Chronic hypercalcaemia from inactivating mutations of vitamin D 24-hydroxylase (CYP24A1): implications for mineral metabolism changes in chronic renal failure

Loss-of-function mutations of vitamin D-24 hydroxylase have recently been recognized as a cause of hypercalcaemia and nephrocalcinosis/nephrolithiasis in infants and adults. True prevalence and natural history of this condition are still to be defined.  … Probands had recurrent nephrolithiasis, chronic hypercalcaemia with depressed parathyroid hormone (PTH) and increased 1,25(OH)2D levels; carriers had nephrolithiasis (two of … Leggi tutto

Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers

enetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na+-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of … Leggi tutto

Genetic Hypercalciuria

Hypercalciuria is an important, identifiable, and reversible risk factor in stone formation. The foremost and most fundamental step in dissecting the genetics of hypercalciuria is understanding its pathophysiology. Hypercalciuria is a complex trait. This article outlines the various factors that compromise the attempt to dissect the genetics of hypercalciuria, summarizes the clinical and experimental monogenic … Leggi tutto

2 – Nephrocalcinosis and urolithiasis in children Kidney International (2012) 82, 493–497; doi:10.1038/ki.2012.142

Correction to: Kidney International (2011) 80:1278–1291; doi:10.1038/ki.2011.336 In the above-cited article, Table 2 was published with incorrect alignment of age ranges and erroneous unit changes concerning the cystine and urate excretion levels. The urate gram units needed to be multiplied by 10. In Table 1, the diagnosis related to NPT2a mutations should read ‘Urolithiasis, osteoporosis, … Leggi tutto

Nephrocalcinosis and urolithiasis in children

The incidence of adult urolithiasis has increased significantly in industrialized countries over the past decades. Sound incidence rates are not available for children, nor are they known for nephrocalcinosis, which can appear as a single entity or together with urolithiasis. In contrast to the adult kidney stone patient, where environmental factors are the main cause, … Leggi tutto

Update on Hereditary Kidney Stone Disease and Introduction of a New Clinical Patient Registry in Germany

Kidney stone disease is an increasingly prevalent condition with remarkable clinical heterogeneity, with regards to stone composition, age of manifestation, rate of recurrence, and impairment of kidney function. Calcium-based kidney stones account for the vast majority of cases, but their etiology is poorly understood, notably their genetic drivers. As recent studies indicate, hereditary conditions are … Leggi tutto

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia

Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1)weredescribed that lead to increased sensitivity to vitaminD due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal … Leggi tutto

Classical and Modern Genetic Approach to Kidney Stone Disease

Heritability estimation by twin study remains a relevant reference for modern genetic studies. The overall analysis of loci associated with nephrolithiasis combined with findings of lifestyle analysis and epigenomic investigation may provide stone-risk parameters useful for the clinical evaluation of patients by also taking into account gender variability. 0