Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0032617 (polyuria)
3,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Gla^tm mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the Gla^tmTg(CAG-A4GALT) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit polyuria and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of polyuria and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodies and had lost their characteristic structure ( i.e., extensive infolding and numerous elongated mitochondria). Decreased expression of the major molecules-Na⁺-K⁺-ATPase, uromodulin, and Na⁺-K⁺-2Cl^- cotransporter-that are involved in Na⁺ reabsorption in mTALs and the associated loss of urine-concentrating ability resulted in progressive water- and salt-loss phenotypes. Gla^tmTg(CAG-A4GALT) mice exhibited fibrosis around mTALs and renal dysfunction. These and other features were consistent with pathologic findings in patients with Fabry disease. Results demonstrate that mTAL dysfunction causes polyuria and renal impairment and contributes to the pathophysiology of Fabry nephropathy.-Maruyama, H., Taguchi, A., Nishikawa, Y., Guili, C., Mikame, M., Nameta, M., Yamaguchi, Y., Ueno, M., Imai, N., Ito, Y., Nakagawa, T., Narita, I., Ishii, S. Medullary thick ascending limb impairment in the Gla^tmTg(CAG-A4GALT) Fabry model mice.
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PMID:Medullary thick ascending limb impairment in the Gla^tmTg(CAG-A4GALT) Fabry model mice. 2955 30

Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal acidification due to a failure of type A intercalated cells (A-ICs) in the collecting tubule. dRTA is characterized by persistent hyperchloremia, a normal plasma anion gap, and the inability to maximally lower urinary pH in the presence of systemic metabolic acidosis. Common clinical features of dRTA include vomiting, failure to thrive, polyuria, hypercalciuria, hypocitraturia, nephrocalcinosis, nephrolithiasis, growth delay, and rickets. Mutations in genes encoding three distinct transport proteins in A-ICs have been identified as causes of dRTA, including the B1/ATP6V1B1 and a4/ATP6V0A4 subunits of the vacuolar-type H⁺-ATPase (H⁺-ATPase) and the chloride-bicarbonate exchanger AE1/SLC4A1. Homozygous or compound heterozygous mutations in ATP6V1B1 and ATP6V0A4 lead to autosomal recessive (AR) dRTA. dRTA caused by SLC4A1 mutations can occur with either autosomal dominant or AR transmission. Red blood cell abnormalities have been associated with AR dRTA due to SLC4A1 mutations, including hereditary spherocytosis, Southeast Asia ovalocytosis, and others. Some patients with dRTA exhibit atypical clinical features, including transient and reversible proximal tubular dysfunction and hyperammonemia. Incomplete dRTA presents with inadequate urinary acidification, but without spontaneous metabolic acidosis and recurrent urinary stones. Heterozygous mutations in the AE1 or H⁺-ATPase genes have recently been reported in patients with incomplete dRTA. Early and sufficient doses of alkali treatment are needed for patients with dRTA. Normalized serum bicarbonate, urinary calcium excretion, urinary low-molecular-weight protein levels, and growth rate are good markers of adherence to and/or efficacy of treatment. The prognosis of dRTA is generally good in patients with appropriate treatment. However, recent studies showed an increased frequency of chronic kidney disease (CKD) in patients with dRTA during long-term follow-up. The precise pathogenic mechanisms of CKD in patients with dRTA are unknown.
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PMID:Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead. 3058 51

Chronic lithium administration for the treatment of bipolar disorder leads to nephrogenic diabetes insipidus (NDI), characterized by polyuria, natriuresis, kaliuresis, and collecting duct remodeling and cell proliferation among other features. Previously, using a 2-week lithium-induced NDI model, we reported that P2Y₂ receptor (R) knockout mice are significantly resistant to polyuria, natriuresis, kaliuresis, and decrease in AQP2 protein abundance in the kidney relative to wild type mice. Here we show this protection is long-lasting, and is also associated with significant amelioration of lithium-induced collecting duct remodeling and cell proliferation. Age-matched wild type and knockout mice were fed regular (n = 5/genotype) or lithium-added (40 mmol/kg chow; n = 10/genotype) diet for 5 months and euthanized. Water intake, urine output and osmolality were monitored once in every month. Salt blocks were provided to mice on lithium-diet to prevent sodium loss. At the end of 5 months mice were euthanized and serum and kidney samples were analyzed. There was a steady increase in lithium-induced polyuria, natriuresis and kaliuresis in wild type mice over the 5-month period. Increases in these urinary parameters were very low in lithium-fed knockout mice, resulting in significantly widening differences between the wild type and knockout mice. Terminal AQP2 and NKCC2 protein abundances in the kidney were significantly higher in lithium-fed knockout vs. wild type mice. There were no significant differences in terminal serum lithium or sodium levels between the wild type and knockout mice. Confocal immunofluorescence microscopy revealed that lithium-induced marked remodeling of collecting duct with significantly increased proportion of [H⁺]-ATPase-positive intercalated cells and decreased proportion of AQP2-positive principal cells in the wild type, but not in knockout mice. Lithium-induced collecting duct cell proliferation (indicated by Ki67 labeling), was significantly lower in knockout vs. wild type mice. This is the first piece of evidence that purinergic signaling is potentially involved in lithium-induced collecting duct remodeling and cell proliferation. Our results demonstrate that genetic deletion of P2Y₂-R protects against the key structural and functional alterations in Li-induced NDI, and underscore the potential utility of targeting this receptor for the treatment of NDI in bipolar patients on chronic lithium therapy.
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PMID:Genetic Deletion of P2Y₂ Receptor Offers Long-Term (5 Months) Protection Against Lithium-Induced Polyuria, Natriuresis, Kaliuresis, and Collecting Duct Remodeling and Cell Proliferation. 3061 88

Distal renal tubular acidosis is a defect of acidification of urine in distal tubule. Full-blown form is characterized by polyuria, growth deficiency, nephrolithiasis or nephrocalcinosis. Mutations in genes encoding Cl-/HCO3 - exchanger (autosomal dominant) or H+-ATPase (autosomal recessive) are the most frequent in children.
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PMID:[Accidentally diagnosed distal renal tubular acidosis with nephrocalcinosis - a case report]. 3091 26


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