Acid excretion is impaired in calcium oxalate stone formers

To compare the frequency of urine infection in calcium oxalate and calcium phosphate stone formers, we reviewed charts from patients whose last renal stone submitted for analysis was predominantly composed of calcium phosphate in 118 and of calcium oxalate in 223. Positive cultures were commoner, but not significantly, in the phosphate than the oxalate stone formers, both in men (17 vs. 7.6%) and women (22 vs. 15%). Bacteria frequently producing urease were found in only 4% of the phosphate group. Urine leucocytes were slightly more frequent in the oxalate group for men and significantly so for women. The results do not support the concept that calcium phosphate stones are mainly due to infection with urease-producing or other bacteria.

MP41-14 IMPACT OF URINE PH ON URINARY SUPERSATUATION OF CALCIUM OXALATE

Background: Calcium oxalate renal stones are the most predominant cases of renal stones, their formation is more complex and no specific cause for the stone can be identified so called 'idiopathic'. This study was designed to analyze the metabolic and biochemical alterations in serum, urine and their relation to pathophysiology of calcium oxalate stone formation Patients and Methods : In this study, individuals have been classified into three groups: Group (A) included (29) apparently healthy persons of non calcium oxalate stone formers aged (20-35 years), group (B) included (16) patients with calcium oxalate renal stone aged (20-35 years) and group(C) included (15) patients with calcium oxalate renal stone aged (40-70 years). Fasting serum, random urine and 24hours urine samples were collected from all individuals to determine urine volume, creatinine clearance, serum and urine levels of calcium, phosphate ,uric acid ,zinc, copper and serum levels of total cholesterol, high density lipoproprotien-cholesterol and urea . Results: Calcium oxalate stone formers group (B) exhibited significantly decreased serum levels of uric acid (P=0.015),zinc (P=0.031) with increased serum level of total cholesterol(P=0.034) when compared to similar age group of healthy control ,group (A). Urinary parameters in calcium oxalate stone formers also showed significantly increased levels of 24-hour urine calcium(P=0.05) and urine calcium: creatinine ratio (P=0.05)when compared to healthy control. While, older age calcium oxalate stone formers, group (C) showed significantly decreased urine volume (P=0.015)with increased kidney stone size(P=0.03) when compared to younger age calcium oxalate stone formers, group (B). Conclusions: Level of urinary calcium and urine volume are the most important urinary factors in enhancing calcium oxalate stone formation. While the observed changes in biochemical measurements of serum in calcium oxalate stone formers may indicate a probable metabolic relation in pathogenesis of this disease.

Animal Protein and the Risk of Kidney Stones: A Comparative Metabolic Study of Animal Protein Sources

STONE FORMATION IS PROPORTIONAL TO PAPILLARY SURFACE COVERAGE BY RANDALL'S PLAQUE

Metabolic testing of the first-time calcium oxalate stone former: Is it indicated? No

Purpose: Although both intrinsic and environmental factors contribute to urinary stone formation, recent epidemiologic studies have suggested the importance of lifestyle and dietary habit in urolithiasis. The aim of this study was to compare clinical and metabolic characteristics between calcium oxalate (CaOx) and uric acid (UA) stone formers (SF). Materials and Methods: A database of patient histories and serum and urine chemistries was analyzed for 172 consecutive stone formers [124 pure CaOx SF, 25 mixed (CaOx-UA) SF, and 23 pure UA SF]. We compared the clinical profiles and urinary metabolites among these groups. Urinary CaOx supersaturation was assessed by using the Okawa index. Results: Compared with pure CaOx SF, SF with an increased UA component were older (p=0.01) and had a higher body mass index (BMI) (p=0.02). However, there were no significant differences in gender, stone episodes, family history, or serum chemistry among the three groups (p> 0.05). In the SF with a greater calcium component, urinary excretion of calcium and CaOx supersaturation were significantly elevated (p<0.01, respectively). On the contrary, SF with an increased UA component had significantly decreased urine pH (p=0.03). Conclusions: This study revealed that CaOx stone formation was associated with a young age, hypercalciuria, and high CaOx supersaturation, whereas UA stone formation was associated with high BMI and low urine pH. This study suggests that modification of risk factors in urolithiasis may contribute to preventing stone formation and stone recurrence. (Korean J Urol 2009;50:897-901) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

To determine the association of the basic metabolic panel with stone type. The present study was a retrospective review of 492 stone formers with both stone composition analysis and basic metabolic panel available. Analysis of a basic metabolic panel across stone types was carried out using Fisher's exact test and analysis of variance. Multinomial logistic regression was used to predict stone type based on a basic metabolic panel. A total of 272 (55%) patients had predominantly calcium oxalate stones, 100 (21%) had uric acid stones, 93 (19%) had calcium phosphate stones, 16 (3%) had mixed stones and 11 (2%) had other types of stones. Uric acid stone formers had the highest serum glucose, blood urea nitrogen and creatinine levels. Calcium oxalate stone formers had the highest serum sodium. No significant differences in mean serum calcium levels across different stone types were identified. The predicted risk of uric acid stone over the other stone types increased with an increase in serum glucose and decreased with an increase in carbon dioxide levels. The predicted risk of calcium oxalate stones increased with an increase in serum sodium and chloride levels. The predicted risk of calcium phosphate and oxalate stones over the other stone types increased with an increase in serum calcium levels. The overall accuracy of the basic metabolic panel alone to predict stone type was 59%. A basic metabolic panel alone or in combination with 24-h urinalysis and demographics does not accurately predict stone type. However, it can be used in combination with other variables to predict stone composition.

The Impact of Cystinuria on Renal Function

The Conundrum of Alkali Therapy in Calcium Phosphate Stone Formers

To explore the roles microbiome of urinary tract played in calcium oxalate stones (CaOx) formation, we collected two sides’ pelvis urine of patients with unilateral CaOx stones to set self-control to diminish the influence of systemic factors. Patients with unilateral CaOx stones were recruited in our study according to strict criteria. 16S rRNA gene sequencing was applied to every pair of pelvis urine. Bacterial genome sequencing of Enterobacter cloacae was conducted and bioinformatic analysis was applied to explore the possible pathways of Enterobacter cloacae inducing CaOx stones formation. In vivo experiments were conducted to validate our claims. Von Kossa staining, TUNEL assay and Western Blot were applied to SD rats exploring the mechanism of stone formation. We found 26 significantly different bacteria between stone sides and non-stone sides’ pelvis urine, among which Enterobacter cloacae ranked the most different. Bacterial genome sequencing of Enterobacter cloacae revealed that its virulence factors included Flagellin, LPS and Fimbrial. GO and KEGG analysis revealed it probably induced CaOx stone formation via ion binging and signaling transduction pathways. The results of animal experiments indicated that Glyoxylic Acid could promote apoptosis and crystal depositions of kidney comparing with control group while pre-injected with Enterobacter cloacae could apparently compound the effects. While Western Blot demonstrated that Glyoxylic Acid or Enterobacter cloacae could increase the expression of IL-6, Mcp-1, BMP2 and OPN in rats’ kidney, Glyoxylic Acid and Enterobacter cloacae together could aggravate these increases. These findings indicated that Enterobacter cloacae might play important roles in CaOx stones formation. However, this study is just a preliminary exploration; further studies still need to be conducted.

Aims: To isolate, characterize, and quantify the 23-kD calcium oxalate monohydrate (COM) binding protein in the urine of controls and calcium oxalate stone formers and to study its role in kidney stone formation. Methods: Calcium oxalate crystals were prepared and allowed to interact with human control kidney homogenate as well as urine of controls and calcium oxalate stone formers. EDTA extract was used for the separation of the 23-kD COM-binding protein (partially purified). This partially purified 23-kD COM-binding protein was further separated by DEAE-cellulose column chromatography. SDS-PAGE confirmed the molecular weight. An antibody was raised against the renal 23-kD COM-binding protein in rabbits. The 23-kD COM-binding protein was quantified in the urine from controls and stone formers by ELISA. Thiol group quantification, oxalate-binding assay, and calcium oxalate crystal nucleation and aggregation were performed. Morphological changes of the calcium oxalate crystals induced by the urinary 23-kDa protein were determined using scanning electron microscopy. The expression of this protein using different concentrations of oxalate was also determined in an in vitro model. Results: The urinary excretion of the 23-kD COM-binding protein varies between 0.5 and 1.5 mg/24 h in controls, while in stone former its excretion was found to range from 5 to 7 mg/24 h. The protein isolated from urine was found to inhibit crystal nucleation and aggregation in controls, while the protein isolated from stone formers exhibited less inhibitory activity with reduced thiol groups. The 23-kD COM-binding protein derived from control urine formed COM crystals and intertwined calcium oxalate dihydrate crystals in a crystal growth system, while protein isolated from stone formers’ urine induced aggregation of COM crystals. This protein expression was found to be increased with increasing concentration of oxalate in renal epithelial cells of the African green monkey kidney (VERO) cell line. Conclusions: Increased expression and excretion of the 23-kD protein was observed in oxalate stress conditions, and in stone formers this protein exhibited a promoting activity. The increased excretion of this protein with promoting activity favors the lithogenic process in stone formers.

Prospective study on the efficacy of a selective treatment and risk factors for relapse in recurrent calcium oxalate stone patients.

Randall’s plaque is microscopically a plaque of calcium deposited in the interstitial tissue of the renal papilla. These plaques are thought to serve as a nidus for urinary stone formation. Large amounts of Randall’s plaque are unique to idiopathic calcium oxalate stone formers. Although Randall’s plaques can be found in other stone formers, only in idiopathic calcium oxalate stone formers, the detailed mechanism of stone overgrow on plaque was thoroughly studied. Calcification is invariably located in the basement membrane of the loops of Henle and from there plaques spread through the interstitium toward urothelium. Within the basement membrane, mineral deposits are individual laminated particles in which zones of crystal and organic matrix overlay each other. In the interstitium, the particles appear to fuse on the collagen bundles to form a syncytium of crystal islands in an organic sea. By loss of integrity of urothelium, regions of plaque are exposed to urine. The exposed surface will touch and be covered by molecules of urine origin, including osteopontin, Tamm Horsfall protein, and crystals formed under urine supersaturations, resulting in a ribbon of alternating matrix and crystal. Eventually crystallization escapes from matrix modulation and crystals extend outward into the space of urine and begin to form a calcium oxalate stone proper. Randall’s plaque plays an important role and is prerequisite of kidney stone formation in idiopathic calcium oxalate stone formers.

Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.