UMLS:C0033687 - FACTA Search

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)

Patients with nephrotic syndrome (NS), even with normal GFR, often display altered mineral homeostasis and abnormal bone histology. However, the latter, mostly osteomalacia and increased bone resorption, cannot be readily explained by the prevalent concentrations of parathyroid hormone and vitamin D metabolites. The transmembrane receptor activator of NF-kappaB ligand (RANKL) of osteoblasts is essential for osteoclast formation and differentiation. Osteoblasts activity and the expression of RANKL were tested in cultures of normal human osteoblasts with sera obtained from patients with NS and normal GFR (129 +/- 26 ml/min per 1.73 m2) during relapse and remission of their NS. Osteoblasts that were cultured in vitro with sera during relapse displayed elevated concentrations of alkaline phosphatase (AP) and increased expression of RANKL. By contrast, during remission, AP concentrations were significantly lower (P < 0.05) and RANKL expression notably attenuated or absent. AP correlated with the proteinuria (r = 0.5, P < 0.05) and was not significantly affected by the therapeutic administration of corticosteroids. Whereas parathyroid hormone levels were normal (35 +/- 21 pg/ml), the serum markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) were lower during relapse compared with remission. Thus, sera from patients with NS and normal GFR stimulate the activity of osteoblasts and upregulate their expression of RANKL. These alterations, more prominent during clinically active NS, are transient and reversible upon remission. These disturbances of bone biology may play an important pathogenic role in the abnormal bone histology observed in patients with NS even before a decline in GFR occurs.
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PMID:Increased osteoblastic activity and expression of receptor activator of NF-kappaB ligand in nonuremic nephrotic syndrome. 1588 64

Mutations in ClC-5 cause Dent's disease, a disorder associated with low molecular weight proteinuria, hyperphosphaturia, and kidney stones. ClC-5 is a Cl(-)/H(+)-exchanger predominantly expressed in the kidney, where it facilitates the acidification of proximal tubular endosomes. The reduction in proximal tubular endocytosis resulting from a lack of ClC-5 raises the luminal concentration of filtered proteins and peptides like parathyroid hormone (PTH). The increase in PTH may explain the hyperphosphaturia observed in Dent's disease. Expression profiling, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and hormone measurements were used to investigate whether the disruption of ClC-5 affects other signalling pathways. Although the upregulation of 25(OH)(2)-vitamin D(3) 1alpha-hydroxylase and downregulation of vitamin D(3) 24-hydroxylase suggested an increased formation of 1,25(OH)(2)-vitamin D(3), the concentration of this active metabolite was reduced in the serum of ClC-5 knockout (KO) mice. However, target genes of 1,25(OH)(2)-vitamin D(3) were upregulated in KO kidneys. Expression analysis of intestine and bone revealed that the upregulation of 1,25(OH)(2)-vitamin D(3) target genes was kidney intrinsic and not systemic. In spite of reduced serum levels of 1,25(OH)(2)-vitamin D(3) in ClC-5 KO mice, 1,25(OH)(2)-vitamin D(3) is increased in later nephron segments as a consequence of impaired proximal tubular endocytosis. This leads to a kidney-specific stimulation of 1,25(OH)(2)-vitamin D(3) target genes that may contribute to the pathogenesis of Dent's disease. The activation of genes in distal nephron segments by hormones that are normally endocytosed in the proximal tubule may extend to other pathways like those activated by retinoic acid.
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PMID:Kidney-specific upregulation of vitamin D3 target genes in ClC-5 KO mice. 1667 9

The Acadians were French settlers to Nova Scotia in the seventeenth century. In 1755, they were expelled by the British to various sites in the Americas, including Louisiana, where they are referred to as Cajuns. Many later migrated back to the Maritime Provinces of Canada. The objective of this study was to describe a series of pediatric patients representing an Acadian variant of Fanconi syndrome (AVFS). Nineteen children were diagnosed with AVFS between 1971 and 2006 and followed regularly. Data concerning demographics, growth, bone disease, and renal function at presentation and last observation were collected. The commonest reason for referral was assessment of genu valgum at 8.5 +/- 4.2 years (mean +/- SD) with hypophosphatemic rickets confirmed in all patients. Small-body habitus and short stature were confirmed in all patients. Therapy consisting of alkali replacement and phosphate and vitamin D supplements resulted in improvement of rickets and leg alignment but not stature (median height Z-score at presentation -2.05, range -3.6 to 0.21, vs. -2.05 at last observation, range -3.36 to 0.47). Creatinine clearance decreased (65.4 +/- 24.6 vs. 48.0 +/- 36.0 ml/min per 1.73 m(2), P < 0.05) and proteinuria increased (0.38 +/- 0.25 vs. 1.46 +/- 1.52 g/d, P < 0.05) during follow up of 8.4 +/- 6.1 years. Chronic kidney disease developed in 50% by age 13 years. No extrarenal manifestations were identified, although two patients developed lethal pulmonary fibrosis postrenal transplantation. AVFS is characterized by rickets responsive to solute therapy, short stature, and loss of renal function, with progressive proteinuria with age.
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PMID:An Acadian variant of Fanconi syndrome. 1769 Sep 17

Chronic kidney disease is prevalent in Indonesia, running at 29.1% in the population at risk (hypertension, diabetes, and proteinuria). In a recent survey, the incidence rate for end-stage renal disease (ESRD) was 30.7 per million population (pmp), and the prevalence rate was 23.4 pmp. In 2006, about 10,000 patients were being treated with hemodialysis. Nevertheless, many ESRD patients remained untreated. Financial problems, scarcity of dialysis facilities, and insufficient numbers of skilled health care providers were among reasons why renal replacement treatment is not so well developed in Indonesia. The continuous ambulatory peritoneal dialysis (CAPD) program begun in 1985 was slowly growing until an economic crisis in 1998. Afterward, with new development of CAPD and government support, the number of patients on CAPD increased. In the middle of 2007, CAPD patients numbered 774 in total. Drop-out rates remained high, because of death, infection, and catheter failure. Almost all new CAPD patients are older than 35 years of age, and the technique is still costly: 51% of patients receive 4 daily exchanges, costing $6,000 annually; the rest receive 3 daily exchanges, costing $4,800 annually. Government insurance reimburses only 3 exchanges. Expensive drugs such as erythropoietin, intravenous iron, and vitamin D(3) are not covered by insurance. The infection rate for the most recent year was 1 episode in 47.17 patient-months. The cost of antibiotic treatment to cure peritonitis is still expensive. Many patients experience some complication related to catheter obstruction or hemorrhage. In Indonesia, CAPD is relatively new and just beginning to progress. In our archipelago, with its many islands and limited resources and investment, CAPD may be the better choice of therapy. More training is needed to increase the number of skilled and experienced doctors, nurses, and other CAPD team members. We hope that CAPD can be made more affordable for ESRD patients.
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PMID:The development of a continuous ambulatory peritoneal dialysis program in Indonesia. 1855 66

The renal renin-angiotensin system plays a major role in determining the rate of chronic renal disease progression. Treatment with activators of the vitamin D receptor retards the progression of experimental chronic renal disease, and vitamin D is known to suppress the renin-angiotensin system in other organs. Here we determined if the beneficial effects of paricalcitol (19-nor 1,25-dihydroxyvitamin D(2)) were associated with suppression of renin-angiotensin gene expression in the kidney. Rats with the remnant kidney model of chronic renal failure (5/6 nephrectomy) were given two different doses of paricalcitol thrice weekly for 8 weeks. Paricalcitol was found to decrease angiotensinogen, renin, renin receptor, and vascular endothelial growth factor mRNA levels in the remnant kidney by 30-50 percent compared to untreated animals. Similarly, the protein expression of renin, renin receptor, the angiotensin type 1 receptor, and vascular endothelial growth factor were all significantly decreased. Glomerular and tubulointerstitial damage, hypertension, proteinuria, and the deterioration of renal function resulting from renal ablation were all similarly and significantly improved with both treatment doses. These studies suggest that the beneficial effects of vitamin D receptor activators in experimental chronic renal failure are due, at least in part, to down-regulation of the renal renin-angiotensin system.
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PMID:Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. 1914 59

In addition to its actions on bone and mineral metabolism, vitamin D plays various roles in diverse systems. Vitamin D suppresses the renin-angiotensin system, increases insulin secretion and sensitivity, protects against cardiac hypertrophy, and increases left ventricular contraction. Also, vitamin D has anti-atherogenic and anti-inflammatory activities. Observational cohort studies in dialysis and predialysis patients with chronic renal failure show that vitamin D users, as compared to non-users, have better survival rate. Furthermore, the use of active vitamin D is associated with decreased proteinuria and a lower risk for developing end-stage renal disease. Further evidence is needed to establish these pleiotropic actions of vitamin D.
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PMID:[Chronic kidney disease (CKD) and bone. Pleiotropic actions of vitamin D and survival advantage]. 1932 30

Although the endocrine effects of vitamin D are widely recognized, somewhat less appreciated is that vitamin D may serve paracrine functions through local activation by 1-alpha-hydroxylase and thus maintain immunity, vascular function, cardiomyocyte health, and abrogate inflammation and insulin resistance. In the kidney, vitamin D may be important for maintaining podocyte health, preventing epithelial-to-mesenchymal transformation, and suppressing renin gene expression and inflammation. Replacement with pharmacologic dosages of vitamin D receptor agonists (VDRA) in animal models of kidney disease consistently show reduction in albuminuria, abrogation of glomerulosclerosis, glomerulomegaly, and glomerular inflammation, effects that may be independent of BP and parathyroid hormone, but the effects of VDRA in preventing tubulointerstitial fibrosis and preventing the progression of kidney failure in these animal models are less clear. Emerging evidence in patients with chronic kidney disease (CKD) show that vitamin D can reduce proteinuria or albuminuria even in the presence of angiotensin-converting enzyme inhibition. In addition to reducing proteinuria, VDRA may reduce insulin resistance, BP, and inflammation and preserve podocyte loss providing biologic plausibility to the notion that the use of VDRA may be associated with salubrious outcomes in patients with diabetic nephropathy. Patients with CKD have a very high prevalence of deficiency of 25-hydroxyvitamin D. Whether pharmacologic dosages of vitamin D instead of VDRA in patients with CKD can overcome the paracrine and endocrine functions of this vitamin remains unknown. To demonstrate the putative benefits of native vitamin D and VDRA among patients with CKD, randomized, controlled trials are needed.
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PMID:Vitamin D, proteinuria, diabetic nephropathy, and progression of CKD. 1947 99

1. Accumulating evidence suggests that vitamin D and its analogues are renoprotective. However, the precise mechanisms and the molecular targets by which active vitamin D exerts its beneficial effects remain obscure. The objective of the present study was to evaluate the effect of active vitamin D on rats with puromycin aminonucleoside (PAN) nephropathy, a model that is characterized by predominant podocyte injury. 2. The PAN nephropathy rats were created by a single intravenous injection of 100 mg/kg PAN. Changes in renal pathology and podocyte numbers were observed. Real-time polymerase chain reaction (PCR) was performed to examine mRNA expression of nephrin, transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-7. Protein expression of nephrin, TGF-beta1, BMP-7 and p-Smad2/3 and p-Smad1/5/8 was examined by immunofluorescence, immunohistochemistry and western blotting, respectively. Rats were treated with 1,25(OH)(2)D(3) by gastric gavage at a dose of 2.5 microg/kg per day, starting 2 days before PAN injection and continuing throughout the experiment. 3. A single injection of PAN induced massive proteinuria and elevated serum creatinine on Day 7, both of which were significantly suppressed by 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Immunofluorescence and real-time PCR of the podocyte-associated protein nephrin revealed reduced and discontinuous staining and this change was reversed by 1,25(OH)(2)D(3). In PAN nephropathy rats, TGF-beta1 and p-Smad2/3 expression was upregulated, whereas that of BMP-7 and p-Smad1/5/8 was downregulated. Treatment with 1,25(OH)(2)D(3) significantly restored BMP-7/Smad signalling while suppressing TGF-beta1/Smad signalling. 4. In conclusion, 1,25(OH)(2)D(3) can ameliorate podocyte damage and proteinuria induced by PAN. The beneficial effects of 1,25(OH)(2)D(3) on podocytes may be attributable, in part, to direct modulation of TGF-beta1/BMP-7 signalling.
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PMID:Podocyte injury is suppressed by 1,25-dihydroxyvitamin D via modulation of transforming growth factor-beta 1/bone morphogenetic protein-7 signalling in puromycin aminonucleoside nephropathy rats. 1959 54

Vitamin D has proven to be much more than a simple "calcium hormone." The fact that the vitamin D receptor has been found in cells not related to mineral metabolism supports that statement. The interest of nephrologists in vitamin D and its effects beyond mineral metabolism has increased over the last few years, evidencing the importance of this so-called "sunshine hormone." In the present review, we highlight the most recent developments in the traditional use of vitamin D in chronic kidney disease (CKD) patients, namely, the control of secondary hyperparathyroidism (sHPT). Furthermore, we also explore the data available regarding the new possible therapeutic uses of vitamin D for the treatment of other complications present in CKD patients, such as vascular calcification, left ventricular hypertrophy, or proteinuria. Finally, some still scarce but very promising data regarding a possible role of vitamin D in kidney transplant patients also are reviewed. The available data point to a potential beneficial effect of vitamin D in CKD patients beyond the control of mineral metabolism.
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PMID:A new role for vitamin D receptor activation in chronic kidney disease. 1962 76

Several epidemiologic and clinical studies have suggested that there is a strong association between hypovitaminosis D and cardiovascular disease (CVD). Hypovitaminosis D was reported as a risk factor for increased cardiovascular events among 1739 adult participants in the Framingham Offspring Study. Analysis of more than 13,000 adults in the Third National Health and Nutrition Examination Survey (NHANES III) showed that even though hypovitaminosis D is associated with an increased prevalence of CVD risk factors, its association with all-cause mortality is independent of these risk factors. Importantly, epidemiologic studies suggested that patients who had chronic kidney disease and were treated with activated vitamin D had a survival advantage when compared with those who did not receive treatment with these agents. Mechanistically, emerging data have linked vitamin D administration with improved cardiac function and reduced proteinuria, and hypovitaminosis D is associated with obesity, insulin resistance, and systemic inflammation. Preliminary studies suggested that activated vitamin D inhibits the proliferation of cardiomyoblasts by promoting cell-cycle arrest and enhances the formation of cardiomyotubes without inducing apoptosis. Activated vitamin D has also been shown to attenuate left ventricular dysfunction in animal models and humans. In summary, emerging studies suggest that hypovitaminosis D has emerged as an independent risk factor for all-cause and cardiovascular mortality, reinforcing its importance as a public health problem. There is a need to advance our understanding of the biologic pathways through which vitamin D affects cardiovascular health and to conduct prospective clinical interventions to define precisely the cardioprotective effects of nutritional vitamin D repletion.
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PMID:Vitamin D and the cardiovascular system. 1969 20

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