Long-term effect of eplerenone treatment in children with chronic allograft nephropathy.

BACKGROUND: Literature supports the protective role of mineralocorticoid antagonist (MRA) against the renal injury induced by aldosterone in kidney transplant recipients. However, there is limited data available regarding the safety and efficacy of MRAs in pediatric renal transplant patients. Therefore, we aimed to investigate the effect of long-term eplerenone administration in children with chronic allograft nephropathy (CAN). METHODS: Twenty-six renal transplant children with biopsy-proven CAN, an estimated glomerular filtration rate (eGFR ) > 40 mL/min per 1.73 m2 and with a significant proteinuria were included. Selected patients were randomly divided into two groups as follows; Group 1 (n = 10) patients received 25 mg/day eplerenone and Group 2 (n = 16) patients did not receive eplerenone for 36 months. Patients were examined in the renal transplant outpatient clinic biweekly for the first month and once a month thereafter. The primary outcome of the patients was compared. RESULTS: Mean eGFR stayed stable in group 1 patients, but significantly decreased in group 2 at 36 months (57.53 ± 7.53 vs. 44.94 ± 8.04 mL/min per 1.73 m2 , p = .001). Similarly, spot protein-creatinine ratio was significantly lower in group 1 compared to group 2 patients at 36 months (1.02 ± 7.53 vs. 3.61 ± 0.53, p < .001). Eplerenone associated hyperkalemia was not observed in group 1 patients (4.6 ± 0.2 vs. 4.56 ± 0.3, p = .713). CONCLUSION: The long-term eplerenone administration blunted the chronic allograft nephropathy by maintaining a stable eGFR levels and decreasing urine protein-creatinine ratio. Eplerenone associated hyperkalemia was not observed in our study.

The Role of Platelet-Lymphocyte Ratio and Neutrophil-Lymphocyte Ratio in Predicting the Delayed Graft Function in Pediatric Renal Transplant Patients.

OBJECTIVES: Delayed graft function is a common adverse outcome after renal transplant. Attempts for early prediction and prevention of delayed graft function are often challenging and misleading. Herein, we investigated for the first time the correlation between delayed graft function and preoperative noninvasive hematologic parameters to predict the possible adverse outcomes for renal transplant in pediatric patients. MATERIALS AND METHODS: In this study, preoperative hematologic parameters of 51 pediatric renal transplant recipients followed between 2015 and 2021 were analyzed retrospectively. The selected 16 renal transplant patients with delayed graft function and 35 patients without delayed graft function had no concomitant comorbidities. The cutoff values for platelet-to-lymphocyte ratio of <5 and neutrophilto- lymphocyte ratio of <175 were considered low. RESULTS: We retrospectively evaluated a total of 51 (male/female, 33/18) pediatric kidney transplant recipients with a median age of 12 (interquartile range, 8-18) years. Median level of circulating lymphocytes was significantly higher in patients with delayed graft function compared with patients without delayed graft function (2 vs 1, P = .040). The preoperative low values for platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were more prevalent in recipients who developed delayed graft function versus those who did not develop delayed graft function (68.8% vs 31.4% [P = .014] and 68.8% vs 34.3% [P = .023], respectively). CONCLUSIONS: Pretransplant low platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte were associated with increased number of delayed graft dysfunction. These novels and noninvasive inflammatory biomarkers may contribute to an early prediction of delayed graft function in pediatric kidney transplant recipients.

Use of Eculizumab in Pediatric Patients with Late Antibody-Mediated Rejection After Kidney Transplantation.

Late antibody-mediated rejection triggered by donor-specific antibodies is a leading cause of kidney allograft failure. Effective treatment options for late antibody-mediated rejection are limited in renal transplant recipients. Here, we report 2 pediatric cases of severe late antibody-mediated rejection resistant to conventional immunosuppressive therapy who were successfully treated with eculizumab. Two patients who fulfilled the late antibody-mediated rejection diagnostic criteria (positive donor-specific antibodies, elevated mean fluorescence index, acute and/or chronic morphological lesions in the microvasculature, and abnormal kidney function test) were included in this study. Both patients were previously unsensitized with negative panel-reactive antibody. Case 1 was a 12-year-old male patient with kidney failure secondary to vesicoureteral reflux who underwent related-living donor kidney transplantation 2 years ago. Eleven months later, he was diagnosed with late antibody-mediated rejection. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted. After the patient was treated with 2 doses of eculizumab, his mean fluorescence index dropped and serum creatinine decreased from 3.8 to 1.5 mg/dL. Case 2 was an unsensitized 16-year-old male patient with kidney failure secondary posterior urethral valve who underwent related-living donor kidney transplantation 4 years ago. Two years later, he was diagnosed with late antibody-mediated rejection. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted. After treatment with 2 doses of eculizumab, his mean fluorescence index dropped and serum creatinine decreased from 2.1 to 1.01 mg/dL. In both patients, eculizumab therapy effectively reduced the markers of late antibody-mediated rejection and improved the kidney function.

Clinical Features and Outcomes Following SARS-CoV-2 Infection in Pediatric Liver Transplant Patients.

OBJECTIVES: Several studies suggest that chronic immunosuppression in pediatric liver transplant patients may affect the severity and mortality rates of SARS-CoV-2 infection. MATERIALS AND METHODS: We assessed a total of 118 pediatric liver transplant recipients for SARS-CoV-2 infection, aged 1 to 18 years, followed between March 2019 and January 2022. We compared the clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric liver transplant patients to 187 non-liver transplant pediatric patients with SARSCoV-2 infection who had been diagnosed at our institution between March 15, 2020, and December 31, 2020. Demographic data, clinical features, and laboratory findings from the patients were retrospectively collected from hospital reports and telephone inquiries. RESULTS: A total of 20 liver transplant patients with SARS-CoV-2 infection were identified. Median age of liver transplant recipients with SARS-CoV-2 infection was higher than non-liver transplant pediatric patients with SARS-CoV-2 (14.8 [range, 7-16] vs 6.8 [range, 2-14] years; P = .016). There were no significant differences in mild and moderate disease courses of SARS-CoV-2 infection between liver transplant recipients and non-liver transplant pediatric patients (18 [90.0%] vs 133 [71.1%] patients [P = .188] and 2 [10%] vs 49 [26.2%] patients [P = .118], respectively). Fever was less frequently observed in liver transplant patients with SARS-CoV-2 infection compared with non-liver transplant patients (55.0% vs 80.2%; P = .015). We found no intergroup differences in sex (P = .342), hospitalization rate (P = .161), and overall clinical presentation. CONCLUSIONS: Despite the immunosuppression regimens, liver transplant patients in our series survived SARS-CoV-2 infection without serious sequelae and without graft rejection. Overall, liver transplant and non-liver transplant pediatric patients with SARSCoV-2 infection experienced a mild disease course.