Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma renin activity (PRA) was determined in 48 patients with diabetes mellitus in sodium balance on a 10-20 mEq. Na diet. Nine were normotensive (group I), 11 11 were hypertensive without diabetic nephropathy (group III). Results were compared with those in 16 normal subjects and 49 nondiabetic patients with essential hypertension in similar Na balance. Mean supine PRA did not differ significantly among groups I and II, normal subjects, and patients with essential hypertension. Group III diabetics had a supine PRA of 2.4 +/- 0.4 ng./ml./hr. (x +/- S.E.M.), significantly lower than the other diabetic groups (P less than 0.005) and normal subjects (P less than 0.05). Upright PRA was 12.8 +/- 2.2 in group I diabetics, similar to that in normal subjects (13.3 +/- 2.3), and 8.1 +/- 1.4 in group II diabetics, similar to that in essential hypertensives (6.8 +/- 0.8). In group III diabetics, upright PRA was 4.0 +/- 0.5, significantly lower than that in any other group. These results suggest that (1) PRA is normal in normotensive diabetics, (2) upright PRA in diabetics with hypertension but no nephropathy is similar to that in essential hypertension, and (3) patients with diabetes, hypertension, and nephropathy have "low renin hypertension," explaining the virtual absence of malignant hypertension in this group. Although the major mechanism for this low PRA may be volume expansion, indicating the need for potent diuretics, other mechanisms include hyalinization of the afferent arteriole, decreased cathecholamine stimulation of renin release, and inadequate conversion of prorenin to renin.
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PMID:Plasma renin activity and hypertension in diabetes mellitus. 97 6

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

Angiotensin-converting enzyme (ACE) inhibitors act by lowering the level of angiotensin II. The therapeutic benefits of these drugs and their potential side-effects therefore result from suppression of the physiological effects of angiotensin II. It is rational to prescribe an ACE inhibitor when the renin-angiotensin system is activated, as in renin-dependent essential hypertension, malignant hypertension and hypertension associated with heart failure. The beneficial effects of ACE inhibitor must be weighed against the special risks of renovascular hypertension: risk of renal artery thrombosis in case of unilateral stenosis and risk of renal failure if the stenosis is bilateral or affects a solitary kidney. In some situations the renin-angiotensin system is not directly involved in hypertension but may play a local haemodynamic role, as in some cases of primary or diabetic nephropathy. In such case the ACE inhibitors are thought to exert a protective effect. ACE inhibitors were reputed to be less effective in the elderly than in younger patients, but we now know that they can be prescribed with equal success in both instances to reduce peripheral resistance and improve regional blood flow as well as arterial compliance. Finally, ACE inhibitors can be prescribed, albeit with limited effectiveness, when the renin-angiotensin system is not activated, as in low renin hypertension and idiopathic hyperaldosteronism due to adrenal hyperplasia. They are ineffective in case of Conn's adenoma and contra-indicated in pregnant women.
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PMID:[For which hypertensive patient should angiotensin-converting enzyme inhibitor be prescribed or forbidden?]. 129 38

In hypertensive humans and the spontaneously hypertensive rat, increased cellular Na+/H+ antiport activity has been demonstrated in leukocytes, platelets, skeletal muscle, and vascular smooth muscle cells. This membrane abnormality may be associated with medial thickening of resistance vessels. A similar membrane transport abnormality has also been demonstrated in leukocytes and fibroblasts from type 1 diabetic patients with nephropathy. This membrane transport marker of hypertension may indicate a predisposition to essential hypertension in such patients and may lead to diabetic nephropathy, possibly from mesangial expansion.
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PMID:Abnormalities in Na+/H+ antiporter activity in diabetic nephropathy. 133 34

The offspring of essential hypertensive parents have been found to exhibit abnormalities in renal hemodynamics and sodium handling before the eventual occurrence of hypertension. The reported abnormalities represent a wide spectrum of changes including increased GFR, normal or decreased RPF, slight increase in blood pressure (although within the normal range), and an exaggerated natriuresis response to a sodium load. The heterogeneity of these abnormalities may reflect the specific conditions of the studies, the lability of the changes, or different subgroups of subjects with genetic predisposition to essential hypertension. Several lines of evidence have suggested a relationship between hypertension and the development of diabetic nephropathy in insulin-dependent diabetics. This laboratory has found that recent-onset insulin-dependent diabetics can exhibit renal hemodynamics abnormalities very early in the course of diabetes according to a positive or negative family history of essential hypertension. These changes include increased GFR and mean arterial pressure, but no differences in renal sodium and lithium handling in diabetics with a genetic predisposition to essential hypertension. In addition, diabetics with a positive family history of essential hypertension exhibited a more-marked vasodilative response to an acute interruption of the renin-angiotensin system, further suggesting inadequate angiotensin modulation of renal vascular tone. The significance of these abnormalities in relation to the development of diabetic nephropathy requires further investigation.
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PMID:Predisposition to essential hypertension and renal hemodynamics in recent-onset insulin-dependent diabetic patients. 145 59

Less than a quarter of the patients with juvenile-onset IDDM develop diabetic nephropathy during the first 20 years of diabetes. To study the determinants of this complication, we selected patients who had come with newly diagnosed IDDM to the Joslin Clinic between 1967 to 1972, and we examined them in 1986 to 1988, that is, 15 to 21 years after onset of diabetes. Using a case control design we compared three groups of cases, that is, advanced nephropathy (N = 43), only microalbuminuria (N = 41), and hypertension alone (N = 17), with a group of controls who remained normoalbuminuric and normotensive despite the long duration of IDDM (N = 61). In comparison with controls, patients with advanced nephropathy had more parents with hypertension (odds ratio 3.8), higher Vmax values of Na/Li countertransport in red blood cells (odds ratio 10.0 for the highest tertile), and higher mean arterial pressure during adolescence and early adulthood (odds ratio 3.1 for those above the median). They also had significantly poorer glycemic control during their first 12 years of diabetes. Patients with hypertension alone were similar to those with advanced nephropathy with regard to markers of predisposition to hypertension but differed from them with regard to glycemic control, having the best glycemic control of all the study groups. Patients who developed only microalbuminuria during 15 to 21 years of IDDM (some of whom will progress to overt proteinuria later) did not differ significantly from controls with regard to predisposition to hypertension. In conclusion, predisposition to hypertension is a major risk factor for the development of advanced diabetic nephropathy and essential hypertension during the first 20 years of IDDM.
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PMID:Predisposition to hypertension: risk factor for nephropathy and hypertension in IDDM. 151 93

Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 +/- 0.03 mmol/l RBC x hr) than in normotensive patients (0.23 +/- 0.03; P less than 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (greater than 0.41 mmol/l RBC x hr) or normal (less than 0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport. 151 8

Genetic predisposition to essential hypertension has been proposed as a risk factor for the development of diabetic nephropathy in type 1 (insulin-dependent) diabetes mellitus. An increased sodium-lithium countertransport activity (NaLiCT) has been suggested as a genetic marker for essential hypertension. We therefore evaluated NaLiCT in diabetic patients with (N = 39) or without (N = 23) diabetic nephropathy (DNP), patients with non-diabetic renal diseases (N = 42) and in healthy controls (N = 24). The NaLiCT was elevated in both diabetic patient groups compared to healthy controls (median 244; range 134 to 390 mumol.liter cells-1.hr-1), but was not different in patients with DNP (median 314; range 162 to 676), without DNP (median 325; range 189 to 627) and patients with non-diabetic renal disease (median 300; range 142 to 655). The genetic predisposition to DNP is illustrated by the fact that diabetic sibs of probands with DNP showed a higher occurrence of DNP than diabetic sibs of patients without DNP. We analyzed whether familial DNP clustered with an increased NaLiCT. The NaLiCT in sibs concordant for the presence of DNP (N = 10; median 307; range 217 to 428 mumol.liter cells-1.hr-1) was not significantly different from that in sibs concordant for absence of DNP (N = 15; median 279; range 189 to 442). We conclude that erythrocyte sodium-lithium countertransport activity cannot be used as a marker to identify patients at risk for the development of diabetic nephropathy.
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PMID:Is increased erythrocyte sodium-lithium countertransport a useful marker for diabetic nephropathy? 151 9

Patients (pts) with essential hypertension normally exhibit a typical diurnal variation with a nocturnal blood-pressure (BP) decreased. A lack of this periodicity is often reported in pts with secondary hypertension. 24-h BP measurement was therefore performed in 308 pts with essential hypertension, and in 172 pts with secondary hypertension, in order to evaluate the diagnostic value of nocturnal BP decrease. Diagnoses of the secondary hypertensives were: renoparenchymatous hypertension (n = 29), diabetic nephropathy (n = 24), morbus Conn (n = 6), renal artery stenosis (n = 32), pheochromocytoma (n = 5), hemodialysis pts (n = 30), and kidney transplantation (n = 44). Pts with essential hypertension showed a mean systolic and diastolic BP decrease during the nighttime period of 22 +/- 7 mmHg and 17 +/- 5 mmHg, respectively. In contrast, the corresponding values in secondary hypertension were 5.7 +/- 9.2 mmHg (systolic decrease) and 5.2 +/- 5.9 (diastolic decrease). Pts with pheochromocytoma who had a nighttime increase in BP demonstrated the greatest difference from the essential hypertensives, followed by pts with either diabetic nephropathy or after kidney transplantation. A lack of nocturnal BP decline (less than 10% of the daytime values) was detected in 69.8% of pts with secondary hypertension, but only in 5.2% of pts with essential hypertension. In summary, these results suggest that the absence of a nighttime decline in BP during 24-h ambulatory monitoring is an indication of secondary hypertension and should lead to further investigations. Furthermore, a nightly hypertension is associated with a higher risk of complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Diagnostic significance of absent nocturnal blood pressure decrease in 24-hour long-term blood pressure measurement]. 151 20

To assess the effects of genetic predisposition of essential hypertension on early renal function in recent insulin-dependent diabetics, we studied inulin, para-aminohippuric, sodium, and lithium clearances in 69 unselected diabetics with (n = 20) and without (n = 49) a family history of essential hypertension. Despite similar metabolic control, glomerular filtration rate and mean arterial pressure were significantly higher in diabetics with than in those without a family history of hypertension. However, no difference was found between the two groups regarding renal vascular resistance, sodium excretion, or fractional proximal and distal sodium reabsorption. Renal responses to acute captopril (75 mg) administration were evaluated in 27 patients (six with family history of hypertension). Captopril decreased filtration fraction and mean arterial pressure similarly in both groups, whereas glomerular filtration rate and renal vascular resistance decreased more dramatically in diabetics with family history of hypertension. These findings indirectly suggest an abnormal response to angiotensin of vascular tone in recent diabetics with familial predisposition to hypertension. Renal response to acute nicardipine (2.5 mg i.v.) administration was analyzed in 24 patients (five with family history of hypertension). In both groups, nicardipine similarly decreased mean arterial pressure and renal vascular resistance and induced a marked natriuretic effect due to a predominant reduction in proximal reabsorption of sodium. However, the increase in sodium excretion was twofold to threefold more pronounced in diabetics with a family history of hypertension. Whether these early renal abnormalities may contribute to the risk of diabetic nephropathy, as suggested by retrospective studies, remains to be determined.
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PMID:Renal abnormalities in normotensive insulin-dependent diabetic offspring of hypertensive parents. 155 69


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