the 4 quartiles of glucose and HbA1c.
Strict glycemic control before KT might not be related to successful outcomes but poor glycemic control after KT is associated with poor graft outcomes. There was no significant relationship between pre- or post-transplant glycemic control and BPAR.
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