Microscopic nephrocalcinosis in chronic kidney disease patients

Evenepoel, Pieter; Daenen, Kristien; Bammens, Bert; Claes, Kathleen; Meijers, Björn; Naesens, Maarten; Sprangers, Ben; Lerut, E.

doi:10.1093/ndt/gfu400

Cited by 19 publications

(26 citation statements)

References 38 publications

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“…Renal mineralization is a complicated and multifaceted process and its pathogenesis in association with CKD remains unclear. However, increasing evidence suggests that mineral metabolism disturbances, particularly calcium and phosphate, are likely to contribute to nephrocalcinosis 11,12 . In our study, higher plasma tCa at CKD diagnosis, even with tCa within the reference interval, was an independent nephrocalcinosis risk factor; only 1 (2%) cat had total hypercalcemia at baseline.…”

Section: Discussionmentioning

confidence: 41%

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats

Tang

Jepson

Chang

et al. 2022

Veterinary Internal Medicne

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Background Nephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored. Objectives Identify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all‐cause mortality. Animals Fifty‐one euthyroid client‐owned cats with International Renal Interest Society (IRIS) stages 2‐3 azotemic CKD. Methods Retrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner‐reported time‐averaged phosphate‐restricted diet (PRD) intake, where PRD comprised ≥50%, 10‐50%, or none of food intake. Results Nephrocalcinosis was rated as mild‐to‐severe in 78.4% and absent‐to‐minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P = .02) and eating a PRD (10%‐50%: OR = 8.35; P = .01; ≥50%: OR = 5.47; P = .01) were independent nephrocalcinosis risk factors. Cats with absent‐to‐minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P = .002), urea (5.06 ± 1.82 mg/dL/month; P = .01), and phosphate (0.233 ± 0.115 mg/dL/month; P = .05) concentrations over a 1‐year period, and had shorter median survival times than cats with mild‐to‐severe nephrocalcinosis. Conclusion and Clinical Importance Higher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats.

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Section: Discussionmentioning

confidence: 41%

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats

Tang

Jepson

Chang

et al. 2022

Veterinary Internal Medicne

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“…Phosphate nephropathy and nephrocalcinosis are also likely under-recognized causes of ongoing loss of GFR 50, 51 . A recent study by Evenepoel et al demonstrated that microscopic nephrocalcinosis was quite common in patients with CKD and prevalence increased with worsening glomerular filtration rate and correlated with elevated serum phosphate and parathyroid hormone levels 52 . It is likely that OPN is involved in this process as Lorenzen et al discovered that OPN levels increased with worsening GFR 53 .…”

Section: Discussionmentioning

confidence: 99%

Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Paloian

Leaf

Giachelli

2016

Kidney International

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Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease (CKD). The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of pro-calcific and anti-calcific factors. In the CKD population, an elevated phosphate burden is both highly prevalent and a known risk factor for ectopic calcification. Here we tested whether osteopontin, an inhibitor of calcification, protects against high phosphate load-induced nephrocalcinosis and vascular calcification. Osteopontin knockout mice were placed on a high phosphate diet for eleven weeks. Osteopontin deficiency together with phosphate overload caused uremia, nephrocalcinosis characterized by substantial renal tubular and interstitial calcium deposition, and marked vascular calcification when compared to controls. While the osteopontin-deficient mice did not exhibit hypercalcemia or hyperphosphatemia, they did show abnormalities in the mineral metabolism hormone fibroblast growth factor 23. Thus, endogenous osteopontin plays a critical role in the prevention of phosphate induced nephrocalcinosis and vascular calcification in response to high phosphate load. A better understanding of osteopontin’s role in phosphate induced calcification will hopefully lead to better biomarkers and therapies for this disease, especially in patients with CKD and other at risk populations.

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“…A similar association between kidney function and prevalence of microscopic nephrocalcinosis was observed in a more recent renal biopsy study. Nephrocalcinosis (almost exclusively calcium phosphate crystals) was found in 4.6% of deceased kidney donors, compared with 14.3%, 20.2%, and 54% for stages 1–2 CKD, stages 3–4 CKD, and stage 5 CKD or ESRD, respectively (44). According to the precipitation-calcification hypothesis, calcium phosphate crystal deposition in the renal parenchyma may lead to further inflammation and kidney injury (99).…”

Section: Calcium Phosphate Deposition In Human Renal Biopsy Tissuementioning

confidence: 99%

“…Elevations in PTH may increase cytosolic calcium in the tubules and contribute to the pathogenesis of nephrocalcinosis (44, 73, 99). Observational studies have shown associations between elevated FGF23 levels and an increased risk of CKD progression (51, 106, 128, 141).…”

Section: Fgf23 and Pth: Potential Mediators Of Adverse Effects Of Higmentioning

confidence: 99%

Dietary Phosphorus Intake and the Kidney

Chang

Anderson

2017

Annu. Rev. Nutr.

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Although phosphorus is an essential nutrient required for multiple physiological functions, recent research raises concerns that high phosphorus intake could have detrimental effects on health. Phosphorus is abundant in the food supply of developed countries, occurring naturally in protein-rich foods and as an additive in processed foods. High phosphorus intake can cause vascular and renal calcification, renal tubular injury, and premature death in multiple animal models. Small studies in human suggest that high phosphorus intake may result in positive phosphorus balance and correlate with renal calcification and albuminuria. Although serum phosphorus is strongly associated with cardiovascular disease, progression of kidney disease, and death, limited data exist linking high phosphorus intake directly to adverse clinical outcomes. Further prospective studies are needed to determine whether phosphorus intake is a modifiable risk factor for kidney disease.

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Microscopic nephrocalcinosis in chronic kidney disease patients

Abstract: Our data demonstrate that prevalence rates of nephrocalcinosis increase with increasing CKD stage to reach more than 50% in end-stage renal disease patients and suggest that acid-base and mineral metabolism disturbances are implicated in its pathogenesis.

Cited by 19 publications

References 38 publications

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats

Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Dietary Phosphorus Intake and the Kidney

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