Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392525 (nephrolithiasis)
 2,669 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The frequency of hypercalciuria is increasing in western countries with an incidence of nephrolithiasis which can reach 13%. Hypercalciuria appears as an alteration of the calcium transport system (kidney, bowel, bone) which is regulated by calcitriol and parathormone. The aim of this review was to screen etiologies of hypercalciuria taking into account recent genetic advances (calcium epithelial channel and calcium sensing receptor). Hypercalciuria may be favored by nutritional causes (diet rich in calcium, sodium, carbohydrates, proteins, poor in phosphates and potassium). It may also be related to an increase in calcium absorption (vitamin D excess, primary hyperparathyroidism, sarcoidosis, lymphoma, estrogens, and certain genetic causes), an increase in osteoresorption (bone metastasis, myeloma, Paget, hyperthyroidism, immobilization, hypercortisolism and corticosteroid therapy), or a decrease of kidney tubular resorption (diuretics, Cacci and Ricci, acromegally, Bartter, familial dominant hypocalcemia, Fanconi, Dent, familial hypomagnesemia-hypercalciuria syndrome, type 1 distal tubular acidosis, pseudohypoaldosteronism, diabetes). If no cause is identified, persistence of hypercalciuria after instituting a correct diet is defined as idiopathic hypercalciuria. Treatment of the cause is essential in secondary hypercalciuria, in addition to diet (low sodium intake, normocalcic diet, hydration), associated with thiazide diuretics and biphosphonates if necessary.
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PMID:[Hypercalciuria]. 1635 16

The calcium-sensing receptor has a key role in calcium homeostasis, it is involved in the regulation of the serum calcium level within minutes via the secretion and action of parathyroid and the excretion of calcium in the kidney in a negative feedback manner. Mutations of the calcium sensing receptor gene leads to inactivating and activating mutations resulting in diseases with hypercalcaemia and hypocalcaemia. The loss of function mutations are associated with familial benign hypocalciuric hypercalcaemia (FHH), an autosomal dominant disease characterised by lifelong mild hypercalcaemia, low urinary calcium excretion, and inappropriate high parathyroid hormone levels, sometimes difficult to distinguish from mild asymptomatic primary hyperparathyroidism. Patients with FHH did not profit from parathyroidectomy, a calcium lowering therapy is not necessary. The gain of function mutations of the calcium-sensing receptor are associated with autosomal dominant hypocalcaemia (ADH), a disease characterised by a generally asymptomatic hypocalcaemia, inappropriately high urinary calcium excretion and normal PTH levels. A therapy to raise the serum calcium concentration has to be done carefully and is only indicated in symptomatic patients, because of enhancement of hypercalciuria with the risk of nephrocalcinosis and nephrolithiasis. Molecular genetic analysis of the calcium sensing receptor gene facilitates the sometimes difficult diagnosis. The development of compounds modulating the calcium sensing receptor function and thereby the section of PTH may become an important role in treatment of diseases of calcium metabolism.
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PMID:The role of the extracellular calcium-sensing receptor in health and disease. 1703 19

Nephrolithiasis (NL) has high and increasing prevalence in western countries. Most renal stones contain calcium and/or uric acid and often occur as idiopathic stones, while seldom are caused by genetic disorders. Conversely, cystinuria, xantinuria, 2-8 dihydroxyadeninuria only occur in patients with mutations of corresponding genes. Inherited NL must be suspected in case of early onset, positive family history, severe recurrence rate, associated biochemical disorders, abnormal urinary sediment, renal insufficiency, involvement of other organs or apparatus. Pathophysiology is based on different mechanisms: electrolytic abnormalities, altered tubular transport, acid-base imbalances, cystic renal diseases. Sometimes NL is iatrogenic. Here we review some genetic NL, not only characterized by clinical relevance but also by the scientific interest in view of our better understanding of mechanisms of stone formation. Namely, Dents syndrome, calcium sensing receptor mutations, familial hypopomagnesiemic hypercalciuria (FHHNC), hypophosphatemic rickets (HHRH), renal tubular acidosis (dRTA), primary hyperoxaluria (PH), cystinuria, 2-8 dihydroxyadeninuria (2-8 DHA). We will briefly report on prevalence, genetics, pathophysiology, clinical aspects and treatment. The need for early diagnosis stems from the fact that, for most of these, selective treatment may be highly effective and can prevent progression to ESRD. Lastly, a better knowledge and understanding of genetic NL is a premise to study polymorphisms of candidate genes also in the setting of so-called idiopathic disease.
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PMID:[Genetic approach to nephrolithiasis]. 2647 54

Claudins are discovered to be key players in renal epithelial physiology. They are involved in developmental, physiological, and pathophysiological differentiation. In the glomerular podocytes, claudin-1 is an important determinant of cell junction fate. In the proximal tubule, claudin-2 plays important roles in paracellular salt reabsorption. In the thick ascending limb, claudin-14, -16, and -19 regulate the paracellular reabsorption of calcium and magnesium. Recessive mutations in claudin-16 or -19 cause an inherited calcium and magnesium losing disease. Synonymous variants in claudin-14 have been associated with hypercalciuric nephrolithiasis by genome-wide association studies (GWASs). More importantly, claudin-14 gene expression can be regulated by extracellular calcium levels via the calcium sensing receptor. In the distal tubules, claudin-4 and -8 form paracellular chloride pathway to facilitate electrogenic sodium reabsorption. Aldosterone, WNK4, Cap1, and KLHL3 are powerful regulators of claudin and the paracellular chloride permeability. The lessons learned on claudins from the kidney will have a broader impact on tight junction biology in other epithelia and endothelia.
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PMID:Claudins in barrier and transport function-the kidney. 2787 8

Hypophosphatemic rickets, mostly of the X-linked dominant form caused by pathogenic variants of the PHEX gene, poses therapeutic challenges with consequences for growth and bone development and portends a high risk of fractions and poor bone healing, dental problems and nephrolithiasis/nephrocalcinosis. Conventional treatment consists of PO4 supplements and calcitriol requiring monitoring for treatment-emergent adverse effects. FGF23 measurement, where available, has implications for the differential diagnosis of hypophosphatemia syndromes and, potentially, treatment monitoring. Newer therapeutic modalities include calcium sensing receptor modulation (cinacalcet) and biological molecules targeting FGF23 or its receptors. Their long-term effects must be compared with those of conventional treatments.
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PMID:Hypophosphatemic Rickets. 3045 43