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Background: The association between chronic metabolic acidosis and alterations in bone cell functions has been demonstrated in vitro and in animal studies. However, the causal role of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never been systematically demonstrated in humans. This study was conducted to examine the alterations in bone mineral density and bone histology before and after correction of acidosis among patients with distal renal tubular acidosis (dRTA) METHODS: Correction of metabolic acidosis by potassium citrate was done in non-azotemic dRTA patients, 6 females and 4 males, who had never received long-term alkaline therapy before enrolling into this study. Blood chemistries, serum intact parathyroid hormone, and 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, potassium, bone mineral density determination, and transiliac bone biopsy were done in all patients at baseline and after one year of potassium citrate therapy., Results: Significant elevations in serum bicarbonate (16.5 +/- 3.0 vs. 24.6 +/- 2.8 mEq/L, P < 0.05) and urinary potassium excretion (35.2 +/- 7.9 vs. 55.4 +/-3.5 mEq/L, P < 0.05) were observed after potassium citrate therapy. No significant alterations in other serum and urine electrolytes were found after the therapy. Serum intact parathyroid hormone level was also significantly elevated after one year of treatment (12.8 +/- 7.3 vs. 26.2 +/- 8.7 pg/mL, P < 0.05). Bone formation rate was significantly suppressed at baseline and was normalized by the treatment (0.02 +/- 0.02 vs. 0.06 +/- 0.03 microm(3)/microm(2)/day, P < 0.05). There were non-significant elevations in trabecular bone volume, osteoblastic and osteoclastic numbers. Bone mineral densities in dRTA patients were also significantly decreased below normal values in most studied areas at baseline and were significantly elevated at the trochanter of femur (0.677 +/- 0.136 vs. 0.748 +/- 0.144 g/c m(2), P < 0.05) and total femur (0.898 +/- 0.166 vs. 0.976 +/- 0.154 g/c m(2), P < 0.05) after the treatment., Conclusions: This study demonstrates that alkaline therapy corrects abnormal bone cell function and elevates bone mineral density in dRTA patients, indicating the causal role of acidosis in the alterations of bone cell functions and reduction in bone mineral density. Parathyroid gland activity also may be involved in the adaptation of the body to chronic metabolic acidosis.

Background: Distal renal tubular acidosis (RTA) is a common cause of intractable calcium nephrolithiasis. In adults, the use of potassium citrate (PC) in distal RTA effectively decreases metabolic acidosis and the risk of calcium oxalate stone but it cannot decrease the risk of calcium phosphate stone. However, there is no report for the optimal dose of PC and the risk of calcium stone in distal RTA in children., Objective: To evaluate the optimal dose of PC that minimizes the risk of calcium nephrolithiasis in children with distal RTA., Method: Prospective study, Patients: Children who have distal RTA and were followed-up for 4 months. Patients were studied in a control phase, 1 month of PC 2 mEq/kg/day, 2 months of PC 3 mEq/kg/day and 1 month of PC 4 mEq/kg/day. The urine specimens of 41 normal children were measured for the reference value of the parameters determining the risk of calcium stone., Results: Eight children (mean age of 10 +/- 3.7 years, female : male = 6: 2) with distal RTA were studied during the control phase and after receiving PC 2 mEq/kg/day for I month. Treatment with PC 2 mEq/kg/day was not able to normalize serum bicarbonate and caused no significant change in the urine citrate/creatinine ratio, and activity production of calcium phosphate stone but it caused a significant decrease in the urine calcium/citrate ratio. Although PC 3 mEq/kg/day for I month normalized plasma bicarbonate, only this dose given for 2 months caused a significant increase in the urine citrate/creatinine ratio and urine calcium/ citrate ratio to values that were not different from normal children, while the activity production of calcium phosphate stone did not decrease to normal level. The effect of PC 4 mEq/kg/day was similar to that of 3 mEq/kg/day., Conclusion: Potassium citrate 3 mEq/kg/day for 2 months effectively normalized serum bicarbonate and decreased the risk of calcium oxalate stone but this treatment was theoretically unable to reduce the risk of calcium phosphate stone in children with distal RTA.

Potassium citrate is an alkaline agent that has been recommended for the prevention of nephrolithiasis in distal renal tubular acidosis (RTA). Information on the effectiveness and the optimal dose of potassium citrate in the correction of urinary abnormalities in pediatric distal RTA is limited, however. We conducted this study to determine the effectiveness and the optimal dose of potassium citrate for the correction of urinary abnormalities and the prevention of nephrolithiasis in children with distal RTA. Eight pediatric distal RTA patients participated in this study. The mean +/- SEM age was 9.7 +/- 1.2 years, and mean body weight was 29.1 +/- 4.7 kg. After initial evaluation, all patients were treated with increasing dosages of potassium citrate starting from 2 mEq/kg/d in three divided doses. The dosage was increased progressively in a stepwise fashion every 2 months from 2 mEq/kg/d to 3 mEq/kg/d, then to 4 mEq/kg/d. Blood and 8-hour overnight urine samples were obtained at baseline and every 2 months before increasing the dosage of potassium citrate. Urinary saturations for calcium oxalate and calcium phosphate were estimated by using Tiselius's indices. The basal urinary calcium-to-creatinine, phosphate-to-creatinine, and calcium-to-citrate ratios and urinary saturation for calcium oxalate and calcium phosphate were elevated significantly, whereas citrate-to-creatinine ratio was reduced significantly in distal RTA patients. These ratios were normalized gradually with the increasing dosage of potassium citrate. All the aforementioned abnormalities were normalized only after the dosage of potassium citrate was raised to 4 mEq/kg/d. The elevation in urinary saturation of calcium phosphate could not be normalized throughout the study, however. These results suggest that 4 mEq/kg/d of potassium citrate supplement can correct successfully most of the urinary abnormalities and the elevated urinary saturation for calcium oxalate but not for calcium phosphate in children with distal RTA. Monitoring of urinary calcium-to-creatinine ratio or citrate-to-creatinine ratio is valuable to ensure adequate potassium citrate supplementation in this group of patients., (Copyright 2002 by the National Kidney Foundation, Inc.)