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)

In a double-blind, randomized trial with 26 male white patients with essential hypertension in World Health Organization Stages I and II, we examined the impact of calcium entry blockade (5 to 10 mg/day isradipine, N = 14) and beta-blockade (100 to 200 mg/day metoprolol, N = 12) on early markers of hypertensive nephropathy before and after 7 weeks' treatment. Excretion of total protein, albumin, alpha 1-microglobuline, and N-acetyl-beta-glucosaminidase (NAG) were measured in the 24-h urine by radial immunodiffusion and fluorimetric method, respectively. Before therapy, 8 of 26 patients had microproteinuria (31%), six had microalbuminuria (22%), six had elevated urinary NAG activity (22%), and three had elevated alpha 1-microglobulin excretion (11%). In these subjects anti-hypertensive therapy led to a fall in proteinuria (296 +/- 56 v 127 +/- 116 mg/day, P less than .01), albuminuria (44 +/- 24 v 25 +/- 12 mg/day, P less than .05), and NAG excretion (45 +/- 22 v 28 +/- 5, P less than .05). The higher the pretreatment value, the greater the fall was in proteinuria (r = +0.55, P less than .01), albuminuria (r = 0.80, P less than .001), and NAG excretion (r = 0.60, P less than .01). We did not observe any significant difference in clinical characteristics, blood pressure, or urinary excretion of protein, albumin, or NAG between the two treatment groups, either before or after therapy. Thus, antihypertensive therapy reduced excretion of total protein, albumin, and NAG activity in hypertensive patients with elevated pretreatment values, potentially indicating reversal of early hypertensive nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impact of antihypertensive therapy with isradipine and metoprolol on early markers of hypertensive nephropathy. 153 71

Heavy proteinuria in patients with essential hypertension raises the question of underlying primary renal disease. While malignant hypertension may be associated with proteinuria in the nephrotic range, it is generally held that protein excretion in benign nephrosclerosis is almost invariably less than 0.5-1.0 g/24 h. We report 18 patients with biopsy-proven hypertensive nephropathy and heavy proteinuria, of which only 6 had malignant hypertension. In the remaining 12 patients with benign nephrosclerosis, protein excretion reached up to 6.5 g/24 h, and nephrotic range proteinuria was present in 3 patients. All patients with heavy proteinuria suffered from long-standing moderate or severe, poorly controlled hypertension and were azotemic. We suggest that hypertensive nephrosclerosis be included in the differential diagnosis of massive proteinuria accompanying azotemia in poorly controlled hypertensives.
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PMID:Marked proteinuria in hypertensive nephrosclerosis. 316 Feb 40

It had been previously thought that protein excretion in hypertensive nephrosclerosis was less than 0.5 to 1.0 g/24 h. Furthermore, it was believed that proteinuria in the nephrotic range associated with hypertension was probably due to primary renal disease, malignant hypertension, renal artery stenosis, or pheochromocytoma. We report eight patients with biopsy-proven hypertensive nephropathy and heavy proteinuria in the absence of malignant hypertension or renal artery stenosis. The 24-hour protein excretion ranged from 2.7 to 4.3 g. All patients had renal insufficiency, with serum creatinine ranging from 2.0 (176.8) to 7.8 mg/dL (689.5 mumol/L). Renal function worsened in most patients during the follow-up period despite adequate control of the hypertension, and three patients had to be started on hemodialysis. Three patients died during the follow-up period. We conclude that hypertensive nephrosclerosis must be included in the differential diagnosis of marked proteinuria in patients with essential hypertension and that heavy proteinuria, along with renal insufficiency, are poor prognostic indicators in such patients.
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PMID:Proteinuria in hypertension. 368 33

Although hypertension accounts for approximately 15-20% of end-stage renal disease and renal impairment occurs in 15% of patients with essential hypertension, there are few data available on the clinical features of patients with benign hypertensive nephrosclerosis, the histological consequence of hypertension on the kidney. To determine its prevalence on renal biopsy and its clinical features (including proteinuria and renal function), we used the U.K. MRC Glomerulonephritis Registry of 7339 biopsies from 20 centres to define all patients with benign hypertensive nephrosclerosis. In patients with no co-existing disease, 185 biopsies were classified solely as benign hypertensive nephrosclerosis (2.5%). Sixty-nine percent of patients were male and 72% aged over 50 years. Sixty-four percent had diastolic blood pressure above 90 mmHg and severe hypertension (diastolic > 120 mmHg) was present in 9%. Protein excretion of > 1.5 g/day was noted in 40%, with 22% excreting > 3 g/day. Eighteen percent had serum albumin values under 30 g/l. Eighty-one percent had serum creatinine > 120 mumol/l; in 51% this was > 250 mumol/l. There was significant correlation between serum creatinine and systolic blood pressure at time of biopsy (p = 0.01) and between serum creatinine and serum albumin (p = 0.001). Benign hypertensive nephrosclerosis accounts for 2.5% of all registered biopsies. Significant proteinuria is a common finding and proteinuria within the nephrotic range does occur. Systolic blood pressure appears to influence serum creatinine levels. Hypertensive nephropathy should be considered in all patients with heavy proteinuria and renal impairment.
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PMID:Clinical features of benign hypertensive nephrosclerosis at time of renal biopsy. 832 42

A detailed morphometric analysis of glomerular basement membrane (GBM) thickness was carried out on biopsies from 16 patients exhibiting normal histology and unremarkable immunofluorescence. Eleven of these patients presented with proteinuria, 8 in the nephrotic syndrome range, while 5 had hematuria as well. The remaining 5 patients presented with hematuria only. Eight patients had an initial diagnosis of minimal change disease, 4 were diagnosed as thin-membrane nephropathy, 2 had Alport syndrome, and the remaining 2 had hypertensive nephropathy. Quantitative morphometric analysis of GBM identified 3 subsets of patients. The first subset consisted of 6 patients: 5 adults, with an average GBM width of 361 +/- 34 nm, and 1 child. The second subset included 8 patients with thin GBMs and a mean thickness of 253 +/- 15 nm. The last subset comprised 2 patients with Alport syndrome showing marked variability in GBM thickness. This study has confirmed the presence of thin GBMs in hematurics, but has also revealed GBM thinning in 50% of patients with a diagnosis of minimal change disease.
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PMID:Thin glomerular basement membranes in patients with hematuria and minimal change disease. 1044 81

Tight blood pressure control among diabetic and nondiabetic patients with hypertension is perhaps the single most effective intervention used to delay progression to end-stage renal disease (ESRD). The renoprotective actions of angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic and hypertensive nephropathy is well established. Drugs of this class fairly uniformly reduce glomerulosclerosis, delay the deterioration in renal function, and improve proteinuria, a predictive surrogate marker for renal injury. Calcium- channel blockers (CCBs) in the phenylalkylamine (verapamil) and benzothiazepine (diltiazem) classes also improve proteinuria and delay the progression of renal disease in diabetic and nondiabetic hypertensive nephropathy beyond that attributable to blood pressure control. The short-acting dihydropyridine CCBs worsen proteinuria and accelerate renal injury in both animal models and humans with hypertension or diabetes. A very limited number of studies in animals or humans with hypertension or diabetes have demonstrated at least an additive renoprotective effect when the combination of ACE inhibitors and nondihydropyridine CCBs has been compared with each agent administered as monotherapy. Because patients with impaired renal function and either hypertension or diabetes appear to benefit from aggressive blood pressure reduction, many of these patients will require two or more drugs to achieve the currently recommended blood pressure goals. Combinations of ACE inhibitor and CCB are attractive because they may provide better blood pressure control, appear to be better tolerated with fewer side effects than either drug alone, and may exert a greater renoprotective effect in patients at risk for renal failure than either an ACE inhibitor or a CCB.
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PMID:The case for combining angiotensin-converting enzyme inhibitors and calcium-channel blockers. 1098 Nov 4

Hypertensive nephropathy (HN) and focal segmental glomerulosclerosis (FSGS) are significant causes of end-stage renal disease (ESRD), but no genes or loci have been associated with this phenotype among African Americans, a group at high risk. We performed a genomewide linkage scan with approximately 400 microsatellite markers on 23 individuals of a large four-generation African American family with 18 affected individuals (7 with ESRD), in which the 13-year-old proband (also with ESRD) presented with hypertension and proteinuria (2-4 g/day) and underwent a kidney biopsy that revealed FSGS-like lesions with arteriolar thickening. A genomewide scan revealed LOD scores of >2.5 for markers on chromosomes 3 and 9, and fine mapping was performed on 5 additional members (total 28 members) that showed a maximum multipoint LOD score of 5.4 in the 9q31-q32 region, under an autosomal dominant model with 99% penetrance. This 8-cM (6-Mb) region is flanked by markers D9S172 and D9S105, and further candidate gene sequencing studies excluded the coding regions of three genes (ACTL7A, ACTL7B, and CTNNAL1). To our knowledge, this is the first report of a locus, denoted as "HNP1," for the HN/FSGS phenotype in a large African American family with dominantly inherited nephropathy characterized by ESRD, hypertension, and some features of FSGS.
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PMID:African American hypertensive nephropathy maps to a new locus on chromosome 9q31-q32. 1284 Jul 82

Transforming growth factor (TGF)-beta1 has been shown to play a critical role in hypertensive nephropathy. We hypothesized that blocking TGF-beta1 signaling could attenuate renal fibrosis in a rat model of remnant kidney disease. Groups of six rats were subjected to 5/6 nephrectomy and received renal arterial injection of a doxycycline-regulated Smad7 gene or control empty vector using an ultrasound-microbubble-mediated system. Smad7 transgene expression within the kidney was tightly controlled by the addition of doxycycline in the daily drinking water. All animals were euthanized at week 4 for renal functional and histological examination. Hypertension of equivalent magnitude (190 to 200 mmHg) developed in both Smad7- and empty vector-treated rats. However, treatment with Smad7 substantially inhibited Smad2/3 activation and prevented progressive renal injury by inhibiting the rise of 24-hour proteinuria (P < 0.001) and serum creatinine (P < 0.001), preserving creatinine clearance (P < 0.05), and attenuating renal fibrosis and vascular sclerosis such as collagen I and III expression (P < 0.01) and myofibroblast accumulation (P < 0.001). In conclusion, TGF-beta/Smad signaling plays a critical role in renal fibrosis in a rat remnant kidney model. The ability of Smad7 to block Smad2/3 activation and attenuate renal and vascular sclerosis demonstrates that ultrasound-mediated Smad7 gene therapy may be a useful therapeutic strategy for the prevention of renal fibrosis in association with hypertension.
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PMID:Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks transforming growth factor-beta signaling and fibrosis in rat remnant kidney. 1574 88

Podocyte loss contributes to the development of glomerulosclerosis. Although podocyte detachment has been recognized as a new mechanism of podocyte loss in glomerular diseases, its time course and relationship to disease activity are not known. Urinary excretion of viable podocytes was quantified in two models of transient glomerular injury, i.e., rats with puromycin aminonucleoside-induced nephrosis (PAN) and mesangioproliferative nephropathy (anti-Thy 1.1 nephritis model), as well as in a model of continuous glomerular injury, i.e., hypertensive nephropathy (5/6-nephrectomy model), and in aging rats. The number of glomerular Wilm's tumor (WT)-1-positive podocytes and the glomerular expression of cell-cycle proteins in vivo were assessed. Urinary podocyte loss occurred in both primary (PAN) and secondary (anti-Thy 1.1 nephritis) in parallel to the onset of proteinuria. However, subsequently proteinuria persisted despite remission of podocyturia. In continuous glomerular injury, i.e., after 5/6-nephrectomy, podocyturia paralleled the course of proteinuria and of systemic hypertension, whereas no podocyturia became detectable during normal aging (up to 12 mo). Despite podocyte detachment of varying degrees, no decrease in glomerular podocyte counts (i.e., WT-1 positive nuclei) was noted in either disease model. Podocyturia in the PAN and anti-Thy 1.1 nephritis model was preceded by entry of glomerular podocytes into the cell cycle, i.e., cyclin D1, cdc2, and/or proliferating cell nuclear antigen (PCNA) expression. Podocyturia is a widespread phenomenon in glomerular disease and not simply a reflection of proteinuria because it is limited to phases of ongoing glomerular injury. The data suggest that podocyturia may become a more sensitive means to assess the activity of glomerular damage than proteinuria.
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PMID:Urinary podocyte loss is a more specific marker of ongoing glomerular damage than proteinuria. 1582 8

To evaluate the patterns of glomerular disease in our center, we reviewed and categorized a series of 520 kidney biopsies performed for proteinuric patients between June 1994 and June 2001. There were 445 (85.5%) biopsies labeled as primary glomerular disease, 55 (10.5%) as secondary glomerular disease and 20 (4%) as miscellaneous. The primary glomerular disease included 117 (26.3%) cases of focal segmental glomerulo-sclerosis, 100 (22.5%) of mesangial proliferative glomerulonephritis (GN), 76 (17.1%) of minimal change disease, 72 (16.2%) of membranoproliferative GN, 65 (14.5%) of membranous GN, and 15 (3.4%) of rapidly progressive GN. The secondary glomerular diseases included 25 (45.5%) cases of lupus nephritis, 15 (27.3%) of amyloidosis, eight (14.5%) of diabetic nephropathy, six (10.9%) of hereditary nephritis, and one (1.8%) hypertensive nephropathy. Because immunofluorescence was not used, we could not label any biopsy as IgA nephropathy. In conclusion, our study suggests that the patterns of histopathology found in the biopsies of the patients with proteinuria may reflect the patterns in Iraq and may not be different from those in the other Arab countries, especially those in the Middle East.
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PMID:Spectrum of glomerular disease in iraqi patients from a single center. 1766 Jun 78


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