Renal Intratubular Crystals and Hyaluronan Staining Occur in Stone Formers with Bypass Surgery but not with Idiopathic Calcium Oxalate Stones

Abstract Objectives Inflammatory processes play an important role in the initiation and progression of kidney disease. Renal calcium oxalate stone formed from the crystal deposits in the tubular epithelial cells can increase reactive oxygen species and subsequent inflammation. We investigated the gene expression Methods At the time of death the circulating levels of creatinine and SDMA, markers of kidney decline, were significantly higher in cats with renal disease (n = 11) or stone-forming cats (CaOx, n = 12) when compared to controls (n = 19). Results We identified 3 candidate genes including complement C3d receptor (CR2), MMP-7, and IKAROS family zinc finger 3, that were maximally up-regulated in renal disease with fold increases of 14.3, 13.9, and 10.9 when compared to controls (p < 0.01). Other selected inflammatory markers that were significantly increased but less than 10-fold included IL7R, TLR8, CXCR4, LCP1, IL2RB, and MSR1. The profile for maximally up-regulated genes in CaOx cats was somewhat similar when compared with those with renal disease with the exception of MMP-7. In CaOx cats the maximal up-regulation occurred in CR2, IKAROS family zinc finger 3, and L-selectin with fold increases of 33.9, 16.8, and 12.6 when compared to controls (p < 0.01). Selected inflammatory markers that were significantly increased, but less than 10-fold, included CD37, DOCK2, LCP1, CCL19, and TLR7 in CaOx compared to controls. Interestingly, there was a significant increase in Fc fragment of IgM receptor (FCMR) in both renal disease (12.4 fold) and CaOx (13.2 fold) when compared to controls. Our results identify newer immune biomarkers that are novel targets for attenuating kidney dysfunction and while there are similarities in the inflammatory genes upregulated in cats with kidney disease and stone formers, the expression profile of upregulated genes, taken as a whole, is different in both groups. Conclusions These results indicate that there are somewhat different renal responses to calcium oxalate stones and renal disease which suggests the optimal anti-inflammatory nutritional therapy may be different. Funding Sources Hill's Pet Nutrition, Inc.

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Faculty Opinions recommendation of Endoscopic and histologic findings in a cohort of uric acid and calcium oxalate stone formers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725358332.793504447 ◽

2015 ◽

Author(s):

Walter Strohmaier

Keyword(s):

Uric Acid ◽

Calcium Oxalate ◽

Calcium Oxalate Stone ◽

Stone Formers

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Faculty Opinions recommendation of Simple dietary advice targeting five urinary parameters reduces urinary supersaturation in idiopathic calcium oxalate stone formers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738192010.793575812 ◽

2020 ◽

Author(s):

Alberto Trinchieri

Keyword(s):

Calcium Oxalate ◽

Dietary Advice ◽

Calcium Oxalate Stone ◽

Stone Formers ◽

Urinary Parameters ◽

Urinary Supersaturation

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Urinary stone composition analysis and clinical characterization of 1520 patients in central China

Scientific Reports ◽

10.1038/s41598-021-85723-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daling Zhang ◽

Songchao Li ◽

Zhengguo Zhang ◽

Ningyang Li ◽

Xiang Yuan ◽

...

Keyword(s):

Calcium Oxalate ◽

Urinary Stone ◽

Geographic Region ◽

Central China ◽

Urinary Stones ◽

Composition Analysis ◽

Stone Composition ◽

Calcium Oxalate Stones ◽

Significant Difference ◽

Lower Urinary

AbstractA total of 1520 patients with urinary stones from central China were collected and analysed by Fourier transform infrared spectroscopy between October 1, 2016 and December 31, 2019. For all patients, age, sex, comorbidities, stone location, laboratory examination and geographic region were collected. The most common stone component was calcium oxalate (77.5%), followed by calcium phosphate (8.7%), infection stone (7.6%), uric acid (UA) stone (5.3%)and cystine (0.9%). The males had more calcium oxalate stones (p < 0.001), while infection stone and cystine stones occurred more frequently in females (p < 0.001). The prevalence peak occurred at 41–60 years in both men and women. UA stones occurred frequently in patients with lower urinary pH (p < 0.001), while neutral urine or alkaline urine (p < 0.001) and urinary infection (p < 0.001) were more likely to be associated with infection stone stones. Patients with high levels of serum creatinine were more likely to develop UA stones (p < 0.001). The proportion of UA stones in diabetics was higher (p < 0.001), and the incidence of hypertension was higher in patients with UA stones (p < 0.001). Compared to the other types, more calcium oxalate stones were detected in the kidneys and ureters (p < 0.001), whereas struvite stones were more frequently observed in the lower urinary tract (p = 0.001). There was no significant difference in stone composition across the Qinling-Huaihe line in central China except UA stones, which were more frequently observed in patients south of the line (p < 0.001).

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Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

BMC Nephrology ◽

10.1186/s12882-021-02417-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jiqing Zhang ◽

Sanjay Kumar ◽

Muthuvel Jayachandran ◽

Loren P. Herrera Hernandez ◽

Stanley Wang ◽

...

Keyword(s):

Urinary Excretion ◽

Calcium Oxalate ◽

Extracellular Vesicles ◽

Immune Cells ◽

Kidney Stone ◽

Fibroblast Growth Factor 23 ◽

Pathogenic Mechanisms ◽

Phosphorus Excretion ◽

Stone Formers ◽

Calcium Phosphorus

Abstract Backgrounds: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs). Methods Biobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. Results Urine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies. Conclusions Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

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The Relation between the Concentration of Calcium Salts in the Urine and Renal Stone Composition in Patients with Calcium-Containing Renal Stones

Clinical Science ◽

10.1042/cs0430433 ◽

1972 ◽

Vol 43 (3) ◽

pp. 433-441 ◽

Cited By ~ 30

Author(s):

R. W. Marshall ◽

M. Cochran ◽

W. G. Robertson ◽

A. Hodgkinson ◽

B. E. C. Nordin

Keyword(s):

Calcium Phosphate ◽

Calcium Oxalate ◽

Renal Stones ◽

Urine Ph ◽

Stone Composition ◽

Calcium Oxalate Stones ◽

Urine Oxalate ◽

The Difference ◽

Normal Urine ◽

Normal Men

1. Diurnal variations in urine calcium oxalate and calcium phosphate activity products were observed in normal men and patients with recurrent calcium oxalate or mixed oxalate—phosphate renal stones. 2. Maximum and minimum calcium oxalate products were higher in the patients than in the controls, the difference being most marked in the patients with calcium oxalate stones. 3. Maximum and minimum calcium phosphate products expressed as octocalcium phosphate [(Ca8H2(PO4)6], brushite or hydroxyapatite, were significantly higher than normal in the patients with mixed stones but not in the patients with calcium oxalate stones. 4. The raised calcium oxalate products in the patients were due mainly to increased concentrations of Ca2+ ions; these, in turn, were due mainly to an increased rate of excretion of calcium. Raised calcium phosphate products were due mainly to hypercalciuria, combined with abnormally high urine pH values. 5. Patients with recurrent calcium stones appear to fall into two types: (1) patients with calcium oxalate stones associated with hypercalciuria, a normal or raised urine oxalate and a normal urine pH; (2) patients with mixed oxalate—phosphate stones associated with hypercalciuria, a normal or raised urine oxalate and a raised urine pH. 6. The implications of these findings in regard to treatment are discussed.

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