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)

Changes in parathyroid hormone (PTH) and osteocalcin over 3 years were studied in hemodialyzed patients with diabetic nephropathy (HD/DM) and hemodialyzed patients without diabetes (HD/non-DM). In HD/DM patients, concentrations of the carboxyl terminal regions of PTH and osteocalcin in the serum did not change significantly, but in HD/non-DM patients, both concentrations increased significantly. In patients in both groups, the mean concentration of the mid-region of PTH increased significantly. Secondary hyperparathyroidism in HD/DM develops slower than in HD/non-DM.
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PMID:Changes in parathyroid hormone in diabetic patients on long-term hemodialysis. 232 97

Nephromegaly is a prominent feature of diabetic nephropathy and predominantly reflects increased renal tubule mass, mostly due to hypertrophy. To elucidate pathogenetic factors involved, we studied the effects of high glucose (HG) alone, and in combination with hormones/growth promoters: angiotensin II (10(-7) M); parathyroid hormone (10(-7) M); insulin-like growth factor-1 (10(-7) M), or transforming growth factor-beta1 (TGF-beta1, 10 ng/ml) in a renal cell line (LLC-PK1) with many characteristics of the proximal tubule. Activities of lysosomal cathepsins (B, L+B and H) and the protein turnover were investigated. Exposure to HG (25 mM) for up to 48 h increased cellular protein content, due to enhanced protein synthesis, while protein degradation rate and cathepsin activities tended to lower values. Hyperosmotic mechanisms of glucose action were excluded, since these effects were not induced by mannitol. In normoglycemic conditions only TGF-beta1 decreased cathepsin activities and protein degradation rate significantly. However, in HG media all applied hormones/growth factors significantly lowered the protein degradation rate, as well as lysosomal cathepsin activities. The enhanced responsiveness could contribute to the impaired protein turnover, with consequent hypertrophy of the tubulointerstitium in diabetic nephropathy.
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PMID:High-glucose media enhance the responsiveness of tubular cells to growth promoters: effect on lysosomal cathepsins and protein degradation. 955 64

Osteopenia has been ascribed to diabetics without residual insulin secretion and high insulin requirement. However, it is not known if this is partially due to disturbances in the IGF system, which is a key regulator of bone cell function. To address this question, we performed a cross-sectional study measuring serum levels of IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, IGFBP-4 and IGFBP-5 by specific immunoassays in 52 adults with Type 1 (n=27) and Type 2 (n=25) diabetes mellitus and 100 age- and sex-matched healthy blood donors. In the diabetic patients, we further determined serum levels of proinsulin, intact parathyroid hormone (PTH), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and several biochemical bone markers, including osteocalcin (OSC), bone alkaline phosphatase (B-ALP), carboxy-terminal propeptide of type I procollagen (PICP), and type I collagen cross-linked carboxy-terminal telopeptide (ICTP). Urinary albumin excretion was ascertained as a marker of diabetic nephropathy. Bone mineral density (BMD) of hip and lumbar spine was determined by dual-energy X-ray absorptiometry. Data are presented as means+/-s.e.m. Differences between the experimental groups were determined by performing a one-way analysis of variance (ANOVA), followed by Newman-Keuls test. Correlations between variables were assessed using univariate linear regression analysis and partial correlation analysis. Type 1 diabetics showed significantly lower IGF-I (119+/-8 ng/ml) and IGFBP-3 (2590+/-104 ng/ml) but higher IGFBP-1 levels (38+/-10 ng/ml) compared with Type 2 patients (170+/-13, 2910+/-118, 11+/-3 respectively; P<0.05) or healthy controls (169+/-5, 4620+/-192, 3.5+/-0.4 respectively; P<0.01). IGFBP-5 levels were markedly lower in both diabetic groups (Type 1, 228+/-9; Type 2, 242+/-11 ng/ml) than in controls (460+/-7 ng/ml,P<0. 01), whereas IGFBP-4 levels were similar in diabetics and controls. IGF-I correlated positively with IGFBP-3 and IGFBP-5 and negatively with IGFBP-1 and IGFBP-4 in all subjects. Type 1 patients showed a lower BMD of hip (83+/-2 %, Z-score) and lumbar spine (93+/-2 %) than Type 2 diabetics (93+/-5 %, 101+/-5 % respectively), reaching significance in the female subgroups (P<0.05). In Type 1 patients, BMD of hip correlated negatively with IGFBP-1 (r=-0.34, P<0.05) and IGFBP-4 (r=-0.3, P<0.05) but positively with IGFBP-5 (r=0.37, P<0. 05), which was independent of age, diabetes duration, height, weight and body mass index, as assessed by partial correlation analysis. Furthermore, biochemical markers indicating bone loss (ICTP) and increased bone turnover (PTH, OSC) correlated positively with IGFBP-1 and IGFBP-4 but negatively with IGF-I, IGFBP-3 and IGFBP-5, while the opposite was observed with bone formation markers (PICP, B-ALP) and vitamin D3 metabolites. In 20 Type 2 patients in whom immunoreactive proinsulin could be detected, significant positive correlations were found between proinsulin and BMD of hip (r=0.63, P<0.005), IGF-I (r=0.59, P<0.01) as well as IGFBP-3 (r=0.49, P<0.05). Type 1 and Type 2 patients with macroalbuminuria showed a lower BMD of hip, lower IGFBP-5 but higher IGFBP-4 levels, suggesting that diabetic nephropathy may contribute to bone loss by a disturbed IGF system. In conclusion, the findings of this study support the hypothesis that the imbalance between individual IGF system components and the lack of endogenous proinsulin may contribute to the lower BMD in Type 1 diabetics.
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PMID:Serum levels of insulin-like growth factor system components and relationship to bone metabolism in Type 1 and Type 2 diabetes mellitus patients. 979 71

We retrospectively evaluated the factors that are prognostic in long-term continuous ambulatory peritoneal dialysis (CAPD). From 1986 to 1997, 91 CAPD patients (59 male, 32 female, mean age 48 years) entered the study. Their primary renal diseases were chronic glomerulonephritis (CGN, n = 80), diabetic nephropathy (DN, n = 10), and polycystic kidney disease (PKD, n = 1). The roles of primary renal disease, hypertension, left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), cardiac sympathetic activity, anemia, hypoalbuminemia, and plasma concentration of parathyroid hormone (PTH) on patient prognosis were analyzed. Among the 91 CAPD patients, 26 died during the observation period. Of these deaths, 17 resulted from cardiovascular diseases including cerebrovascular events (n = 7), myocardial infarction (n = 2), sudden death (n = 7), and aortic aneurysmal rupture (n = 1). Nine patients died of non cardiovascular events. Sclerosing encapsulating peritonitis and others, mainly cachexia, accounted for 2 and 7 of these deaths, respectively. The 5-year survival rate was 74%; the 10-year rate was 49%. The cumulative 5- and 10-year success rates of CAPD were 69% and 39%, respectively. DN, hypertension, severe LVH (more than 200 g/m2), and hypoalbuminemia were contributors to poor prognosis. Among these, DN and severe LVH were the two main predictors by Cox proportional hazards model. We conclude that CAPD patients with DN or severe LVH, or both, have a greater chance of drop-out from cardiovascular events.
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PMID:Predictors of survival in continuous ambulatory peritoneal dialysis patients: the importance of left ventricular hypertrophy and diabetic nephropathy. 1068 78

Adynamic bone disease and elevated serum levels of advanced glycation end products (AGEs) often are found in patients with renal failure caused by diabetic nephropathy. To clarify the role of AGEs in adynamic bone disease, we investigated the effect of these substances on cultured human osteoblasts and parathyroid cells. After 72 hours of incubation with AGEs-bovine serum albumin (BSA) (1,000 microgram/mL), there was significant inhibition of the synthesis of type I collagen and osteocalcin in response to stimulation with 10(-10) to 10(-8) M of 1,25-dihydroxycholecalciferol. In a human osteoblastic cell line (MG 63), AGEs-BSA did not affect human osteocalcin promoter activity. In human parathyroid cells, a receptor for AGEs was detected by reverse-transcriptase polymerase chain reaction. Incubation with AGEs-BSA for 48 hours significantly inhibited parathyroid hormone secretion in response to a low calcium concentration of 0.81 mM (P < 0.01). In HEK-293 cells, expressing calcium-sensing receptors, the same AGE concentration caused a significant potentiation of the extracellular Ca(2+) induced-intracellular calcium concentration after 24 and 48 hours of incubation (P < 0.05 and P < 0.01). These data suggest that AGEs are involved in the pathogenesis of adynamic bone disease by inhibiting osteoblastic activity and by inhibiting parathyroid hormone secretion in response to hypocalcemia.
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PMID:Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy. 1157 45

Biological interactions between the bone and the blood vessels are gradually being clarified. To investigate the relationship between bone mineral density and atherosclerosis in hemodialysis patients, we examined the bone mineral density and the intima-media thickness of the carotid artery in 83 dialysis patients with non-diabetic nephropathy (44 men and 39 women) aged from 23 to 83 years. The duration of hemodialysis ranged from 2 to 344 months. The bone mineral density of the radius was measured by dual-energy X-ray adsorptiometry, and the ratio of this value to the standard value for the same age and gender was calculated ( Z-score). As an index of atherosclerosis, the intima-media thickness of the carotid artery was measured by high resolution B-mode ultrasonography. Then the relationship between the Z-score and various factors was examined using Spearman's rank correlation analysis and multiple regression analysis. The Z-score showed a negative correlation with the duration of hemodialysis, the carotid intima-media thickness, and the levels of alkaline phosphatase, intact parathyroid hormone, and low-density lipoprotein cholesterol by Spearman's rank correlation analysis. In addition, the Z-score showed a positive correlation with the lipoprotein (a) level and a negative correlation with the duration of hemodialysis, intima-media thickness, intact parathyroid hormone, and low-density lipoprotein cholesterol by multiple regression analysis. These findings suggest that the decrease of bone mineral density in hemodialysis patients is correlated with secondary hyperparathyroidism and hyperlipidemia, which are factors known to promote atherosclerosis, and thus bone density changes might be related to the progression of atherosclerosis, or vice versa.
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PMID:Bone mineral density may be related to atherosclerosis in hemodialysis patients. 1459 55

A 42-year-old woman underwent hemodialysis secondary to diabetic nephropathy. Total parathyroidectomy with forearm autograft was performed due to secondary hyperparathyroidism (HPT) complicated with calciphylaxis. Rapidly progressive enlargement of autograft with unusual "gourd-shape" developed, and then it was removed. Pathologic examination of the autograft disclosed multinodular hyperplasia. Residual parathyroid gland in the retrothyroid region was found later. Rapidly recurrent HPT originating from both the residual parathyroid tissues and the enlarged autograft within such short time after parathyroidectomy is rare in the literature. The multinodular hyperplasia pattern of the parathyroid gland may be a major factor for such rapid recurrence. In addition to good control of calcium and phosphate, regular follow-up of parathyroid hormone level and imaging studies of not only autografted gland at the forearm but also possibly residual parathyroid tissues at the neck are important for monitoring recurrence in maintenance hemodialysis patients after parathyroidectomy with forearm autograft, especially in those with pathologic type of nodular hyperplasia and calciphylaxis.
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PMID:Rapid recurrence of hyperparathyroidism from both nodularly hyperplastic autograft at forearm and residual tissues at neck after parathyroidectomy in a hemodialysis patient with calciphylaxis. 1670 1

A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not necessarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arterial blood HCO(3-). Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally maxacalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D preparation decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%.
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PMID:An overview of regular dialysis treatment in Japan (as of 31 December 2004). 1719 80

The number of patients requiring renal replacement therapy because of diabetic nephropathy has been relentlessly increasing, and diabetes mellitus is now the leading cause of end stage renal disease in most Western Countries. Diabetic nephropathy has specificities. First, it tends to progress rapidly toward end stage renal disease. Second, patients with diabetic nephropathy are at increased risk of cardiovascular disease, when compared to patients with non diabetic nephropathy; similarly to what has been shown for diabetic patients on dialysis. Third, patients with diabetic nephropathy tend to be more severely anemic than patients with non-diabetic chronic kidney disease. Finally, small studies suggest that patients with diabetic nephropathy could have lower serum concentrations of parathyroid hormone than patients with non-diabetic nephropathy and similar glomerular filtration rate.
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PMID:[The diabetic patient: renal insufficiency like other kidney failures?]. 1737 Aug 48

Meprin metalloproteinases have been implicated in the susceptibility to and progression of diabetic nephropathy and inflammatory bowel diseases. Our studies with experimental models of these diseases in mice are congruent with the conclusion that meprins modulate the inflammatory responses and tissue damage. To determine whether the mouse and human enzymes differ, recombinant forms of meprin A from the two species were compared with respect to structure, substrates and inhibitors. Human homo-oligomeric meprin A formed oligomers ranging from 950,000 to 1,500,000 Da vs. 900,000 Da for mouse meprin A. Human and mouse meprin A exhibited similar activity against azocasein, fibronectin, collagen IV, and peptides such as parathyroid hormone, ghrelin, and gastrin-releasing peptide. The human enzyme had lower activity against gelatin, bradykinin, alpha-melanocyte-stimulating hormone and neurotensin, and higher activity against secretin and orcokinin. Human meprin A showed a preference for acidic residues in the P1' position of the substrate, unlike mouse meprin A. Several metalloproteinase inhibitors had IC(50) values in the nanomolar range, but potency ranged from similar values to a difference of several orders of magnitude for meprins from the two species. This work provides valuable data to improve predictability for human systems based on meprin functions in mouse models.
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PMID:Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate and inhibitor specificities. 1797 9


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