Biopsy Proven Medullary Sponge Kidney: Clinical Findings, Histopathology, and Role of Osteogenesis in Stone and Plaque Formation

Abstract

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall’s) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall’s plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation.

Idiopathic hypercalciuria and formation of calcium renal stones

“…A plug from a patient with stones resulting from ileostomy had an hydroxyapatite tubule segment with a pure CaOx overgrowth 31 , and a plug from a patient with primary hyperparathyroidism had an intratubular portion of hydroxyapatite with an overgrowth of hydroxyapatite 31 . In our analysis of 12 patients with medullary sponge kidney disease we found a single plug, which was composed of a mixture of hydroxyapatite and CaOX in the tubule and overgrowth regions 23 . We also found multiple examples of tiny (500 μm diameter) round microliths made of lamina of hydroxyapatite and CaOx in the dilated and pathological inner medullary collecting ducts of these patients.…”

“…A role of osteogenesis can be excluded because the critical bone genes RUNX2 and SP7 (also known as Osterix ) were not expressed at sites of plaque in biopsy samples from nine patients with idiopathic CaOx stones 23 . By contrast, these genes were expressed in samples from 10 of 12 patients with medullary sponge kidney disease 23 . The rather primitive papillary interstitial cells of patients with medullary sponge kidney do express RUNX2 and SP7 , but the sites of expression are never the sites of mineral deposition.…”

“…The organic stones, cystine and uric acid, might theoretically form in free solution, but no experimental test currently exists to prove this hypothesis in humans. The microliths of patients with medullary sponge kidneys are perhaps the most obvious candidates for formation in free solution 23 . These round, unattached, whorls of hydroxyapatite and CaOx form in the lumens of dilated inner medullary collecting ducts but no proof exists that they grow into clinically significant stones.…”

What can the microstructure of stones tell us?

“…[4–11] Briefly, patients who are receiving minimally invasive treatment for renal stones (either percutaneous nephrolithotomy, PNL, or ureteroscopy, URS) are consented for study. (All procedures performed in studies involving human participants are in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.)…”

Nephrocalcinosis in Calcium Stone Formers Who Do Not have Systemic Disease

“…The primary objective of this study was to contrast the frequency and extent of nephrocalcinosis in these three groups of calcium stone formers who were carefully studied endoscopically to distinguish between stones and tissue deposits. The uniquely different patients with medullary sponge kidney are not addressed here 11 .…”