Phenotypic characterization of kidney stone formers by endoscopic and histological quantification of intrarenal calcification

Abstract

Interstitial Randall's plaques and collecting duct plugs are distinct forms of renal calcification thought to provide sites for stone retention within the kidney. Here we assessed kidney stone precursor lesions in a random cohort of stone formers undergoing percutaneous nephrolithotomy. Each accessible papilla was endoscopically mapped following stone removal. The percent papillary surface area covered by plaque and plug were digitally measured using image analysis software. Stone composition was determined by micro-computed tomography and infrared analysis. A representative papillary tip was biopsied. The 24-h urine collections were used to measure supersaturation and crystal growth inhibition. The vast majority (99%) of stone formers had Randall's plaque on at least 1 papilla, while significant tubular plugging (over 1% of surface area) was present in about one-fifth of patients. Among calcium oxalate stone formers the amount of Randall's plaque correlated with higher urinary citrate levels. Tubular plugging correlated positively with pH and brushite supersaturation but negatively with citrate excretion. Lower urinary crystal growth inhibition predicted the presence of tubular plugging but not plaque. Thus, tubular plugging may be more common than previously recognized among patients with all types of stones, including some with idiopathic calcium oxalate stones.

Figure 1. Endoscopic mapping

A papillary still image from a CaOx stone former taken by video is shown pre-processing (Panel A) and post-processing (Panel B) with plaque (green) and plug (yellow) regions outlined and labeled.

Figure 2

A biopsy from the same patient as in Figure 1 as shown by H&E overview (Panels A, C) and Yasue stain (Panels B, D), Subepithelial interstitial plaque (arrows, Panels A,B) and intratubular plugs (stars, Panels C, D) were both observed.

Figure 3. Urinary predictors of significant tubular plugging (> 1%)

Urinary pH (Panel A), Citrate (Panel B), and Brushite SS (Panel C) were all significantly correlated with the incidence of papillary plugging among all stone formers. (p < 0.05).

Figure 4. CaPstone formers have the highest incidence of severe tubular plugging (> 1% surface area) compared to CaOx formers and CaOx stone formers with maladsorption

Within the CaP group, the brushite stone formers had a greater percentage with plugs than those with apatite stones. Black = plugs > 1%, Grey = 0 < plugs < 1%, White = no plugs.

Figure 5. Inhibition activity (Ia) of urine relative to the presence of tubular plugs

Patients with significant plugs (> 1% of the surface area) had reduced crystal growth inhibition activity both among the cohort as a whole (Panel A; p < 0.01) or the CaOx group (Panel B; p < 0.01).

Figure 6. Correlation of endoscopic mapping and histologic staining

Plaque (Panel A) and plug (Panel B) amounts quantitated by endoscopic video mapping using a digital nephroscope correlated significantly with histologic measurements made on a representative papillary tip biopsy (p < 0.05).