Background Impaired renal H+ ion secretion causes acid retention which is known to promote bone dissolution
Objectives To prospectively assess the prevalence of distal renal tubular acidosis (dRTA) in low bone mass patients (LBM) and the effects of alkali treatment.
Methods Between January 1, 2006, and December 31, 2010, we screened all LBM referred for metabolic evaluation of T-Scores ≤ -1.0 at lumbar spine and/or hip (measured by Hologic or Lunar) for dRTA. Calcium intake (mineral waters and dairy products) was assessed by food content tables. In fasting venous blood, Ca++, venous bicarbonate (VenBic) and creatinine (Crea) were measured by blood gas analyzer, 25-OH-vitamin D (25-OH-D) by immunoassay. LBM with hypercalcemic disorders were excluded. In fasting urines, calcium (Ca), citrate (Cit) and Crea were measured, and renal calcium reabsorption (CaR) was calculated as filtered calcium (Ca++) - excreted calcium (CaE). In all 182 LBM (156 F, 26 M, age 17-86 ys.), pH was measured (Metrohm pH-meter) in 2nd morning urines (U-pH) after 12 hrs. of fasting. If U-pH remained >5.80, LBM underwent 1-day acid loading by ammonium chloride (NH4Cl, 50 mg/kg BW in 3 oral doses), and U-pH and venous blood were remeasured the next morning. Normal values for acid loading were obtained from 21 healthy controls (C, 11 F, 10 M, age 25-80 yrs.). The acidifying effect of NH4Cl was assessed by measuring urine Ca, Cit and Crea in 17 C and 35 LBM. All LBM with dRTA were recommended alkali citrate (K-Cit), and follow-up DXAs were obtained until 1/2014. Paired and unpaired t-tests were used for statistics, values are mean±SD.
Results 84 LBM with U-pH >5.80 underwent NH4Cl loading; this caused U-pH to drop from 6.64±0.54 to 5.62±0.69 (p<0.0001) vs. from 5.71±0.55 to 5.09±0.17 in C (p<0.001). The fall in U-Cit/Crea (p<0.0001 in all subjects) proved the systemic effects of NH4Cl. If U-pH remained >5.44 (mean + 2 SDs of C) after NH4Cl, dRTA was diagnosed; this was found in 42 LBM (39 F, 3 M), i.e. 23.1%. Since VenBic was normal, all cases had incomplete dRTA (idRTA) by definition. Daily calcium intake and 25-OH-D were not different between subgroups. At baseline, CaR (mmol/l) was reduced in idRTA (1.17±0.04 vs. 1.22 + 0.03 in C, p=0.005). NH4Cl lowered VenBic (mEq/l) by 1.35±1.75 in C (p<0.005) and 1.44±2.60 in Non-RTA (p<0.05), but only by 0.71±2.59 in idRTA (NS). After NH4Cl, urine CaE rose insignificantly and equally in all subgroups, whereas blood Ca++ (mmol/l) increased only in idRTA (0.023±0.057, p=0.042), suggesting enhanced Ca release from bone. Baseline bone mineral densities were equal in Non-RTA and idRTA. Among idRTA, 15 were lost for follow-up. In idRTA adherent to K-Cit for 1.6-7 years (n=19), T-scores rose from -2.14±0.81 to -1.72±0.88 (p<0.001) at lumbar spine, but did not change at total hip and femoral neck. In idRTA not taking K-Cit (n=7), T-scores at all sites were unchanged.
Conclusions 1) The prevalence of idRTA in LBM is surprisingly high, i.e. 23%; 2) Upon acid loading, idRTA do not lower VenBic and U-pH normally, but rise blood Ca++, suggesting reduced extra-, but increased intracellular acid buffering by bone tissue. 3) Additional K-Cit treatment helps to further improve bone mass at lumbar spine in idRTA.
Disclosure of Interest None declared