UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
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The spontaneously hypertensive fawn-hooded rat (FHH) develops accelerated albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by moderate systemic hypertension, a relatively low afferent to efferent arteriolar resistance ratio, and glomerular hypertension. The FHH study presented here was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in ameliorating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (PGC) Untreated rats developed hypertension and high PGC, and all (N = 22) except one died of ESRD within the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i prevented development of systemic and glomerular hypertension, and it largely prevented proteinuria and FGS; all rats survived throughout the follow-up period. Rats treated with late-onset (22 wk) ACE-i were hypertensive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and PGC but could not fully prevent some hypertension, albuminuria, and FGS at the later stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blood pressure and development of FGS during therapy, but after withdrawal of ACE-i, systemic and glomerular hypertension developed as in untreated animals. This regimen postponed but did not control FGS development and early mortality. The results of this study indicate that: (1) early-onset ACE-i very effectively protects against development of renal damage in the FHH; (2) this protection is associated with normalization of the elevated glomerular capillary pressure; (3) ACE-i cannot completely prevent further development of previously established FGS, despite lowering glomerular capillary pressure; (4) early-temporary ACE-i has no long-term controlling effect on arterial and glomerular pressure, and it cannot control development of FGS.
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PMID:Angiotensin-converting enzyme inhibition in the prevention and treatment of chronic renal damage in the hypertensive fawn-hooded rat. 904 44

The efficacy of an early and late treatment with the angiotensin converting enzyme inhibitor lisinopril or the angiotensin II receptor blocker ICI D8731 was investigated in uninephrectomized spontaneously hypertensive rats (SHR). Rats that underwent uninephrectomy (UNX) at six weeks of age were randomly assigned to receive no treatment, lisinopril shortly after UNX, lisinopril starting 16 weeks after UNX, ICI D8731 shortly after UNX, and ICI D8731 starting 16 weeks after UNX. Blood pressure was normalized with both treatments. After six months inulin clearance was not significant different, while proteinuria and prevalence of interstitial fibrosis were significantly reduced in all treatment groups. Immunohistochemical studies revealed an interstitial, periglomerular and perivascular increase of extracellular matrix proteins in all rats, but a markedly reduced expression of collagen I, IV and fibronectin after early and late treatment compared to untreated controls. We found a significant reduction of infiltrating macrophages and T-lymphocytes in all treated animals compared to untreated controls after 2, 4 and 6 months. Especially early treatment was associated with lower numbers of infiltrating cells. Both treatments reduced proliferation of tubular and interstitial cells. There were no striking differences with regard to nephroprotection between the ACE inhibitor and angiotensin II receptor blocker. These findings show that both treatments have beneficial effects on kidney structure and function. They suggest that both ACE inhibition and angiotensin II blockade decrease renal cell proliferation and suppress the infiltration of mononuclear cells that may trigger expression of extracellular matrix proteins and progressive nephrosclerosis.
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PMID:Effects of early and late antihypertensive treatment on extracellular matrix proteins and mononuclear cells in uninephrectomized SHR. 906 7

A progressive decline in glomerular function occurs in diabetic nephropathy. The predictive effects of progression promoters were examined in 182 non-insulin-dependent diabetic patients from a baseline serum creatinine concentration of 133 mumol/l. During a total of 605 person-years follow-up, 107 patients developed end-stage renal failure requiring dialysis. The rate of decline of renal function was highly variable. Urinary protein excretion was the strongest predictor correlated to the rate of decline, followed by diastolic and systolic blood pressure, total cholesterol and platelet count, while the protective effects were seen in serum albumin and haematocrit. Adjustment for urinary protein excretion revealed that diastolic blood pressure, familial predisposition to hypertension, serum albumin, and smoking were independent significant predictors. Angiotensin converting enzyme inhibitors (ACE-I) significantly retarded the development of end-stage renal failure compared to antihypertensives other than ACE-I (mostly nifedipine), and the effect was evident particularly in patients with proteinuria below the median (2.5 g/24 h) (presumably those who responded to ACE-I). A complex effect of proteinuria in association with blood pressure elevation, familial predisposition to hypertension, hypoalbuminaemia, and smoking may play an important role in the progression of nephropathy.
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PMID:Predictors of the progression of diabetic nephropathy and the beneficial effect of angiotensin-converting enzyme inhibitors in NIDDM patients. 911 17

Multiple risk factors are important predictors in the development of diabetic nephropathy (DN). Once DN has developed, it progresses steadily to renal failure. To determine the rate of renal function decline and the parameters that influence the rate of decline, we retrospectively reviewed the charts of patients with DN who had undergone dialysis or kidney transplantation at the Mayo Clinic from 1983 to 1993. Forty patients were found to have two or more iothalamate clearance (IothmCl) measurements where a slope of renal function decline over time, expressed as mL/ min/month/1.73 m2, can be calculated. The parameters examined included age of onset and duration of diabetes (DM); age at initial presentation, insulin dosage, glycosylated hemoglobin level, proteinuria, blood pressure (BP), number of antihypertensive medications (HTM), use of ACE inhibitors, creatinine, and initial IothmCl. The mean overall decline of clearance was 1.36 +/- 1.1 mL/min/month, corrected. Univariate regression analysis showed that only systolic and mean BP (p < 0.05), use of HTM (p = 0.02), and the number of HTM used (p = 0.0001) correlated with the rate of clearance decline. No other parameter was significant. The decline of IothmCl was 0.72 +/- 0.41, 1.20 +/- 0.9, and 2.34 +/- 1.38 mL/min/month, for patients taking no HTM, < 3 HTM, and > or = 3HTM, respectively. Of the eight patients on HTM who presented with initial IothmCl of < 30 mL/min/1.73 m2, seven (88%) had clearance of < 10 mL/min/1.73 m2 within 1 yr. We conclude that hypertension is an important marker of DN progression, and that the more HTM required for control of BP, the faster the decline of renal function. We recommend that a suitable transplant candidate with DN who presents with hypertension requiring HTM and a clearance of < 30 mL/min should be placed on the transplant waiting list.
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PMID:Predictors of progression of diabetic nephropathy: implication for timing of kidney transplantation. 926 25

The number of patients with non-insulin-dependent-diabetes mellitus (NIDDM) is dramatically increasing in Japan and estimated to be 6 million, more than one of ten adults. It is well known that more than a half of diabetics are hypertensive. Therefore, it is very important to treat hypertension to reduce cardiovascular events as well as end-stage renal disease. At first, life style modification such as body weight reduction, exercise and restriction of salt and alcohol intake will be recommended. Improved glycemic control by such a non-pharmacological therapy will lower blood pressure. Recent studies demonstrated that hypoglycemic agents improving insulin resistance such as metformin and troglitazone reduce blood pressure. If these maneuvers do not lower blood pressure, hypotensive medication will be necessary. As a first line therapy, ACE inhibitor, alpha 1-blocker or Ca-channel blocker will be selected. In diabetics with proteinuria or micro-albuminuria, ACE inhibitors will be effective to delay the progression of diabetic nephropathy.
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PMID:[Treatment of hypertension associated with diabetes mellitus]. 928 29

During the development to overt nephropathy, diabetic patients go through several characteristic stages of renal disease, moving from normo- to micro- to macroalbuminuria. Microalbuminuria is defined as a urinary albumin excretion between 20 and 200 microg/min; values <20 microg/min are designated as normoalbuminuria, and values >200 microg/min are designated as macroalbuminuria. Only with macroalbuminuria does the glomerular filtration rate (GFR) fall consistently. The decisive intermediary endpoints are postponement or prevention of micro/macroalbuminuria and reduction or prevention of the fall in GFR (stronger endpoint), with postponement of end-stage renal disease as a final endpoint. Good metabolic control can prevent or postpone the development of microalbuminuria, the earliest sign of diabetic renal disease. The ideal realistic therapeutic window may be an HbA1c value between 7 and 8.5% (mean reference value 5.5%). Thus, efforts should aimed at implementing the best possible control before the onset of microalbuminuria, with the other important aim of minimizing hypoglycemic side effects. In patients with microalbuminuria, blood pressure gradually increases, and early antihypertensive treatment becomes crucial. Good glycemic control (with the same glycemic goal as above) may be difficult to achieve in some of these patients, but it is still important. With overt nephropathy, defined as clinical proteinuria, a relentless decline in GFR is inflicted, unless patients are carefully treated with antihypertensive agents, often in combination therapy. Good metabolic control is still strongly warranted because patients with high HbA1c progress much more rapidly. The natural history of the rate of fall in GFR may be reduced from 12 to 3 ml x min(-1) x year(-1), but genetic factors may be involved; the ACE-genotype DD seems to progress more rapidly during treatment. Protein restriction is also of some interest. Early screening is recommended in all guidelines, with emphasis on testing for albuminuria, including microalbuminuria, along with careful control of glycemia and blood pressure.
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PMID:How to protect the kidney in diabetic patients: with special reference to IDDM. 928 10

The greatest change in GFR in response to treatment with cyclosporin occurs in the first 3-6 months and the magnitude of the decrement in the first year (or perhaps the first few months) appears to be a vital indicator of future problems. However, the apparent stabilization of renal function, particularly when monitored only by plasma creatinine, can conceal progressive tubulointerstitial injury, and increasing proteinuria is an ominous sign. Although lower doses of cyclosporin and careful monitoring of renal function may be helpful, there is at present no pharmacological intervention to protect or reverse the reduction in GFR that occurs. We believe that the vascular lesion induced by cyclosporin is fundamental, with early and initially reversible cyclosporin-induced vasospasm leading to progressive vascular damage with activation of endothelial cells and increased platelet interactions. Amongst other determinants, the renal response to this vasculopathy will depend on the balance between the presence of vasoactive factors with the vasoconstrictors promoting interstitial fibrosis and the vasodilators inhibiting proliferation. It is likely that the kidneys of heart-transplant recipients are chronically ischaemic and as a consequence their renin-angiotensin systems massively activated, which may further sensitize their kidneys to cyclosporin. Overproduction of angiotensin II, associated with the DD ACE genotype, has already been associated with poor prognosis in diabetic and IgA nephropathy. It is interesting to speculate that this ACE genotype, which is associated with a poor outcome in non-ischaemic heart disease can influence renal sensitivity to cyclosporin and predict the development of morphological injury. Extension of these experimental findings into the clinical arena with a placebo-controlled trial of early introduction of ACE inhibitor therapy in recipients of cardiac transplants would be timely.
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PMID:Cyclosporin nephrotoxicity following cardiac transplantation. 935 Oct 63

Little attention has been paid to nephropathies and proteinuria in renovascular hypertension (RVH). Recently there has been a growing interest in the conditions induced by RVH. 10 cases of RVH were diagnosed by angiography and renin sampling from renal veins in the last 6 years in our hospital. The patients were all male and mean age was 64 +/- 8 (SD) years. Data were as follow: protein excretion was 3.8 +/- 2.2 g/day (> or = 3.5 g/day in 8 patients), sBP 202 +/- 24 mmHg, dBP 113 +/- 17 mmHg, serum renin concentration 64 +/- 45 pg/ml, and ipsilateral/contralateral renal vein renin ratio 3.3 +/- 1.0. RVH was treated by nephrectomy in 3 patients, percutaneous transluminal renal angioplasty (PTA) in 2, and angiotensin converting enzyme inhibitors (ACE-I) administration in 8. Biopsies were performed on contralateral kidney in 4 patients. Focal segmental glomerulosclerosis (FGS) was found in 3 patients, and nephrosclerosis in 1, whereas only nephrosclerosis was found in nephrectomized kidneys in all 3 patients. After nephrectomy, PTA and the treatment by ACE-I, not only blood pressure but also proteinuria was markedly reduced. These findings suggest that severe stenosis of the renal artery led to renal ischemia, which activated renin excretion, to cause glomerular hyperfiltration through vasoconstriction of the efferent arterioles in the contralateral kidney. FGS-like lesion thus induced appeared to have caused massive proteinuria.
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PMID:Renovascular hypertension may cause nephrotic range proteinuria and focal glomerulosclerosis in contralateral kidney. 935 55

Several trials clearly demonstrate the importance of correcting hypertension and proteinuria in slowing chronic renal insufficiency (CRI) progression. The relationship between hypertension and CRI is at least partly the consequence of impaired renal hemodynamics, mainly mediated by the renin-angiotensin system. Two classes of drugs have so far been shown to have an antiproteinuric and renoprotective effect, in addition to their antihypertensive action: ACE inhibitors and calcium-channel blockers (at least the non-dihydropyridines) which also interfere with the actions of angiotensin II. The same should be true for the newest angiotensin II receptor antagonists. To find conclusive evidence about the superior renoprotective effect of ACE inhibitors (or angiotensin II receptor antagonists) or calcium-channel blockers, we need well-designed, prospective, controlled and randomized long-term trials; the pharmacological rationale for combining the two classes of antihypertensive drugs is supported by the clinical need to reach a target blood pressure (120/80 mmHg) in CRI patients with proteinuria.
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PMID:Treatment of hypertension in chronic renal insufficiency. 937 31

Racial and ethnic minority populations are growing segments of our society. The prevalence of hypertension in these populations differs across groups, and control rates are not as good as in the general population. Clinicians should be aware of these management challenges, taking social and cultural factors into account. Guidelines are provided for management of children and women with hypertension. In older persons, diuretics are preferred and long-acting dihydropyridine calcium antagonists may be considered. Specific therapy for patients with LVH, coronary artery disease, and heart failure are outlined. Patients with renal insufficiency with greater than 1 g/d of proteinuria should be treated to a therapy blood pressure goal of 125/75 mm Hg; those with less proteinuria should be treated to a blood pressure goal of 130/85 mm Hg. ACE inhibitors have additional renoprotective effects over other antihypertensive agents. Patients with diabetes should be treated to a therapy blood pressure goal of below 130/85 mm Hg. Hypertension may coexist with various other conditions and may be induced by various pressor agents.
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PMID:The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. 1187 36

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