Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used to treat type 2 diabetes (T2D). Lowering blood glucose is expected also to reduce the progression of diabetic nephropathy. We experienced a patient with T2D who achieved good glycemic control with a DPP-4 inhibitor but experienced rapid deterioration of renal function. Therefore, we performed a retrospective study of similar patients treated at our hospital. Methods: Out of 56 patients with biopsy-proven diabetic nephropathy who underwent native kidney biopsy at Toranomon Hospital from January 2018 through December 2022, we selected 22 patients who had been receiving DPP-4 inhibitors for at least 9 months at the time of kidney biopsy. Of these patients, we evaluated 16 diagnosed with class IIa diabetic nephropathy according to Tervaert's pathologic classification. The yearly estimated glomerular filtration rate (eGFR) slope in the 16 patients was arranged from the highest to the lowest slope. Ten patients with a large eGFR slope had thrombotic microangiopathy (TMA)-like lesions characterized by glomerular endothelial cell proliferation and GBM duplication on kidney biopsy (group A), whereas the remaining 6 patients did not have TMA-like lesions (group B). Results: Group A had a median (interquartile range [IQR]) eGFR of 18.2 (16.2, 26.2) and a yearly median (IQR) eGFR slope of -11.2 (-17.6, -9.2) mL/min/1.73 m2 after of DPP-4 administration, whereas group B had a median (IQR) eGFR of 31.5 (21.9, 34.8) mL/min/1.73 m2 and a yearly median (IQR) eGFR slope of -1.6 (-3.1, -0.3). Renal function declined significantly more rapidly in group A than in group B, and proteinuria was higher in group A than in group B (median [IQR], 3.4 [2.6, 4.4] g/day vs 0.8 [0.4, 1.3] g/day, respectively). Five patients in group A progressed to dialysis during follow-up, but none of the patients in group B did. Median (IQR) hemoglobin A1c was 6.2 % (6.0 %, 6.6 %) in group A and 5.8 % (5.7 %, 6.6 %) in group B. Conclusion: DPP-4 inhibitors promote vascular endothelial regeneration, but when this effect occurs in the glomerulus, glomerular endothelial cell proliferation leads to TMA-like lesions, which may cause an increase in proteinuria and rapid decline in renal function.
ObjectivesTo 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.MethodsData 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.ResultsA 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).ConclusionsIn 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.
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.
Abstract Background Patients with lateral node metastasis in low rectal cancers have a poor prognosis. However, variability in patient survival in terms of lateral metastatic status has not been thoroughly investigated. This study was conducted to assess the prognostic value of lateral node involvement and to review nodal classification. Methods Patients with stage III low rectal cancers who underwent lateral node dissection were retrospectively reviewed. Two cohorts were set: the first one (1995–2006) was selected using a Japanese multi-institutional database and was used for development of a new nodal system, and the second (2007–2013) was collected from referral institutions for validation of findings. Variables correlated with poor prognosis were investigated. Next, a modified classification of lateral-positive nodal cancers was created. Finally, this new classification was compared with TNM and Japanese classification-based systems according to the Akaike information criterion (AIC) and concordance index (c-index). Results Overall, 742 and 508 patients were selected for cohorts 1 and 2, respectively. Based on the analyses on cohort 1, patients with two or more lateral metastatic nodes partially spreading into regions outside of internal iliac area exhibited poor prognosis; accordingly, a modified N classification was created, where TNM-N1 and N2a cancers with this feature were upgraded, respectively, to N2a and N2b. The modified N classification yielded the most favourable indices (AIC = 2661.08; c-index = 0.6477) compared with the TNM (AIC = 2662.36; c-index = 0.6457) and Japanese classification-based systems (AIC = 2684.06; c-index = 0.6302). All findings were confirmed by analysing cohort 2. Conclusion A modified nodal system is proposed to account for the significance of lateral node metastasis.
We report on hepatitis C virus genotype 2c infection in 12 human immunodeficiency virus-infected men who have sex with men in Tokyo, Japan. The uncommon strains from the 12 patients were genetically clustered; they suggested an emerging outbreak in this population at high risk of sexually transmitted infections.
