161 Rapid somatic growth and gain in body weight are associated with accelerated deterioration of renal function [42] Patient age, reflecting body growth, is a general risk factor for progression in c[.]
11 Preservation of Residual Renal Function in Children Reaching End-Stage Renal Disease Rapid somatic growth and gain in body weight are associated with accelerated deterioration of renal function [42] Patient age, reflecting body growth, is a general risk factor for progression in children [41, 42, 80]; specifically, adolescents seem to progress more rapidly than prepubertal patients Accelerated disease progression during puberty has been observed in patients with CKD due to diabetes mellitus, posterior urethral valve, reflux nephropathy, and renal hypoplasia [81] The physiological pubertal rise in blood pressure, an increased metabolic load due to statural growth which cannot be compensated by proportionate renal growth, and vascular or tissue- specific effects of sex steroids are possible mechanisms underlying these associations On the other hand, administration of recombinant human growth hormone (rhGH), which induces body growth, was not associated with accelerated loss of renal function in children [82] Interestingly, in adult patients on long-term dialysis, obesity is associated with an accelerated decline of RRF [50, 73, 83] The role of genetic factors in determining the rate of renal failure progression is not yet fully understood Whereas no gender difference has been noted in CKD and ESRD cohorts encompassing the pediatric age range [41, 66], GFR appears to decline more rapidly in adult and adolescent males [34, 58], compatible with an adverse impact of androgens (or a protective effect of female sex steroids) on the conservation of RRF in CKD. However, in children on PD, RRF was not affected by gender [45, 51] African-American ethnicity is a significant risk factor of progression in pediatric CKD patients [41] Non-white race also predicts rapid loss of RRF in adults on dialysis [69] Increasing evidence suggests that the individual variability of CKD progression may in part be related to common genetic and epigenetic variation The DD genotype, a common variant of the ACE gene, was found overrepresented in pediatric ESRD as compared to the general population [84] This was confirmed in children with hypodysplasia, obstructive uropathy, and reflux nephropathy, but not in those with other congenital or hereditary diseases or acquired glomerular 161 disorders [85] Other studies suggested an association of the DD genotype with declining renal function also in pediatric glomerular diseases with normal renal function [86, 87] Furthermore, single nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1, KLK1, and vascular endothelial growth factor genes were reported to modify the risk of renal deterioration in reflux nephropathy [80, 88] SNPs in the D-loop of mitochondrial DNA allele 146 were identified as an independent predictor of kidney survival time [89] Glutathione-S-transferase-μ1 (GSTM1) null and apolipoprotein L-1 (APOL1) high-risk alleles were also reported to affect CKD progression with hypertension [90, 91] Moreover, several microRNAs (miR-30d, miR- 140-3p, miR-532-3p, miR-194, miR-190, miR- 204, miR-206) were downregulated in renal tissues from progressive CKD [92] Recently, a genome-wide association study (GWAS) identified several genetic variants associated with the decline of renal function in adults with CKD. SNPs in LINC00923 was associated with CKD progression and variants in genes, NAT8B, CASP9, and MUC1, with estimated GFR [93, 94] The Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) consortium identified 10 SNPs associated with estimated GFR across three large pediatric CKD cohorts [95] pecific Risk Factors for Loss of RRF S in Patients on Dialysis RRF decreases with time on dialysis [69], and the loss over time is exponential rather than linear [52] In adult patients on hemodialysis and PD, the decline of RRF was most prominent during the first 3 months after the start of dialysis [37] Repetitive intravascular volume depletion and hypotensive events are considered important causes of a rapid loss of RRF [73] The choice of dialysis modality has a crucial impact on RRF. There is ample evidence both in adults and in children that RRF is preserved better with PD than with hemodialysis [51, 56, 69, 96, 97] A more than two times faster decline of I.-S Ha and F Schaefer 162 Fig 11.3 Time to oliguria (daily diuresis