Nephrolithiasis in renal tubular acidosis

INTRODUCTION

Hypercalciuria, hypocitraturia, nephrolithiasis (often composed of calcium phosphate), nephrocalcinosis, and skeletal abnormalities are frequently associated with untreated type 1 renal tubular acidosis (RTA) [1-4]. Stone disease is also seen with carbonic anhydrase inhibitors but typically not with type 2 RTA. Most of the studies on RTA and nephrolithiasis were quite small, and there is variability in individual phenotype and the response to therapy. As a result, the following statements should be read with these cautions in mind.

PATHOGENESIS

Type 1 RTA — Several factors can contribute to the relationship between type 1 RTA and stone formation or nephrocalcinosis. In some families, for example, hypercalciuria appears to be the primary abnormality, with calcium-induced interstitial and tubular damage possibly responsible for the RTA [2].

In most cases, however, RTA is the initial condition with subsequent acidemia, promoting stone formation both by increased calcium phosphate release from bone during bone buffering of retained acid and by direct reduction of the tubular reabsorption of these ions [1,5,6]. The degree of hypercalciuria is roughly proportional to the severity of the acidemia.

Two other factors also contribute importantly to stone formation in this disorder: the persistently high urine pH, which favors the precipitation of calcium phosphate (but not calcium oxalate, the solubility of which is relatively insensitive to pH); and reduction citrate excretion [7], since acidemia enhances proximal citrate reabsorption [8]. Citrate is normally a potent inhibitor of stone formation, both by forming a soluble complex with calcium and by inhibiting stone growth by agglomeration of calcium crystals. (See "Risk factors for calcium stones in adults".)

Kidney histopathology of stone formers with type 1 RTA reveals calcium phosphate deposits plugging inner medullary collecting and Bellini ducts [9]. Significant interstitial fibrosis is also observed, even in areas without plugging. Although further study is needed to verify these results, the findings suggest that some of the radiographic calcifications in these patients may represent surgically approachable stones rather than nephrocalcinosis.