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

The incidence of diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) may depend on factors other than the quality of diabetes control. Hypertension is an additional factor associated with a high degree of renal involvement in IDDM. One abnormality consistently observed in various tissues of patients with essential hypertension is enhanced activity of the Na+/H+ antiport. In the present study we have therefore studied platelet antiport activity in 41 healthy subjects (control), in 22 patients with untreated essential hypertension (EH), and in 35 normotensive IDDM patients (type 1). Of these patients 17 exhibited signs of diabetic nephropathy (group 1) while 18 had no evidence for renal involvement of IDDM in spite of a duration of IDDM of at least 10 years (group 2). The two IDDM patient groups were undistinguishable with respect to age, body mass index, and arterial blood pressure (group 1, 117.9 +/- 2.4/78.4 +/- 1.5 mmHg; group 2, 113.9 +/- 3.6/76.1 +/- 1.8 mmHg). Antiporter activity was determined from the rate of cell volume changes induced by propionic acid. Platelet Na+/H+ exchange activity averaged 23.43 +/- 0.43 10(-3).s-1 in control subjects and was markedly elevated in EH (28.38 +/- 0.62 10(-3).s-1; P < 0.01). Antiport activity in group 2 patients without nephropathy averaged 24.54 +/- 0.57 10(-3).s-1 and was undistinguishable from the control group. However, platelet Na+/H+ antiport activity was significantly stimulated in group 1 patients with nephropathy as compared to group 2 (26.95 +/- 0.73 10(-3). s-1; P < 0.025). Our results show that renal involvement in IDDM is associated with enhanced activity of the platelet Na+/H+ antiport.
 ...
PMID:Platelet Na+/H+ antiport activity in patients with insulin-dependent diabetes mellitus with and without diabetic nephropathy. 838 10

Patients who develop diabetic nephropathy, one of the leading causes of end-stage renal diseases in Western communities, have an increased red cell Li+/Na+ countertransport (CT). Li+/Na+ CT is a membrane function which exchanges intracellular Li for extracellular Na in vitro. High Li+/Na+ CT reflects abnormal kinetic properties of red cell membrane Na/H exchange. A widespread abnormality of Na/H exchange could play a major role in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases since Na/H exchange is involved in the regulation of cell pH and cell volume; in the cellular response to hormones, mitogens, and growth factors; and in the renal reabsorption of Na and bicarbonate. Li+/Na+ CT is under genetic control and raised in a subgroup of patients with essential hypertension. Among these patients, high Li+/Na+ CT is associated with increased glomerular filtration rate, filtration fraction, proximal fractional Na reabsorption, microalbuminuria, plasma renin activity, and kidney and cardiac volume. Increased Li+/Na+ CT is often associated with hyperlipidemia, hyperuricemia, reduced insulin sensitivity, and obesity. The whole of these observations may explain why patients with diabetes or essential hypertension and increased Li/Na CT are at risk of early renal and cardiac impairment.
 ...
PMID:Red blood cell Li+/Na+ exchange in patients with diabetic nephropathy and essential hypertension: therapeutic implications. 851 86

The overall quality of antihypertensive care in diabetic patients in Germany is poor. Only a minority of unselected hypertensive patients reach permanent normotensive blood pressure control. Previously, we have shown in a prospective randomized 3-year follow-up study in essential hypertension that implementation of a hypertension teaching and treatment program into routine care results in a significant improvement of blood pressure control. Subsequently, we have performed a prospective, controlled 5-year follow-up trial in hypertensive type I diabetic patients with nephropathy. One-half of a sequential sample of about 100 hypertensive patients with overt nephropathy participated in the program based on blood pressure self-monitoring with the goal of normalization of blood pressure values below 140/90 mm Hg (intensified care, IC). The remaining patients followed routine antihypertensive therapy and formed the control group (routine care, RC). During 5 years of follow-up in IC group patients, blood pressure control was significantly improved. The occurrence of primary study end points (need for dialysis and death) was significantly lower in the IC group patients. In conclusion, in patients with diabetic nephropathy, participation in a hypertension teaching treatment program results in a long-term improvement of blood pressure control and a decrease in mortality and morbidity.
 ...
PMID:Effects of intensification of antihypertensive care in diabetic nephropathy. 857 55

In order to evaluate tubular damage in diabetic patients, the activity of renal proximal tubule derived enzymes excreted in 24-hour urine were recorded in 5 groups as follows: (i) 48 noninsulin-independent diabetic patients with normal renal function and a urinary albumin excretion rate within the normal range; (ii) 45 noninsulin-dependent diabetic patients with normal renal function and a high urinary albumin level; (iii) 26 noninsulin-dependent diabetic patients with renal failure; (iv) 40 patients with essential hypertension and normal renal function, and (v) 48 normal control subjects. Regardless of whether cases were noninsulin-dependent diabetics with normal or high urinary albumin excretion rate or cases with renal dysfunction, urinary dipeptidyl aminopeptidase IV and N-acetyl-beta-D-glucosaminidase excretions were significantly higher than in healthy subjects, and urinary gamma-glutamyl transpeptidase excretion was significantly lower than in healthy subjects. No significant changes in urinary enzyme excretions showed specific variations in the essential hypertensive patients. These results suggest that there is tubular damage in the early stages of noninsulin-dependent diabetic patients with normal renal function and normal urinary albumin excretion rate. Detection of urinary excretion of dipeptidyl aminopeptidase IV, N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transpeptidase may be especially useful for the early diagnosis of diabetic nephropathy.
 ...
PMID:Diagnostic significance of urinary enzymes for diabetes mellitus and hypertension. 858 4

Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension. In addition, a polymorphism in the angiotensinogen gene substituting methionine for threonine (T174M) has been associated with hypertension in nondiabetic populations. We studied the relationship between these polymorphisms in the angiotensinogen gene in IDDM patients with diabetic nephropathy (121 men, 74 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years). There was no difference in M235T genotype distribution between IDDM patients with diabetic nephropathy and those with normoalbuminuria: 73/97/25 (37/50/13%) vs. 67/95/23 (36/52/12%) had MM/MT/TT genotypes, respectively. No difference in distribution of T174M genotypes between nephropathic and normoalbuminuric IDDM patients was observed either: 148/44/1 (77/23/0.5%) vs. 141/42/2 (76/23/1%) had TT/TM/MM genotypes, respectively. In patients with nephropathy, systolic blood pressure was higher (161 +/- 22 mmHg [mean +/- SD]) in patients carrying TT genotype of the M235T angiotensinogen polymorphism as compared with patients with MM or MT genotypes (150 +/- 23 mmHg; P = 0.03). We conclude that neither the M235T nor the T174M polymorphism in the angiotensinogen gene contributes to genetic susceptibility to diabetic nephropathy in white IDDM patients, whereas the TT genotype of the M235T is associated with elevated blood pressure in patients with diabetic nephropathy.
 ...
PMID:Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy. 859 44

Diabetic nephropathy in Jewish insulin-dependent diabetes mellitus (IDDM) patients has been found to correlate to their ethnic origin. It has also been found that increased sodium-lithium countertransport (SLC) in erythrocytes, as a genetic marker for essential hypertension, may identify those patients at risk for diabetic nephropathy. The purpose of this study was to investigate a possible correlation between this genetic marker and the ethnic origin of Jewish IDDM patients and their parents and the risk for developing diabetic nephropathy. Although SLC was slightly increased in IDDM patients with microalbuminuria, SLC was not correlated with the existence of diabetic nephropathy nor with the ethnic origin and blood pressure of these Jewish IDDM patients. Thus, other genetic factors may play a role in the different prevalence of diabetic nephropathy in Jewish IDDM patients of different ethnic origin.
 ...
PMID:Sodium-lithium countertransport: a predictor of diabetic nephropathy in Jewish insulin-dependent diabetes mellitus patients of different ethnic origin? 863 45

It is now well-established in experimental models in rodents that increased glomerular pressure results in the development of focal and segmental glomerulosclerosis, proteinuria and progressive renal functional deterioration. In humans, direct measurement of glomerular capillary pressure is impossible. However, it is widely accepted that glomerular hypertension is present in different clinical situations, like diabetic nephropathy, chronic renal failure associated with glomerulonephritides, some forms of essential hypertension and cadaveric kidney transplantation. Many studies were performed on the effects of protein-restricted died and/or angiotensin converting enzyme inhibition on the rate of progression of renal failure in these renal diseases. Although controversial, the overall results suggest that these therapeutic strategies may reduce the rate of progression, particularly in diabetic nephropathy.
 ...
PMID:[Intraglomerular hypertension. Physiopathology and therapeutic implications]. 868 50

Recent studies have suggested that an inherited predisposition to essential hypertension may increase susceptibility to nephropathy for patients with IDDM. Essential hypertension has been linked to the angiotensinogen (AGT) gene in genetic linkage studies in American and European populations. A molecular variant (M235T), which has a functional effect, has been described with highest plasma AGT levels being associated with the TT genotype. In a case-control study, we have evaluated the role of this functional genetic marker in patients with IDDM and nephropathy and in IDDM patients without nephropathy. We studied 195 IDDM patients, of whom 95 had established diabetic nephropathy; the remaining 100 patients, who had no evidence of microalbuminuria, served as control subjects. All patients were whites born in Northern Ireland. The point mutation in the AGT gene was analyzed using restriction typing. The background frequency of the M235T variant was assessed in 80 healthy blood donors, and the TT genotype was present in 9%. This genotype occurred in 8% of control IDDM patients without nephropathy and 19% of IDDM patients with nephropathy (P = 0.025). The odds ratio for diabetic nephropathy associated with the TT genotype was 2.7 (95% CI 1.04-7.52). There was no relationship between blood pressure and AGT genotypes in the control group. We cannot exclude the possibility that the observed association in the nephropathy group is due to an association between AGT genotype and hypertension. This evidence may help to explain the predisposition to diabetic nephropathy afforded by hypertension and merits further investigation.
 ...
PMID:A molecular variant of angiotensinogen is associated with diabetic nephropathy in IDDM. 877 23

Increased erythrocyte (RBC) sodium-lithium (Na-Li) counter transport (CT) has been reported to be a genetic marker for essential hypertension (EHT). In addition, increased RBC Na-Li CT has been demonstrated in insulin-dependent diabetic (IDDM) patients with nephropathy, indicating that a predisposition to hypertension may cause renal damage and impaired renal function. Therefore, the present study was designed to determine RBC Na-Li CT in subjects with essential hypertension (EHT) and non-insulin-dependent diabetics (NIDDM) with or without hypertension (NIDDMHT or NIDDMNT), using the method of Canessa et al. with a slight modification by flame photometry and expressed as nmol Li/5 x 10(6) RBC/h. Na-Li CT in patients with EHT (0.159 +/- 0.051 (S.D.), n = 26) or NIDDMHT (0.168 +/0 0.083, n = 42) was higher than that in NIDDMNT patients (0.127 +/- 0.059, n = 27, P < 0.05). Among the NIDDMHT patients, those with clinical nephropathy had the same levels of Na-Li CT as those without nephropathy. When the NIDDM patients were divided into two groups with or without insulin treatment, the Na-Li CT in hypertensives was higher than that in normotensives, irrespective of whether or not they were on insulin therapy. Addition of insulin to RBCs in vitro did not augment the Na-Li CT activity. These results suggest that an increase of Na-Li CT may not be due to the stimulatory effect of endogenous or exogenous insulin, and reflect a genetic predisposition for hypertension, and hence diabetic nephropathy, not only in IDDM but also NIDDM patients.
 ...
PMID:Elevated erythrocyte sodium-lithium counter-transport in hypertensive patients with non-insulin-dependent diabetes mellitus. 879

An enhancement of Na+/H+ exchange (NHE) in blood cells of selected patients with essential hypertension and with diabetic nephropathy has been described by various investigators. Recent studies have shown that enhanced NHE activity persists in immortalized lymphoblasts from these patients after prolonged cell culture and, thus, appears to be under genetic control. Available evidence strongly argues against a mutation in the encoding gene or an overexpression of the NHE. Immortalized cells from hypertensive patients with enhanced NHE activity display two-fold enhanced agonist-induced rises of the cytosolic free Ca2+ concentration and the underlying reason was identified as an increased activation of pertussis toxin (PTX)-sensitive G proteins. The molecular mechanism(s) of this phenomenon have not yet been elucidated. It appears likely that similar changes contribute to the enhanced NHE activity phenotype in diabetic nephropathy, although experimental evidence for this is still lacking. An enhanced activation of PTX-sensitive G proteins could explain many of the hitherto unexplained phenomena in essential hypertension, e.g. inheritance, increased vasoconstriction, hypertrophy of remodeling of arterial blood vessels and the heart, enhanced platelet aggregation etc. In diabetes the same defect could provide the basis for the susceptibility to nephropathy, e.g. by enhancing the deleterious effects of autocrine and paracrine growth factors. Thus, the experimental approach of immortalizing blood cells from patients with essential hypertension and diabetic nephropathy has opened new horizons in the identification of genetically fixed abnormalities in intracellular signal transduction which could contribute to both pathologies and which can now be studied without the confounding influences of the diabetic or hypertensive in vivo milieu.
 ...
PMID:Na+/H+ exchange in hypertension and in diabetes mellitus--facts and hypotheses. 883 37


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