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)

Protectin (CD59) is a low molecular weight glycophosphoinositol-anchored inhibitor of the membrane attack complex of complement (MAC) that is present, for example, on the membranes of endothelial cells and on epithelial cells of glomeruli and distal tubuli. To examine for the possibility that CD59 becomes detached from cell surfaces following cell injury, this study evaluated renal excretion of CD59 in patients with idiopathic membranous glomerulonephritis (MGN; N = 21), diabetic nephropathy (DNP; N = 15) and in healthy control subjects (N = 13). CD59 in human urine was quantitated by a competitive solid-phase radioimmunoassay having approximately 13 kDa soluble urinary CD59 as a standard. Immunofluorescence microscopy demonstrated a decreased expression of CD59 in the glomeruli of MGN patients. Using a Triton X-114 phase separation method 91 to 97% of urinary CD59 was found to be in a soluble form without anchor-associated phospholipid. The mean (+/- SEM) level of urinary CD59 was 5.6 +/- 0.2 micrograms/ml in MGN patients, 3.7 +/- 0.4 micrograms/ml in healthy controls (P < 0.001) and 2.6 +/- 0.1 in DNP patients (P < 0.001). When related to urinary creatinine (UCr) the corresponding values were 11.9 +/- 5.6, 4.8 +/- 0.3 (P = 0.021) and 4.4 +/- 0.2 (P < 0.002), respectively. The amount of CD59 in urine correlated with the urinary excretion of soluble terminal complement complexes, SC5b-9 (r = 0.594, P < 0.006) in MGN patients. The excretion of CD59 also correlated with the excretion of the inflammatory mediator IL-1 beta (r = 0.671, P = 0.001) but not with TNF-alpha (r = 0.314, P = 0.178). No correlation of CD59 excretion was observed with duration of the disease level of proteinuria, serum albumin concentration or serum creatinine level. Based on these findings we speculate that the increased excretion of CD59 into urine in MGN patients is due to complement activation and inflammation induced shedding of CD59 from glomerular cells.
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PMID:Urinary excretion of protectin (CD59), complement SC5b-9 and cytokines in membranous glomerulonephritis. 754 24

Although increased plasma fibronectin (PF) levels have been found in diabetic patients with microalbuminuria, there is still controversy about its clinical implication for detecting early diabetic nephropathy. To evaluate the PF concentration as a possible marker for early diabetic nephropathy, three groups of sex-and age-matched patients were studied I) 22 insulin dependent diabetic (IDDM) patients with microalbuminuria (mean age +/- SEM: 23.3 +/- 3.6 years, mean urinary albumin excretion rate (AER) +/- SEM: 47.1 +/- 39.5 micrograms/min); II) 17 IDDM patients with normoalbuminuria (mean age: 23.4 +/- 4.4 years, mean AER: 7.8 +/- 2.1 micrograms/min) and III) 20 healthy control subjects (mean age: 22.6 +/- 4.1 years, mean AER: 6.7 +/- 2.1 micrograms/min). PF and urinary excretion of albumin were measured by an immunoturbidimetric method using commercially available kits (Boehringer Mannheim GMBH FRG, and Miles Lab., UK). The mean PF was significantly higher in the group with microalbuminuria (406.5 +/- 122.9 micrograms/ml) than in the group with normoalbuminuria (295.6 +/- 96.9 micrograms/ml, P < 0.01) or in the control group (299.54 +/- 105.5 micrograms/ml, P < 0.01). A weak positive correlation was found between PF and urinary albumin values (r = 0.35, P < 0.05). There were no significant correlations between PF and the other variables such as age, duration of diabetes, body mass index, arterial blood pressure, fasting blood glucose, fructosamine and HbA1 in the diabetic patients or in the control group. Our results suggest that the PF concentration could be a weak marker for early diabetic nephropathy. We cannot therefore use PF instead of microalbuminuria because there is only a weak correlation between PF and microalbuminuria.
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PMID:Can we use plasma fibronectin levels as a marker for early diabetic nephropathy. 762 76

Interstitial fibrosis is a marker of progression of renal impairment in diabetic nephropathy. Transforming growth factor (TGF)-beta 1 is one of a group of pro-fibrotic cytokines and growth factors that have been associated with the development of interstitial fibrosis. We have examined the modulating influence of glucose on the production of TGF-beta 1 by cultured human proximal tubular cells. Incubation of growth-arrested human proximal tubular cells (HPTC) (72 hours in serum free medium) in 25 mmol/L D-glucose resulted in increased expression of TGF-beta 1 mRNA (as assessed by reverse transcription polymerase chain reaction). This was apparent after 6 hours and increased up to 120 hours exposure. TGF-beta 1 secretion, however, as measured by specific enzyme-linked immunoassay, was unaffected by exposure to 25 mmol/L D-glucose. Sequential stimulation of HPTC, first with 25 mmol/L D-glucose for 48 hours and then with platelet-derived growth factor (PDGF) isoforms, resulted in a dose-dependent secretion of TGF-beta 1. Pre-exposure to 5 mmol/L D-glucose or 25 mmol/L L-glucose did not prime for TGF-beta 1 release. At 50 ng/ml PDGF this effect was greatest for the AA isoform (AA 31.4 +/- 7.1, AB 20.98 +/- 8.9, BB 7.8 +/- 2.2, P < 0.05 for all versus control, n = 3, mean +/- SEM ng/10(6) cells/24 hours). These effects were blocked by the addition of antibody to the PDGF alpha-receptor. TGF-beta 1 secretion was inhibited in a dose-dependent manner by pretreatment with cyclohexamide, but was not affected by pretreatment with actinomycin D. Stimulation of HPTC with a single dose of PDGF induced TGF-beta 1 mRNA; however, only after application of a second dose of PDGF (after TGF-beta 1 mRNA induction) did TGF-beta 1 protein secretion occur. We also demonstrated that PDGF stimulation of HPTC induced an inherently more stable TGF-beta 1 mRNA transcript. These findings demonstrate that elevated D-glucose concentration alone is insufficient to lead to increased TGF-beta 1 secretion by HPTC despite increased mRNA expression. However, application of a second stimulus such as PDGF, when TGF-beta 1 mRNA expression is increased, leads to increased protein synthesis and secretion of TGF-beta 1. This implies that elevated glucose concentrations might prime proximal tubular cells for TGF-beta 1 synthesis and thus contribute to the development of interstitial fibrosis.
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PMID:Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor. 763 30

To evaluate the possibility that platelet dysfunctions contribute to the cardiovascular risk of microalbuminuric insulin-dependent diabetic (IDD) patients, we have measured beta-thromboglobulin (BTG) and platelet factor 4 (PF4) in 74 IDD patients with different degrees of albuminuria (8 macro-, 36 micro- and 30 normoalbuminuric) and in 30 non-diabetic control subjects. BTG values (20.4 +/- 1.5 SEM in normo-, 22.2 +/- 1.2 in micro-, 101.1 +/- 2.9 in macroalbuminuric patients and 21.8 +/- 1.1 IU/ml in control subjects) were significantly higher (P < 0.001) in the macroalbuminuric patients, but similar among the other groups. These results suggest that platelet hyperactivation is not present in the microalbuminuric stage of diabetic nephropathy, only in overt nephropathy.
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PMID:Plasma beta-thromboglobulin and platelet factor 4 are not increased in insulin-dependent diabetic patients with microalbuminuria. 782 49

The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Results of a 2-year prospective, randomized study. 774 19

Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively.
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PMID:Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation. 800 95

The present study was undertaken to evaluate the effects of a selective thromboxane synthetase inhibitor (OKY-046) on urinary prostaglandins (PGs) excretion and renal parameters such as endogenous creatinine clearance rate (Ccr) and urinary protein excretion in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were divided into two groups; one fed standard chow (DM1) and the other, standard chow mixed with 0.1% OKY-046 (DM2) for 24 weeks. Male Wistar rats were fed standard chow for 24 weeks as control (C). Urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha excretions significantly increased in STZ-induced diabetic rats (DM1 and DM2) compared with C after 24 weeks. The increased urinary TXB2 excretion in DM2 was significantly reduced (p < 0.05) compared with that in DM1 (261.1 +/- 18.6 ng/gCr versus 380.0 +/- 48.4 ng/gCr, mean +/- SEM). No significant difference could be found in urinary protein excretion between DM1 and DM2, which was significantly higher in both diabetic groups than C after 12 and 24 weeks. Ccr in both DM1 and DM2 significantly increased (p < 0.05) compared with C after 12 weeks. In contrast, after 24 weeks, Ccr in DM1 fell down to 0.18 +/- 0.02 mL/min 100 g body weight (BW), thus being significantly lower (p < 0.05) than that in C (0.27 +/- 0.03 mL/min 100 g BW) and DM2 (0.25 +/- 0.02 mL/min 100 g BW). Electron microscopic findings in diabetic rats after 24 weeks were the typical change of early diabetic nephropathy, whereas there were no obvious differences between DM1 and DM2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of thromboxane synthetase inhibitor (OKY-046) on urinary prostaglandin excretion and renal function in streptozotocin-induced diabetic rat. 806 49

Exaggerated vascular reactivity has been implicated in the pathogenesis of diabetic nephropathy, and several studies suggest that smoking accelerates its progression. We therefore assessed the vasoactive effects of smoking by comparing noradrenaline-induced vasoconstriction in dorsal hand-veins between smoking and non-smoking groups of Type I diabetic patients with and without microalbuminuria and in non-diabetic subjects. Smokers had a significantly higher dose causing 50% vasoconstriction (reduced sensitivity to noradrenaline) in all three groups: microalbuminuric diabetic smokers vs. nonsmokers, 20.2(4.6) (SEM) vs. 6.6(2.3) ng min-1 (P = 0.02); normoalbuminuric, 76.9(29.4) vs. 22.8(9.1) ng min-1 (P = 0.03); non-diabetic subjects, 97.8(30.0) vs. 38.0(12.8) ng min-1 (P = 0.01). Both microalbuminuric diabetic groups showed significantly greater sensitivity to noradrenaline-induced vasoconstriction than the other smoking and non-smoking groups, respectively (P < 0.01). Vasoconstrictors responses to noradrenaline are attenuated in smokers, possibly due to alpha-adrenoceptor down-regulation. Smoking could increase urinary albumin losses and accelerate renal damage through catecholamine surges which raise systemic and, perhaps, intraglomerular blood pressure. This hypothesis deserves further consideration.
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PMID:Smoking attenuates the vasoconstrictor response to noradrenaline in type I diabetic patients and normal subjects: possible relevance to diabetic nephropathy. 808 9

The influence of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, on quantitative and qualitative changes in lipoprotein metabolism was investigated in 18 patients (group I, 10 with primary kidney disease and group II, 8 with diabetic nephropathy) with nephrotic syndrome. Nephrotic patients exhibited severe hyperlipidemia (serum cholesterol 390 +/- 17 mg/dl and triglyceride 335 +/- 42 mg/dl; mean +/- SEM) and had significantly higher lipoprotein (a) [Lp(a)] levels (54 +/- 12 mg/dl; median 31 mg/dl, p < 0.01) compared with 20 healthy subjects (mean 12 +/- 1.8 mg/dl; median 7 mg/dl). Fifty-six percent of the patients and 15% of the controls had values greater than 30 mg/dl. Treatment with simvastatin in increasing doses over a period of three months (13 patients received 40 mg/day and 5 patients 20 mg/day at the end of the third month) reduced LDL-cholesterol in both groups of patients (35% and 54%) as well as apolipoprotein B (apoB) (31% and 46%) significantly, but Lp(a) levels were not influenced (57 +/- 21 vs 59 +/- 20 and 50 +/- 14 vs 53 +/- 16 mg/dl, respectively). On the other hand a complex change in lipoprotein composition occurred. The ratio of LDL apoB/LDL cholesterol-ester increased significantly (0.75 +/- 0.03 to 0.84 +/- 0.03 and 0.80 +/- 0.03 to 1.02 +/- 0.1, respectively) and cholesterol concentration in VLDL (64 +/- 16 to 39 +/- 7 and 74 +/- 18 to 55 +/- 74 mg/dl, respectively) was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of simvastatin on lipoprotein (a) and lipoprotein composition in patients with nephrotic syndrome. 818 55

Taking into account both the importance of microalbuminuria (MA) as a predictive parameter of clinical nephropathy in diabetic patients and the efficiency of exertion to show and/or to increase MA in both diabetic patients and normal individuals, we studied 37 type I diabetic patients divided into two groups: group A, with no MA at rest (n = 19), and group B, with MA at rest (n = 18). Group C comprised 10 healthy volunteers as controls. Changes of basal MA during exercise and postexercise were studied in all three groups. Normotensive patients with no metabolic disorders, normal renal function, and no proteinuria underwent an ergometric test up to 600 kg. This test was repeated after the administration of 20 mg enalapril in a single daily dose for 60 days. Body weight, systolic and diastolic arterial pressure, creatinine, and creatinine clearance were determined and showed no significant variations either between groups or with treatment. Microalbuminuria was studied in the three groups with and without administration of enalapril throughout the 2 months of the study. Determinations were performed under conditions of rest, exercise, and postexercise. Mean baseline MA values +/- SEM were as follows: at rest, 5.22 +/- 0.49, 58.36 +/- 13.24, and 4.73 +/- 0.45 micrograms/min for groups A, B, and C, respectively; with exercise, 15.19 +/- 4.43, 74.70 +/- 14.89, and 16.76 +/- 4.62 micrograms/min for groups A, B, and C, respectively; and postexercise, 32.04 +/- 6.64, 253.15 +/- 63.88, and 9.23 +/- 3.25 micrograms/min, respectively. The geometric means of the baseline to posttreatment MA ratio were as follows: at rest, 0.95, 1.59 (P < 0.01), and 1.03 for groups A, B, and C, respectively; with exercise, 1.53 (P < 0.01), 1.91 (P < 0.01), and 1.69 for groups A, B, and C, respectively; and postexercise, 2.94 (P < 0.01), 3.24 (P < 0.01), and 1.03 for groups A, B, and C, respectively. In conclusion, in the early diagnostic suspicion of diabetic nephropathy, the screening of postexercise MA during an ergometric test could be of help. Treatment with enalapril decreased MA in diabetic groups A (no MA at rest) and B (MA at rest) during exercise and postexercise, and also decreased MA in group B while at rest.
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PMID:Decrease of exercise-induced microalbuminuria in patients with type I diabetes by means of an angiotensin-converting enzyme inhibitor. 854 35


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