ESPN 51th Annual Meeting

ESPN 2018


 
Assessment of urine parameters after administration of ADV7103 in healthy adults and dRTA patients
LUC-ANDRE GRANIER 1 CATHERINE GUITTET 1 MARIA A. MANSO 1 AURELIA BERTHOLET 2

1- ADVICENNE S.A., NîMES, FRANCE
2- CENTRE DE REFERENCE DES MALADIES RENALES RARES – NEPHROGONES – HôPITAL FEMME MERE ENFANT, BRON, FRANCE
 
Introduction:

Distal renal tubular acidosis (dRTA) is characterised, among others, by hypercalciuria and hypocitraturia leading to nephrocalcinosis and nephrolithiasis. Alkalisers used for treatment of dRTA have the ability to modify urine parameters and particularly calciuria and citraturia. The excretion of different urine ions with ADV7103, a new prolonged-release combination of potassium citrate and potassium bicarbonate, was evaluated in healthy adult subjects and in dRTA patients.

Material and methods:

In healthy adult subjects (n=4) receiving 1.5 mEq/kg ADV7103 morning and evening during 5 days urine electrolytes were measured on 24h-urine collections and compared to baseline values. In dRTA patients (n=37 enrolled) receiving ADV7103 at appropriate doses to normalise bicarbonataemia during a 5-day period, urine parameters were measured on urine spots collected before treatment administration on Day 4 and Day 5.

Results:

In healthy adults, a 2-fold increase of citraturia was observed following ADV7103 intake, while calciuria and phosphaturia were reduced to a half of their baseline values, and natriuresis was slightly reduced. In dRTA patients, citraturia was within normal values (mean urine citrate/creatinine ratios > 0.05 to 0.17 mmol/mmol, according to age and sex) in approximately 40% of the subjects evaluated (7/17). Calciuria was within normal values in most patients (mean urine calcium/creatinine ratios < 0.7 mmol/mmol, for all age subsets, and mean 24h-calciuria < 2.8 mmol, for the 9 patients evaluated for this end-point). Urine pH values were high in all dRTA age groups, as a consequence of the condition, and tended to decrease with age.

Conclusions:

Increased citraturia was observed in both populations with ADV7103, with a part of the treated dRTA patients presenting normal values. Calciuria was reduced in both study populations, reaching normal values in most dRTA patients. The short-term evolution of these urine parameters under ADV7103 treatment would be in favour of a reduced risk of nephrocalcinosis/nephrolithiasis at long-term.