Immunological risk and complement genetic evaluations in early onset de novo thrombotic microangiopathy after living donor kidney transplantation: A Japanese multicenter registry.

BACKGROUND: Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the allogeneic clinical factors and complement genetic background of dnTMA after KTx. METHODS: Perioperative dnTMA after KTx within 1 week after KTx were diagnosed based on pathological or/and hematological criteria at each center, and their immunological backgrounds were researched. Twelve aHUS-related gene variants were examined in dnTMA cases. RESULTS: Seventeen recipients (15 donors) were enrolled, and all dnTMA cases were onset within 72-h of KTx, and 16 of 17 cases were ABO incompatible. The implementation rate of pre-transplant plasmaphereses therapies were low, including cases with high titers of anti-A/anti-B antibodies. Examination of aHUS-related gene variants revealed some deletions and variants with minor allele frequency (MAF) in Japan or East Asian genome databases in genes encoding alternative pathways and complement regulatory factors. These variants was positive in 8 cases, 6 of which were positive in both recipient and donor, but only in one graft loss case. CONCLUSIONS: Although some immunological risks were found for dnTMA after KTx, only a few cases developed into TMA. The characteristic variations revealed in the present study may be novel candidates related to dnTMA in Japanese or Asian patients, but not pathogenic variants of aHUS. Future studies on genetic and antigenic factors are needed to identify factors contributing to dnTMA after KTx.

Pregnancy Complications and Impact on Kidney Allograft After Kidney Transplantation in IgA Nephropathy.

Pregnancy in kidney transplantation (KT) recipients has been challenging because of the high risk of maternal, fetal, and renal complications. Although patients with immunoglobulin A nephropathy (IgAN)-chronic kidney disease (CKD) are at a high risk for hypertension in pregnancy (HIP), the maternal risk in KT recipients with IgAN as the etiology remains unclear. We retrospectively reviewed the medical records of pregnant KT recipients who delivered at our hospital. The incidence of maternal and fetal complications and the impact on kidney allografts between the group with IgAN as the primary kidney disease and the group with other primary diseases were compared. The analysis included 73 pregnancies in 64 KT recipients. The IgAN group had a higher incidence of HIP than the non-IgAN group (69% vs. 40%, p = 0.02). IgAN as primary kidney disease and interval from transplantation to conception were associated with HIP (OR 3.33 [1.11-9.92], p = 0.03, OR 0.83 [0.72-0.96], p < 0.01, respectively). The 20-year graft survival or prevention of CKD stage 5 in group with IgAN was lower than that in the group with other primary disease (p < 0.01). KT recipients should be informed of the risk of HIP and possibility of long-term worsening of postpartum renal function.

A Case Report of Successful Kidney Transplantation in a Patient With Autosomal Dominant Polycystic Kidney Disease Who Underwent Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with several cardiovascular disorders, including aortic dissection, which preferentially occurs at the thoracic or abdominal level. Because there are few case reports describing surgical repair for aortic dissection followed by renal transplantation in patients with ADPKD, kidney transplantation performed after repair for aortic dissection remains challenging. CASE PRESENTATION: A 34-year-old Japanese man with end-stage renal disease secondary to ADPKD underwent thoracic endovascular aortic repair for complicated acute type B aortic dissection 12 months earlier. A contrast computed tomography scan before transplantation revealed an aortic dissection involving the descending aorta proximal to the common iliac arteries and confirmed multiple large bilateral renal cysts. After simultaneous right native nephrectomy, the patient underwent preemptive living-donor kidney transplantation obtained from his mother. Intraoperatively, we noted that dissection of the external iliac vessels was difficult because of dense adhesions. Arterial clamping was performed immediately below the bifurcation of the internal iliac artery to prevent further aortic dissection of the external iliac artery. After end-to-end anastomosis to the internal iliac artery was completed and the vascular clamp was released, the kidney began to produce urine immediately. CONCLUSION: This case suggests that kidney transplantation in patients undergoing endovascular aortic repair for aortic dissection can be performed by adequately applying a vascular clamp proximal to the internal iliac artery during vascular anastomosis.

A Case Report of Successful Renal Transplantation After Surgically Treated Type A Aortic Dissection.

BACKGROUND: Aortoiliac lesions can influence the results of kidney transplantation and increase technical difficulties during surgery. Aortic dissection (AD) is a rare and infrequently reported event before transplantation, whereas immediate optimal perfusion is paramount for kidney transplantation. Thus, adequate blood flow imposed by the flow from the true lumen must be considered when choosing a target inflow vessel. CASE PRESENTATION: A 67-year-old man on dialysis with end-stage renal disease caused by immunoglobulin A nephropathy was referred for kidney transplantation. He had successfully undergone conventional Stanford type A AD surgery 3 years ago. Pretransplant contrast-enhanced computed tomography angiography revealed termination of the distal intimal flaps within the common iliac arteries. Dilation of the descending aorta was also observed. Based on the meticulous vascular assessment, including consultation with the cardiovascular surgery department, the right internal iliac artery (IIA) was considered usable for anastomosis. He underwent living unrelated kidney transplantation from his 66-year-old wife. The patency and blood flow in the right IIA were also verified using intraoperative findings. Without any special procedure, we used a side-to-end arterial anastomosis between the donor renal artery and recipient IIA. After vascular clamp removal, the allograft was perfused homogeneously and immediately functioned. CONCLUSION: Patients receiving previous surgery for type A AD can successfully undergo kidney transplantation if the patency of the iliac arteries from the true lumen is confirmed by perioperative evaluation, and the artery can be carefully clamped to avoid possible further dissection.

Long-term prolonged-release tacrolimus outcomes in living donor kidney transplantation: The Japan Academic Consortium of Kidney Transplantation study-II.

OBJECTIVES: To evaluate the 10-year efficacy and safety of a prolonged-release tacrolimus-based combination immunosuppressive regimen on longer-term outcomes in living donor kidney transplantation. METHODS: Data from Japanese living donor kidney transplant recipients (n = 410) maintained on continuous prolonged-release tacrolimus-based immunosuppression from 2009-2013 were analyzed with a median follow-up of 9.9 years. RESULTS: A prolonged-release, tacrolimus-based combination regimen provided death-censored graft failure and all-cause death rates at 10 years of 7.0% and 6.8%, respectively. In multivariable analyses, acute and chronic rejection and 'throughout' (new-onset plus preexisting) diabetes mellitus were risk factors for death-censored graft failure. Recipient age ≥ 65 years, throughout diabetes mellitus and malignancy were common risk factors for all-cause death. Throughout diabetes mellitus was the most common risk factor for both death-censored graft failure and all-cause death. Additional analyses showed 10-year cumulative rates of death-censored graft failure were 14.0% and 5.4% for recipients with or without preexisting diabetes mellitus, respectively (log-rank test: p = 0.009). All-cause death rates were 12.7% and 5.4% in the preexisting and non-diabetes mellitus groups, respectively (log-rank test: p = 0.023). CONCLUSIONS: In this real-world, retrospective, living donor kidney transplantation study, a prolonged-release tacrolimus-based immunosuppressive combination regimen provided 10-year death-censored graft failure rates of 14.0% and 5.4% in diabetes mellitus and non-diabetes mellitus patients, respectively; Similarly, 10-year all-cause death rates were 12.7% and 5.4% in diabetes mellitus and non-diabetes mellitus patients, respectively. To our knowledge, the data in this study are the first to provide 10-year transplant outcomes in living donor kidney transplant recipients under prolonged-release tacrolimus-based regimen.

[A CASE OF TESTICULAR TUMOR DIAGNOSED DUE TO ACUTE SCROTUM].

A 32-year-old man visited the emergency department complaining of the right scrotal pain, which occurred suddenly during sexual intercourse. Palpation revealed induration and tenderness on the caudal side of the right testis. Ultrasonography revealed a mosaic-like mass on the caudal side of the testis and no difference in blood flow between the right and left testes. The patient underwent a thorough examination the next day. Although the blood test did not show elevated tumor marker levels, testicular MRI revealed a mass with heterogeneous signal in the right scrotum. Subsequently, the patient was referred to another hospital for surgery. The pathological examination revealed a mixed germ cell tumor: seminoma (60%), teratoma (20%), and embryonal carcinoma (20%). One year postoperatively, the patient has had no recurrence. Testicular tumors are rarely discovered in acute scrotum, and few such cases have been reported. Torsion of the tumor, hemorrhage, necrosis, rupture, and infection have been reported as mechanisms of occurrence. When acute scrotum is diagnosed, testicular tumor should be considered as a differential diagnosis.

Role of Early Serial Renal Transplant Allograft Protocol Biopsies in Living Kidney Transplantations.

PURPOSE: This study aimed to analyze the incidence of subclinical rejection (SCR) in kidney transplantation patients and risk factors associated with SCR. METHODS: We assessed 80 protocol biopsies taken within 2 years postoperatively in 41 adult patients who underwent living donor kidney transplantation between 2017 and 2020. All patients were on immunosuppressant therapy that included tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The prevalence of Banff Borderline classification at 3, 6, and 12 months after transplantation was 4%, 5%, and 8 %, respectively, whereas none of the biopsies met the Banff criteria for acute T cell-mediated rejection throughout the study period. Active antibody-mediated rejection (ABMR) was only present in 8% of patients at 3 months after transplantation and chronic active ABMR at 6, 12, and 24 months after transplantation was detected in 10%, 13%, and 11% of the patients, respectively. Subgroup analysis revealed that 50% of the 6 patients with preformed anti-donor specific antibodies (DSAs) developed clinical or subclinical active ABMR within 3 months after transplantation, followed by chronic active ABMR according to serial histologic assessment. Conversely, only a small proportion of patients (3%) without preformed DSAs exhibited clinically active ABMR. CONCLUSIONS: SCR occurs too infrequently in patients with low immunologic risk and strong contemporary immunosuppression therapy to justify the diagnostic effort of serial protocol biopsies. However, protocol biopsies remain an indispensable tool in renal transplant monitoring and may be especially important in immunologically high-risk patients with pre-existing DSAs.

Living-Donor Kidney Transplantation Performed in a Low-Volume Center by Visiting Surgeons From a High-Volume Center and Managed Clinically Solely by Nephrologists: 1-Year Outcomes.

BACKGROUND: Little is known about the outcome of living-donor kidney transplantation (LDKT) performed in low-volume centers lacking the services of full-time transplant surgeons. This retrospective cohort study assessed the outcome of LDKT performed in a low-volume center by visiting transplant surgeons from a high-volume center and managed perioperatively by transplant nephrologists. METHODS: We compared Japanese adult patients who had no donor-specific antibodies and underwent LDKT between 2006 and 2015 either in a low-volume (n = 31) or high-volume (n = 481) center. In the low-volume center, visiting transplant surgeons from the high-volume center conducted LDKT and transplant nephrologists managed the recipients peri- and postoperatively. The primary outcome was the composite of infection, cardiovascular disease, or cancer during 1-year follow-up. The outcomes of the low- and high-volume centers were compared using 1:2 propensity score matching. RESULTS: After matching, 9 of 29 patients in the low-volume center (31.0%) and 16 of 58 patients in the high-volume center (27.6%) experienced the primary composite outcome (risk ratio = 1.13; 95% confidence interval, 0.57-2.23). There were no significant differences between the 2 groups in graft function at 1 year, all-cause graft loss, biopsy-proven rejection, and urological complications. However, the median duration of post-LDKT hospitalization was significantly longer in the low-volume center than in the high-volume center (23 and 16 days, respectively). CONCLUSIONS: Among Japanese patients without preformed donor-specific antibodies, LDKT conducted at a low-volume center by visiting transplant surgeons from a high-volume center and managed clinically by transplant nephrologists was not associated with significantly higher risk of postoperative complications.

Predictors of return to work after kidney transplantation: a 12-month cohort of the Japan Academic Consortium of Kidney Transplantation study.

OBJECTIVES: To investigate the cumulative return-to-work (RTW) rate and to identify predictors of employment after kidney transplantation (KT). DESIGN: Retrospective, outpatient-based cohort study. SETTING: This was a single-centre study of the largest Japanese kidney transplant centre. PARTICIPANTS: We selected Japanese kidney transplant recipients aged 20-64 years who were employed in paid jobs at the time of transplantation and who visited an outpatient clinic from December 2017 to March 2018. From 797 patients, we evaluated 515 in this study. INTERVENTIONS: We interviewed patients at an outpatient clinic and investigated the timing and predictors of RTW using logistic regression models. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the cumulative RTW rate, and the secondary outcome was to investigate the predictors of RTW after KT. RESULTS: Among the 515 included recipients, the cumulative overall partial/full RTW rates at 2, 4, 6 and 12 months were 22.3%, 59.0%, 77.1% and 85.0%, respectively. The median duration from transplantation to RTW was 4 months. Regarding partial/full RTW, according to the multivariable analysis including all variables, male sex was a greater predictor for RTW than female sex (OR 2.05, 95% CI 1.32 to 3.20), and a managerial position was a greater predictor than a non-managerial position (OR 2.23, 95% CI 1.42 to 3.52). Regarding full RTW, male sex (OR 1.95, 95% CI 1.25 to 3.06) and managerial position (OR 1.95, 95% CI 1.25 to 3.06) were also good predictors. CONCLUSIONS: The cumulative RTW rate was 85.0% 1-year post-transplantation. Given that cumulative RTW rates varied by sex and position, transplant and occupational physicians should support kidney transplant recipients in the aspect of returning to work. TRIAL REGISTRATION NUMBER: UMIN000033449.

Post-donation satisfaction in kidney transplantation: a survey of living donors in Japan.

BACKGROUND: No studies using a valid, standardized method to measure post-donation satisfaction levels among living kidney donors (LKDs) have been published. METHODS: Donor satisfaction levels were measured using the Japanese version of the Client Satisfaction Questionnaire-8 (CSQ-8), a validated, self-report questionnaire. To identify factors related to post-donation satisfaction levels, we compared donors' sociodemographic and psychological characteristics and health-related quality of life (HRQoL), using the Short Form-36 Health Survey (SF-36), as well as recipients' clinical characteristics and SF-36 scores between donors with and without low satisfaction. In addition, donors' perceptions of the donation results and transplant procedure were assessed using measures that we developed. RESULTS: The mean (standard deviation [SD]) CSQ-8 score for the 195 participants was 26.9 (3.4). Twenty-nine (14.9%) respondents with total scores < 1 SD below the mean CSQ-8 score were placed into the low satisfaction group. Multiple logistic regression analysis demonstrated that lower perceptions of receiving adequate information prior to transplantation (odds ratio [OR] = 0.17; 95% confidence interval [CI] = 0.079-0.379; p < 0.001), lower optimism according to the Life Orientation Test (OR = 1.24; 95% CI = 1.045-1.470; p = 0.014), and increased serum creatinine levels in the paired recipient (OR = 0.05; 95% CI = 0.250-1.011; p = 0.054) independently increased the odds of having less satisfaction with donation. CONCLUSIONS: Our findings suggest that careful pre-donation education and more detailed informed consent may be needed, especially in LKDs with low constitutional optimism.

Higher immunoglobulin A nephropathy recurrence in related-donor kidney transplants: The Japan Academic Consortium of Kidney Transplantation study.

OBJECTIVE: To investigate the 10-year biopsy-proven recurrence rates and risk factors for immunoglobulin A nephropathy recurrence in kidney transplant recipients. METHODS: We included 299 kidney transplant recipients from 1995 to 2015, who had biopsy-proven underlying immunoglobulin A nephropathy and underwent zero-hour biopsy. The primary end-point was recurrence of immunoglobulin A nephropathy. We compared clinical, treatment and graft failure among those with and without recurrent immunoglobulin A nephropathy. A time-to-recurrence analysis was carried out using the competing risk analysis and time-dependent Cox model. RESULTS: Of 299 recipients, 80 had recurrent immunoglobulin A nephropathy (66.3% with clinical biopsy and 33.7% with protocol biopsy, post-transplant biopsy rate: 90.6%). The 10-year recurrence rate was 34.3% (95% confidence interval 27.6-41.1). Related-donor transplantation (hazard ratio 2.28, P = 0.009) and post-transplant increased proteinuria (hazard ratio 1.59, P < 0.001) were identified as potential risk factors for immunoglobulin A nephropathy recurrence. The 10-year rates were 41.5% in related donor recipients and 16.3% in unrelated donor recipients. There was no conclusive evidence that the calcineurin inhibitor, antimetabolites, basiliximab and rituximab reduce immunoglobulin A nephropathy recurrence. Immunoglobulin A nephropathy recurrence was associated with an increased risk of death-censored graft failure (hazard ratio 5.29, 95% confidence interval 1.39-20.17, P = 0.015). However, related donor itself was not associated with an increased risk of graft failure. CONCLUSIONS: The present results have clinical implications in that the signs of recurrent immunoglobulin A nephropathy should be evaluated carefully in recipients receiving related-donor transplants. There is a need for further studies related to genetic and/or familial interactions in kidney transplant recipients with immunoglobulin A nephropathy and related donors.

The interaction between post-transplant anemia and allograft function in kidney transplantation: The Japan Academic Consortium of Kidney Transplantation-II study.

BACKGROUND: The interaction between post-transplant anemia (PTA) and allograft function in kidney transplantation has not been evaluated directly. PTA, defined by WHO/AST criteria, was investigated in 1307 adult kidney transplant recipients between 2000 and 2015 (median follow-up, 7 years). METHODS: We investigated the impact of hemoglobin (Hb) on graft failure (non-censored for death) and their interactions, time-dependent Cox model, and subgroup analysis were used. RESULTS: PTA prevalence was 43.6% at 7 years and varied according to allograft function, recipient sex, and follow-up period. Decreased Hb considering the time-varying effect was associated with an increased risk of graft failure (hazard ratio = 1.83, 95% CI 1.66-2.02, P < 0.001). In subgroup analysis, allograft function (post-transplant time-averaged estimated glomerular filtration rate and cut point: 45 mL/min/1.73 m2) had significant interaction (P = 0.032). The 7-year graft failure rate in recipients with PTA and high eGFR was 7.7% (HR 1.52, 95% CI 1.25-1.84), whereas in those with PTA and low eGFR was 19.9% (HR 2.00, 95% CI 1.74-2.31). CONCLUSIONS: The unfavorable impact of PTA was significantly enhanced by low allograft function. PTA is likely to be associated with graft failure due to interaction with allograft function. Therefore, we should consider both Hb level and allograft function while determining the treatment strategy.

Once-daily vs twice-daily tacrolimus for de novo living kidney transplantation patients including ABO/HLA compatible and incompatible: A randomized trial.

Tacrolimus (TAC) is available as a twice-daily capsule (TAC-BID), once-daily capsule (TAC-QD), and once-daily tablet. Recipients with ABO-incompatible/anti-human leukocyte antigen (HLA)-incompatible transplantation were excluded in previous trials and have thus not been evaluated. We conducted a 5-year trial to determine whether TAC-QD is noninferior to TAC-BID for transplant outcomes. Adults who underwent de novo living kidney transplantation were randomly assigned (62 TAC-QD; 63 TAC-BID). We did not exclude ABO-/HLA- incompatible transplantation. TAC was initiated 7 days preoperatively (0.10 mg/kg/d). Mycophenolate mofetil, methylprednisolone, and basiliximab were administered. The primary endpoint was graft failure (non-censored for death). We performed a noninferiority test. The noninferiority margin was 10% in risk difference. Five-year graft failure rates were 6.5% and 9.5% for TAC-QD and TAC-BID, respectively (noninferiority, P = 0.009). The estimated glomerular filtration rates were similar between the groups (noninferiority, P < 0.001). TAC-QD did not have point estimates of risk difference above the inferiority margin in any assessed endpoints. However, a tendency of interaction was observed between biopsy-proven acute rejection and the follow-up period. In a living kidney transplant population with 40% of patients with ABO/HLA incompatibility, the effect of TAC-QD was not appreciably worse on various clinical transplant outcomes than that of TAC-BID over 5 years.

Clinical and Pathological Features of Plasma Cell-Rich Acute Rejection After Kidney Transplantation.

BACKGROUND: Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection characterized by the presence of mature plasma cells. In general, the prognosis of PCAR is poor, and its clinical and pathological features remain unclear. METHODS: We performed a retrospective observational study and compared allograft survival between kidney transplant recipients who developed PCAR and those who did not develop PCAR. We further analyzed clinical and pathological risk factors for allograft failure in PCAR patients. RESULTS: Of 1956 recipients, 40 developed PCAR. There was a higher prevalence of deceased donor transplants (27.5% vs 11.7%, P = 0.0059), longer median total ischemia time (99 minutes; interquartile range, 71-144 vs 77 minutes; interquartile range, 59-111; P = 0.0309), and lower prevalence of ABO-incompatible transplantation (7.5% vs 22.5%; P = 0.0206) in patients with PCAR than in those without PCAR.Multivariate Cox regression analysis showed that development of PCAR was associated with allograft loss (hazard ratio, 8.03; 95% confidence interval, 3.89-14.80; P < 0.0001).We classified PCAR according to the Banff 2015 criteria into a borderline change group, a T cell-mediated rejection (TCMR) group, an antibody-mediated rejection (AMR) or suspected of having AMR (AMR/sAMR) group, and a mixed rejection (TCMR/AMR) group. The AMR/sAMR group was associated with a lower rate of allograft survival without significant difference (log-rank test, P = 0.1692). CONCLUSIONS: The results indicated that PCAR was an independent risk factor for allograft loss. PCAR presented with all types of rejection in the Banff 2015 criteria, and AMR/sAMR was associated with poor allograft survival.

False Elevation of the Blood Tacrolimus Concentration, as Assessed by an Affinity Column-mediated Immunoassay (ACMIA), Led to Acute T Cell-mediated Rejection after Kidney Transplantation.

Tacrolimus is the most commonly used immunosuppressant. Because of its narrow therapeutic range, it is necessary to frequently monitor its concentration. We report the case of a 25-year-old man who underwent kidney transplantation whose tacrolimus concentrations, as measured by an affinity column-mediated immunoassay, were falsely elevated. As we reduced the dose of tacrolimus, the recipient developed T cell-mediated rejection. Using the same blood samples, an enzyme-multiplied immunoassay technique showed that the patient's levels of tacrolimus were extremely low. A further examination indicated that the false increase in the tacrolimus concentration was likely due to an unknown interfering substance. We administered methylprednisolone and antithymocyte-globulin. The patient's serum creatinine level decreased and remained stable after these treatments.

Preemptive anti-cytomegalovirus therapy in high-risk (donor-positive, recipient-negative cytomegalovirus serostatus) kidney transplant recipients.

OBJECTIVES: Universal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (R-)). METHODS: This retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/R-) and intermediate-risk recipients (D+/R+ or D-/R+), all managed with preemptive therapy. RESULTS: Of 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow-up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p=0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p<0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post-transplantation. Kaplan-Meier analysis showed no difference in the probability of mortality (log-rank p=0.63) or graft loss (log-rank p=0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p=0.24). CONCLUSIONS: These results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection.

Interstitial fibrosis is the critical determinant of impaired renal function in transplant glomerulopathy.

AIM: Transplant glomerulopathy (TG) is a feature of chronic antibody-mediated injury in the glomerular capillaries in renal transplant recipients. TG is generally associated with proteinuria; however, renal function at the diagnosis of TG varies. This study aimed to determine which morphological abnormalities are associated with renal function and proteinuria at the diagnosis of TG. METHODS: A total of 871 renal transplantations were performed at Tokyo Women's Medical University between 2005 and 2013. TG was diagnosed in 127 biopsies from 58 (6.7%) recipients. Renal function was evaluated by the estimated glomerular filtration rate (eGFR). Proteinuria was assessed by a dipstick test: positive for +1 and over. RESULTS: At diagnosis, of 127 biopsies, 72, 37, and 18 had mild, moderate, and severe TG (Banff cg). The severity of TG was not associated with decreased eGFR at the time of biopsy (cg1: 36.1 ± 14.8, cg2-3: 38.8 ± 14.5 mL/min per 1.73 m(2) , P = 0.25), whereas the severity of interstitial fibrosis (IF) (Banff ci) was significantly associated with decreased eGFR (ci0-1: 42.75 ± 13.32, ci2-3: 27.69 ± 11.94 mL/min per 1.73 m(2) , P < 0.0001). The multivariate analysis revealed that IF was the only independent risk factors for decreased eGFR (OR = 4.38, P = 0.0006). Meanwhile, TG was identified as the only independent risk factor for the incidence of proteinuria (OR = 2.67, P = 0.014). CONCLUSION: Interstitial fibrosis was a critical determinant of impaired renal function at the diagnosis of TG. The severity of TG was significantly associated with proteinuria, but did not contribute to renal dysfunction.