An increasing number of calcium oxalate stone events worsens treatment outcome

An increasing number of calcium oxalate stone events worsens treatment outcome. Current practice recommends metabolic evaluation of patients who have formed multiple renal stones, but not those with one stone or temporally remote stones. This presumes that recentness and recurrence imply greater risk of new future stones. We hypothesize that number of stones reflects how long patients are permitted to form stones untreated, and that forming more stones, itself, raises risk of future stones despite treatment. Our report is a retrospective analysis of 371 male patients selected from a comprehensive clinical and laboratory data base containing 2,527 patients with nephrolithiasis. Before treatment, number of stone events rises with time of observation, and rate of stone event occurrence is constant or falls. During treatment, relapse is correlated with number of pretreatment stones. Life table analysis showed increasing relapse for patients grouped into those with one, two, and three or more stones. Even though number of stones seems controlled by the interval of observation before treatment, more stones predict higher relapse during treatment. Perhaps by leaving nuclei of crystals as residues, stones appear to promote new stones, and the practice of waiting while patients declare themselves multiple stone formers may not always be the best

Pathophysiology-based treatment of idiopathic calcium kidney stones

Idiopathic calcium oxalate (CaOx) stone-formers (ICSFs) differ from patients who make idiopathic calcium phosphate (CaP) stones (IPSFs). ICSFs, but not IPSFs, form their stones as overgrowths on interstitial apatite plaque; the amount of plaque covering papillary surface is positively correlated with urine calcium excretion and inversely with urine volume. The amount of plaque predicts the number of recurrent stones. The initial crystal overgrowth on plaque is CaP, although the stone is mainly composed of CaOx, meaning that lowering supersaturation (SS) for CaOx and CaP is important for CaOx stone prevention. IPSFs, unlike ICSFs, have apatite crystal deposits in inner medullary collecting ducts, which are associated with interstitial scarring. ICSFs and IPSFs have idiopathic hypercalciuria, which is due to decreased tubule calcium reabsorption, but sites of abnormal reabsorption may differ. Decreased reabsorption in proximal tubules (PTs) delivers more calcium to the thick ascending limb (TAL), where increased calcium reabsorption can load the interstitium, leading to plaque formation. The site of abnormal reabsorption in IPSFs may be the TAL, where an associated defect in bicarbonate reabsorption could produce the higher urine pH characteristic of IPSFs. Preventive treatment with fluid intake, protein and sodium restriction, and thiazide will be effective in ICSFs and IPSFs by decreasing urine calcium concentration and CaOx and CaP SS and may also decrease plaque formation by increased PT calcium reabsorption. Citrate may be detrimental for IPSFs if urine pH rises greatly, increasing CaP SS. Future trials should examine the question of appropriate treatment for IPSFs

Idiopathic hypercalciuria and formation of calcium renal stones

The most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate and form on a base of interstitial apatite deposits, known as Randall’s plaque. By contrast some stones are composed largely of calcium phosphate, as either hydroxyapatite or brushite (calcium monohydrogen phosphate), and are usually accompanied by deposits of calcium phosphate in the Bellini ducts. These deposits result in local tissue damage and might serve as a site of mineral overgrowth. Stone formation is driven by supersaturation of urine with calcium oxalate and brushite. The level of supersaturation is related to fluid intake as well as to the levels of urinary citrate and calcium. Risk of stone formation is increased when urine citrate excretion is 200 mg per day also increase stone risk and often result in negative calcium balance. Reduced renal calcium reabsorption has a role in idiopathic hypercalciuria. Low sodium diets and thiazide-type diuretics lower urine calcium levels and potentially reduce the risk of stone recurrence and bone disea

Clinical decision support improves physician guideline adherence for laboratory monitoring of chronic kidney disease: a matched cohort study

Sample graph page of relevant test results. (PDF 289 kb

Micro-CT imaging of Randall's plaques

Micro-computed tomographic imaging (micro-CT) provides unprecedented information on stone structure and mineral composition. High-resolution micro-CT even allows visualization of the lumens of tubule and/or vessels within Randall's plaque, on stones or in papillary biopsies, thus giving a non-destructive way to study these sites of stone adhesion. This paper also shows an example of a stone growing on a different anchoring mechanism: a mineral plug within the lumen of a Bellini duct (BD plug). Micro-CT shows striking structural differences between stones that have grown on Randall's plaque and those that have grown on BD plugs. Thus, Randall's plaque can be distinguished by micro-CT, and this non-destructive method shows great promise in helping to elucidate the different mechanisms by which small stones are retained in the kidney during the development of nephrolithiasis

Label-free proteomic methodology for the analysis of human kidney stone matrix composition.

Background: Kidney stone matrix protein composition is an important yet poorly understood aspect of nephrolithiasis. We hypothesized that this proteome is considerably more complex than previous reports have indicated and that comprehensive proteomic profiling of the kidney stone matrix may demonstrate relevant constitutive differences between stones. We have analyzed the matrices of two unique human calcium oxalate stones (CaOx-Ia and CaOx-Id) using a simple but effective chaotropic reducing solution for extraction/solubilization combined with label-free quantitative mass spectrometry to generate a comprehensive profile of their proteomes, including physicochemical and bioinformatic analysis.` Results: We identified and quantified 1,059 unique protein database entries in the two human kidney stone samples, revealing a more complex proteome than previously reported. Protein composition reflects a common range of proteins related to immune response, inflammation, injury, and tissue repair, along with a more diverse set of proteins unique to each stone. Conclusion: The use of a simple chaotropic reducing solution and moderate sonication for extraction and solubilization of kidney stone powders combined with label-free quantitative mass spectrometry has yielded the most comprehensive list to date of the proteins that constitute the human kidney stone proteome. Electronic supplementary material: The online version of this article (doi:10.1186/s12953-016-0093-x) contains supplementary material, which is available to authorized users

A test of the hypothesis that oxalate secretion produces proximal tubule crystallization in primary hyperoxaluria type I

The sequence of events by which primary hyperoxaluria type 1 (PH1) causes renal failure is unclear. We hypothesize that proximal tubule (PT) is vulnerable because oxalate secretion raises calcium oxalate (CaOx) supersaturation (SS) there, leading to crystal formation and cellular injury. We studied cortical and papillary biopsies from two PH1 patients with preserved renal function, and seven native kidneys removed from four patients at the time of transplant, after short-term (2) or longer term (2) dialysis. In these patients, and another five PH1 patients without renal failure, we calculated oxalate secretion, and estimated PT CaOx SS. Plasma oxalate was elevated in all PH1 patients and inverse to creatinine clearance. Renal secretion of oxalate was present in all PH1 but rare in controls. PT CaOx SS was >1 in all nonpyridoxine-responsive PH1 before transplant and most marked in patients who developed end stage renal disease (ESRD). PT from PH1 with preserved renal function had birefringent crystals, confirming the presence of CaOx SS, but had no evidence of cortical inflammation or scarring by histopathology or hyaluronan staining. PH1 with short ESRD showed CaOx deposition and hyaluronan staining particularly at the corticomedullary junction in distal PT while cortical collecting ducts were spared. Longer ESRD showed widespread cortical CaOx, and in both groups papillary tissue had marked intratubular CaOx deposits and fibrosis. CaOx SS in PT causes CaOx crystal formation, and CaOx deposition in distal PT appears to be associated with ESRD. Minimizing PT CaOx SS may be important for preserving renal function in PH1

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