Dataset Information

Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis.

ABSTRACT: BACKGROUND AND OBJECTIVES:African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS:We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16?years with mild to moderate kidney disease. RESULTS:A total of 140 AA children in the CKiD study were genotyped. High risk (HR) APOL1 genotypes were present in 24% of AA children (33/140) and were associated with FSGS, p??3?mg/l (33 vs. 15%, p?=?0.12), and obesity (48 vs. 19%, p?=?0.01). There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product. CONCLUSION:AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of chronic kidney disease and LVH management in this population.

SUBMITTER: Woroniecki RP

PROVIDER: S-EPMC5110572 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Renal and Cardiovascular Morbidities Associated with <i>APOL1</i> Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis.

Woroniecki Robert P RP Ng Derek K DK Limou Sophie S Winkler Cheryl A CA Reidy Kimberly J KJ Mitsnefes Mark M Sampson Matthew G MG Wong Craig S CS Warady Bradley A BA Furth Susan L SL Kopp Jeffrey B JB Kaskel Frederick J FJ

Frontiers in pediatrics 20161117

<h4>Background and objectives</h4>African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how <i>APOL1</i> genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children.<h4>Design setting participants and measurements</h4>We examined the prevalence of <i>APOL1</i> genotypes and associated cardiovascular phenotypes among children with FSGS in the ...[more]

PMID: 27900314

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Project description:Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g, glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g, to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

Dataset Information

Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis.

Publications

Renal and Cardiovascular Morbidities Associated with <i>APOL1</i> Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis.

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