Long-term Effects of Kidney Transplantation Compared With Dialysis on Intima-media Thickness in Children-Results From the 4C-T Study.

BACKGROUND: Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events. METHODS: We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study. RESULTS: A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (ß = 0.0053 mm/y, P   =  0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate. CONCLUSIONS: IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk.

Findings from 4C-T Study demonstrate an increased cardiovascular burden in girls with end stage kidney disease and kidney transplantation.

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m2 per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m2 per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure.

Early predictive value of baseline renal transplant scintigraphy in pediatric patients.

OBJECTIVES: The value of baseline renal transplant scintigraphy (RTS) with technetium-99m diethylenetriaminepentaacetic acid (Tc-DTPA) performed within 2 days after transplantation in predicting early renal transplant outcome in pediatric recipients was assessed in this study. PATIENTS AND METHODS: Baseline RTS of 48 pediatric patients were studied retrospectively. Hilson's perfusion index, graft index (GI), time between peak perfusion and iliac artery (ΔP), and the ratios of peak perfusion to plateau (P : Pl), to peak iliac artery (P : A), and to peak uptake (P : U) were obtained. In 14 patients younger than 9 years old, because of faint visualization of iliac artery, the perfusion indices and GI could not be calculated. The 'Bedside Schwartz' formula was used for calculation of follow-up estimated glomerular filtrate rate (eGFR) values. The need for dialysis in the first week or decreasing serum creatinine of less than 10%/day during 3 consecutive days after the transplantation was accepted as delayed graft function (DGF). The patients, whose creatinine reduction ratio was less than 70% on day 7 after transplantation without DGF, were accepted as slow graft function (SGF). RESULTS: The means of GI, P : U, and Hilson's perfusion index were significantly high in SGF/DGF (n=10). GI and P : U had very high accuracy in the diagnosis of DGF/SGF (area under the curve>0.90). A strong correlation was found between P : U and same day and between GI and day 15 eGFR values. GI, P : U, and P : A were significant for the prediction of follow-up eGFR of less than 60 ml/min/1.73 m. GI was more accurate than the others. CONCLUSION: Our experience in this study underlines the importance of RTS, especially with the use of GI and P : U, which are very valuable in diagnosing DGF/SGF and predicting early transplant outcome in pediatric recipients.

Critical points in the management of pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA-1, MIM #264350) is caused by defective transepithelial sodium transport. Affected patients develop life-threatening neonatal-onset salt loss, hyperkalemia, acidosis, and elevated aldosterone levels due to end-organ resistance to aldosterone. In this report, we present a patient diagnosed as PHA-1 who had clinical and laboratory findings compatible with the diagnosis and had genetically proven autosomal recessive PHA-1. The patient received high doses of sodium supplementation and potassium-lowering therapies; however, several difficulties were encountered in the management of this case. The aim of this presentation was to point out the potential pitfalls in the treatment of such patients in the clinical practice and to recommend solutions.