Dramatic changes have occurred in our understanding of the etiology of the growth retardation associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD) during the past 50 years. ...Significant interest has been focused on preventing and/or correcting the growth retardation because of the emergence of the dual therapeutic modalities of dialysis and renal transplantation to prolong the lives of infants, children, and adolescents afflicted with CKD and ESRD. These efforts have resulted in a significant improvement in the height Z-score over the past two decades of children with CKD and ESRD. This has had a salutary impact on the final adult height of such children which should hopefully lead to an enhanced quality of life in the future. This report addresses the progress that has been made in the management of growth retardation in the pediatric population with CKD and ESRD.
Growth following renal transplantation in infants, children, and adolescents was evaluated from 20 years of data reported to the registry of the North American Pediatric Renal Transplant Cooperative ...Study (NAPRTCS). The analysis of more than 10,000 recipients addressed the following questions: 1. What is the impact of age, pubertal growth, gender, transplant history, donor source and allograft function on growth after transplantation? 2. Has the height Z score at the time of transplantation changed during the past two decades and has this influenced final adult height? 3. To what extent has recombinant human growth hormone (rhGH) been utilized in growth retarded recipients after transplantation and has its use resulted in accelerated post-transplantation growth? 4. Has the use of steroids for maintenance immunosuppression changed over the past 20 years and how have the perturbations of steroid usage influenced post-transplantation growth? 5. Have changes in clinical care resulted in improved final adult height Z score during the past two decades? Only younger children (<6 years) had initial accelerated post-transplantation growth. The mean increment in height during puberty was 18.8 cm (21.7 cm in 4.7 years for boys and 14.3 cm in 4.5 years for girls). Gender, source of donor graft, or number of grafts did not influence growth. Height Z score at transplantation has improved over the past two decades, as has final adult height with each succeeding era. The use of rhGH after transplantation results in a delta Z score of +0.5 standard deviation (SD). Post-transplantation growth improves with steroid avoidance and changes in estimated glomerular filtration rate (eGFR) impact on growth.
The incidence of recurrence of nephrotic syndrome/focal segmental glomerulosclerosis (NS/FSGS) is variable (~30%). The incidence of recurrence is less in African-Americans than in whites and ...Hispanics. Graft survival rates are decreased in recipients with FSGS, especially if remission of the NS is not achieved in those with recurrence. Although controversial, the use of living donor (LD) transplants are not contraindicated; however, obligatory heterozygote parental grafts with a podocin mutation should be used with caution. Optimal treatment to induce a remission post-transplant has not been delineated. Pre-transplant and/or prophylactic post-transplant pre-operative plasmapheresis (PP) for high-risk patients--especially those with recurrence in a previous graft--may be promising. An international multicenter controlled study is required to delineate the optimal approach to prevent and/or treat the recurrence of NS/FSGS.
Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to ...evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival.
Cohort analysis of clinical trial participants.
Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone.
Reduction in proteinuria measured during 26 weeks after initiating treatment.
Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization.
Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome.
138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44).
Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years.
These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.
To present our experience in a single pediatric urology practice over a 10-year period with bladder tumors in the pediatric population in an effort to add to the relatively small amount of existing ...data. We hope to expand the community's knowledge of presentations, management and natural history of pediatric bladder tumors.
We retrospectively queried our electronic medical records for International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes relevant for bladder tumors. Patients with underlying bladder pathology, such as neurogenic bladder, history of bladder exstrophy, and history of bladder augmentation, were excluded.
We identified 30 patients with bladder tumors from 2011 to 2021. There were 21 males and 9 females. Age at diagnosis ranged from 16 months to 19 years. Tumors identified were: 11 of various inflammatory subtypes; 4 papillomas; 4 rhabdomyosarcomas; 3 papillary urothelial neoplasms of low malignant potential and 8 of other types. Treatment included transurethral resection of bladder tumor, chemoradiation and laparoscopic partial cystectomy. Twenty nine patients had disease limited to the bladder and 1 had disease outside the bladder. Follow-up ranged from 2 weeks to 13 years (median 19 months). All patients had no evidence of disease at most recent follow-up.
Pediatric bladder tumors range from aggressive rhabdomyosarcomas to more benign urothelial lesions. Fortunately, the latter type of tumor is the more prevalent lesion. Knowledge of the treatment options and natural history of these tumors will hopefully be of benefit to clinicians and parents alike.
Tolerance in Solid-Organ Transplant Fine, Richard N
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation,
11/2016, Volume:
14, Issue:
Suppl 3
Journal Article
Peer reviewed
Immunotolerance, which is nonimmunologic reactivity to specific tissue, was demonstrated in animals in the 1950s. However, despite assiduous efforts, it has not been reproduced in human solid-organ ...transplant to date. Fortuitously, clinical operational tolerance, which is stable graft function for > 1 year with no immunosuppression, has been demonstrated, primarily in a few nonadherent recipients of kidney and liver transplant. Vigorous efforts to identify a biomarker to distinguish recipients with clinical operational tolerance from nontolerant recipients have so far not been successful. However, weaning of immunosuppression in stable pediatric and adult liver transplant recipients has been successful in 60% and 20% of recipients. In kidney transplant recipients, clinical operational tolerance has been induced by combined kidney and hematopoietic cell transplant to induce chimerism and subsequent weaning of immunosuppression. Recently, the ex vivo expansion of autologous regulatory T cells with subsequent infusion has facilitated weaning of immuno suppression in liver transplant recipients. Protocols have been initiated to expand the use of regulatory T cells to kidney transplant recipients. These new methodologies have the potential to induce clinical operational tolerance in all recipients of a solid-organ transplant in the future, thus avoiding the long-term consequences of continued dependence on immunosuppressive medications for stable graft function.
Height at First RRT and Mortality in Children Ku, Elaine; Fine, Richard N; Hsu, Chi-Yuan ...
Clinical journal of the American Society of Nephrology,
05/2016, Volume:
11, Issue:
5
Journal Article
Peer reviewed
Open access
Poor linear growth is common in children with CKD and has been associated with higher mortality. However, recent data in adult dialysis patients have suggested a higher risk of death in persons of ...tall stature. In this study, we aimed to examine the risk of all-cause and cause-specific mortality in children at both extremes of height at the time of first RRT.
Using the US Renal Data System, we performed a retrospective analysis of 13,218 children aged 2-19 years, who received their first RRT (dialysis or transplant) during 1995-2011. We used adjusted Cox models to examine the association between short (<3rd percentile) and tall (>3rd percentile) stature and risk of death, compared with less extreme heights.
Over a median follow-up of 7.1 years, there were 1721 deaths. Risk of death was higher in children with short (hazard ratio, 1.49; 95% confidence interval, 1.33 to 1.66) and tall stature (hazard ratio, 1.32; 95% confidence interval, 1.03 to 1.69) in adjusted analysis. In secondary analyses, there was a statistically significant interaction between height and body mass index categories (P=0.04), such that the association of tall stature with higher mortality was limited to children with elevated body mass index (defined as ≥95th percentile for age and sex). Children with short stature had a higher risk of cardiac- and infection-related death, whereas children with tall stature had a higher risk of cancer-related death.
Children with short and tall stature are at higher mortality risk, although this association was modified by body mass index at time of first RRT. Studies to further explore the reasons behind the higher risk of mortality in children with extremes of height at the time of first RRT are warranted.
PDF
