Acute interstitial nephritis with acute kidney injury after COVID-19 vaccination: a case report.

In the context of the massive spread of coronavirus disease 2019 (COVID-19), the development of a COVID-19 vaccine is urgently needed. The Pfizer-BioNTech COVID-19 vaccine has been widely applied across global populations. Herein, we report a case of acute interstitial nephritis with acute kidney injury in a young healthy subject after administration of the COVID-19 vaccine. A 20-year-old man was admitted with abdominal discomfort and nausea. He had received the Pfizer-BioNTech COVID-19 vaccine 6 days before. At 9 days after vaccination, his kidney function was decreased, with serum creatinine levels of 1.8 mg/dL. Even with supportive care with hydration, his kidney function worsened, and he underwent a kidney biopsy. The pathology findings revealed diffuse interstitial infiltration of inflammatory cells, predominantly comprising lymphocytes, with preservation of the glomerulus. No abnormal findings were noted by immunofluorescence or electron microscopy. Based on a diagnosis of drug-related acute interstitial nephritis, we treated the patient with high-dose prednisolone. After administration of prednisolone, kidney function slowly improved. A close linkage between COVID-19 vaccination and acute interstitial nephritis should be considered in the clinic, despite the low incidence.

Impact of albuminuria on the various causes of death in diabetic patients: a nationwide population-based study.

Diabetes mellitus (DM) is a well-known risk factor for mortality, and the risk is exacerbated by coexisting diabetic kidney disease (DKD). We aimed to explore the impact of DM on each cause of mortality according to kidney function and the presence of albuminuria. Data on subjects with DM were extracted from the Nationwide Health Insurance Database of South Korea between 2009 and 2012. Subjects were divided by eGFR and albuminuria into five groups. To evaluate the risk of diabetes, we used the Cox proportional hazards model. A total of 2,614,662 patients were enrolled in this study. Most causes of death showed a higher incidence in an advanced stage of DKD. In addition to all-cause mortality and cardiovascular death, the risk of death from neoplasms and diseases of the endocrine, respiratory, and digestive systems is increased by albuminuria. The synergistic effect of a reduced eGFR and the presence of albuminuria was prominent in death from circulatory diseases, and endocrine and metabolic diseases. The risk for mortality was different according to the stage of DKD. Even in patients with a favorable eGFR, the presence of albuminuria significantly increased the risk for mortality, especially that due to cardiovascular causes.

Association between physical activity and risk of renal function decline and mortality in community-dwelling older adults: a nationwide population-based cohort study.

BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

Clinical characteristics and risk factors for kidney failure in patients with autosomal dominant polycystic kidney disease: A retrospective study.

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary and progressive renal disease. By the age of 65 years, 45% to 70% of patients with ADPKD reach end-stage renal disease (ESRD). Although there are various treatments for this condition, no standard therapy exists to delay the progression of ADPKD. Hence, understanding the factors that affect disease progression may be helpful for the treatment of ADPKD. The medical records of 288 patients with ADPKD at Keimyung University Dongsan Medical Center between January 1989 and August 2018 were analyzed retrospectively. Furthermore, we inspected the risk factors involved in the progression of ADPKD and the kidney survival rates of patients using the Cox proportional hazards model and Kaplan-Meier survival analysis. The mean age at the time of diagnosis was 43.1 ±â€…14.1 years, and there were 146 males (50.7%). In total, 197 patients (68.4%) had hypertension and 11 patients (3.8%) had cerebral aneurysm. Stroke occurred in 35 patients (12.1%), including 11 cases of cerebral hemorrhage and 24 cases of cerebral infarction. Twenty-eight patients (9.7%) died during the follow-up period (117.1 ±â€…102.1 months). Infection (42.9%) was the most common cause of mortality, followed by sudden cardiac death (25.0%). Overall, 132 patients (45.8%) progressed to ESRD and 104 patients (36.1%) required renal replacement therapy (RRT). The mean duration from diagnosis to RRT was 110.8 ±â€…93.9 months. Age at diagnosis after 30 years (odd's ratio [OR], 2.737; 95% confidence interval [CI], 1.320-5.675; P = .007), baseline serum creatinine levels (OR, 1.326; 95% CI, 1.259-1.396; P < .001), and cyst infection (OR, 2.065; 95% CI, 1.242-3.433; P = .005) were the independent risk factors for kidney failure in multivariable analysis. To delay the advance of ADPKD to ESRD, early diagnosis and close observation for the onset of cyst infection are crucial.

Urate-lowering efficacy and renal safety of febuxostat in patients with hyperuricemia and stage 4-5 chronic kidney disease not yet on dialysis: A meta-analysis of observational studies.

OBJECTIVE: The efficacy and safety of febuxostat in patients with stage 4-5 chronic kidney disease (CKD) remains unclear. We evaluated the urate-lowering efficacy and renal safety of febuxostat in patients with stage 4-5 CKD not yet on dialysis, through a meta-analysis of observational studies. METHODS: We performed a systematic search in PubMed, Ovid MEDLINE, Embase, and the Cochrane Library databases for observational studies of patients with advanced CKD starting febuxostat. Articles describing changes in serum urate levels and/or renal function assessed by the estimated glomerular filtration rate (eGFR) were included. RESULTS: Among 148 retrieved studies, five relevant observational studies with 327 patients were included in the meta-analysis. Febuxostat was administered daily at 10-120 mg for 3-12 months. Serum urate reduced in response to febuxostat (weighted mean difference, -1.85 mg/dL; 95% CI, -2.04--1.67 mg/dL; I2; 0%). Three studies involving 145 patients included eGFR assessments. Renal function, assessed through the eGFR, did not change after febuxostat use (weighted mean difference, 0.11 mL/min/1.73m2; 95% CI, -0.25-0.47 mL/min/1.73m2; I2; 45%). CONCLUSION: Overall, febuxostat has acceptable urate-lowering efficacy and renal safety in patients with hyperuricemia and stage 4-5 CKD who are not yet on dialysis.

Chaga mushroom-induced oxalate nephropathy that clinically manifested as nephrotic syndrome: A case report.

RATIONALE: The Chaga mushroom (Hymenochaetaceae, Inonotus obliquus) is a fungus belonging to the Hymenochaetaceae family. It is parasitic on birch and other tree species. Chaga mushrooms are rich in various vitamins, minerals, and nutrients. Some people consider these mushrooms medicinal as they have been reported to suppress cancer progression through anti-inflammatory and antioxidant effects. However, recent studies have reported that excessive ingestion of Chaga mushrooms can cause acute oxalate nephropathy. PATIENT CONCERNS: A 69-year-old man who ingested Chaga mushroom powder (10-15 g per day) and vitamin C (500 mg per day) for the past 3 months developed acute kidney injury (AKI) with the clinical manifestations of nephrotic syndrome (NS). DIAGNOSIS: Pathological findings showed focal acute tubular injury and the deposition of calcium oxalate crystals in the tubules. Light microscopy showed interstitial fibrosis and tubular atrophy, and electron microscopy showed the effacement of the foot processes in podocytes. Based on these results, the diagnosis was acute oxalate nephropathy accompanied by minimal change disease (MCD). INTERVENTIONS: The patient's kidney function did not improve with supportive care, such as hydration and blood pressure control. Thus, we recommended hemodialysis and the administration of a high dose of steroids (intravenous hydrocortisone 500 mg twice a day for 3 days and oral prednisolone at 1 mg/kg). OUTCOMES: The patient's kidney function recovered just 1 month after the start of treatment, and the MCD was completely remitted. LESSONS: In cases of AKI with an unknown cause, it is important to closely observe the patient's medication history, and it is recommended to perform kidney biopsy. Furthermore, this study showed that active dialysis and high-dose steroid treatment can restore kidney function in patients with AKI caused by acute oxalate nephropathy with MCD.

Clinical Significance of C3d Assay in Kidney Transplant Recipients With Donor-Specific Anti-Human Leukocyte Antigen Antibodies.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of allograft loss in kidney transplant. Although donor-specific anti-human leukocyte antigen antibody (DSA) is a key cause of AMR, not all patients with DSA are diagnosed as having AMR and show poor allograft outcomes. This study aimed to evaluate clinical significance of C3d-binding activity in patients with DSA identified by single-antigen bead (SAB) assay. METHODS: A total of 168 recipients screened for DSA from 2015 to 2018 were enrolled. Among them, 52 patients had DSA confirmed by SAB assay. Sera were tested using the C3d assay on Luminex platform. AMR was defined by kidney allograft biopsy results using Banff 2015 criteria. RESULTS: Of 52 patients, C3d-binding DSAs were detected in 22 patients (42.3%). Indication allograft biopsy was performed in 35 patients, with 31 (88.6%) diagnosed as having AMR. Patients with C3d-binding DSA had more class II SAB-DSA (73.3% vs 100%, P = .015) and showed significantly higher mean (SD) fluorescence intensity of class II SAB-DSA than the C3d-binding DSA(-) group (9606.7 [6096.6] vs 1921.0 [1483.8], P < .001). There was a positive correlation in the highest mean fluorescence intensity between class II SAB-DSA and class II C3d-binding DSA (r = 0.70, P < .001). Patients with C3d-binding DSA showed worse death-censored graft survival than those with non-C3d-binding DSA (P = .023). CONCLUSIONS: This study showed that presence of C3d-binding DSA was significantly associated with allograft loss in SAB-DSA-positive patients. Further trials are warranted.

Clinical significance of serum galactose-deficient immunoglobulin A1 for detection of recurrent immunoglobulin A nephropathy in kidney transplant recipients.

BACKGROUND: Recurrent glomerulonephritis (GN) is a common cause of allograft loss in kidney transplantation (KT), the most frequent of which is immunoglobulin A (IgA) nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) plays a major role in the pathophysiology of IgAN, but the association between Gd-IgA1 and recurrent IgAN in kidney transplant recipients (KTRs) is uncertain. We aimed to evaluate the efficacy of Gd-IgA1 for prediction of recurrent IgAN and graft and patient survival according to Gd-IgA1 level. METHODS: We enrolled 27 KTRs who underwent allograft biopsy between 2009 and 2016 and measured the serum Gd-IgA1 level of each KTR. We divided the patients into two groups: nonrecurrent IgAN (patients with IgAN prior to KT who were not diagnosed with recurrent IgAN) and recurrent IgAN (patients with IgAN prior to KT who were diagnosed with recurrent IgAN). RESULTS: The mean serum Gd-IgA1 level was significantly higher in the recurrent IgAN group than in the nonrecurrent IgAN group (6,419 ± 3,675 ng/mL vs. 3,381 ± 2,844 ng/mL, p = 0.02). The cutoff value of serum Gd-IgA1 in receiver operating characteristic curve analysis was 4,338 ng/mL (area under the curve, 0.76; 95% confidence interval [CI], 0.57-0.95, p = 0.02). Serum Gd-IgA1 level was an independent factor for recurrent IgAN (odds ratio, 17.60; 95% CI, 1.33-233.03, p = 0.03). There was no significant difference in graft or patient survival between the two groups. CONCLUSION: Serum Gd-IgA1 can be used as a diagnostic biomarker for recurrent IgAN in KT.

Impact of delayed graft function on clinical outcomes in highly sensitized patients after deceased-donor kidney transplantation.

Background: We investigated whether the development of delayed graft function (DGF) in pre-sensitized patients affects the clinical outcomes after deceased-donor kidney transplantation (DDKT). Methods: The study included 709 kidney transplant recipients (KTRs) from three transplant centers. We divided KTRs into four subgroups (highly sensitized DGF, highly sensitized non-DGF, low-sensitized DGF, and low-sensitized non-DGF) according to panel reactive antibody level of 50%, or DGF development. We compared post-transplant clinical outcomes among the four subgroups. Results: Incidence of biopsy-proven acute rejection (BPAR) was higher in two highly sensitized subgroups than in low-sensitized subgroups. It tended to be higher in highly sensitized DGF subgroups than in the highly sensitized non-DGF subgroups. In addition, the highly sensitized DGF subgroup showed the highest risk for BPAR (hazard ratio, 3.051; P=0.005) and independently predicted BPAR. Allograft function was lower in the two DGF subgroups than in the non-DGF subgroup until one month after transplantation, but thereafter it was similar. Death-censored graft loss rates and patient mortality tended to be low when DGF developed, but it did not reach statistical significance. Conclusions: DGF development in highly sensitized patients increases the risk for BPAR in DDKT compared with patients without DGF, suggesting the need for strict monitoring and management of such cases.

Nephrologists' Perspectives on Decision Making About Life-Sustaining Treatment and Palliative Care at End of Life: A Questionnaire Survey in Korea.

Background: Nephrologists commonly engage in decision making regarding the withholding or withdrawal of dialysis and palliative care in patients at end of life (EoL). However, these issues remain an unsolved dilemma for nephrologists. Objective: To explore nephrologists' perceptions on the decision-making process about withholding or withdrawing dialysis and palliative care in Korea. Design: A nationwide 25-item questionnaire online survey via e-mail. Setting/Subjects: A total of 369 Korean nephrologists completed the survey. Results: The proportions of respondents who stated that withholding or withdrawing dialysis at EoL is ethically appropriate were 87.3% and 86.2%, respectively. A total of 72.4% respondents thought that withdrawal of dialysis in a maintenance dialysis patient is ethically appropriate. Responses regarding patient features that should be considered to withhold or withdraw dialysis were as follows: dialysis intolerance (84.3%), poor performance status (74.8%), patient's active request (47.2%), age (28.7%), very severe dementia (27.1%), and several comorbidities (16.5%). Among those nephrologists who responded to the question about the minimum age, at which dialysis should be withheld or withdrawn, most specified an age between 80 and 90 years (94.3%). Fifty-eight percent of respondents stated that terminally ill dialysis patients should be allowed to use palliative care facilities. In addition, a number of nephrologists thought that adequate palliative care facilities, specific treatment guidelines, enough time to manage patients, financial support, and adequate medical experts are necessary. Conclusions: Korean nephrologists thought that withholding or withdrawing dialysis at EoL is ethically appropriate, even in maintenance dialysis patients. Therefore, consensus guidelines for palliative care after withholding or withdrawal of dialysis are needed.

Glomerular Hyperfiltration and Cancer: A Nationwide Population-Based Study.

BACKGROUND: Glomerular hyperfiltration is associated with all-cause mortality. Herein, we evaluated the association between glomerular hyperfiltration and the development of cancer, the most common cause of death, in an Asian population. METHODS: We retrospectively reviewed the National Health Insurance Service database of Korea for people who received national health screenings from 2012 to 2013. Glomerular hyperfiltration was defined as the 95th percentile and greater after stratification by sex and age decile. We performed a multivariate Cox regression analysis using glomerular hyperfiltration at the first health screening as the exposure variable and cancer development as the outcome variable to evaluate the impact of glomerular hyperfiltration on the development of cancer. RESULTS: A total of 1,953,123 examinations for patients with a median follow-up time of 4.4 years were included in this study. Among the 8 different site-specific cancer categories, digestive organs showed significant associations between glomerular hyperfiltration and cancer. The population with glomerular hyperfiltration showed an increased risk for stomach cancer [adjusted hazard ratio (aHR) = 1.22], colorectal cancer (aHR = 1.16), and liver or intrahepatic malignancy (aHR = 1.35). CONCLUSIONS: Glomerular hyperfiltration was associated with an increased risk for the development of cancer in specific organs, such as the stomach, colorectum, and liver and intrahepatic organ. IMPACT: Glomerular hyperfiltration needs to be considered a significant sign of the need to evaluate the possibility of hidden adverse health conditions, including malignancies.

Impact of calcineurin inhibitors on rat glioma cells viability.

Background: Although kidney transplantation outcomes have improved dramatically after using calcineurin inhibitors (CNIs), CNI toxicity continues to be reported and the mechanism remains uncertain. Here, we investigated the neurotoxicity of CNIs by focusing on the viability of glioma cells. Methods: Glioma cells were treated with several concentrations of CNIs for 24 hours at 37℃ and their cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results: Exposure to 0, 0.25, 0.5, 2.5, 5.0, and 10.0 mM concentrations respectively showed 100%, 64.3%, 61.3%, 68.1%, 62.4%, and 68.6% cell viability for cyclosporine and 100%, 38.6%, 40.8%, 43.7%, 37.8%, and 43.0% for tacrolimus. The direct toxic effect of tacrolimus on glioma cell viability was stronger than that of cyclosporine at the same concentration. Conclusion: CNIs can cause neurological side effects by directly exerting cytotoxic effects on brain cells. Therefore, we should carefully monitor the neurologic symptoms and level of CNIs in kidney transplant patients.

Changing pattern and safety of pretransplant malignancy in kidney transplant recipients.

BACKGROUND: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades. METHODS: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969-1998, 1999-2006, 2007-2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy. RESULTS: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999-2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48). CONCLUSION: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.

Long-term Clinical Significance of Tacrolimus Trough Level at the Early Period After Kidney Transplantation.

BACKGROUND: The stable immunosuppressant level at the early period after kidney transplantation (KT) is one of the most important factors for the prognosis of KT. However, the extent of immunosuppression varies according to the policies of each KT center. We investigated the relationship between the clinical outcome and tacrolimus trough level (TTL) at the early post-transplant period. MATERIALS AND METHODS: We retrospectively analyzed medical records of patients who underwent KT between July 2007 and June 2016. We investigated TTLs at 3 months after KT. We evaluated the incidence of biopsy-proven acute rejection (BPAR), cytomegalovirus infection, and graft survival according to the TTLs. RESULTS: A total of 426 patients who received KT during the study period were enrolled. The mean age of KT recipients was 46.3 ± 11.5 years, and 55.5% of patients were men. The incidence of BPAR within 1 year after KT was significantly higher when TTLs at 3 months were less than 4.0 ng/mL (P = .020). Death-censored graft survival rates were significantly lower in KT recipients with BPAR and TTL less than 4.0 ng/mL (P < .001, P < .001, respectively). In multivariate analysis, BPAR and TTL less than 4.0 ng/mL at 3 months after KT were independent risk factors for graft failure. CONCLUSION: BPAR and TTL less than 4.0 ng/mL at 3 months after KT are important risk factors for allograft failure. Therefore, TTL should be kept at least 4.0 ng/mL or more at 3 months after KT to reduce the incidence of BPAR within 1 year after KT.

Clinical Significance of Mycophenolate Mofetil Withdrawal in Kidney Transplant Recipients.

INTRODUCTION: The most effective immunosuppressant protocol in kidney transplantation (KT) is the combination of a calcineurin inhibitor, steroid, and mycophenolate mofetil (MMF) until now. However, MMF withdrawal (MW) is performed for many reasons, and the clinical course of the KT recipients after MW is not clearly known. The purpose of this study was to investigate the clinical outcomes of KT after MW. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 626 KT recipients between 2000 and 2016. We evaluated the incidence of biopsy-proven acute rejection (BPAR), graft and patient survival rates, and risk factors related with graft failure. RESULTS: The proportion of MW was 33.2% (208 of 626 patients). The median time between KT and MW was 6.4 months (range, 3.2-32.1 months). The common causes of MW were infection (70.7%), hematologic abnormalities (9.1%), and gastrointestinal trouble (7.7%). The incidence of BPAR was significantly higher in the MW group compared with the MMF continuation group (27.4% vs 8.9%, respectively, P < .001). Death-censored graft survival and patient survival rates were significantly lower in the MW group compared with the MMF continuation group (P < .001; P < .001, respectively). In the multivariate analysis, BPAR after MW was an independent risk factor for graft failure (hazard ratio 6.058, 95% confidence interval, 3.172-11.569, P < .001). CONCLUSIONS: The incidence of rejection, graft failure, and patient mortality in KT were high after MW. Therefore, MW should be considered carefully.

Effectiveness of Antithymocyte Globulin Induction Dosing Regimens in Kidney Transplantation Patients: A Network Meta-analysis.

BACKGROUND: Antithymocyte globulin (ATG) is an induction therapy in kidney transplantation, but our knowledge about the relation between outcomes and ATG regimens is limited. We compared ATG effectiveness in kidney transplantation according to dosage and administration schedule. METHODS: Reports from 1970 until May 2018 in CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded were searched. We performed direct and indirect network meta-analysis using Bayesian models and generated rankings for ATG dosage and injection number variations by generation mixed treatment comparison.We compared ATG dose and schedule in kidney transplantation in relation to all-cause death, graft failure, antibody-mediated rejection, T-cell mediated rejection, biopsy-proven acute rejection, and bacterial and viral infection. RESULTS: Ten studies (N = 1065) were analyzed by forming 6 groups: ATG alternate doses, 9 mg/kg, 6 mg/kg, and 4.5 mg/kg; single dose, 6 mg/kg, and 4.5 mg/kg; and control. Compared to placebo, ATG regimen variations were not associated with significant differences in survival, viral infection, renal function, or graft survival. ATG regimens 9 and 4.5 mg alternate dosing tended to reduce biopsy-proven acute rejection but without statistical significance. According to the highest rank probability, the 9 mg alternate dosing group had the highest tendency for cytomegalovirus and bacterial infections but without statistical significance. CONCLUSIONS: The rejection frequency tended to be lower for the 9 and 4.5 mg alternate dosing groups. Infections occurred at a higher rate in the 9 mg alternate dosing group, but the differences in the risk of infection among the groups with different ATG regimens were not statistically significant.

Differences in Pathologic Features and Graft Outcomes of Rejection on Kidney Transplant.

BACKGROUND: Rejection is still a barrier to long-term allograft survival, but there are not many reports of clinical outcomes according to rejection types. The purpose of this study was to investigate differences in pathologic features and graft outcomes of rejection on kidney transplant (KT). MATERIALS AND METHODS: We retrospectively analyzed 139 kidney transplant recipients diagnosed to rejection by allograft biopsy results between 2006 and 2018. We divided kidney transplant recipients into 3 groups as follows: T cell-mediated rejection (TCMR), antibody-mediated rejection, and mixed rejection. We investigated clinical characteristics, pathologic findings, death-censored graft survival rates, and patient survival rates among the 3 groups. RESULTS: Mean follow-up duration was 113.5 (SD, 80.6) months. The mixed rejection group was the youngest significantly. There were no significant differences of the proportion of sex, KT type, KT number, number of HLA mismatches, induction immunosuppressant, and maintenance immunosuppressant among the 3 groups. In pathologic findings, microvascular inflammation and C4d were significantly different among the 3 groups. Death-censored graft survival of mixed rejection was the least. In multivariate analysis, recipient age, TCMR, and positive C4d were the risk factors associated with graft failure. However, patient survival rates showed no significant differences among the 3 groups. CONCLUSIONS: Our study showed that mixed rejection had poor prognosis in comparison with TCMR and antibody-mediated rejection groups, and TCMR and positive C4d were the most important risk factors for graft survival. Therefore, constant monitoring through allograft biopsy and early treatment for rejection are very important in post-transplant clinical outcomes.

Long-term prognosis of BK virus-associated nephropathy in kidney transplant recipients.

BACKGROUND: The long-term prognosis of BK virus-associated nephropathy (BKVAN) in kidney transplant recipients (KTRs) is uncertain. We evaluated the long-term prognosis in KTRs with BKVAN and the clinical significance of BKVAN on post-transplant clinical outcome. METHODS: We retrospectively analyzed the medical records of 582 patients who underwent kidney transplant (KT) between 2001 and 2014. We divided the patients into a BKVAN group (15 patients) diagnosed by allograft biopsy and a control group (356 patients). RESULTS: The incidence of BKVAN was 4.0%, and the mean follow-up duration was 93.1 ± 52.3 months. Median time from KT to BKVAN diagnosis was 5.9 months (interquartile range [IQR], 4.4-8.7). In the BKVAN group, 9 (60.0%) KTRs with combined acute rejection progressed to graft failure, and the median time from BKVAN diagnosis to graft failure was 36.2 months (IQR, 9.7-65.5). Death-censored graft survival rate and patient survival rate in the BKVAN group were significantly lower than those in the control group. BKVAN and rejection were independent risk factors for graft failure. In the subgroup analysis, death-censored graft survival rate of KTRs with BKVAN with acute rejection was significantly worst in comparison with similar patients without BKVAN regardless of acute rejection (P < 0.001). CONCLUSION: The long-term prognosis of BKVAN with acute rejection was very poor because of graft failure caused by inadequate treatment for acute rejection considering BKVAN. Therefore, we should carefully monitor the allograft status of KTRs through regular surveillance tests after treatment for BKVAN with acute rejection.

A Pedigree with c.179 Cytosine to Threonine Missense Mutation of SLC12A3 Gene Presenting Gitelman's Syndrome.

A 42-year-old man came to the hospital presenting chest discomfort and general weakness. He had come to the hospital with the same symptoms 3 months ago and 12 years prior. His laboratory test showed hypokalemia, hypomagnesemia and hypocalciuria. The arterial blood gas analysis showed hypochloremic metabolic alkalosis. He had an ultrasonography guided renal biopsy, the result was normal at light microscopy and immunofluorescence microscopy. However, a special stain for Na-Cl cotransporter was weakly expressed compared with the control. The patient and his family underwent genetic sequencing about the SLC12A3 gene. He had a homozygous mutation in the 179(th) nucleotide of Exon 1 on the SLC12A3 gene (p.Thr60Met) and his parents and sisters were diagnosed as carrier state of Gitelman's syndrome (GS). GS is an inherited tubular disorder which presents mild hypokalemia, hypomagnesemia and hypocalciuria. Since the symptoms and laboratory results are not severe, it can go unnoticed by physicians. Herein we present a family with GS, diagnosed by genetic sequencing.