The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites grant applications for Research Centers of Excellence in pediatric nephrology. The purpose of the research center is to attract a partnership of interdisciplinary research among investigators with scientific expertise who will use complementary and integrated approaches to study kidney diseases endemic to the pediatric population. In approaching the study of these disease processes it is anticipated that extensive collaboration will be required among individuals in the clinical and basic sciences, including cell biology, molecular biology, immunology, virology, genetics, epidemiology, biochemistry, physiology and pathology. Studies designed to foster and extend the development of new approaches into the causes, early diagnoses, improved treatment, and where possible, prevention of these diseases and disorders are appropriate.
The current Centers of Excellence in Pediatric Nephrology include Vanderbilt University and the Medical College of Wisconsin.
Background
Kidney disease is a major cause of illness and death in infants, children and adolescents. The incidence of end-stage renal disease (ESRD) in patients age 0 – 19 years in the United States is about 15 per million population, according to the 2005 USRDS Annual Data Report. The primary etiologies vary with age, but structural anomalies predominate. Data in the most recent report from the Chronic Renal Insufficiency arm of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) indicate that overall, about 60% of the patients in the registry had some type of structural anomaly. This diagnosis approaches 80% in infants. Approximately one third of adolescents in the study have some type of glomerular disease.
There are also several causes of acute renal failure (ARF) particularly pertinent to the pediatric population, which are in need of translational research. These include hemolytic uremic syndrome (HUS), postinfectious glomerulonephritis, post cardiac surgery ARF, and treatment of various childhood malignancies.
Progress is being made in molecular and genetic analyses to link specific gene products to normal or abnormal kidney growth and development and some human kidney diseases. For example the nephrin mutation in congenital nephrotic syndrome, a glomerular disease characterized by massive amounts of proteinuria and progressive renal failure in infants. Similarly specific podocin mutations have been linked to some forms of familial FSGS. However, the basic cellular and molecular mechanisms of the majority of pediatric kidney disorders are poorly understood. Progression often occurs even when the primary disease process has been thought to be adequately treated and the disorder appears to have become inactive. Several diseases that lead to chronic renal disease and end-stage renal disease (ESRD) in adults likely have their origin in childhood; notable examples are diabetes and hypertension. Up to one third of children who develop Type 1 diabetes will develop ESRD in their twenties or thirties. Therefore strategies to prevent kidney disease should begin in childhood, ideally. A great need exists to better understand the pathogenesis of these conditions. In addition, the child’s special growth and developmental needs present particular challenges.
The NIDDK has funded three pediatric multicenter studies in recent years: (1) Clinical trial in children and young adults with FSGS (FSGS-CT); (2) Prospective Study of Chronic Kidney Disease in Children (CKiD); (3) Clinical Study of Vesicoureteral Reflux in Children (RIVUR). Preliminary findings from these studies over the next several years might inform the designs of clinical trials in pediatric kidney disease patients in the near future.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) supports through the Division of Kidney, Urologic and Hematologic Diseases (DKUHD) seven George M. O’Brien Kidney Research Centers, two Centers of Excellence in Pediatric Nephrology, and four Centers for Polycystic Kidney Disease Research. These Centers are part of an integrated program of kidney-related research support within the NIDDK. Centers have provided a focus for increasing the efficiency and collaborative effort among groups of successful investigators at institutions with established comprehensive kidney research bases.
Research Goals and Scope
Representative, but not all-inclusive areas of research appropriate for investigation include:
(1) studies of renal disorders of genetic and congenital origin that may lead to progressive loss of renal function or cause severe metabolic imbalances in children;
(2) further identification and study of genes and gene mutations and molecular events involved in renal and urogenital morphogenesis and differentiation;
(3) studies of events involved in cellular signaling in renal morphogenesis in health and disease, including the definition of events involved in cellular communication and mechanisms by which growing cells influence and are influenced by extracellular matrix;
(4) immune-mediated disorders, including such diseases as post-infectious glomerulonephritis, human immunodeficiency virus (HIV), immunoglobulin A (IgA) nephropathy, and Wegner’s granulomatosis;
(5) studies to understand the molecular mechanisms underlying the renal hypertension in infants and children;
(6) studies addressing the short and long-term effects of anti-hypertensive agents in infants and children;
(7) identification of risk factors and predisposing factors contributing to renal disease progression in infants and children;
(8) studies addressing the etiology, pathophysiology, and treatment strategies for end-stage renal disease in infants and young children, including determinants of abnormal growth and development, the development of animal models to quantitate the contribution of selective variables in growth retardation in chronic renal failure, the effects of exogenous recombinant hormones, and the role of uremia in protein synthesis in young growing infants;
9) cellular and molecular studies underlying the development and progression of glomerulonephritis in children, including the molecular changes affecting the glomeruli, alterations of the basement membrane, mechanisms leading to proteinuria, and the biochemistry of the nephron during pathological states.
NIDDK/KUH Project Officer: Marva Moxey-Mims, M.D., 301-594-7717.
