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Background: Aortic dilatation is a cardiovascular complication in pediatric renal transplant recipients and may have an increased risk of aortic dissection, aortic rupture, and death. Studies failed to show an association between blood pressure and aortic dilatation; however, 24-hours ambulatory blood pressure monitoring (ABPM) was not performed. There was also no comparison between preemptive transplantation and dialysis., Methods: After ethics approval, a retrospective cross-sectional study was performed on all prevalent pediatric renal transplant recipients from a single tertiary care center. The presence of aortic dilatation was determined using standard echocardiographic measurements, and those with other risk factors for aortic dilatation were excluded. Associations between 24-hours ABPM, renal function, dialysis history, and aortic dimensions were determined., Results: We enrolled 37 participants with the following characteristics: 46% female, mean age 14.5 ± 3.7 years, 16% preemptive transplantation, and median end-stage renal disease (ESRD) combined vintage (time from ESRD onset to echocardiogram) 597 days (range 289-1290 days). We found 16/37 patients (43%) with aortic dilatation at any level, mostly mild. There was no association between 24-hours ABPM measurements and aortic dilatation. None of the preemptively transplanted children had aortic dilatation., Conclusion: This study confirms a high prevalence of aortic dilatation among pediatric renal transplant recipients, which appears to be independent of hypertension on 24-hour ABPM. Patients with preemptive renal transplantation did not have aortic dilatation, suggesting that the effects of dialysis may contribute to the high prevalence of this complication. Pediatric cardiologists need to carefully assess aortic dimensions in these at-risk patients., (© 2020 Wiley Periodicals LLC.)

Objectives: MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre-, peri-, and post-transplant course of all children with MMA who underwent liver or combined liver-kidney transplant in our centers., Design and Methods: Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years., Results: Five children with MMA underwent liver transplant (4/5) and combined liver-kidney transplant (1/5). Three were Mut 0 and two had a cobalamin B disorder. Four of five were transplanted between ages 3 and 5 years. Renal dysfunction prior to transplant was seen in 2/5 patients. Post-transplant (one liver transplant and one combined transplant) renal function improved slightly when using creatinine-based GFR formula. We noticed in 2 patients a big discrepancy between creatinine- and cystatin C-based GFR calculations. One patient with no renal disease developed renal failure post-liver transplantation. Serum MMA levels have decreased in all to <300 μmol/L. Four patients remain on low protein diet, carnitine, coenzyme Q, and vitamin E post-transplant., Conclusions: MMA is a complex metabolic disorder. Renal disease can continue to progress post-liver transplant and close follow-up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post-transplant can halt the progression of renal disease remains unclear., (© 2019 Wiley Periodicals, Inc.)

Management of late humoral rejection remains challenging, and DSA may persist. A case report illustrates how individual DSA titers using solid-phase-based assays may help to assess for accommodation. A male cystinosis patient received a cadaveric renal transplant at the age of 12 yr with a daclizumab, tacrolimus, MMF, and steroids-based immunosuppression. After three acute rejection episodes over the first eight months, interstitial fibrosis/tubular atrophy (IF/TA) was diagnosed on biopsy, while the immunosuppression was left unchanged with a high target exposure for both tacrolimus and MPA. One yr later, AMR type III (C4d and DSA positive) was treated with daily plasmapheresis, IVIG 100 mg/kg and pulse steroids 5 mg/kg. DSA (DR 53, DQ4, and DQ 2) were not responding until the plasma volume was increased to 2.5 plasma volumes. A second rise of creatinine confirmed worse humoral rejection; daily plasma exchange was resumed, and two doses of rituximab (375 mg/m(2)) were given. Subsequently, all DSA dropped, but only DR53 DSA remained unchanged, whereas the DQ antibodies rebounded to very strong titers. With a follow-up of over 120 days after recovery of the CD19 count, off all additional treatment and on identical immunosuppression with tacrolimus and MMF and prednisone, the patient's creatinine remained stable between 45 and 50 um while DQ DSA remain strong to very strong. We conclude that the patient is in a state of accommodation. DSA titers should be monitored when managing late humoral rejection., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To compare the pattern of serum FGF23 levels in pediatric renal transplant recipients and GFR-matched controls. We performed a cross-sectional matched pair study in 19 stable pediatric renal transplant recipients and 19 GFR-matched controls with native CKD. After assessment for normal distribution, demographic and bone metabolism parameters were compared with Student's t-test, Wilcoxon's matched pairs (for non-normal distribution) test, and correlation analysis. The groups were comparable for anthropometric parameters, cystatin C eGFR (71.10 ± 37.28 vs. 76.11 ± 26.80 mL/min/1.73 m(2) ), cystatin C, urea, creatinine, intact PTH, pH, CRP, alkaline phosphatase, phosphate, calcium, ionized calcium, FGF-23 (63.44 [IQR 38.42, 76.29], 49.92 [IQR 42.48, 76.97]), albumin, and urinary calcium/creatinine ratio. The renal transplant patients had significantly lower 25-(OH) vitamin D levels (66.63 ± 17.54 vs. 91.42 ± 29.16 ng/mL), and higher 1,25-(OH)(2) vitamin D levels (95.78 ± 34.54 vs. 67.11 ± 35.90 pm). FGF-23 levels correlated negatively with cystatin C eGFR (r = -0.3571, p = 0.02770) and positively with PTH (r = 0.5063, p = 0.0026), but not with serum phosphate (r = 0.2651, p = 0.1077). We conclude that the increase in FGF23 levels with GFR decline in pediatric renal transplant patients remains similar to that in the patients with CKD. The relationship between FGF23 and serum vitamin D needs further evaluation., (© 2011 John Wiley & Sons A/S.)

SRL has been increasingly used in renal transplantation, but limited sampling approaches for estimation of AUC remain elusive. A post-hoc analysis of 94 PK profiles in 75 patients from four previous studies was performed to generate limited sampling approaches for approximation of AUC based on two to four time points for both BID and OD SRL dosing. AUC was calculated using the trapezoid rule. Stepwise linear regression was performed to generate an abbreviated AUC from the limited sampling approaches. For BID dosing, complete AUC had a strong correlation with the trough levels (r(2) = 0.882, p < 0.0001) and with C2 level (r(2) = 0.9025, p < 0.0001). A three-point and a four-point limited sampling approach showed improved agreement with complete AUC compared with single-point sampling. A convenient and accurate (r(2) = 0.992) four-point limited sampling approach reads: AUC = 10;(1.085 + 0.117 x log C0 + 0.164 x log C1-0.131 x log C2 + 0.823 x log C4). Similarly, complete AUC had a statistically significant correlation with the trough levels (r(2) = 0.549, p < 0.0001) and with C2 level (r(2) = 0.716, p < 0.0001) for OD dosing. The estimation of AUC for OD dosing was improved over single-point sampling (r(2) = 0.951) using the formula: AUC = 10;(1.100 + 0.115 x log C0 + 0.803 x log C4). This study represented the first limited sampling approach for SRL. Further studies are required to determine the optimal SRL target AUC.

BKVN has emerged as an important cause of pediatric renal allograft nephropathy, with significant graft dysfunction in majority of the cases. Reduced immunosuppression and cidofovir therapy are the most commonly used therapeutic options for the treatment of BKVN in these patients. Recently, a preliminary study in adult renal allograft recipients with BKVN showed a therapeutic response to a combined approach of immunosuppression reduction and IVIg administration. A therapeutic benefit of IVIg without another concomitant treatment intervention has not been evaluated. We report stabilization of renal functions, histological resolution of BKVN and significant reduction in BK viremia in pediatric renal transplant with the use of IVIg, after an inadequate response to immunosuppression reduction and cidofovir therapy. In addition, we review the current literature on the use of cidofovir in pediatric renal transplant patients with BKVN and the potential of IVIg use in this condition.

The aim is to review the tools for early detection of renal dysfunction after pediatric solid organ transplantation. Currently, the most widely used marker for detection of renal dysfunction involves measurement of GFR. Inulin clearance forms the "gold standard" method for measuring GFR; however, nuclear medicine methods ((51)Cr EDTA and (99)Tc DTPA isotope clearance studies) have replaced inulin clearance. The measurement of serum creatinine has a low sensitivity for the early detection of renal damage. The Schwartz formula using patient height and serum creatinine requires center-specific constants and has limitations associated with creatinine determination. These limitations may be overcome using a cystatin C-based GFR estimation. In diabetic nephropathy, and more recently in hemolytic uremic syndrome, microalbuminuria has been established as a useful screening tool for renal damage, while its predictive value in the transplantation setting needs to be established. All transplant recipients should be screened for hypertension. Early referral for ambulatory 24-h blood pressure monitoring and involvement of pediatric nephrologists should be considered. All pediatric solid organ transplant recipients receiving CNI should be screened regularly for high blood pressure and early evidence of renal damage using either GFR scans or cystatin C-based GFR estimations.