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)

Edema, proteinuria, hypertension (EPH)-gestosis, known also as preeclampsia, is the most common, pregnancy-associated pathological syndrome. It is accompanied by a significant increase in collagen content in the umbilical cord arteries and premature replacement of hyaluronic acid by sulfated glycosaminoglycans both in these arteries and in Wharton's jelly. This remodelling of the umbilical cord tissues is accompanied by a distinct increase in insulin-like growth factor-I (IGF-I) concentration in the umbilical cord serum. Such a serum introduced into the culture medium of fibroblasts growing in vitro strongly stimulated the incorporation of radioactive proline into collagen (hydroxyproline-containing and collagenase-sensitive protein). Biosynthesis of noncollagenous proteins was not stimulated. Since IGF-I is known as a stimulator of collagen and sulfated glycosaminoglycan biosynthesis, the high concentration of this growth factor in the umbilical cord plasma may be an agent responsible for preeclampsia-associated remodelling of the umbilical cord, which results in dysfunction in fetal circulation.
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PMID:Stimulation of collagen biosynthesis by the umbilical cord serum of newborns delivered by mothers with EPH-gestosis (preeclampsia). 1107 61

Hyperalimentation solutions, with low protein content but rich in amino acids, have been more frequently used as a dietary treatment for renal terminal patients, with the purpose to increase their survival. However, the literature in this respect is contradictory. Some authors justify the use of amino acids due to the fact that they seem to regenerate damaged tubular cells (glycine, for example). Other authors, on the contrary, do not agree with this position, since some amino acids, like L-Serine and Lysine, are nephrotoxic. In 1977, it was demostrated that Lysine and Arginine inhibited protein tubular reabsorption, inducing proteinuria, while Glycine, Alanine, Asparagine and Glutamic Acid did not. In order to clarify this issue, we carried out a controlled animal study using uninephrectomized rats fed during nine weeks, with different hypoproteinic diets (4% protein content), enriched individually with five different amino acids. The hypoproteinic diets were enriched with Lysine and Arginine (essential amino acids) and Proline, Glutamic Acid and Asparagine (non essential amino acids). Assays for serum biochemical markers and renal function were carried-out pre-nephrectomy, two weeks after nephrectomy (post-nephrectomy control) and nine weeks post-diet for all the animals, no matter the diet to which they were subjected, the serum biochemistry results showed that all the hypoproteinic diets, enriched with amino acids, affected the renal function. The nephrotoxicity of the tested amino acids, followed this decreasing order: Glutamic Acid > Proline > Lysine > Asparagine > Arginine. hypoproteinic diets enriched with Lysine, Asparagine and Arginine, produced glomerular hyperfiltration, without proteinuria. In summary, our results point towards the idea that, contrarily to what has been described in the literature by some authors: enrichment of hypoproteinic diets with certain amino acids does not seem to protect against progression of renal disease in physiologically compromised kidneys.
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PMID:[Effect of hypoproteic diets enriched with essential and non-essential amino acids on the uninephrectomized rat ]. 1221 96

It has been previously shown that 2-hydroxyestradiol (2-OHE) attenuates the development of renal disease in genetic nephropathy associated with obesity and the metabolic syndrome. The purpose of this study was to test the hypothesis that 2-OHE, irrespective of its effects on metabolic status and/or obesity, exerts direct renoprotective effects in vivo. First, the effects of increasing doses of 2-OHE on mesangial cell growth, proliferation, and collagen synthesis in isolated rat glomerular mesangial cells were evaluated in vitro. Second, the effects of 12-wk administration of 2-OHE (10 micro g/h per kg) on renal function and structure in chronic puromycin aminonucleoside (PAN)-induced nephropathy in rats were evaluated in vivo. 2-OHE concentration-dependently (0.001 to 1 micro mol/L; P < 0.001) inhibited serum (2.5%)-induced cell growth ((3)H-thymidine incorporation), collagen synthesis ((3)H-proline incorporation), and cell proliferation (cell number). Importantly, the inhibitory effects of 2-OHE (0.1 micro mol/L) were not blocked by ICI182780 (50 micro mol/L), an estrogen receptor antagonist. In vivo, chronic administration of PAN (75 mg/kg + 5 x 20 mg/kg) over 12 wk induced severe chronic renal disease. Chronic treatment with 2-OHE significantly (P < 0.05) attenuated PAN-induced decrease in glomerular filtration, reduced proteinuria, and the elevated BP, and it had no effect on PAN-induced increase in plasma cholesterol and triglycerides levels. 2-OHE had no effects on plasma testosterone levels in male nephropathic animals. Immunohistochemical staining for collagen IV and proliferating cell nuclear antigen (PCNA) in glomeruli and transforming growth factor-beta (TGF-beta) in renal tubular cells were significantly higher in PAN nephropatic rats versus control animals with intact kidneys. PAN also markedly increased glomerular and interstitial macrophage infiltration (ED1(+) cells). 2-OHE had no effects on renal tubular cell TGF-beta, but it significantly reduced glomerular PCNA and collagen IV and glomerular and interstitial macrophage infiltration. In summary, this study provides the first evidence that 2-OHE exerts direct renoprotective effects in vivo. These effects are mediated by estrogen receptor-independent mechanisms and are due, at least in part, to the inhibition of some of the key proliferative mechanisms involved in glomerular remodeling and sclerosis.
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PMID:2-Hydroxyestradiol attenuates renal disease in chronic puromycin aminonucleoside nephropathy. 1239 44

Proteinuria is quantified for diagnostic and prognostic purposes and to assess responses to therapy. Methods used to assess urinary protein include 24-hour urine collection (24-Up) and determination of the ratio of protein to creatinine concentration (Up/Ucr) in simple voided urine samples (Up/Ucr quantitative method). However, these methods are costly and time consuming. The Multistix PRO 11 (Bayer Medical Co., Ltd., Tokyo, Japan) is a new urine dipstick that allows rapid measurement of Up/Ucr. Results obtained with the Multistix PRO 11 coincided well with those obtained with the 24-Up method (kappa = 0.68) and the Up/Ucr quantitative method (kappa = 0.75). However, Multistix PRO 11 did not accurately measure moderate to severe proteinuria (> or = 500 mg/g. Cr). Our findings suggest that Multistix PRO 11 is useful for the screening, assessment, and follow-up of mild proteinuria.
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PMID:[Estimation of quantitative proteinuria using a new dipstick in random urine samples]. 1505 5

HPLC-MS-based metabonomic analysis was used to investigate urinary metabolic perturbations associated with D-serine-induced nephrotoxicity. D-Serine causes selective necrosis of the proximal straight tubules in the rat kidney accompanied by aminoaciduria, proteinuria and glucosuria. Alderely Park (Wistar-derived) rats were dosed with either D-serine (250 mg/kg ip) or vehicle (deionised water) and urine was collected at 0-12, 12-24, 24-36 and 36-48 h post-dosing. Samples were analysed using a Waters Alliance HT 2795 HPLC system coupled to a Waters Micromass Q-ToF-micro equipped with an electrospray source operating in either positive or negative ion mode. Changes to the urinary profile were detected at all time points compared to control. In negative ion mode, increases were observed in serine (m/z=103.0077), m/z=104.0376 (proposed to be hydroxypyruvate) and glycerate (m/z=105.0215), the latter being metabolites of D-serine. Furthermore, an increase in tryptophan, phenylalanine and lactate and decreases in methylsuccinic acid and sebacic acid were observed. Positive ion analysis revealed a decrease in xanthurenic acid, which has previously been assigned and reported using HPLC-MS following exposure to mercuric chloride and cyclosporine A. A general aminoaciduria, including proline, methionine, leucine, tyrosine and valine was also observed as well as an increase in acetyl carnitine. Investigation of additional metabolites altered as a result of exposure to D-serine is on-going. Thus, HPLC-MS-based metabonomic analysis has provided information concerning the mechanism of D-serine-induced renal injury.
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PMID:D-Serine-induced nephrotoxicity: a HPLC-TOF/MS-based metabonomics approach. 1559 49

Although the quantification of protein excretion is valuable for diagnosing and monitoring renal disease, accurate, timed, urine collection entails practical difficulties in children. Several authors have shown that the random urine protein/creatinine ratio (UP/UC) correlates well with timed protein excretion. A novel dipstick, Multistix PRO, has recently enabled us to analyze concentrations of both urinary protein and creatinine, semi-quantitatively, in 60 s. The aim of this study was to investigate whether the UP/UC values obtained by Multistix PRO correlate well with those obtained by quantitative methods and daily urinary protein excretion. In order to obtain the UP/UC values, we measured urinary protein and creatinine concentrations both semi-quantitatively by Multistix PRO and quantitatively by conventional methods. The relationship between the semi-quantitative UP/UC by Multistix PRO and the quantitative UP/UC by conventional methods was analyzed. Similarly, the relationship between the semi-quantitative UP/UC and daily urinary protein excretion was studied. Semi-quantitative UP/UC by Multistix PRO correlated closely with both quantitative UP/UC and daily urinary protein excretion (r=0.86 and r=0.91, respectively). A cut-off level of heavy proteinuria, i.e., nephrotic range of proteinuria (>3.5 g/day) corresponded to 3.0, assessed by UP/UC by Multistix PRO. The semi-quantitative UP/UC by Multistix PRO correlated well with both quantitative UP/UC and daily urinary protein excretion, and use of the Multistix PRO would avoid errors and difficulties associated with timed urine collection. It is, therefore, a useful tool to monitor the urinary protein excretion in children with renal diseases at outpatient clinic.
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PMID:Simplified quantification of urinary protein excretion using a novel dipstick in children. 1577 46

Alterations in the cellular architecture, adhesion, and/or loss of glomerular podocytes are causal factors in the development of proteinuria and the progression to end-stage renal failure. With the use of an inducible podocyte differentiation system, it was found that the cellular levels of PINCH-1, integrin linked kinase (ILK), and alpha-parvin, cytoplasmic components of cell-extracellular matrix adhesions, were significantly increased during podocyte differentiation. Concomitantly, an increased amount of the PINCH-1-ILK-alpha-parvin complex was detected in the differentiated, foot process-containing podocytes. Overexpression of the PINCH-1-binding ankyrin repeat domain of ILK but not that of a PINCH-1-binding defective mutant form of the ankyrin domain effectively inhibited the formation of the PINCH-1-ILK-alpha-parvin complex. Disruption of the PINCH-1-ILK-alpha-parvin complex significantly reduced the podocyte-matrix adhesion and foot process formation. Furthermore, a marked increase of apoptosis in the podocytes in which the assembly of the PINCH-1-ILK-alpha-parvin complex was compromised was detected. Inhibition of ILK with a small compound inhibitor also altered podocyte cytoskeleton and increased apoptosis. Finally, it is shown that alpha-parvin is phosphorylated in podocytes. Mutations at the alpha-parvin N-terminal proline-directed serine phosphorylation sites reduced its complex formation with ILK and resulted in defects in podocyte adhesion, architecture, and survival. These results provide important evidence for a crucial role of the PINCH-1-ILK-alpha-parvin complex in the control of podocyte adhesion, morphology, and survival.
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PMID:Formation and phosphorylation of the PINCH-1-integrin linked kinase-alpha-parvin complex are important for regulation of renal glomerular podocyte adhesion, architecture, and survival. 1587 73

The level of proteinuria is one of the most important risk factors for progressive renal function loss in renal diseases. Any therapeutic measure that reduces proteinuria will slow or halt the progression of proteinuric nephropathies. Blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE) inhibitors or AT1-receptor antagonists (ARA) is currently the most powerful available antiproteinuric treatment. Recent investigations point out that blockade of RAAS at other levels (e.g., aldosterone or renin antagonists) could also induce a significant decrease in proteinuria. Because angiotensin II is also generated from angiotensin I by enzymes other than ACE, ARA would provide a more effective blockade of angiotensin II; however, ACE inhibition increases plasma levels of substances such as bradykinin and N-acetyl-seryl-aspartyl-lysyl-proline, which have strong antifibrotic properties. These differential effects of ACE inhibitors and ARA are the rationale for combined administration of both agents, which in clinical studies has demonstrated a significantly higher antiproteinuric and renoprotective effect than by either drug alone. Salt and protein restriction, as well as cautious use of diuretics, can also increase the antiproteinuric effect of RAAS blockade. Treatment with statins or other lipid-lowering agents leads to reduction in proteinuria levels, as some meta-analyses have demonstrated. Smoking is associated with an increased risk for the appearance of proteinuria, so cessation of smoking should be mandatory in proteinuric renal diseases. Recent studies have highlighted an epidemic increase of obesity-related proteinuric glomerulopathies; weight loss is effective not only in this condition, but also in overweight patients with proteinuric nephropathies of other etiologies.
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PMID:Therapeutic measures in proteinuric nephropathy. 1633 67

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is hydrolyzed by angiotensin-converting enzyme, is a natural regulator of hematopoiesis. Here it is shown that Ac-SDKP inhibits TGF-beta action in mesangial cells. Because TGF-beta is thought to play a pivotal role in the development and progression of glomerulonephritis, the therapeutic effects of Ac-SDKP on an established model of renal dysfunction and histologic alteration in Wistar-Kyoto rats with anti-glomerular basement membrane nephritis was examined. Fourteen days after the induction of anti-glomerular basement membrane nephritis, the rats were treated subcutaneously with Ac-SDKP at a dose of 1 mg/kg per d for 4 wk. Treatment with Ac-SDKP significantly improved proteinuria and renal dysfunction, including increased plasma blood urea nitrogen and creatinine levels and decreased creatinine clearance. Histologic examination showed severe glomerulosclerosis and interstitial fibrosis in the vehicle-treated rats, whereas these histologic injuries were significantly ameliorated in rats that were treated with Ac-SDKP. The histologic improvements were accompanied by the suppression of gene and protein expression of fibronectin, interstitial collagen, and TGF-beta1 in the nephritic kidney. Furthermore, treatment with Ac-SDKP resulted in the inhibition of Smad2 phosphorylation, an increase in Smad7 expression in the kidney, and reduction of macrophage accumulation into the glomeruli and tubulointerstitium in nephritic rats. In conclusion, Ac-SDKP significantly ameliorated the progression of renal dysfunction and fibrosis even after the establishment of nephritis. The inhibitory effect of Ac-SDKP was mediated in part by the inhibition of TGF-beta/Smad signal transduction and the inflammatory response. These findings suggest that Ac-SDKP treatment may be a novel and useful therapeutic strategy for the treatment of progressive renal diseases.
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PMID:N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the progression of renal dysfunction and fibrosis in WKY rats with established anti-glomerular basement membrane nephritis. 1645 98

Serum amyloid P component (SAP) is a universal constituent of amyloid deposits and contributes to their formation and/or persistence. We therefore developed CPHPC ((R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexa-noyl]pyrrolidine-2 carboxylic acid), a novel bis(D-proline) drug, to specifically target SAP and report here a first, exploratory, open label proof of principle study in systemic amyloidosis. CPHPC produced sustained, >95% depletion of circulating SAP in all patients and c. 90% reduction in the SAP content of the two amyloidotic organs that became available. There were no significant adverse effects of either SAP depletion or CPHPC itself. No accumulation of amyloid was demonstrable by SAP scintigraphy in any patient on the drug. In hereditary fibrinogen amyloidosis, which is inexorably progressive, proteinuria was reduced in four of five patients receiving CPHPC and renal survival was prolonged compared to a historical control group. These promising clinical observations merit further study.
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PMID:Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis. 2006 57


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