title: The impact of sodium chloride and volume depletion in the chronic kidney disease of congenital chloride diarrhea.
abstract: Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(-) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with sodium and potassium chloride offers protection from renal involvement in childhood, the long-term renal outcome remains unclear. Here we describe two cases of congenital chloride diarrhea-associated end-stage renal disease with transplantation. Further, we show that there is a high incidence of mild chronic kidney disease in 35 other patients with congenital chloride diarrhea. The main feature of the renal injury was nephrocalcinosis, without hypercalciuria or nephrolithiasis with small sized kidneys and commensurately reduced glomerular filtration rates. This suggests that diarrhea-related sodium chloride and volume depletion, the first signs of non-optimal salt substitution, promote urine supersaturation and crystal precipitation. The poor compliance with salt substitution along with long-lasting hypochloremic and hypokalemic metabolic alkalosis is likely to induce progressive calcification and renal failure. Both our patients developed nephrocalcinosis in the transplanted kidneys suggesting that this complication is a consequence of intestinal SLC26A3 deficiency. Interestingly, the transporter is expressed in the distal nephron but the recurrence of nephrocalcinosis in the transplanted kidney suggests that it does not play a significant renal role in this syndrome.
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. satu.wedenoja@helsinki.fi
authors.forename: Satu
authors.initials: S
authors.lastname: Wedenoja
authors.forename: Timo
authors.initials: T
authors.lastname: Ormälä
authors.forename: Ulla B
authors.initials: UB
authors.lastname: Berg
authors.forename: Stella F Edström
authors.initials: SF
authors.lastname: Halling
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.forename: Riitta
authors.initials: R
authors.lastname: Karikoski
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Christer
authors.initials: C
authors.lastname: Holmberg
authors.forename: Pia
authors.initials: P
authors.lastname: Höglund
mesh_terms: D000293:Adolescent; D000328:Adult; D017920:Antiporters / Q000235:genetics; D002675:Child, Preschool; D027963:Chloride-Bicarbonate Antiporters; D002908:Chronic Disease; D003967:Diarrhea / Q000139:chemically induced / Q000151:congenital* / Q000235:genetics; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology*; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis; D009929:Organ Size; D012965:Sodium Chloride / Q000009:adverse effects*; D000076988:Sulfate Transporters; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; C081011:SLC26A3 protein, human; D000076988:Sulfate Transporters; D012965:Sodium Chloride