UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
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Interruption of the renin-angiotensin-aldosterone system (RAAS) at different levels is target-organ protective in several disease states; however, complete blockade is unlikely to be achieved due to escape mechanisms whenever blockade is attempted, incomplete knowledge of the role of all elements of the RAAS, and lack of pharmacotherapy against some elements that have been shown to contribute to disease states. Aldosterone has been overlooked as a mediator of RAAS escape and a key factor in target-organ injury despite the use of available RAAS blockers. Aldosterone is thought to play a role in the development of hypertension, alteration in vascular structure, vascular smooth muscle hypertrophy, endothelial dysfunction, structural renal injury, proteinuria, left ventricular remodeling, collagen synthesis, and myocardial fibrosis. Aldosterone receptor antagonists have been shown to antagonize all these effects in experimental models. Clinical trials with aldosterone antagonists showed an improvement in survival and left ventricular mass index in patients with congestive heart failure, and a reduction in urinary protein excretion and left ventricular mass index in patients with type 2 diabetes and early nephropathy who developed aldosterone synthesis escape. Consequently, aldosterone receptor antagonists may have specific benefits for reducing target-organ injury, particularly if there is evidence of RAAS escape.
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PMID:RAAS escape: a real clinical entity that may be important in the progression of cardiovascular and renal disease. 1294 34

The liver is a common site of amyloid deposition in primary systemic amyloidosis. We reviewed the clinical features and natural history of patients with primary systemic amyloidosis and biopsy-proven hepatic involvement who were evaluated at Mayo Clinic from January 1, 1975, to December 31, 1997. The median age of the study group (68 men; 30 women) was 58.5 years. Seventy-one patients (72%) had involuntary weight loss. Hepatomegaly was found in 79 patients (81%). Eighty-two patients (89%) had proteinuria, and 81 patients (86%) had elevated serum alkaline phosphatase levels. Seventy-six patients (83%) had either a serum or urine monoclonal protein. Before liver biopsy, clinicians considered amyloidosis in the differential diagnosis for only 14 patients (26%). None of our patients experienced hepatic rupture or death due to liver biopsy, and only 4 (4%) bled after liver biopsy. The median survival of the 98 patients was 8.5 months. Predictors of a poor prognosis were congestive heart failure, elevated concentrations of bilirubin, and a platelet count greater than 500 x 109/L. In conclusion, clinicians should consider the diagnosis of primary hepatic amyloidosis in patients who present with involuntary weight loss or hepatomegaly. Other clues to the diagnosis include an unexplained elevated serum alkaline phosphatase level, proteinuria, and evidence for hyposplenism (for example, Howell-Jolly bodies on peripheral blood smear). Liver biopsy was safe. Some patients benefit from systemic chemotherapy.
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PMID:Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. 1453 Jul 78

In men with classical Fabry disease (alpha-galactosidase A [alpha-Gal A] deficiency), kidney failure occurs as early as the second decade of life. In contrast, men with the mild "cardiac variant" have late-onset cardiac involvement and proteinuria but usually do not have renal failure. To investigate the nature of renal involvement in the cardiac variant of Fabry disease, the renal function and morphology were assessed in a 75-year-old affected man. He had mild congestive heart failure, a reduced left ventricular ejection fraction, and hypercholesterolemia but lacked the classical Fabry disease manifestations, including angiokeratoma, acroparesthesias, corneal and lenticular opacities, and hypohidrosis. At age 75 years, he had significant proteinuria, and mildly decreased renal function (serum creatinine, 1.8 mg/dL [159 micromol/L]), presumably secondary to hypertensive arteriosclerosis. He had about 4% residual alpha-Gal A activity in leukocytes, and mutation analysis identified the N215S missense mutation, the common lesion in cardiac variants. Histologic and ultrastructural studies of kidney tissue showed that lysosomal glycosphingolipid deposition was extensive in podocytes, rare in tubular epithelial cells, and absent in mesangial, interstitial, and vascular endothelial and smooth muscle cells. This cardiac variant serves as an "experiment of nature" showing that the residual alpha-Gal A activity precludes glycosphingolipid deposition in the renal endothelial and other cells that lead to early renal failure in classically affected men, whereas marked podocyte accumulation is associated with proteinuria and possibly late-onset renal dysfunction. These findings have important implications for the renal effectiveness of enzyme replacement therapy in classically affected patients and for the aggressive treatment of proteinuria in Fabry disease.
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PMID:Fabry disease: renal involvement limited to podocyte pathology and proteinuria in a septuagenarian cardiac variant. Pathologic and therapeutic implications. 1471 41

The activity of the renin-angiotensin-aldosterone system (RAAS) is elevated both in the circulation and in the renal tissue of diabetic and nondiabetic nephropathies. The increased RAAS activity plays an important role in the hemodynamic and nonhemodynamic pathogenetic mechanisms involved in kidney disease. Previous studies have demonstrated that albuminuria is not only a marker of glomerular lesions, but also a progression promoter, and finally a powerful predictor of the long-term beneficial effect of blood pressure-lowering therapy. Randomized crossover and parallel blind studies in patients with diabetic nephropathy have demonstrated that angiotensin II receptor blockers (ARB) induce favorable changes in systemic blood pressure, renal hemodynamics, and proteinuria similar to those induced by angiotensin-converting enzyme (ACE) inhibition. Studies have revealed the optimal renoprotective dose for some ARBs; however, additional dose titration studies are urgently needed to obtain the maximum benefit of this valuable new class of compounds. The combination of ARB and ACE inhibition is well tolerated and even more effective than monotherapy in reducing systemic blood pressure and albuminuria in diabetic nephropathy. In addition, dual RAAS blockade is safe and well tolerated. Impaired autoregulation of glomerular filtration rate (GFR); demonstrated with some blood pressure-lowering agents implies disturbances in the downstream transmission of the systemic blood pressure into the glomerulus, leading to capillary hypertension or hypotension depending of the level of blood pressure. ARB does not interfere with GFR autoregulation in hypertensive diabetic patients. In contrast to previous observational studies with ACE inhibition, long-term treatment with ARB has similar beneficial renoprotective effect on progression of diabetic kidney disease in hypertensive diabetic patients with ACE II and DD genotypes. ARB can prevent/delay development of diabetic nephropathy independently of its beneficial blood pressure-lowering effect in patients with type 2 diabetes and microalbuminuria. Recently, two landmark studies led to the following conclusion: "Losartan and Irbesartan conferred significant renal benefit in patients with type 2 diabetes and nephropathy. This protection is independent of the reduction in blood pressure it causes. The ARB is generally safe and well tolerated." A recent metaanalysis indicates that ARBs reduce cardiovascular events mainly because of reduction in first hospitalization for congestive heart failure in hypertensive type 2 diabetic patients with albuminuria. The studies mentioned here suggest that ARB represents a beneficial treatment of hypertension and proteinuria in incipient and overt diabetic nephropathy.
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PMID:Angiotensin receptor blockers in diabetic nephropathy: renal and cardiovascular end points. 1501 27

The angiotensin II receptor blockers (ARBs), are highly selective for the AT1 subtype and will block the effects of angiotensin II on peripheral vessels. Several short- and long-term studies have shown these agents to be safe and effective antihypertensive drugs. Since monotherapy of hypertension may be ineffective in lowering the blood pressure to goal, the use of an ARB, especially in combination with a diuretic or another medication, is frequently necessary to bring the blood pressure <140/90 mm Hg (<130/80 mm Hg among people with diabetes mellitus or chronic renal failure), according to JNC 7 guidelines. Besides hypertension, the ARBs have been shown to reduce left ventricular hypertrophy in hypertensive patients. Other benefits of these medications, as well as the angiotensin I converting enzyme inhibitors (ACEIs), include a decrease in cardiovascular morbidity and mortality in patients with heart failure, or hypertensive diabetic nephropathy with proteinuria. Some of the beneficial effects noted with the ACEIs and ARBs (congestive heart failure, left ventricular hypertrophy), have also been demonstrated with the use of b blockers alone and in combination with a diuretic. These drugs, i.e., b blockers, ARBs, and ACEIs, seem to exert their beneficial action through the blockade of the renin-angiotensin-aldosterone system. The role of this system in cardiovascular remodeling and its blockade will be discussed in this review, which will specifically summarize data with the ARB, valsartan.
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PMID:Clinical experience with angiotensin receptor blockers with particular reference to valsartan. 1530 83

Diabetic nephropathy contributes significantly to end-stage renal disease in Nigeria. The earliest clinically detectable stage is that of microalbuminuria when interventions could halt or retard the progression to end-stage renal disease. To investigate the prevalence of microalbuminuria in newly diagnosed type 2 diabetic patients and its clinical correlates in Jos, consecutive patients with newly diagnosed type 2 diabetes attending two large hospitals in Jos were evaluated at three different occasions of monthly intervals for microalbuminuria using Micral test strips 11. Patients with proteinuria, positive nitrite test/ urine microbial culture, acute illnesses or cardiac decompensation were excluded. Out of a total of 99 patients recruited, only 65 completed the study. Microalbuminuria was present in 32(49.2%) of the patients, and was significantly associated with mean arterial pressure, systemic hypertension and diabetic retinopathy (P < 0.05). Microalbuminuria is common in newly diagnosed patients with type 2 diabetes mellitus. Our finding supports routine screening for microalbuminuria as part of the initial evaluation of these patients.
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PMID:Prevalence of microalbuminuria in newly diagnosed type 2 diabetic patients in Jos Nigeria. 1549 Jul 88

The results issued from experimental models and randomized controlled clinical trials have shown that the more intense is the blockade of the renin-angiotensin system (RAS), the more effective is the prevention of target organ damage. Combined inhibition of the RAS is aimed at more complete blockade of the system through action at two different sites, angiotensin I converting enzyme (ACE) and AT1 receptors. This is achieved either by neutralizing the rise in renin and angiotensin (Ang) I, which follows the interruption of the Ang II-renin negative feed-back loop, or by directly antagonizing Ang II, whose synthesis is in part independent of the RAS. By comparison with higher doses of single site RAS blockers, a combination of an ACE inhibitor and an AT1 receptor antagonist block more effectively the RAS. After the demonstration of its synergistic or additive blood pressure lowering effects in sodium depleted normotensive subjects and animal models, combined blockade of the RAS was shown to be more efficient than single site RAS blockade: 1. in lowering blood pressure in hypertensive patients; 2. in lowering proteinuria and possibly retarding progression of renal failure in patients with diabetic and non-diabetic nephropathy; 3. finally, in improving left ventricular remodelling, cardiac function status and cardiovascular morbidity and mortality in patients with congestive heart failure. The advantage offered by combining two RAS blockers is to increase the beneficial effect of cardioprotection and nephroprotection which are currently demonstrated with the highest doses of an ACE inhibitor or an AT1 receptor antagonist.
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PMID:[Blockade of the renin-angiotensin system by a combination of ACE inhibitors and AT1 receptor antagonists]. 1549 22

The aim of the present study is to describe the prevalence of proteinuria in a series of type 2 diabetic patients registered and followed up in the diabetes clinic of a primary health care center (PHCC) in Abha city, southern Saudi Arabia and to relate the proteinuria to some clinical manifestations. The study involved the files of 208 diabetic patients (118 females and 90 males). They were chosen from 475 files of diabetic patients receiving care in the PHC center of Shamasan in Abha City. The selection for this study was based on the fulfillment of certain criteria: type 2 diabetic patients, registered for at least 12 months and visited the clinic for at least once during that period. For each patient the age, sex, family history, diabetes duration, body mass index, the last readings of fasting blood sugar, total cholesterol level, systolic and diastolic blood pressure were used. Proteinuria was considered whenever the last and any of the preceding 3 urine analysis revealed it by the dipstick test provided the patient was not suffering on the day of the test from fever, urinary tract infections, other renal diseases or congestive heart failure. Further, the last recorded subjective evaluation of the treating physician concerning diet, drug and appointment compliance as poor or good was used. The mean age is 56.2+/-8.8 years. The mean duration of diabetes was 9.6+/-4.7 years, while the fasting blood sugar shows a considerably high mean of 218.0+/-72.0 mg/dl. The total cholesterol level on the other hand showed a slight high average of 233.7+/-55.2 mg/dl. The mean systolic and diastolic blood pressure were within normal ranges (136.4+/-18.9mmHg and 87.5+/-10.8mmHg) respectively. The results of the three different types of compliance as scored by the treating physician. The poor scores dominate with 74%, 82.7% and 78.4% of patients' diet, drug and appointment compliances. Proteinuria is present in more than half of the patients (54.3%). The outcome of the logistic regression model for proteinuria showed that the significant factors were the poor glycemic control with an odds ratio (OR) of 3.13, diabetes duration (OR= 1.08 for every year) and diastolic blood pressure (OR= 6.11). The overall model prediction was 72.12%. Diabetic patients treated in the PHC level should be regularly monitored for microalbuminuria and not gross proteinuria to prevent progression to overt nephropathy which will eventually lead to ESRD. The risk increases with poorly controlled and hypertensive patients.
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PMID:Significance of proteinuria in type 2 diabetic patients treated at a primary health care center in Abha City, Saudi Arabia. 1558 31

A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the key to its prevention and treatment. Progressive tissue damage can result in morbidity from congestive heart failure, end-stage heart disease, nephrotic proteinuria and dementia and, eventually, death from cardio- or cerebrovascular causes. The renin-angiotensin-aldosterone system (RAAS) is involved at all stages of the cardiovascular continuum, because the effector molecules of the RAAS, angiotensin II in particular, have direct pathobiological effects on a variety of tissues, including the endothelium, vascular smooth muscle and the renal mesangium. Clinical trials of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have demonstrated the essential validity of this hypothesis. Interruption of the RAAS has been shown to reduce cardiovascular morbidity and mortality in patients with left ventricular hypertrophy, heart failure and post-myocardial infarction, as well as renal disease in patients with type 2 diabetes. Key questions remain, however. What are the clinical effects of combination ARB and ACE inhibitor treatment? How will combinations of RAAS blockade with other agents, such as statins, affect the cardiovascular continuum? Answers to these questions will require well-planned, adequately powered clinical trials, such as the Programme of Research tO evaluate Telmisartan End-organ proteCTION (PROTECTION) and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programmes. However, it is already clear that RAAS blockade is an essential part of blocking progression along the cardiovascular continuum.
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PMID:The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. 1582 52

The major challenge for the treatment of hypertensive patients with type 2 diabetes is to achieve the uniformly recommended blood pressure goal of 130/80 mmHg, and 120/75 mmHg in proteinuric patients. Such low target blood pressure levels require the administration of multiple drugs. Angiotensin receptor blockers and the combination of angiotensin receptor blockers with diuretics fulfil the criteria to lower blood pressure effectively with a placebo-like side-effect profile. Beyond pressure control, clinical prospective trials have documented that it does matter what kind of antihypertensive agent is used to control blood pressure. Large-scale follow-up trials have documented blood pressure independent effects of angiotensin receptor blocker on cardiac [left-ventricular hypertrophy (LVH), congestive heart failure] and renal protection (proteinuria, chronic renal failure). Of note, in these trials, angiotensin receptor blockers have been combined with diuretics, and most of the included patients have been on combination therapy comprising two to four antihypertensive agents. In addition to the combination of an angiotensin receptor blocker with a diuretic, the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor appeared to be most effective in reducing proteinuria, attenuating chronic renal failure and treating congestive heart failure.
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PMID:Optimizing therapeutic strategies to achieve renal and cardiovascular risk reduction in diabetic patients with angiotensin receptor blockers. 1583 71

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