Antibiotic treatment-induced tubular dysfunction as a risk factor for renal stone formation in cystic fibrosis.
OBJECTIVE
Our purpose was to characterize the decisive pathophysiologic factors that lead to renal stone formation (nephrolithiasis) in patients with cystic fibrosis (CF).


METHODS
Patients with CF (n = 96) were investigated with respect to lithogenic and inhibitory factors of urolithiasis and compared with 30 healthy control patients. They were subdivided into 2 groups, 86 without renal stones and 10 with renal stones.


RESULTS
All stones were exclusively composed of calcium oxalate. As a major pathogenic factor, a urinary disequilibrium between promoting and inhibitory components of stone formation, characterized mainly by hypercalciuria, hyperoxaluria, and hypocitraturia, was found in the patients with nephrolithiasis. They tended to have lower plasma phosphate concentrations and an increased urinary phosphate excretion. The citrate/calcium ratio proved to be a valuable means to discriminate patients with renal stones from control patients. Patients with stones had ingested more cotrimoxazole and ceftazidim, cumulatively, than patients without stones. There was an inverse correlation between the amounts of antibiotics ingested and the percentage of tubular phosphate reabsorption (r = -0.91, P <.0046).


CONCLUSIONS
Renal stone formation in patients with CF is caused by a disequilibrium between promoting and inhibitory components of stone formation, which is dominated by hypercalciuria, hyperoxaluria, and hypocitraturia. Treatment with cotrimoxazole and ceftazidim, primarily, may lead to renal proximal tubular damage with an ensuing sequence of phosphate loss, increase of parathyroid hormone secretion, increased 1,25-dihydroxyvitamin D3 formation, and absorptive hypercalciuria.
Böhles
Hansjosef
H
Department of Pediatrics, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
Gebhardt
Boris
B
Beeg
Thomas
T
Sewell
Adrian C
AC
Solem
Eivind
E
Posselt
Georg
G
D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects*; D002442:Ceftazidime / Q000009:adverse effects*; D002511:Cephalosporins / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000209:etiology*; D007684:Kidney Tubules / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D012307:Risk Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*
D000890:Anti-Infective Agents; D002511:Cephalosporins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D002442:Ceftazidime