Kidney Cysts in Hypophosphatemic Rickets With Hypercalciuria: A Case Series

Hanna, Christian; Potretzke, Theodora A.; Chedid, Maroun; Rangel, Laureano J.; Arroyo, Jennifer; Zubidat, Dalia; Tebben, Peter J.; Cogal, Andrea G.; Torres, Vicente E.; Harris, Peter C.; Sas, David J.; Lieske, John C.; Milliner, Dawn S.; Chebib, Fouad T.

doi:10.1016/j.xkme.2022.100419

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…As such, there is currently no published evidence to suggest that patients with hereditary forms of chronic phosphaturia, such as X-linked hypophosphatemic rickets, are at increased risk for developing CKD. However, a recent investigation in patients with hereditary hypophosphatemic rickets with hypercalciuria, a condition resulting in chronic urinary phosphate wasting, did find a high prevalence of kidney cyst formation in this patient population [38].…”

Section: Evidence For Phosphaturia and Phosphate-based Crystal Format...mentioning

confidence: 61%

Contribution of phosphate and FGF23 to CKD progression

Jansson

Stubbs

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewProgressive forms of chronic kidney disease (CKD) exhibit kidney inflammation and fibrosis that drive continued nephron loss; however, factors responsible for the development of these common pathologic features remain poorly defined. Recent investigations suggest pathways involved in maintaining urinary phosphate excretion in CKD may be contributing to kidney function decline. This review provides an update on recent evidence linking altered phosphate homeostasis to CKD progression. Recent findingsHigh dietary phosphate intake and increased serum concentrations of fibroblast growth factor 23 (FGF23) both increase urinary phosphate excretion and are associated with increased risk of kidney function decline. Recent investigations have discovered high concentrations of tubular phosphate promote phosphate-based nanocrystal formation that drives tubular injury, cyst formation, and fibrosis. SummaryStudies presented in this review highlight important scientific discoveries that have molded our current understanding of the contribution of altered phosphate homeostasis to CKD progression. The collective observations from these investigations implicate phosphaturia, and the resulting formation of phosphatebased crystals in tubular fluid, as unique risk factors for kidney function decline. Developing a better understanding of the relationship between tubular phosphate handling and kidney pathology could result in innovative strategies for improving kidney outcomes in patients with CKD.

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Section: Evidence For Phosphaturia and Phosphate-based Crystal Format...mentioning

confidence: 61%

Contribution of phosphate and FGF23 to CKD progression

Jansson

Stubbs

2022

Current Opinion in Nephrology &Amp; Hypertension

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“…3 A prior case series of 12 patients with SLC34A3 pathogenic variants (7 monoallelic, 5 biallelic) described a higher preponderance for kidney cysts than the general population. 6 SLC34A3 Ser192Leu heterozygotes had numerically more kidney/liver cyst ICD codes, although this was not statistically significant. Although we were limited by the lack of standardized laboratory testing, such as 24-hour kidney stone risk profiles, strengths of our study included a largely unselected cohort with long follow-up, allowing us to better capture nephrolithiasis burden.…”

mentioning

confidence: 75%

“…The primary outcome was nephrolithiasis; secondary outcomes included eGFR <60 ml/min per 1.73 m 2 , outpatient hypophosphatemia (lowest phosphate <2.5 mg/dl; median phosphate <3.0 mg/dl; meeting both criteria), mean phosphate, mean eGFR, and any kidney/liver cyst (ICD codes for autosomal dominant polycystic kidney disease, cystic kidney diseases, congenital kidney cyst, or liver cystic disease). 6,7 Chart reviews were performed by a nephrology fellow. EHR-based renal phenotypes were compared between SLC34A3 Ser192Leu heterozygotes and controls (without any SLC34A3 variants) using logistic and linear regression for categorical and continuous outcomes, respectively, adjusted for age, sex, and genetic ancestry and clustered by family network.…”

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confidence: 99%

Risk of Nephrolithiasis in Adults Heterozygous for SLC34A3 Ser192Leu in an Unselected Health System Cohort

Nwachukwu,

Singh,

Moore

et al. 2023

JASN

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“…Dasgupta et al reported that individuals with biallelic mutations in SLC34A3 alleles had an approximately tenfold higher risk of nephrolithiasis and nephrocalcinosis whereas heterozygotes had approximately 3-fold higher risk of nephrolithiasis (16.4%) compared with the general population (3). Another recent case series of 12 patients with SLC34A3 pathogenic variants (7 monoallelic, 5 biallelic) described a higher preponderance for kidney cysts than the general population (7). In our study SLC34A3 Ser192Leu heterozygotes had numerically more kidney/liver cyst ICD codes though this result was not statistically significant.…”

Section: Resultsmentioning

confidence: 99%

Risk of Nephrolithiasis in adults heterozygous forSLC34A3Ser192Leu in an unselected health system cohort

Nwachukwu

Singh

Moore

et al. 2023

Preprint

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Homozygous or compound heterozygous mutations in solute carrier family 34, member 3 (SLC34A3) cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Patients heterozygous for SLC34A3 pathogenic variants may be at increased risk for renal calcification but reports have been mostly limited to family members of patients with autosomal recessive HHRH. To determine the phenotypic spectrum of SLC34A3 Ser192Leu, we examined the most pathogenic SLC34A3 variant Ser192Leu (238 out of 174,417 participants) in an unselected, health system-based research cohort in central and northeast Pennsylvania. SLC34A3 Ser192Leu heterozygotes had higher risks of nephrolithiasis ICD diagnosis (13% vs. 6%), hypophosphatemia <2.5 mg/dL (31/96 [32%] vs. 6226/39636 [16%]), lower eGFR (-4.43, 95% CI: -7.03, -1.83; p=0.001) and tended to have higher prevalence of kidney/liver cyst ICD codes (5% vs. 3%; p=0.09), compared to controls. Further studies are needed to determine whether personalized approaches (i.e. phosphate supplementation) to patients heterozygous for SLC34A3 pathogenic variants can reduce kidney stone burden and risk of kidney function decline.

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Kidney Cysts in Hypophosphatemic Rickets With Hypercalciuria: A Case Series

Cited by 8 publications

References 12 publications

Contribution of phosphate and FGF23 to CKD progression

Contribution of phosphate and FGF23 to CKD progression

Risk of Nephrolithiasis in Adults Heterozygous for SLC34A3 Ser192Leu in an Unselected Health System Cohort

Risk of Nephrolithiasis in adults heterozygous forSLC34A3Ser192Leu in an unselected health system cohort

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