Kidney Stones, Proteinuria and Renal Tubular Metabolic Acidosis: What Is the Link?

Ilzkovitz, Maxime; Kayembe, Elikyah Esther; Geers, Caroline; Pozdzik, Agnieszka

doi:10.3390/healthcare10050836

Cited by 6 publications

(5 citation statements)

References 28 publications

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“…In our study, low urinary citrate was present in 12.19% (5/41) of the included patients, two of whom had complete RTA. In the literature, we found reports of patients with SD renal tubular acidosis and hypocitraturia [28][29][30][31] . Data from Norway showed low levels of urinary citrate in 25.8% (16/62) of patients with SD.…”

Section: Discussionmentioning

confidence: 99%

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögrens disease

Coradin,

Lopes,

Goldani

et al. 2024

Preprint

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Introduction: Sjögren's disease (SD) is an immune-mediated chronic inflammatory disease that affects epithelial tissues, especially salivary and lacrimal glands, as well as extra glandular manifestations. The main renal manifestation is tubulointerstitial nephritis (TIN), which may present clinically as renal tubular acidosis (RTA). Urinary citrate may be an early biomarker of RTA in these patients. The aim of this study was to evaluate whether hypocitraturia is a predictive biomarker of ATR in a sample of patients with SD in a tertiary hospital in southern Brazil. Methods: All patients with SD who met the inclusion and exclusion criteria and participated in the rheumatology outpatient clinic at Irmandade Santa Casa de Misericórdia of Porto Alegre were included. Demographic data, SD data, and serological and urinary data were obtained. Patients who persistently had urinary pH above 5.5 underwent a urine acidification test with furosemide and fludrocortisone. Continuous variables with a normal distribution were expressed as the mean and standard deviation. The others were expressed as medians and interquartile ranges. Categorical variables are expressed as numbers and frequencies. The association between hypocitraturia and ATR was assessed using the chi-square test. Results: Forty-two patients were included, 95.2% female with a median age of 61.73 years. The prevalence of complete distal RTA was 4.88%. Twenty-eight patients underwent urine acidification testing. Five patients had hypocitraturia, and two of them had complete distal RTA. The association between hypocitraturia and ATR was statistically significant (p< 0.012), with a sensitivity of 100%, specificity of 91.2% and accuracy of 91.7%. The negative predictive value was 100%. The renal evaluation of the population demonstrated, in addition to two patients with ATR, one patient with impaired renal function and six patients with proteinuria greater than 0.5 g/24 hours. Conclusion: The prevalence of ATR in the studied population was 4.88%. Hypocitraturia had high sensitivity and accuracy for the diagnosis of ATR.

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Section: Discussionmentioning

confidence: 99%

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögrens disease

Coradin,

Lopes,

Goldani

et al. 2024

Preprint

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“…The rise in urine pH can be caused by renal damage from stone crystals or procedures or treatments for stones [24]. If this is the case, it is possible that the treatments producing greater amounts of local inflammation could result in a higher likelihood of acidic blood pH that would result in elevated urinary pH and greater local crystal deposition in the future [25]. This may also offer a possible explanation for the lack of a response in some patients' experiences with urinary alkalinization for calcium stone treatment.…”

Section: Discussionmentioning

confidence: 99%

The Rise in Tubular pH during Hypercalciuria Exacerbates Calcium Stone Formation

Gombedza,

Shin,

Sadiua

et al. 2024

IJMS

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In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca2+ entry triggers a transepithelial Ca2+ flux to regulate proximal tubular (PT) luminal [Ca2+], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca2+ signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca2+ entry compared to the WT counterparts because of significant inhibition by the store-operated Ca2+ entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca2+ entry) inhibitors (Pyr10), Ca2+ entry by WTT cells was moderately inhibited, suggesting that the Ca2+ and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.

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“…In our study, low urinary citrate was present in 12.19% (5/41) of the included patients, two of whom had complete RTA. In the literature, we found reports of patients with SD renal tubular acidosis and hypocitraturia [29][30][31][32]. Data from Norway showed low levels of urinary citrate in 25.8% (16/62) of patients with SD.…”

Section: Discussionmentioning

confidence: 99%

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögren’s disease

Coradin,

Lopes,

Goldani

et al. 2024

Adv Rheumatol

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Introduction Sjögren’s disease (SD) is an immune-mediated chronic inflammatory disease that affects epithelial tissues, mainly salivary and lacrimal glands. It also presents extraglandular manifestations. The main renal manifestation is tubulointerstitial nephritis (TIN), which can manifest as renal tubular acidosis (RTA). Urinary citrate may be a biomarker of RTA in these patients. The objective of this study was to evaluate whether hypocitraturia is a predictive biomarker of RTA in a sample of patients with SD in a tertiary hospital in southern Brazil. Methods All patients with SD who met the inclusion criteria and who participated in the rheumatology outpatient clinic of the Irmandade Santa Casa de Misericórdia de Porto Alegre were included. Demographic, SD, serological and urinary data were obtained. RTA was considered in those patients who persistently presented urinary pH above 5.5 and serum pH below 7.35. Patients who persistently had urinary pH above 5.5 underwent a urinary acidification test with furosemide and fludrocortisone. These patients received 1 mg of fludrocortisone and 40 mg of furosemide and had their urine samples tested 2, 4 and 6 h after taking the medications. The test was stopped at any urine sample with pH 5.5 or less. The variables were expressed as mean and standard deviation or interquartile range. The association between hypocitraturia and RTA was assessed using the chi-square. Results Forty-two patients were included, 95.2% female with a median age of 61.73 years. The prevalence of complete distal RTA was 4.88%. Twenty-eight patients underwent urine acidification testing. Five patients had hypocitraturia, and two of them had complete distal RTA. The association between hypocitraturia and RTA was statistically significant (p < 0.012), with a sensitivity of 100%, specificity of 91.2% and accuracy of 91.7%. The negative predictive value was 100%. The global renal assessment of the population demonstrated two patients with RTA, one patient with decreased renal function and six patients with proteinuria greater than 0.5 g/24 h. Conclusion The prevalence of RTA in the studied population was 4.88%. Hypocitraturia had high sensitivity and accuracy for the diagnosis of RTA.

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Kidney Stones, Proteinuria and Renal Tubular Metabolic Acidosis: What Is the Link?

Cited by 6 publications

References 28 publications

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögrens disease

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögrens disease

The Rise in Tubular pH during Hypercalciuria Exacerbates Calcium Stone Formation

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögren’s disease

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