TY - JOUR
T1 - Results of a gene panel approach in a cohort of patients with incomplete distal renal tubular acidosis and nephrolithiasis
AU - D'Ambrosio, Viola
AU - Azzarà, Alessia
AU - Sangiorgi, Eugenio
AU - Gurrieri, Fiorella
AU - Hess, Bernhard
AU - Gambaro, Giovanni
AU - Ferraro, Pietro Manuel
N1 - Publisher Copyright:
© 2021 The Author(s).
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Background: Distal renal tubular acidosis (dRTA) is characterized by an impairment of urinary acidification resulting in metabolic acidosis, hypokalemia, and inappropriately elevated urine pH. If not treated, this chronic condition eventually leads to nephrocalcinosis, nephrolithiasis, impaired renal function, and bone demineralization. dRTA is a well-defined entity that can be diagnosed by genetic testing of 5 genes known to be disease-causative. Incomplete dRTA (idRTA) is defined as impaired urinary acidification that does not lead to overt metabolic acidosis and therefore can be diagnosed if patients fail to adequately acidify urine after an ammonium chloride (NH4Cl) challenge or furosemide and fludrocortisone test. It is still uncertain whether idRTA represents a distinct entity or is part of the dRTA spectrum and whether it is caused by mutations in the same genes of overt dRTA. Methods: In this cross-sectional study, we investigated a group of 22 stone formers whose clinical features were suspicious of idRTA. They underwent an NH4Cl challenge and were found to have impaired urinary acidification ability. These patients were then analyzed by genetic testing with sequencing of 5 genes: SLCA1, ATP6V1B1, ATP6V0A4, FOXI1, and WDR72. Results: Two unrelated individuals were found to have two different variants in SLC4A1 that had never been described before. Conclusions: Our results suggest the involvement of other genes or nongenetic tubular dysfunction in the pathogenesis of idRTA in stone formers. However, genetic testing may represent a cost-effective tool to recognize, treat, and prevent complications in these patients.
AB - Background: Distal renal tubular acidosis (dRTA) is characterized by an impairment of urinary acidification resulting in metabolic acidosis, hypokalemia, and inappropriately elevated urine pH. If not treated, this chronic condition eventually leads to nephrocalcinosis, nephrolithiasis, impaired renal function, and bone demineralization. dRTA is a well-defined entity that can be diagnosed by genetic testing of 5 genes known to be disease-causative. Incomplete dRTA (idRTA) is defined as impaired urinary acidification that does not lead to overt metabolic acidosis and therefore can be diagnosed if patients fail to adequately acidify urine after an ammonium chloride (NH4Cl) challenge or furosemide and fludrocortisone test. It is still uncertain whether idRTA represents a distinct entity or is part of the dRTA spectrum and whether it is caused by mutations in the same genes of overt dRTA. Methods: In this cross-sectional study, we investigated a group of 22 stone formers whose clinical features were suspicious of idRTA. They underwent an NH4Cl challenge and were found to have impaired urinary acidification ability. These patients were then analyzed by genetic testing with sequencing of 5 genes: SLCA1, ATP6V1B1, ATP6V0A4, FOXI1, and WDR72. Results: Two unrelated individuals were found to have two different variants in SLC4A1 that had never been described before. Conclusions: Our results suggest the involvement of other genes or nongenetic tubular dysfunction in the pathogenesis of idRTA in stone formers. However, genetic testing may represent a cost-effective tool to recognize, treat, and prevent complications in these patients.
KW - Distal renal tubular acidosis
KW - Genetics
KW - Metabolic acidosis
KW - Nephrocalcinosis
KW - Nephrolithiasis
UR - http://www.scopus.com/inward/record.url?scp=85114037143&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114037143&partnerID=8YFLogxK
U2 - 10.1159/000516389
DO - 10.1159/000516389
M3 - Article
C2 - 34107482
AN - SCOPUS:85114037143
VL - 46
SP - 469
EP - 474
JO - Kidney and Blood Pressure Research
JF - Kidney and Blood Pressure Research
SN - 1420-4096
IS - 4
ER -