Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nineteen children with clinical diagnoses of renal tubular acidosis were followed for periods ranging from 3 months to 20 years. Twelve patients had Type 1 renal tubular acidosis, five had Type 2, and two had Type 4. No sex predilection was found for any one of the types. Most patients had been diagnosed before 18 months of age, with failure to thrive the most common presentation. Tachypnea, polydipsia, polyuria, and vomiting were frequent symptoms. Some of these children had associated renal hypoplasia, vesicoureteral reflux, unilateral renal agenesis, glomerulocystic disease, adult polycystic kidney disease, and cyanotic congenital heart disease. Urinary anion gap may be useful for differential diagnosis of altered distal urinary acidification from other hyperchloremic metabolic acidosis. Furosemide test may need further investigation. Inability to raise urine to blood pCO2 gradient is helpful for diagnosis of Type 1 renal tubular acidosis. Hypokalemia, hypocalcemia, hypophosphatemia, decreased tubular reabsorption of phosphate, and hypercalciuria occurred in some patients. Complications included rickets in two, nephrocalcinosis in one, and episodic hematuria in one. There was relative bicarbonate wasting in children with Type 1 renal tubular acidosis, with a mean therapeutic bicarbonate requirement of 4.4 +/- 2.6 meq/kg/day. The mean bicarbonate dose for patients with Type 2 renal tubular acidosis was 8.3 +/- 2.6 meq/kg/day. Most children had good response to treatment with complete catch-up linear growth in 13, improved growth in 4, and continuing poor growth in 2. Two patients died during follow-up. Two other patients maintained normal growth without medication.
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PMID:Renal tubular acidosis in childhood. 226 80

Despite the frequency and morbidity of nephrolithiasis in autosomal dominant polycystic kidney disease (ADPKD), this association has not been subject to a detailed study. One hundred fifty-one of 751 ADPKD patients seen at the Mayo Clinic between 1976 and 1986 had nephrolithiasis. Seventy-four had passed calculi or had stones surgically removed. Stone analysis was available in 30 patients: uric acid, calcium oxalate, calcium phosphate, and struvite were present in 56.6%, 46.6%, 20%, and 10%, respectively. Calculi were observed in 71 of 79 patients with excretory urograms available for review. Faintly opaque and bull's eye stones, probably containing uric acid, were present in 12.7% and 14.1% of these patients, respectively. Precaliceal tubular ectasia was observed in 15.5%. Ninety-seven patients had preserved renal function (serum creatinine less than 1.5 mg/dL) at the initial evaluation. Six were excluded because they had other known causes of stone disease. The most common metabolic abnormality in the remaining 91 patients was hypocitric aciduria (ten of 15 patients with measurements). The urine pH in the first voided morning specimens (5.66 +/- 0.05) was significantly lower than that of an unselected control population (5.92 +/- 0.03, P less than 0.001). Hyperuricosuria, hyperoxaluria, and hypercalciuria were observed in six of 32 (18.8%), six of 31 (19.4%), and three of 39 (9.7%) patients with preserved renal function. The composition of the stones, the frequency of hypocitric aciduria, and the low urine pH (possibly related to the defect in excretion of ammonia described in ADPKD), suggest that metabolic, along with mechanical, factors are responsible for the frequent occurrence of nephrolithiasis in this disease.
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PMID:The association of nephrolithiasis and autosomal dominant polycystic kidney disease. 335 68

Multiple cationic channels with variable selectivity for Ca(2+) , K(+) and Na(+) have been identified in smooth muscle cells (SMC) as well as non-excitable cells. They control Ca(2+) store refilling and depletion, G-protein-mediated receptor activation, apoptosis and cell growth, membrane potential, intracellular pH, oxidative stress, phospholipid signaling, and other critical cell functions. A novel superfamily of divalent cation channels has been recently characterized as highly conserved heterotetramer homologues of Drosophila transient receptor potential (TRP). At least 50 members of seven major TRP channel families have been identified to date. The involvement of TRP in store-operated Ca(2+) - gating has been demonstrated in various tissues, along with intestinal and renal epithelial cell Ca(2+) and Mg(2+) transport, indicating a role in total body homeostasis of divalent cations. TRPV5-null mice display phenotypic defects including hypercalciuria and impaired bone mineral density. TRPP2 or polycystin 2 (PC2), encoded by the PKD2 gene, is an integral protein of epithelial cilia whose mutation is associated with autosomal dominant polycystic kidney disease (ADPKD). A TRPP1 (polycystin 1)-PC2 channel complex is actually implicated in the transduction of environmental signals (i.e. luminal tubular fluid flow and composition) into cellular events, such as epithelial cell growth. TRP channels can eventually play a role in the pathogenesis of arterial hypertension via direct effects on vascular smooth muscle contraction, renal blood flow, glomerular hemodynamics and the tubular handling of Ca(2+) and electrolytes.
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PMID:Transient receptor potential channels in the kidney: calcium signaling, transport and beyond. 1652 21

The transient receptor potential (TRP) superfamily consists, in mammals, of six protein subfamilies, TRPC, TRPM, TRPV, TRPA, TRPML and TRPP. TRPs are cation channels involved in many physiological processes and in the pathogenesis of various disorders. In the kidney, TRP channels are expressed along the nephron, and a role for some of these channels in renal function has been proposed. TRPC3 is thought to facilitate calcium ion influx into the principal cells of the collecting duct in response to vasopressin. TRPM3 and TRPV4 might be osmosensors, whereas the TRPP1/TRPP2 complex could function as a mechanosensor in the cilia of renal epithelial cells. A number of kidney diseases have also been linked to dysfunctional activity of TRPs. TRPC6 dysfunction has been associated with the onset of focal segmental glomerosclerosis; TRPP2 dysfunction is linked to autosomal-dominant polycystic kidney disease, TRPM6 mutations underlie hypomagnesemia with secondary hypocalcemia, and TRPV1 dysfunction is implicated in renal hypertension. A link between TRPC1 dysfunction and diabetic nephropathy has also been suggested in an animal model. Animal studies have implicated a role for TRPV5 in idiopathic hypercalciuria and vitamin D-dependent rickets, although these observations have not been confirmed in patients. This Review focuses on the role of renal TRP channels in health and disease.
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PMID:The role of transient receptor potential channels in kidney disease. 1954 62

The Drosophila trp homologue Transient Receptor Potential (TRP) cation channels are ubiquitous in most species and cell types. The functional TRP subclasses TRPC, TRPV and TRPP gate Ca2+ and other cations in mammalian tissues, including the kidney. It is now clear that TRP channels play an important role in renal physiology and in certain genetic disorders of the kidney. Hence, there is considerable interest in targeting mutated or dysfunctional TRP channels in an effort to treat such diseases. Transcellular epithelial cell Ca2+ reabsorption occurs in the distal tubule via luminal TRPV5/V6 channels. Indeed, TRPV5 KO mice display phenotypic defects of renal disease, including hypercalciuria and impaired bone mineral density. Similar to Ca2+, Mg2+ transcellular reabsorption occurs in the distal convoluted tubule via apical TRPM6/TRPM7 channels. TRPC6 is a component of the glomerular podocyte "slit diaphragm" and its autosomic dominant mutation has been linked to a familial, steroid-resistant form of nephrotic syndrome. A more common inherited disorder of the tubular epithelium, autosomal dominant polycystic kidney disease (ADPKD), is at least in part related to mutation of polycystin 2 (PC2), a protein encoded by the PKD2 gene. PC2 is now identified as TRPP2, a Ca(2+)-permeable non-selective cation channel located on the cilia of tubular epithelial cells. TRP-related ion transport may also play a role in the pathogenesis of arterial systemic and/or pulmonary hypertension through regulation of vascular smooth muscle contraction, renal perfusion/hemodynamics, as well as the total body balance of divalent cations. Thus, multiple renal TRP channels are potential targets for pharmacological intervention aimed at preventing or attenuating the burden of chronic kidney disease.
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PMID:TRP channels as therapeutic targets in kidney disease and hypertension. 2343 67