Combined evaluation of glomerular phospholipase A2 receptor and immunoglobulin G subclass in membranous nephropathy.

Background: Phospholipase A2 receptor (PLA2R) is a major target antigen in idiopathic membranous nephropathy (MN). Anti-PLA2R antibodies are mainly of the immunoglobulin G (IgG) subclass IgG4, although other IgG subclass depositions in glomeruli may also be detected. However, the importance of the subclass of the IgG deposit has not been proven. Thus we investigated clinical findings from patients with idiopathic MN in relation to glomerular PLA2R deposition and IgG subclass. Methods: We enrolled 132 Japanese patients with biopsy-proven idiopathic MN in a multicentre retrospective observational study. We investigated the complete remission rate as the primary outcome and the development of end-stage kidney disease (ESKD) as the secondary outcome in relation to glomerular PLA2R deposition. Moreover, we evaluated prognostic factors, including glomerular IgG subclass, in the PLA2R-positive group. Results: The percentage of cases with glomerular PLA2R deposition was 76.5% (n = 101). The first complete remission rate of the PLA2R-positive group was worse than that of the PLA2R-negative group (logrank test P < .001). ESKD incidence did not significantly differ between the glomerular PLA2R-negative and PLA2R-positive MN groups (logrank test P = .608). In the PLA2R-positive group, higher PLA2R intensities and IgG2 staining were associated with a poorer first complete remission rate (logrank test P < .001 and P = .032, respectively). Cox proportional hazards analysis also showed that strong PLA2R deposition and positive IgG2 staining were significantly associated with a failure to reach complete remission [hazard ratio 2.09 (P = .004) and 1.78 (P = .030), respectively]. Conclusions: Our results suggest that intense glomerular PLA2R and IgG2 positivity predict a poor proteinuria remission rate in idiopathic MN.

Association between Hemoglobin A1c and Renal Arteriolar Sclerosis in Subjects Presenting without any Apparent Kidney Dysfunction.

AIMS: Diabetic kidney disease is a major vascular complication in patients with diabetes mellitus (DM). However, the association between the hemoglobin (Hb)A1c levels, notably the prediabetic levels, and renal pathological changes remains unclear. We investigated the association between the HbA1c levels and renal arteriolar lesions in subjects without any apparent kidney dysfunction using a living kidney donor cohort. METHODS: Between January 2006 and May 2016, 393 living kidney donors underwent a "zero-time" biopsy at Kyushu University Hospital. The patients were divided into four groups (HbA1c levels ＜5.6%, 5.6%-5.7%, 5.8%-6.4%, and ≥ 6.5%, or diagnosed with DM [DM group]). Renal arteriolar hyalinization and wall thickening were assessed using semi-quantitative grading. We then investigated the association between the HbA1c levels and renal pathological changes. RESULTS: 158 (40.2%) patients had arteriolar hyalinization and 148 (37.6%) showed wall thickening. A significant correlation was observed between the HbA1c levels and wall thickening (p for trend ＜0.001). An elevated HbA1c level was significantly associated with wall thickening according to a multivariable logistic analysis in subjects with HbA1c levels of 5.6%-5.7% and 5.8%-6.4%, and the DM group, compared with those with HbA1c levels of ＜5.6% (odds ratio [OR], 1.91; 95% confidence interval [CI]: [1.03-3.54] for 5.6%-5.7%, OR, 1.96; 95% CI: [1.09-3.53] for 5.8%-6.4%, and OR, 2.86; 95% CI: [0.91-9.01] for the DM group), whereas arteriolar hyalinization did not increase within the nondiabetic HbA1c levels. CONCLUSIONS: Elevated high-normal HbA1c levels are considered to be independent risk factors for arteriolar wall thickening. Subclinical renal arteriolar sclerosis may develop in patients with prediabetic HbA1c levels.

Significance of Perivascular Aggregates in Kidney Allografts: Evaluation of 1-Year Protocol Biopsies Using Recent Banff Classification.

BACKGROUND: Perivascular aggregates (PVAs) often occur in kidney allografts; however, their significance needs to be re-evaluated in light of changes in the concept and criteria of allograft rejection. METHODS: We reviewed 1-year protocol biopsies in 258 patients with kidney transplants to identify PVAs and concurrent pathology based on the Banff 2017 classification, including revised criteria for chronic active T-cell mediated rejection (CA-TCMR). We investigated the incidence of PVA, concurrent allograft lesions, diagnosis, and graft survival. No prisoners were used in this study, and no participants were coerced or paid. RESULTS: We identified PVA in 81 biopsies (31.4%). The incidence of previous rejection (32.1% vs 12.4%, P= .0003) and total inflammation (1.3 ± 0.8 vs 0.6 ± 0.8, P < .0001), inflammation (0.7 ± 0.8 vs 0.2 ± 0.5, P < .0001), inflammation in the area of interstitial fibrosis and tubular atrophy (1.3 ± 1.2 vs 0.7 ± 0.9, P < .0001), tubulitis (1.4 ± 1.1 vs 0.6 ± 0.9, P < .0001), and interstitial fibrosis scores (1.2 ± 0.9 vs 0.9 ± 0.9, P= .01) were higher in PVA-positive compared with patients with PVA-negative. Diagnoses in the PVA-positive group revealed no rejection in 49.4%, CA-TCMR in 21.0%, borderline changes in 18.5%, and acute TCMR in 6.2%. CA-TCMR was more frequent in patients with PVA-positive (21.0% vs 4.0%, P < .0001). Graft survival was similar in both groups among all patients, no-rejection, any type of rejection, and CA-TCMR subgroups. CONCLUSIONS: PVAs occur heterogeneously and are associated with previous rejection or concurrent CA-TCMR. The prognostic significance of PVAs in kidney transplantation is inconclusive, and further investigations are needed.

A Single-Center Retrospective Study of Re-Transplantation After Allograft Failure in Kidney Transplant Recipients.

BACKGROUND: This study aimed to examine the outcomes of kidney retransplantation in patients with allograft failure at Kyushu University. METHODS: We reviewed data from 1043 consecutive patients (including 1001 in a first kidney transplantation [KT] group and 42 in a second KT group) who had undergone KT alone at our institution between January 2008 and September 2022. We also studied immunologic risks and outcomes of patients who had undergone preoperative testing for KT at Kyushu University during the same period. RESULTS: No patient received more than 2 transplants. Donor-specific anti-HLA antibody (DSA) had been detected in a greater percentage of patients in the second KT group than in the first (31% vs 11%, respectively; P < .001). There were no significant differences in 5-year death-censored/overall graft survival rates, rates of surgical complications, or incidence of delayed graft function between the groups. During the study period, significantly more candidates for second than first KT were rejected for this procedure because of their high immunologic risk (20% vs 2%, P < 001). Seven of the 42 patients in the second KT group required the removal of the primary graft during the second transplantation. CONCLUSION: There is a higher percentage of patients whose DSA has been detected among patients undergoing retransplantation after allograft failure than among those receiving first KTs, which often leads to remaining on the waiting list in the former group. However, if the immunologic risk is within acceptable limits, the graft survival for retransplantation is not inferior to that of a first KT.

Cumulative smoking dose is associated with subclinical renal injury: a pathological study in individuals without chronic kidney disease.

BACKGROUND: Epidemiological studies have identified smoking as an independent risk factor for development of chronic kidney disease. However, the early renal pathological lesions have not been clearly elucidated. METHODS: We investigated time-zero biopsy specimens from 547 living kidney donors and evaluated the relationships between smoking and renal histological changes, including arteriolar hyalinization, intimal thickening of small-medium arteries, global glomerulosclerosis, and interstitial fibrosis and tubular atrophy (IF/TA). RESULTS: A total of 199 subjects (36.4%) had smoking history; 92 (16.8%) and 107 (19.6%) subjects had <20 pack-years and ≥20 pack-years of smoking, respectively. Cumulative smoking dose was significantly associated with prevalence of arteriolar hyalinization: the multivariable-adjusted odds ratio (OR) per 20 pack-year increase was 1.50 (95% confidence interval 1.15-1.97). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.76 (1.01-3.09) and 2.56 (1.48-4.44), respectively. Smoking was also associated with prevalence of >10% global glomerulosclerosis: the OR per 20 pack-year increase was 1.24 (0.96-1.59). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.50 (0.98-2.78) and 2.11 (1.18-3.79), respectively. The ORs for these pathological changes increased significantly depending on cumulative smoking dose. Intimal thickening of small-medium arteries and IF/TA were not associated with smoking status. The prevalence of arteriolar hyalinization remained higher in patients with ≥10 years since smoking cessation than in never-smokers [OR 2.23 (1.03-4.83)]. CONCLUSIONS: Subclinical pathological injury caused by smoking is potentially associated with renal arteriolar hyalinization and glomerular ischaemia.

Allograft adenovirus nephritis accompanied by Crohn's disease in a kidney transplant recipient: a novel case report.

Excessive immunosuppression after kidney transplantation (KT) is often encountered in patients undergoing therapy for anti-rejection or autoimmune disease that requires further treatment using immunosuppressive medications (IMs), including biologic agents. We report a novel case wherein a kidney transplant recipient developed severe acute allograft injury and hemorrhagic cystitis at 4.5 years after KT due to adenovirus nephritis after treatment with infliximab for Crohn's disease. The diagnosis was made based on adenovirus immunohistochemistry staining and urine polymerase chain reaction tests. The patient was successfully treated by reducing IMs and administration of immunoglobulin even though allograft function was eventually partially recovered. When new immunosuppressive agents, particularly biologic agents, are initiated for other diseases in addition to maintenance IMs, the following points need to be regarded: (1) pay attention to opportunistic infections even in the late phase of KT, and (2) maintain communication with other specialists who prescribe biologics to ensure appropriate administration of IMs.

Treatment of chronic active T cell-mediated rejection after kidney transplantation: A retrospective cohort study of 37 transplants.

AIM: Data on the treatment of chronic active T cell-mediated rejection (CA-TCMR) are scarce, and therapeutical strategies for CA-TCMR have not been established. We retrospectively evaluated the outcomes and effects of treatment on pathological and clinical findings in patients with CA-TCMR. METHODS: This study comprised 37 patients who underwent kidney transplantation at our institute who were diagnosed with CA-TCMR between January 2018 and December 2020. Patients were followed until October 2021. RESULTS: A total of 32 of the 37 patients were treated. During the observation period, two patients died (5%), and five patients developed allograft loss (13%). A univariate Cox proportional hazards model showed that indication biopsy, higher spot urine protein/creatinine ratio (UPCR) and Banff ci/ct scores were risk factors for allograft loss. Of the treated patients, 23 underwent follow-up biopsies. The Wilcoxon signed-rank test showed significant improvement in the Baff scores for "ti", "i-IFTA", "t" and "t-IFTA" after treatment. On pathology, 13 (57%) of the patients who underwent follow-up biopsy improved to "no evidence of rejection" or "borderline change." Assuming that improvement in pathology to "borderline change" or "no evidence of rejection" on follow-up biopsy indicates response to treatment, multivariate logistic analysis showed that lower UPCR was a predictive factor for response to treatment. No specific effect of treatment type was observed. CONCLUSIONS: Our results indicate that treatment could improve the pathological findings in CA-TCMR.

Outcomes of Everolimus Plus Standard-Dose Tacrolimus Immunosuppression in De Novo Kidney Transplant: A Retrospective, Single-Center Study of 225 Transplants.

OBJECTIVES: In this study, our aim was to compare the outcomes of everolimus versus mycophenolate mofetil plus standard-dose tacrolimus immunosuppression in patients who received de novo kidney transplant at our center in Fukuoka, Japan. MATERIALS AND METHODS: In this retrospective, observational, single-center, inverse probability of treatment weighting analysis study, 225 recipients who underwent kidney transplant at our center between January 2013 and December 2018 were included. The variables considered were recipient age/sex, duration of dialysis, cytomegalovirus mismatch (seronegative recipient and seropositive donor), cause of end-stage renal disease, donor age/sex, and number of HLA mismatches. RESULTS: Our analyses included 85 transplant recipients in the everolimus group and 141 transplant recipients in the mycophenolate mofetil group (n = 226 overall). There were no significant differences between the groups at 1 year for incidence of patient death and allograft loss, biopsy-proven acute rejection, BK virus-associated nephropathy, surgical complications, delayed graft function, and posttransplant diabetes mellitus. Incidence of cytomegalovirus infection and estimated glomerular filtration rate were significantly lower in the everolimus group than in the mycophenolate mofetil group. Posttransplant triglyceride and low-density lipoprotein were higher in the everolimus group than in the mycophenolate mofetil group. Multivariate ordered logistic analysis showed that older donor age and an acute rejection episode, but not induction with everolimus or mean tacrolimus trough concentration throughoutthe firstpostoperative year,were significant risk factors for severity of interstitial fibrosis/tubular atrophy at the 1-year protocol biopsy (P = .004 and P < .001,respectively). CONCLUSIONS: Short-term outcomes with everolimus plus standard-dose tacrolimus in recipients of de novo kidney transplant were comparable to those with mycophenolate mofetil plus standard-dose tacrolimus.

A case of peritoneal dialysis-related peritonitis caused by dialysate leakage with successful treatment by intravenous and intraperitoneal antibiotic therapy.

Dialysate leakage is one of the causes of peritoneal dialysis (PD)-related peritonitis. The rate of catheter removal in PD-related peritonitis caused by dialysate leakage (PDPDL) is high, and the correct treatment is unclear. We experienced a case of PDPDL that was treated with intravenous and intraperitoneal antibiotic therapy. A 44-year-old Japanese man had high glucose discharge from the exit site after 14 days of initiating PD, and he had a fever and cloudy effluent with a high white cell count. We diagnosed him with PDPDL and began to administer vancomycin and ceftazidime intraperitoneally. However, the peritonitis could not be ameliorated. A culture examination showed Staphylococcus aureus from the effluent of peritoneal cavity and exit site cultures. We began intraperitoneal cefazolin administration according to a drug susceptibility test, but the effluent cell count remained high. As we added intravenous cefazolin administration, his symptoms and cloudy effluent improved, and the effluent cell count normalized. He has not developed any recurrence of dialysate leakage or peritonitis. Our findings suggest that PD-related peritonitis accompanied by other infectious sites, such as PDPDL, should be treated with additional intravenous antibiotic therapy to taking effect on the infectious sites except for peritoneum and to keep plasma concentration of antibiotics sufficient especially in cases with preserved residual kidney function.

Initiation of dialysis for kidney graft failure: A retrospective single-center cohort study.

Few studies have focused on the outcome of dialysis for kidney graft failure. We investigated the outcomes of dialysis for graft failure. We retrospectively studied 52 patients undergoing dialysis for graft failure at our facility from January 2004 to December 2018. The mean age at initiation of dialysis was 51.8 ± 13.5 years. The patient survival rates after initiation of dialysis at 1, 3, and 5 years were 96.0%, 93.8%, and 82.4%, respectively. The rate of unplanned initiation was 44.2%. In multivariate logistic analysis, lack of follow-up by nephrologists and pre-emptive kidney transplantation (PEKT) tended to be risk factors for unplanned initiation (P = 0.065 and P = 0.014, respectively). Our study suggests that the prognosis of patients with dialysis for graft failure is acceptable. Dialysis for graft failure, especially in patients with PEKT, tends to be unplanned, and for safe initiation, early involvement of nephrologists may be necessary.

Autophagy gene ATG7 regulates albumin transcytosis in renal tubule epithelial cells.

Receptor-mediated albumin transport in proximal tubule epithelial cells (PTECs) is important to control proteinuria. Autophagy is an evolutionarily conserved degradation pathway, and its role in intracellular trafficking through interactions with the endocytic pathway has recently been highlighted. Here, we determined whether autophagy regulates albumin transcytosis in PTECs and suppresses albumin-induced cytotoxicity using human proximal tubule (HK-2) cells. The neonatal Fc receptor (FcRn), a receptor for albumin transcytosis, is partially colocalized with autophagosomes. Recycling of FcRn was attenuated, and FcRn accumulated in autophagy-related 7 (ATG7) knockdown HK-2 cells. Colocalization of FcRn with RAB7-positive late endosomes and RAB11-positive recycling endosomes was reduced in ATG7 knockdown cells, which decreased recycling of FcRn to the plasma membrane. In ATG7 or autophagy-related 5 (ATG5) knockdown cells and Atg5 or Atg7 knockout mouse embryonic fibroblasts, albumin transcytosis was significantly reduced and intracellular albumin accumulation was increased. Finally, the release of kidney injury molecule-1, a marker of tubule injury, from ATG7 or ATG5 knockdown cells was increased in response to excess albumin. In conclusion, suppression of autophagy in tubules impairs FcRn transport, thereby inhibiting albumin transcytosis. The resulting accumulation of albumin induces cytotoxicity in tubules.NEW & NOTEWORTHY Albumin transport in proximal tubule epithelial cells (PTECs) is important to control proteinuria. The neonatal Fc receptor (FcRn), a receptor for albumin transcytosis, is partially colocalized with autophagosomes. Recycling of FcRn to the plasma membrane was decreased in autophagy-related 7 (ATG7) knockdown cells. In addition, albumin transcytosis was decreased in ATG7 or autophagy-related 5 (ATG5) knockdown PTECs. Finally, release of kidney injury molecule-1 from ATG7 or ATG5 knockdown cells was increased in response to excess albumin.

Significance of revised criteria for chronic active T cell-mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation.

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P < .001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P < .001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.

Development and validation of a risk score for the prediction of cardiovascular disease in living donor kidney transplant recipients.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in kidney transplant (KT) recipients. To improve their long-term survival, it is clinically important to estimate the risk of CVD after living donor KT via adequate pre-transplant CVD screening. METHODS: A derivation cohort containing 331 KT recipients underwent living donor KT at Kyushu University Hospital from January 2006 to December 2012. A prediction model was retrospectively developed and risk scores were investigated via a Cox proportional hazards regression model. The discrimination and calibration capacities of the prediction model were estimated via the c-statistic and the Hosmer-Lemeshow goodness of fit test. External validation was estimated via the same statistical methods by applying the model to a validation cohort of 300 KT recipients who underwent living donor KT at Tokyo Women's Medical University Hospital. RESULTS: In the derivation cohort, 28 patients (8.5%) had CVD events during the observation period. Recipient age, CVD history, diabetic nephropathy, dialysis vintage, serum albumin and proteinuria at 12 months after KT were significant predictors of CVD. A prediction model consisting of integer risk scores demonstrated good discrimination (c-statistic 0.88) and goodness of fit (Hosmer-Lemeshow test P = 0.18). In a validation cohort, the model demonstrated moderate discrimination (c-statistic 0.77) and goodness of fit (Hosmer-Lemeshow test P = 0.15), suggesting external validity. CONCLUSIONS: The above-described simple model for predicting CVD after living donor KT was accurate and useful in clinical situations.

Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch-Schönlein purpura nephritis.

OBJECTIVES: Immunoglobulin A vasculitis/Henoch-Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose-deficient IgA1 was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear. METHODS: We compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA. RESULTS: GNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin- and/or granzyme B-positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up-regulated surface expressions of human leucocyte antigen DR (HLA-DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8+ cells and/or CD56+ cells and up-regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level. CONCLUSION: Activated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN.

Parvovirus B19-Infected Tubulointerstitial Nephritis in Hereditary Spherocytosis.

BACKGROUND: Human parvovirus B19 (B19V) causes glomerulopathy or microangiopathy, but not tubulopathy. We experienced an 11-year-old girl with spherocytosis who developed acute kidney injury on a primary infection of B19V. She presented with anuria, encephalopathy, thrombocytopenia, and coagulopathy, along with no apparent aplastic crisis. METHODS: Continuous hemodiafiltration, immunoglobulin, and intensive therapies led to a cure. RESULTS: A kidney biopsy resulted in a histopathological diagnosis of tubulointerstitial nephritis without immune deposits. The virus capsid protein was limitedly expressed in the tubular epithelial cells with infiltrating CD8-positive cells. CONCLUSIONS: Viral and histopathological analyses first demonstrated B19-infected tubulointerstitial nephritis due to the aberrant viremia with hereditary spherocytosis.

Reduced Recurrence of Primary IgA Nephropathy in Kidney Transplant Recipients Receiving Everolimus With Corticosteroid: A Retrospective, Single-Center Study of 135 Transplant Patients.

BACKGROUND: Long-term kidney allograft survival remains a major clinical challenge. Recurrent glomerulonephritis disease, including recurrence of IgA nephropathy (IgAN), is a significant barrier to long-term kidney allograft survival. We performed a retrospective, observational study to evaluate the role of everolimus (EVR) in the risk of recurrent IgAN. METHODS: The study included data from 135 patients aged ≥16 years with biopsy-proven IgAN on native kidneys who underwent a kidney transplant (KT) between December 2002 and December 2018. RESULTS: Patients who underwent de novo KT received mycophenolate mofetil (MMF) (n = 107) or EVR (n = 28). The mean recipient age in the MMF and EVR groups was 44.9 ± 13.7 and 41.1 ± 10.1, respectively. The median (interquartile range) follow-up period was 90.9 (64.9-115.3) and 21.2 (11.4-30.6) months, respectively (< .0001). All patients received continuous corticosteroid and tacrolimus therapy. The death-censored graft survival rate after KT and the recurrence-free survival rate did not differ significantly between the groups. Univariate and multivariate Cox regression analyses identified EVR for de novo KT as an independent predictive factor for recurrence-free survival (P = .024). CONCLUSIONS: Our findings suggest that EVR-based regimens with tacrolimus and corticosteroid therapy for de novo KT reduce the recurrence of IgAN compared with MMF-based regimens with tacrolimus and corticosteroid therapy.

Reintroduction of nivolumab in a patient with gastric cancer after improvement of nivolumab-induced acute interstitial nephritis: a case report.

Nivolumab, an anti-programmed cell death-1 (PD-1) antibody, has attracted increasing attention as a new treatment modality for gastric cancer. Herein, a case of acute kidney injury in a 66-year-old man with gastric cancer treated with nivolumab is presented. Kidney biopsy revealed severe acute interstitial nephritis and mild immunoglobulin A nephropathy. The cause of acute kidney injury was considered as acute interstitial nephritis because the main site of the lesion was the tubulointerstitium. Cessation of nivolumab and oral prednisolone administration rapidly improved the patient's renal function. Nivolumab was then restarted without worsening of renal function. To the best of the authors knowledge, this is the first case in which reintroduction of nivolumab was successfully performed in a patient with gastric cancer. Further, the relevant literature was reviewed on nivolumab-induced acute interstitial nephritis.

One-year Outcome of Everolimus With Standard-dose Tacrolimus Immunosuppression in De Novo ABO-incompatible Living Donor Kidney Transplantation: A Retrospective, Single-center, Propensity Score Matching Comparison With Mycophenolate in 42 Transplants.

BACKGROUND: Despite improvement in immunosuppressive therapy, long-term kidney allograft survival remains a major challenge. The outcomes of therapy with everolimus (EVR) and standard-dose tacrolimus (Tac) have not been compared with those of mycophenolate mofetil (MMF) and standard-dose Tac in recipients of de novo ABO-incompatible (ABOi) living donor kidney transplantation (LDKT). METHODS: This retrospective, observational, single-center, propensity score matching (PSM) study compared the outcomes of EVR and standard-dose Tac with those of MMF and standard-dose Tac following de novo ABOi LDKT. In total, 153 recipients of ABOi LDKT between January 2008 and March 2018 were screened for inclusion in the study. The variables considered for PSM were: recipient age/sex, duration of dialysis, cytomegalovirus mismatch (seronegative recipient and seropositive donor), cause of kidney disease, donor age/sex, and numbers of mismatches (HLA-A, HLA-B, and HLA-DR). After PSM, there were 21 patients in each group (n = 42 overall). RESULTS: Four patients in the EVR group and 1 patient in the MMF group were withdrawn because of adverse effects. There were no significant differences between the 2 groups in 1-year outcomes regarding patient death, graft loss, delayed graft function, biopsy-proven acute rejection, infection requiring hospital admission, or estimated glomerular filtration rate. The 1-year protocol biopsy showed that the severity of interstitial fibrosis/tubular atrophy was significantly milder in the EVR group than in the MMF group. CONCLUSIONS: The findings suggest that the renal efficacy and safety of EVR and standard-dose Tac in recipients of de novo ABOi LDKT are comparable with those of MMF and standard-dose Tac.