Follow-Up of Blood Pressure, Arterial Stiffness, and GFR in Pediatric Kidney Transplant Recipients

Pediatric renal transplant recipients (RTx) were studied for longitudinal changes in blood pressure (BP), arterial stiffness by pulse wave velocity (PWV), and graft function.Patients and Methods: 52 RTx patients (22 males) were included; office BP (OBP) and 24 h BP monitoring (ABPM) as well as PWV were assessed together with glycemic and lipid parameters and glomerular filtration rate (GFR) at 2.4[1.0–4.7] (T1) and 9.3[6.3–11.8] years (T2) after transplantation (median [range]).Results: Hypertension was present in 67 and 75% of patients at T1 and T2, respectively. Controlled hypertension was documented in 37 and 44% by OBP and 40 and 43% by ABPM. Nocturnal hypertension was present in 35 and 30% at T1 and T2; 24 and 32% of the patients had masked hypertension, while white coat hypertension was present in 16 and 21% at T1 and T2, respectively. Blood pressure by ABPM correlated significantly with GFR and PWV at T2, while PWV also correlated significantly with T2 cholesterol levels. Patients with uncontrolled hypertension by ABPM had a significant decrease in GFR, although not significant with OBP. Anemia and increased HOMAi were present in ~20% of patients at T1 and T2.Conclusion: Pediatric RTx patients harbor risk factors that may affect their cardiovascular health. While we were unable to predict the evolution of renal function based on PWV and ABPM at T1, these risk factors correlated closely with GFR at follow-up suggesting that control of hypertension may have an impact on the evolution of GFR.

Subclinical Rejection and Immunosuppression in Pediatric Kidney Transplant Recipients : Single Centre Study

Background: By the time of histological confirmation of rejection is achieved, renal scarring may for treatment as a realistic option . This study aims to study the subclinical pathological graft data and to evaluate the histopathological impact of different immunosuppression protocols in pediatric renal transplant recipients. Methods: This is a case series that included twenty living donor renal transplant recipients. All included cases received the classic triple immunotherapy for at least one month post-transplantation [Steroids, calconurine inhibitors (CNI), and mycofenlolic mofetile (MMF)]. Based on their immunological risk stratification; included cases were divided into 2 groups: group (A) continued on CNI based triple therapy protocol; group (B) shifted to evirolimus /low dose CNI protocol. Surveillance biopsies were done for all cases at one and four month post-transplantation. Results: One and four month biopsies revealed subclinical rejection (including borderline changes) in 4 (20%) cases and 6 (30%) cases respectively. The number of patients received tacrolimus/MMF therapy significantly increased (p=0.02) while that of patients on everloimus/low dose CNI significantly decreased (p=0.014) due to drug modifications based on four month surveillance biopsy data. Conclusion: Subclinical rejection is not uncommon in pediatric renal graft recipients which makes surveillance biopsy might be of help. Early usage of evirolimus/low CNI protocol is associated with higher rejection rate than triple therapy.

Hemoglobin and Cholesterol Affect Apparent Tacrolimus Clearance in Pediatric Transplant Recipients – a Retrospective Cohort Study

Introduction: Tacrolimus has a narrow therapeutic index with substantial inter- and intra-patient variability. Factors beyond genetic and developmental factors are poorly understood. Recent adult studies suggest that hemoglobin affects the apparent clearance (CL/F), whereas this and other potential factors in children are understudied. Methods: After ethics approval, we performed a single center retrospective cohort study of pediatric renal transplant recipients, who were followed between January 1st, 2004, and June 30th, 2018. Patients without tacrolimus therapy or concomitant sirolimus were excluded. The aim was to show the impact of hemoglobin, albumin, cholesterol and HDL on the apparent tacrolimus clearance (CL/F = Dose/AUC). Data were collected from electronic health record. We used 12-point pharmacokinetic (PK) profiles. Results: Thirty-three patients were included. Median age at transplantation was 10 years, 52% were female, the median tacrolimus area under the curve (AUC) was 133 ng*h/mL. CL/F mainly correlated with hemoglobin (n=1,257, r=-0.3767, p<0.0001), HDL-cholesterol (n=236, r=-0.3973, p<0.0001) and total cholesterol (n=373, r=-0.1821, p=0.0004). Conclusion: The present study suggests a moderate impact of the biochemical factors studied in the tacrolimus CL/F. Lower hemoglobin seems to increase it, while higher cholesterol decreases it. Physicians should be aware of this association during the TDM follow up.

Treatment of Post-Transplant Recurrent FSGS in Children Using Plasmapheresis and Augmentation of Immunosuppression

Background: Up to 60% of pediatric renal transplant recipients with end-stage renal disease due to primary focal and segmental glomerulosclerosis (FSGS) may develop recurrent disease. Such recurrence is associated with poor prognosis if no remission is achieved. We report a single center experience with a protocol based on plasmaphereis and increased immunosuppression that resulted in a high long-lived remission rates.Methods: This retrospective cohort study included consecutive pediatric renal transplant patients with recurrent FSGS treated with a standardized protocol using plasmapheresis and cyclophosphamide to supplement usual post-transplant immunosuppression with calcineurin inhibitors and steroids. Relapse was defined as urinary protein/creatinine ratio >1.0g/g and remission as <0.5g/g. Results: 15 patients with FSGS recurrence post-transplant were treated. All had therapy-resistant FSGS in native kidneys and had been on dialysis from 4-10 years. Of the 15, one died perioperatively from a pulmonary thromboembolism. 13 others achieved a complete remission within 3 months of treatment for FSGS recurrence. After a median follow-up period of 4 years, there were no recurrences of significant proteinuria. Conclusion: The addition of plasmapheresis and cyclophosphamide to a calcineurin- and steroid-based immunosuppression regime was highy successful in inducing high remission rates with recurrent FSGS. Prospective trials are needed to evaluate further the efficacy of increased immunosuppression along with plasmapheresis in this setting.