Background: This study aimed to investigate the safety and efficacy of steroid withdrawal therapy in kidney transplant recipients with tacrolimus, mycophenolate mofetil, everolimus based immunosuppression.Methods: We analyzed 274 recipients who underwent kidney transplantation from August 2014 and July 2022.Among these recipients, 180 patients maintained an immunosuppressive regimen including steroids (steroid continuation [SC] group).The 94 patients were determined to withdraw steroid therapy (steroid withdrawal [SW] group).All patients in the SW group received tacrolimus-mycophenolate mofetil-everolimus based immunosuppression.Results: The observation period was 4.96±2.11years in the SC group and 4.38±2.03years in the SW group.Five-year patient survival was 97.2% and 96.8%, and 5-year graft survival was 97.8% and 94.7% in SC and SW groups, respectively, with no significant difference.Estimated glomerular filtration rates were 43.6±18.3mL/min/1.73m 2 in the SC group and 42.0±15.3mL/ min/1.73m 2 in the SW group.There was no significant difference in the 24-hour urinary protein excretion between two groups.The blood concentration of tacrolimus was 3.9±1.6ng/dL and 3.6±1.5 ng/dL in the SC and SW groups, respectively.No significant difference was found in the incidence of borderline change, interstitial fibrosis and tubular atrophy, calcineurin inhibitor nephrotoxicity revealed by graft biopsy between two groups.However, the incidence of T cell-mediated rejection and transplant glomerulopathy were higher in the SW group (P=0.05 and P<0.01).The incidence of de novo donor-specific human leukocyte antigen (HLA) antibody (DSA) and non-DSA were similar in both groups.There was no significant difference in the incidence of cytomegalovirus or BK infection.The SW group had higher incidence of coronavirus disease 2019 than the SC group, but the difference was not significant (17.0% vs. 10.0%,P=0.12).Conclusions: The early steroid withdrawal therapy using everolimus may lead to a higher incidence of transplant glomerulopathy.A longer follow-up is necessary to thoroughly assess this impact.
Introduction The coronavirus disease 2019 pandemic emerged in December 2019. Renal transplant recipients receiving chronic immunosuppression are considered to be at a high risk of infection. Aside from upper respiratory tract symptoms, coronavirus disease 2019 has also been reported to cause acute kidney injury in 20–50% of infected cases. Case presentation A 62‐year‐old male renal transplant recipient presented with high fever, diarrhea, and cough, concurrent with rapid deterioration of graft function. The patient tested positive for coronavirus disease 2019. The pathological findings of the graft biopsy revealed diffuse flattening of tubular epithelial cells and extensive loss of the brush border in proximal tubular cells. Mycophenolate mofetil was discontinued and sotrovimab, remdesivir, intravenous immunoglobulin, and intravenous methylprednisolone were administered, resulting in gradual improvements in clinical symptoms and renal function. Conclusion We describe a case of a coronavirus disease 2019‐infected kidney transplant recipient who developed severe acute kidney injury caused by severe acute tubular necrosis.
Background/Objectives: The accurate prediction of postoperative renal function (post-RF) in living kidney donors is essential for optimizing donor safety and long-term health. After nephrectomy, renal function can be significantly altered, owing to the functional adaptation of the remaining kidney; however, the extent of this has not been investigated. This study aimed to examine how various donor factors affect functional adaptation after nephrectomy, and to develop a new predictive model. Methods: In total, 310 patients who underwent donor nephrectomy were included. Preoperative split renal function (pre-SRF) of the remaining kidney was measured. Post-RF was measured 1 month after surgery. The functional adaptation rate was calculated from the difference between pre-SRF and post-RF. Multiple regression analysis was performed to develop a predictive formula for post-RF, incorporating donor age and pre-SRF. Results: The median age of the donors was 60 years, and 38.7% were men. The median pre-SRF was 36.4 mL/min/1.73 m2. The median functional adaptation rate was 26.8%, with donor age, pre-SRF, and a history of hyperuricemia (HUA) being significant predictors of the functional adaptation rate. The equation for post-RF was established as 0.94 × pre-SRF − 0.12 × age + 18.87 mL/min/1.73 m2. The estimated post-RF showed a high coefficient of determination (R2 = 0.76), with a mean bias of –0.01 mL/min/1.73 m2. Conclusions: Donor age, pre-SRF, and HUA are key predictors of renal functional adaptation after nephrectomy. The developed formula accurately estimates post-RF, supporting clinical decision-making and donor counseling for living kidney donations.
Abstract Background and hypothesis Measurement of glomerular filtration rate (GFR) is subject to inaccurate urine collection. Clearances of d-serine and d-asparagine, rare enantiomers of amino acids, are the measures of GFR since they are almost free of tubular secretion and reabsorption. We hypothesize that d-serine and d-asparagine can accurately determine urine volume and GFR. Methods This cross-sectional observational study included 209 living kidney transplant donors and recipients for whom GFR was measured using the clearance of inulin. Assuming that urine excretions of d-serine and d-asparagine are constant and using urine levels of d-serine and d-asparagine from each urine collection, an equation for estimated urine volume (eUV) was established. Based on the eUV, the abnormal urine volume was replaced with an estimate with which the GFR was re-evaluated. Result Clearances of d-serine and d-asparagine were minor in proportional biases when compared with that of creatinine. Using 627 urine collection, the equation for eUV (mL/min) was established as 21.88/urine d-Ser (0.40 + 0.20 × log10(urine d-Asn)). Using eUV, we identified 20 instances where urine collection volumes varied significantly from the estimated values. After replacement with eUV, measured GFR (mGFR) was corrected to adjusted mGFR, which was within approximately 20 mL/min/1.73m2 of the mGFR. Conclusion d-Serine and d-asparagine are nearly completely excreted in urine after glomerular filtration, enabling the estimation of urine volume and correct mGFR. Besides reflecting GFR, d-serine and d-asparagine can be used to estimate urine volume. By applying the eUV method, mGFR determined using clearance methods becomes more accurate.
ABSTRACT Introduction This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor‐specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries. Methods We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended‐release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post‐surgery. Results No significant differences were observed between the MVI+DSA‐C4d‐ and MVI‐DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, p = 0.772) or patient survival rates (95.7% vs. 95.9%, p = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA‐C4d‐ (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; p = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; p = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA‐C4d‐ (OR, 0.994; 95% CI, 0.554–1.780; p = 0.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA‐C4d‐ (OR, 1.980; 95% CI, 0.318–12.000; p = 0.470). Conclusion Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody‐independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.
