Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injury to podocytes is considered a major contributor to diabetic kidney disease: their loss causes proteinuria and progressive glomerulosclerosis. Podocyte depletion may result from improper calcium handling due to abnormal activation of the calcium permeant TRPC (Transient Receptor Potential Canonical) channels. Angiotensin II (Ang II) levels are found to be elevated in diabetes; furthermore, it was reported that Ang II causes activation of TRPC6 in podocytes. We hypothesized here that Ang II-mediated calcium influx is aggravated in the podocytes under the conditions of type 1 diabetic nephropathy (DN). Diabetes was induced in the Dahl Salt-Sensitive rats by an injection of streptozotocin (STZ-SS). Eleven weeks post treatment was sufficient for the animals to develop hyperglycemia, excessive urination, weight loss, microalbuminuria, nephrinuria and display renal histological lesions typical for patients with DN. Patch-clamp electrophysiology performed on podocytes of the freshly isolated glomeruli showed enhanced basal TRPC channel activity in the STZ-SS rats, and increased response to Ang II; total calcium influx triggered by Ang II application was also augmented in podocytes of these rats. Our studies have a strong potential for advancing the understanding of TRPC-mediated effects on podocytopenia in DN initiation.
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PMID:Podocyte injury in diabetic nephropathy: implications of angiotensin II-dependent activation of TRPC channels. 2665 1

Stroke-prone spontaneously hypertensive rats (SHR-A3) develop strokes and progressive kidney disease as a result of naturally occurring genetic variations. We recently identified genetic variants in immune signaling pathways that contribute to end-organ injury. The present study was designed to test the hypothesis that a dysregulated immune response promotes stroke susceptibility. We salt-loaded 20 wk old male SHR-A3 rats and treated them with the immunosuppressant mycophenolate mofetil (MMF, 25 mg/kg/day po) (n = 8) or vehicle (saline) (n = 9) for 8 wk. Blood pressure (BP) was measured weekly by telemetry. Compared with vehicle-treated controls, MMF-treated SHR-A3 rats had improved survival and lower neurological deficit scores (1.44 vs. 0.125; P < 0.02). Gross morphology of the brain revealed cerebral edema in 8 of 9, and microbleeds and hemorrhages in 5 of 9 vehicle-treated rats. These lesions were absent in MMF-treated rats. Brain CD68 expression, indicating macrophage/microglial activation, was upregulated in vehicle-treated rats with microbleeds and hemorrhages but was undetectable in the brains of MMF-treated rats. MMF also prevented renal injury in SHR-A3 rats, evidenced by reduced proteinuria (albumin:creatinine) from 7.52 to 1.05 mg/mg (P < 0.03) and lower tubulointerstitial injury scores (2.46 vs. 1.43; P < 0.01). Salt loading resulted in a progressive increase in BP, which was blunted in rats receiving MMF. Our findings provide evidence that abnormal immune activation predisposes to cerebrovascular and renal injury in stroke-prone SHR-A3 rats.
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PMID:Mycophenolate mofetil prevents cerebrovascular injury in stroke-prone spontaneously hypertensive rats. 2801 82

Objective Salt loading induces renal damage independently of blood pressure (BP) elevation via reactive oxygen species and sympathetic activity. Melatonin, a hormone that regulates the circadian rhythm, has multiple functions, including anti-oxidant effects and the inhibition of sympathetic activity. We have shown that impaired melatonin secretion is associated with renal damage in chronic kidney disease (CKD) patients. However, the associations between salt loading, melatonin secretion, and urinary albumin and protein have not been clarified. Methods We recruited 32 CKD patients, conducted 24-hour ambulatory BP monitoring and collected daytime and nighttime urine while the patients were consuming a standard salt (10 g/day) or low salt (6 g/day) diet. The excretion levels of albumin, protein and 6-sulfatoxymelatonin (aMT6s), a metabolite of melatonin, in daytime and nighttime urine were investigated in patients consuming standard salt and low salt diets. Results The urinary aMT6s levels in daytime and nighttime of the patients consuming standard salt and low salt diets did not differ to a statistically significant extent. However, the urinary aMT6s levels in patients consuming a standard salt diet-but not patients consuming a low salt diet-were significantly and negatively correlated with the daytime and nighttime urinary albumin and protein levels. Contrarily, no significant correlations were found between the urinary aMT6s levels and the BP levels, renal function, and plasma angiotensin II levels in patients consuming either a standard salt or low salt diet. A multiple regression analysis adjusted for age, sex, and body mass index revealed that the urinary albumin and protein levels were significantly and negatively associated with the urinary aMT6s levels in patients consuming a standard salt diet, but not in patients consuming a low salt diet. Conclusion Salt loading aggravates the relationship between melatonin secretion and albuminuria or proteinuria.
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PMID:Salt Loading Aggravates the Relationship between Melatonin and Proteinuria in Patients with Chronic Kidney Disease. 3071 30

Edema is a common symptom with mostly extrarenal causes. Nevertheless, it may also be a sign of glomerular disease. So renal causes should always be clarified to avoid serious complications, such as renal insufficiency, cardiovascular or thrombembolic events. The determination of the albumin-creatinine ratio in spot urine is easy to perform and the method of choice to diagnose nephrotic-range proteinuria. Renal biopsy then usually allows the definitive assignement to either glomerular or systemic disease. Salt restriction in combination with diuretics and antiproteinuric treatment are essential for an effective therapy. Depending on the underlying disease and individual risk factors, anticoagulation should also be considered.
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PMID:[Edema - the nephrologist's perspective]. 3087 Aug 67

Salt-sensitive (SS) hypertension is accompanied with an early onset of proteinuria, which results from the loss of glomerular podocytes. Here, we hypothesized that glomerular damage in the SS hypertension occurs in part due to mitochondria dysfunction, and we used a unique model of freshly isolated glomeruli to test this hypothesis. In order to mimic SS hypertension, we used Dahl SS rats, an established animal model. Animals were fed a 0.4% NaCl (normal salt, NS) diet or challenged with a high salt (HS) 4% NaCl diet for 21 days to induce an increase in blood pressure (BP). Similar to previous studies, we found that HS diet caused renal hypertrophy, increased BP, glomerulosclerosis, and renal lesions such as fibrosis and protein casts. We did not observe changes in mitochondrial biogenesis in the renal cortex or isolated glomeruli fractions. However, Seahorse assay performed on freshly isolated glomeruli revealed that basal mitochondrial respiration, maximal respiration, and spare respiratory capacity were lower in the HS compared to the NS group. Using confocal imaging and staining for mitochondrial H2O2 using mitoPY1, we detected an intensified response to an acute H2O2 application in the podocytes of the glomeruli isolated from the HS diet fed group. TEM analysis showed that glomerular mitochondria from the HS diet fed group have structural abnormalities (swelling, enlargement, less defined cristae). Therefore, we report that glomerular mitochondria in SS hypertension are functionally and structurally defective, and this impairment could eventually lead to loss of podocytes and proteinuria. Thus, the glomerular-mitochondria axis can be targeted in novel treatment strategies for hypertensive glomerulosclerosis.
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PMID:Renal Glomerular Mitochondria Function in Salt-Sensitive Hypertension. 3211 33


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