Contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite, brushite, or calcium oxalate stones

Our previous work has shown that stone formers who form calcium phosphate (CaP) stones that contain any brushite (BRSF) have a distinctive renal histopathology and surgical anatomy when compared with idiopathic calcium oxalate stone formers (ICSF). Here we report on another group of idiopathic CaP stone formers, those forming stone containing primarily hydroxyapatite, in order to clarify in what ways their pathology differs from BRSF and ICSF. Eleven hydroxyapatite stone formers (HASF) (2 males, 9 females) were studied using intra-operative digital photography and biopsy of papillary and cortical regions to measure tissue changes associated with stone formation. Our main finding is that HASF and BRSF differ significantly from each other and that both differ greatly from ICSF. Both BRSF and ICSF patients have significant levels of Randall's plaque compared with HASF. Intra-tubular deposit number is greater in HASF than BRSF and nonexistent in ICSF while deposit size is smaller in HASF than BRSF. Cortical pathology is distinctly greater in BRSF than HASF. Four attached stones were observed in HASF, three in 25 BRSF and 5-10 per ICSF patient. HASF and BRSF differ clinically in that both have higher average urine pH, supersaturation of CaP, and calcium excretion than ICSF. Our work suggests that HASF and BRSF are two distinct and separate diseases and both differ greatly from ICSF

Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation

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

Renal crystal deposits and histopathology in patients with cystine stones

We have biopsied the papillae of patients who have cystine stones asking if this stone type is associated with specific tissue changes. We studied seven cystine stone formers (SF) treated with percutaneous nephrolithotomy using digital video imaging of renal papillae for mapping and obtained papillary biopsies. Biopsies were analyzed by routine light and electron microscopy, infrared spectroscopy, electron diffraction, and micro-CT. Many ducts of Bellini (BD) had an enlarged ostium, and all such were plugged with cystine crystals, and had injured or absent lining cells with a surrounding interstitium that was inflamed to fibrotic. Crystal plugs often projected into the urinary space. Many inner medullary collecting ducts (IMCD) were dilated with or without crystal plugging. Apatite crystals were identified in the lumens of loops of Henle and IMCD. Abundance of interstitial Randall's plaque was equivalent in amount to that of non-SF. In the cortex, glomerular obsolescence and interstitial fibrosis exceeded normal. Cystine crystallizes in BD with the probable result of cell injury, interstitial reaction, nephron obstruction, and with the potential of inducing cortical change and loss of IMCD tubular fluid pH regulation, resulting in apatite formation. The pattern of IMCD dilation, and loss of medullary structures is most compatible with such obstruction, either from BD lumen plugs or urinary tract obstruction from stones themselves

Identifying Bedrest Using Waist-worn Triaxial Accelerometers in Preschool Children

Purpose To adapt and validate a previously developed decision tree for youth to identify bedrest for use in preschool children. Methods Parents of healthy preschool (3-6-year-old) children (n = 610; 294 males) were asked to help them to wear an accelerometer for 7 to 10 days and 24 hours/day on their waist. Children with ≥3 nights of valid recordings were randomly allocated to the development (n = 200) and validation (n = 200) groups. Wear periods from accelerometer recordings were identified minute-by-minute as bedrest or wake using visual identification by two independent raters. To automate visual identification, chosen decision tree (DT) parameters (block length, threshold, bedrest-start trigger, and bedrest-end trigger) were optimized in the development group using a Nelder-Mead simplex optimization method, which maximized the accuracy of DT-identified bedrest in 1-min epochs against synchronized visually identified bedrest (n = 4,730,734). DT\u27s performance with optimized parameters was compared with the visual identification, commonly used Sadeh’s sleep detection algorithm, DT for youth (10-18-years-old), and parental survey of sleep duration in the validation group. Results On average, children wore an accelerometer for 8.3 days and 20.8 hours/day. Comparing the DT-identified bedrest with visual identification in the validation group yielded sensitivity = 0.941, specificity = 0.974, and accuracy = 0.956. The optimal block length was 36 min, the threshold 230 counts/min, the bedrest-start trigger 305 counts/min, and the bedrest-end trigger 1,129 counts/min. In the validation group, DT identified bedrest with greater accuracy than Sadeh’s algorithm (0.956 and 0.902) and DT for youth (0.956 and 0.861) (both P\u3c0.001). Both DT (564±77 min/day) and Sadeh’s algorithm (604±80 min/day) identified significantly less bedrest/sleep than parental survey (650±81 min/day) (both P\u3c0.001). Conclusions The DT-based algorithm initially developed for youth was adapted for preschool children to identify time spent in bedrest with high accuracy. The DT is available as a package for the R open-source software environment (“PhysActBedRest”)

Renal histopathology of stone-forming patients with distal renal tubular acidosis

To define the renal tissue changes in stone-forming patients with distal renal tubular acidosis (dRTA), we performed intra-operative papillary and cortical biopsies in five patients. The main abnormalities were plugging of inner medullary collecting ducts (IMCD) and Bellini ducts (BD) with deposits of calcium phosphate in the form of apatite; epithelial cell injury and loss was marked. Plugged ducts were surrounded by interstitial fibrosis, but the fibrosis was generalized, as well, and was a main feature of the histopathology even when plugging was not present. In contrast, common idiopathic calcium oxalate stone formers (SF) never manifest intra-tubule crystals or interstitial fibrosis. Patients with brushite (calcium monohydrogen phosphate) stones and those with cystine stones have many fewer IMCD and BD plugged with apatite (or cystine, in cystinuria), and interstitial fibrosis is limited to the regions around plugged ducts. Patients with dRTA often present a radiographic picture of nephrocalcinosis. Our direct surgical observations reveal that these may be surgically removable stones, especially in patients with well preserved renal function. In all, dRTA SF have a more diffuse papillary renal disease than other SF thus studied, and are also unusual for the degree of interstitial fibrosis