Evaluation of long-term treatment with indomethacin in hereditary hypokalemic salt-losing tubulopathies.
OBJECTIVE
Evaluation of the benefit/risk ratio of long-term treatment with indomethacin in salt-losing tubulopathies with special attention to renal function.


METHODS
Twelve patients (median age, 14.9 years) had received indomethacin for a median of 13 years (median cumulative dose, 10.7 g/kg). Creatinine clearance, serum electrolyte levels, endocrine status, and excretion of prostaglandins and electrolytes were examined during indomethacin therapy and after its withdrawal. All patients underwent ultrasound-guided renal biopsy. For statistical evaluation, the Wilcoxon test and Pearson correlation coefficient were used.


RESULTS
After indomethacin withdrawal, the biochemical features of the tubulopathy reappeared. The median creatinine clearance rose from 67.4 to 96.5 mL/min/1.73 m(2) (P <.05) but remained subnormal in 4 patients. Ultrasonography elucidated medullary nephrocalcinosis in 8 patients. Renal tissue showed slight/moderate focal tubular atrophy and interstitial fibrosis in 8 patients. Comparison with biopsy specimens, obtained 11 to 14 years before study participation from 5 patients, revealed no progression. A correlation between fractional sodium and magnesium excretion and percentage of altered tubulointerstitial compartment was found (P <.001). The 4 patients with mutations in the gene of the inwardly rectifying adenosine triphosphate-regulated potassium channel (ROMK) had almost normal renal histologic findings and normal renal function.


CONCLUSIONS
Renal function and histology are unaffected by long-term indomethacin treatment.
Reinalter
S C
SC
Department of Pediatrics, Philipps University, Marburg, Germany.
Gröne
H J
HJ
Konrad
M
M
Seyberth
H W
HW
Klaus
G
G
D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001835:Body Weight; D002648:Child; D003404:Creatinine / Q000097:blood; D004573:Electrolytes / Q000097:blood; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007213:Indomethacin / Q000627:therapeutic use*; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D011188:Potassium / Q000627:therapeutic use; D014463:Ultrasonography
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004573:Electrolytes; D003404:Creatinine; D011188:Potassium; D007213:Indomethacin