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

Hypertensive nephrosclerosis is a leading cause of end-stage renal disease; therefore, strategies to prevent the development of renal disease require close study. Here it is demonstrated that transient treatment of prepubescent rats with angiotensin inhibitors attenuated their susceptibility to the development of hypertensive nephrosclerosis after maturation. Stroke-prone spontaneously hypertensive Izumo strain rats were divided into four groups, treated with vehicle, the angiotensin-converting enzyme inhibitor (ACEI) delapril (40 mg/kg per d), the angiotensin receptor antagonist (AT1R-Ant) candesartan cilexetil (1 mg/kg per d), or the vasodilator hydralazine (25 mg/kg per d) from weaning to puberty (3 to 10 wk of age), and then monitored without treatment for 6 mo. BP in the ACEI- and AT1R-Ant-treated groups remained significantly decreased, compared with the untreated and hydralazine-treated groups. Moreover, marked proteinuria and nephrosclerosis developed in the untreated and hydralazine-treated groups at 30 wk but were suppressed in the ACEI- and AT1R-Ant-treated groups. Of interest, plasma renin activity, plasma angiotensin II concentrations, and renal renin mRNA levels were reduced by >50% in the ACEI- and AT1R-Ant-treated rats, suggesting that the treatments may have attenuated the development of nephrosclerosis by overcoming the susceptibility of stroke-prone spontaneously hypertensive rats to overactivation of the renin-angiotensin system.
 ...
PMID:Temporary treatment of prepubescent rats with angiotensin inhibitors suppresses the development of hypertensive nephrosclerosis. 1127 26

We compared the antihypertensive and renoprotective effects of the angiotensin II receptor antagonist losartan and the calcium channel blocker verapamil in the rat with chronic renal failure. One month after five-sixths nephrectomy, male WKY rats were treated for 2 months with either losartan or verapamil. Both resulted in a similar reduction in blood pressure: from 147.1 to 112 mm Hg in losartan-treated and from 155 to 118 mm Hg (p = NS) in verapamil-treated rats. Losartan improved the creatinine clearance (difference + 17.1% as compared with + 6.6% for verapamil, p = 0.039) and prevented the increase in proteinuria: 12.26 +/- (SE) 2.33 mg/day before and 18.48 +/- 2.19 mg/day (p = NS) after therapy in the losartan-treated and 17.27 +/- 2.73 mg/day before and 32.27 +/- 10.29 mg/day after therapy (p = 0.0484) in the verapamil-treated group. In addition, losartan resulted in minimal mesangial proliferation and significantly less glomerular sclerosis and thickening of the small arterial and arteriolar walls. The changes in interstitial fibrosis and tubular hypertrophy, however, were similar in both the verapamil- and losartan-treated groups. Treatment with losartan 1 month after five-sixths nephrectomy in male WKY rats resulted in reduced blood pressure, similar to that of the verapamil-treated group. However, despite similar antihypertensive properties, losartan improved creatinine clearance and reduced proteinuria. The losartan-treated group also had a marked reduction in mesangial proliferation and less glomerular sclerosis and less reduced vascular wall thickness in renal small arteries and arterioles. However, losartan did not totally eliminate nephrosclerosis. The tubular and interstitial changes were fewer in the losartan-treated group. Thus losartan has an additional, although only partial, renoprotective effect when compared with verapamil.
 ...
PMID:Renoprotective effect of angiotensin II receptor antagonists in experimental chronic renal failure. 1127 39

End-stage renal disease (ESRD) comprises an enormous public health burden, with an increasing incidence and prevalence. Hypertension is a major risk factor for progressive renal disease. This escalating prevalence suggests that newer therapeutic interventions and strategies are needed to complement current antihypertensive approaches. Although much evidence demonstrates that angiotensin II mediates progressive renal disease, recent evidence also implicates aldosterone as an important pathogenetic factor in progressive renal disease. Several lines of experimental evidence demonstrate that selective blockade of aldosterone, independent of renin-angiotensin blockade, reduces proteinuria and nephrosclerosis in the spontaneously hypertensive stroke-prone rat model and reduces proteinuria and glomerulosclerosis in the subtotally nephrectomized rat model (i.e. remnant kidney). Whereas pharmacological blockade with angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors reduces proteinuria and nephrosclerosis/ glomerulosclerosis, selective reinfusion of aldosterone restores these abnormalities despite continued renin-angiotensin blockade. Aldosterone may promote fibrosis by several mechanisms, including plasminogen activator inhibitor-1 expression and consequent alterations of vascular fibrinolysis, by stimulation of transforming growth factor-beta 1, and by stimulation of reactive oxygen species. Based on this theoretical construct, randomized clinical studies will be initiated to delineate the potential renal-protective effects of antihypertensive therapy utilizing aldosterone receptor blockade.
 ...
PMID:Aldosterone and the hypertensive kidney: its emerging role as a mediator of progressive renal dysfunction: a paradigm shift. 1139 64

Epidemiological surveys have suggested that intrauterine growth retardation is a risk factor for the development of hypertension in later life. A rat model of intrauterine growth retardation, induced by maternal low-protein diet during the second half of pregnancy, was used to study the relationship between birth weight and adult hypertension. The offspring were born at term and were allowed to nurse normally until weaned to standard chow at 4 weeks of age. They had 15% lower birth weights than control offspring, with complete catch-up growth by age 4 weeks. Both females and males developed progressively worsening hypertension beginning at 8 weeks. The 11-month survival rate was 69% versus 100% in control animals. During the early stages of the hypertension, plasma creatinine was normal, plasma sodium concentration was slightly higher than that of control animals, plasma renin activity was suppressed, and the males had mild proteinuria. Renal function remained normal throughout the 11-month observation period, but plasma renin activity gradually rose above control values. Angiotensin-converting enzyme inhibition by enalapril, begun at 8 weeks of age, was effective in completely normalizing the blood pressure, but did not totally prevent the extra mortality. Sprague-Dawley and Wistar rat strains developed equally severe hypertension after maternal protein deprivation, despite their different susceptibilities to nephrosclerosis with aging. In conclusion, maternal low-protein diet resulted in low birth weight and adult hypertension in the rat. Primary sodium retention and expanded extracellular volume may be critical factors during the development of the hypertension.
 ...
PMID:Low birth weight-associated adult hypertension in the rat. 1140 16

In the present work, 199 patients with leprosy who underwent autopsy between 1970 and 1986 were retrospectively studied to determine the prevalence, types, clinical characteristics, and etiologic factors of renal lesions (RLs) in leprosy. Patients were divided into two groups: 144 patients with RLs (RL+) and 55 patients without RLs (RL-). RLs observed in 72% of the autopsied patients were amyloidosis (AMY) in 61 patients (31%), glomerulonephritis (GN) in 29 patients (14%), nephrosclerosis (NPS) in 22 patients (11%), tubulointerstitial nephritis (TIN) in 18 patients (9%), granuloma in 2 patients (1%), and other lesions in 12 patients (6%). AMY occurred most frequently in patients with lepromatous leprosy (36%; nonlepromatous leprosy, 5%; P < 0.01), recurrent erythema nodosum leprosum (33%; P < 0.02), and trophic ulcers (27%; 0.05 < P < 0.10). Ninety-seven percent of AMY was found in patients with lepromatous leprosy, 88% showed recurrent trophic ulcers, and 76% presented with erythema nodosum leprosum. NPS was found in older patients with arterial hypertension, neoplastic diseases, infectious diseases, and vasculitis associated with GN. Most patients with AMY presented with proteinuria (95%) and renal failure (88%). The most frequent causes of death were renal failure in patients with AMY (57%), infectious diseases in patients with GN (41%) and TIN (45%), and cardiovascular diseases in patients with NPS (41%). No difference in survival rates was observed among RL- patients and those with AMY, GN, NPS, or TIN.
 ...
PMID:Renal lesions in leprosy: a retrospective study of 199 autopsies. 1143 Nov 77

In September, 2000, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health called an early halt to the amlodipine arm of the African American Study of Kidney Disease and Hypertension (AASK) trial after careful deliberation by an independent data and safety monitoring board. An interim analysis of the AASK at 3 years revealed a renoprotective effect of the angiotensin-converting enzyme inhibitor ramipril as compared to the dihydropyridine calcium channel blocker (DHP-CCB) amlodipine in patients with mild to moderate renal insufficiency. This differential effect was independent of the blood pressure (BP) levels reached and was evident in proteinuric patients and suggestive in patients with baseline proteinuria < 300 mg/d, but was not conclusive. The AASK trial data suggest that DHP-CCBs should be used cautiously in the presence of mild to moderate renal insufficiency. Judgment should be reserved for the use of other CCBs, such as verapamil or diltiazem, since these are fundamentally different CCBs with the potential for a different impact on hypertensive nephrosclerosis. The blinded observation period for AASK will be completed at the end of September, 2001, at which time additional, clinically useful information is expected to become available. (c)2001 Le Jacq Communications, Inc.
 ...
PMID:The African American Study of Kidney Disease and Hypertension (AASK): new findings. 1149 55

End-stage renal disease (ESRD) comprises an enormous public health burden, with an incidence and prevalence that are increasingly on the rise. This escalating prevalence suggests that newer therapeutic interventions and strategies are needed to complement current therapeutic approaches. Although much evidence demonstrates conclusively that angiotensin II mediates progressive renal disease, recent evidence also implicates aldosterone as an important pathogenetic factor in progressive renal disease. Recently, several lines of experimental evidence demonstrate that selective blockade of aldosterone, independent of renin-angiotensin blockade, reduces proteinuria and nephrosclerosis in the spontaneously hypertensive stroke-prone rat (SHRSP) model and reduces proteinuria and glomerulosclerosis in the subtotally nephrectomized rat model (ie, remnant kidney). Whereas pharmacologic blockade with angiotensin II receptor blockers and angiotensin-converting enzyme (ACE) inhibitors reduces proteinuria and nephrosclerosis/glomerulosclerosis, selective reinfusion of aldosterone restores these abnormalities despite continued renin-angiotensin blockade. Aldosterone may promote fibrosis by several mechanisms, including plasminogen activator inhibitor-1 (PAI-1) expression and consequent alterations of vascular ribrinolysis, by stimulation of transforming growth factor-beta1 (TGF-beta1), and by stimulation of reactive oxygen species (ROS). Based on this formulation, randomized clinical studies will be initiated to delineate the potential renal-protective effects of aldosterone receptor blockade.
 ...
PMID:Aldosterone as a mediator of progressive renal dysfunction: evolving perspectives. 1150 95

Nephrosclerosis constitutes a major cause of end-stage renal disease. Independently of blood pressure control, ACE inhibitors (ACEIs) are considered to be more nephroprotective than other antihypertensive agents. We have reviewed the long-term evolution of renal function in our series of essential hypertensive patients diagnosed as having nephrosclerosis when first seen in our unit. The analysis was performed depending on whether or not their antihypertensive therapy contained an ACEI alone or in combination for the whole follow-up. The end point was defined as the confirmation of a 50% reduction in creatinine clearance or entry in a dialysis program. A historical cohort of 295 patients was included in the analysis. Mean follow-up was 7.4+/-3.9 years. Diabetes prevalence was higher in ACEI-treated patients (25.7% versus 7.1%, P=0.000), but the diagnosis of diabetic nephropathy could not be confirmed on clinical grounds, including renal biopsy. Twenty-three out of 183 (12.6%) patients in the ACEI group and 23 out of 112 (20.5%) patients in the non-ACEI group experienced a renal event (P=0.0104 by log rank test). Similar results were observed when only nondiabetic patients were considered for the analysis. Cox regression analysis showed that baseline serum creatinine, absence of ACEI administration, mean proteinuria during follow-up, and age were independent predictors for the development of a renal event. In hypertensive nephrosclerosis, therapy containing an ACEI alone or in combination significantly reduces the incidence of renal events. This effect is independent of blood pressure control.
 ...
PMID:ACE inhibitors and appearance of renal events in hypertensive nephrosclerosis. 1156 48

Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known. Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies. Thirteen biopsy specimens with nonlupus nephritides were identified in 13 patients, who belonged to 3 clinically distinct groups. Group I included 6 patients in whom SLE was diagnosed at the time of index biopsies. The index biopsies in these patients showed focal segmental glomerusclerosis (FSGS; 3 cases), Immunoglobulin (Ig) M nephropathy (1 case), and thin basement membrane disease (1 case). The diagnostic features for FSGS included segmental sclerosis involving at least 1 glomerulus, absence of lupus nephritis or other conditions that may cause nonspecific segmental sclerosis of glomeruli such as ischemia or nephrosclerosis, and nephrotic-range proteinuria. There was uniform, global, diffuse and marked thinning of the glomerular basement membrane in the case of thin basement membrane disease. Group II included 3 patients in whom SLE was diagnosed 2 to 9 years before the time of index biopsies and SLE was active at the time of biopsy. The index biopsies in these patients showed FSGS (2 cases) and hypertensive nephrosclerosis (1 case). Group III included 4 patients in whom SLE was diagnosed 5 to 36 years before the time of index biopsies and SLE was inactive at the time of biopsy. The index biopsies in these patients showed 1 case each of amyloidosis, FSGS, hypertensive nephrosclerosis, and allergic acute tubulointerstitial nephritis. Previous renal biopsies, performed in 5 patients, showed IgM nephropathy (1 case), diffuse proliferative lupus GN (1 case), focal proliferative lupus GN (1 case), and mesangial proliferative lupus GN (2 cases). Follow-up biopsies, performed in 3 patients, confirmed the diagnosis of FSGS (2 cases) and hypertensive nephrosclerosis (1 case) noted in the index biopsies. Nonlupus nephritides may occasionally be encountered in SLE patients, regardless of clinical or serologic disease activity. These renal lesions display a broad morphologic spectrum in which FSGS seems most frequent. Renal biopsy plays a crucial role in identifying these lesions, which may have prognostic and therapeutic implications distinct from those of lupus nephritis.
 ...
PMID:Nonlupus nephritides in patients with systemic lupus erythematosus: a comprehensive clinicopathologic study and review of the literature. 1167 48

Four apolipoprotein (apo) E variants have been reported to be associated with lipoprotein glomerulopathy (LPG), which is characterized by type III hyperlipoproteinemia (type III HLP) and proteinuria and frequently leads to nephrotic syndrome. We report the histologic findings in the kidneys of a type III HLP patient with an apo E variant, apo E Toranomon, in which the glutamine at residue 187 in apo E is substituted by glutamic acid (Q187E). The patient also had type 2 diabetes mellitus. No evidence of lipoprotein thrombi suggestive of LPG was detected, however, and the histologic diagnosis was diabetic nephrosclerosis. This unique case illustrates that not all apo E variants result in LPG, and the location of mutations in the apo E protein is one of the important determinants for the development of LPG.
 ...
PMID:A patient with apolipoprotein E2 variant (Q187E) without lipoprotein glomerulopathy. 1187 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>