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Proximal tubular defects in idiopathic hypercalciuria: resistance to phosphate administration
Insights
Idiopathic hypercalciuria (IH) in kidney stone patients involves impaired proximal tubular reabsorption of sodium and fluid. This defect, independent of parathyroid hormone, may cause both hypercalciuria and phosphate wasting.
Area of Science:
- Nephrology
- Urology
- Endocrinology
Background:
- Recurrent renal calculi (kidney stones) are a common clinical problem.
- Idiopathic hypercalciuria (IH) is a frequent metabolic abnormality found in patients with kidney stones.
- The underlying pathophysiology of IH remains incompletely understood.
Purpose of the Study:
- To investigate the tubular handling of phosphate and fluid in patients with idiopathic hypercalciuria.
- To differentiate between diet-dependent and fasting hypercalciuria.
- To explore the potential role of proximal tubular dysfunction in the pathogenesis of IH.
Main Methods:
- Outpatient evaluation of 100 consecutive patients with recurrent renal calculi.
- Classification of hypercalciuria as diet-dependent or fasting.
- Measurement of serum intact parathyroid hormone (iPTH), urinary cyclic AMP, serum phosphate, and tubular reabsorption of phosphate (TmPO4/GFR).
- Renal clearance studies to assess urine flow rate factored for GFR (V/GFR).
- Calcium infusion tests to assess PTH suppression.
- Phosphate administration studies.
Main Results:
- 43% of patients exhibited idiopathic hypercalciuria (IH).
- Patients with IH showed reduced serum phosphate and TmPO4/GFR compared to normocalciuric stone formers.
- Clearance studies revealed an elevated V/GFR in IH patients.
- Despite normal PTH suppression and phosphate administration reducing urine calcium, the abnormal V/GFR persisted.
- Phosphate administration did not correct the elevated V/GFR.
Conclusions:
- Idiopathic hypercalciuria, in both fasting and diet-dependent forms, is associated with a defect in proximal tubular sodium and fluid reabsorption.
- This proximal tubular dysfunction leads to PTH-independent phosphate wasting.
- The observed tubular defect may be a primary cause of hypercalciuria and phosphate wasting, rather than a consequence.
Abstract:
Of 100 consecutive patients with recurrent renal calculi, 43 had idiopathic hypercalciuria (IH) on outpatient evaluation. Hypercalciuria was classified as diet-dependent or fasting; all patients had normal serum iPTH and urinary cyclic AMP, and serum phosphate and TmPO4/GFR were reduced in IH compared to normocalciuric stone formers. In 16 patients with IH, clearance studies revealed an elevated urine flow are factored for GFR (V/GFR) as compared with normal controls (p less than 0.05). In 12 patients, serum PTH was normally suppressed by calcium infusion but TmPO4/GFR was persistently reduced. Acute and chronic phosphate administration significantly reduced urine calcium excretion but did not correct the abnormal V/GFR. We conclude that in IH of both the fasting and the diet-dependent type, there is a defect in the proximal tubular reabsorption of sodium and fluid as well as PTH-independent tubular phosphate wasting. The proximal tubular defect is not a consequence of hypercalciuria nor of phosphate depletion but may be a cause of these abnormalities.