Features of the phenotype and renal prognosis of congenital sanomalies of the kidney and urinary tract, isolated and associated with orphan syndromes in children

THE AIM: to estimate the characteristics of the phenotype of congenital anomalies of the kidneys and urinary tract (CAKUT), renal function and survival using the method of E. Kaplan-P. Meier (1958) in children to predict the progression of chronic kidney disease (CKD). PATIENTS AND METHODS : The study included 127 patients aged from 1 month to 17 years 11 months: Group I – 113 (89 %) patients with CAKUT, without association with syndromes (isolated); Group II – 14 (11 %) patients with CAKUT associated with orphan syndromes and numerical chromosomal diseases (syndromic). As defined by K/DOQI (2002) and R. Hogg et al. (2003), in pediatric patients CKD stages were stratified according to glomerular filtration rate (GFR) criteria, calculated by creatinine clearance (mmol/l) in the formula G.J. Schwartz, and albuminuria/proteinuria categories. The study of renal survival in patients with CAKUT involved the construction of life tables and the moment non-interval E.L. Kaplan - P. Meier method (1958). The term “survivors” is used for children with CAKUT who have preserved GFR or compensated CKD. CONCLUSION: In the structure of CAKUT in children with isolated phenotypes, a predominance of renal/renal anomalies (76.9 %), vesicoureteral reflux (53.1 %), ureterohydronephrosis/ hydronephrosis (41.6 %) was revealed. In the structure of CAKUT in hereditary syndromes and numerical chromosomal diseases, out of 14 patients, 13 (92.8 %) had kidney anomalies, 9 (62.3 %) hydronephrosis, 3 (21.4 %) VUR. Features of CAKUT in orphan syndromes due to gene mutations have been established in pediatric patients: Fraser type 1 ( FRAS1 ), Pierson ( LAMB2 ), Lowe ( OCLR ), Lowe ( OCRL , ROBO2 ), FOXP1 ( FOXP1 ), Schuurs–Hoeijmakers ( PACS1 ), Dent 2 ( OCLR ), Renal–Coloboma ( PAX2 ), chromosomal Shereshevsky–Turner disease (monosomy 45X); Down (trisomy 21 chromosome) associated with Sensenbrenner ( WDR35 ) syndrome; autosomal dominant renal hypoplasia/aplasia syndrome type 3 ( GREB1L ). The progression of CKD was established in 92 children aged over 2 years with isolated CAKUT from C1 with preserved GFR (27.2 %) to С2 (8,7 %), С3 (50 %), С4 (9,8 %), С5 (4,3 %). In 11 children aged over 2 years with CAKUT in orphan syndromes, CKD stage was stratified C1 with preserved GFR (5); C2 (5); C5 (1). The probability of 5-year, 10-year and 15-year renal survival in children and adolescents with isolated CAKUT is 94.4 %, 89.5 % and 66.5 %, respectively. The probability of 5-year and 10-year preservation of renal function (CKD C1 with a normal level of GFR) in children and adolescents over 2 years of age with CAKUT associated with hereditary syndromes is reduced (58.5 % and 32.0 %, respectively).