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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A shared and additive genetic variance component-long-term survivor (LTS) model for familial aggregation studies of complex diseases with variable age-at-onset phenotype and non-susceptible subjects in the study cohort is proposed. LTS has been used from the early 1970s, especially in epidemiological studies of cancer. The LTS model utilizes information on the age at onset (survival) distribution to make inference on partially latent susceptibility. Bayesian modeling with uninformative priors is used and estimates of the posterior distribution of age at onset and susceptibility parameters of interest have been obtained using Bayesian Markov chain Monte Carlo (MCMC) methods with OpenBugs program. A simulation study confirms that we obtain posterior estimates of the model parameters on shared and genetic variance components of age at onset and susceptibility with good coverage rates. Further, we analyze familial aggregation of diabetic nephropathy (DN) in large Finnish cohort of 528 sibships with type 1 diabetes (T1D). According to the variance components estimated a substantial familial variation in the susceptibility to DN exist among families, while time to DN is less influenced by shared familial factors.
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PMID:Genetic random effects model for family data with long-term survivors: analysis of diabetic nephropathy in type 1 diabetes. 1748 84

Reactive oxygen species (ROS) are considered to be chemically reactive with and damaging to biomolecules including DNA, protein, and lipid, and excessive exposure to ROS induces oxidative stress and causes genetic mutations. However, the recently described family of Nox and Duox enzymes generates ROS in a variety of tissues as part of normal physiological functions, which include innate immunity, signal transduction, and biochemical reactions, e.g., to produce thyroid hormone. Nature's "choice" of ROS to carry out these biological functions seems odd indeed, given its predisposition to cause molecular damage. This review describes normal biological roles of Nox enzymes as well as pathological conditions that are associated with ROS production by Nox enzymes. By far the most common conditions associated with Nox-derived ROS are chronic diseases that tend to appear late in life, including atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, Alzheimer's disease, and others. In almost all cases, with the exception of a few rare inherited conditions (e.g., related to innate immunity, gravity perception, and hypothyroidism), diseases are associated with overproduction of ROS by Nox enzymes; this results in oxidative stress that damages tissues over time. I propose that these pathological roles of Nox enzymes can be understood in terms of antagonistic pleiotropy: genes that confer a reproductive advantage early in life can have harmful effects late in life. Such genes are retained during evolution despite their harmful effects, because the force of natural selection declines with advanced age. This review discusses some of the proposed physiologic roles of Nox enzymes, and emphasizes the role of Nox enzymes in disease and the likely beneficial effects of drugs that target Nox enzymes, particularly in chronic diseases associated with an aging population.
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PMID:Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. 1760 48

The influence of the type of dialysis on survival of patients with end-stage renal disease (ESRD) is controversial. To compare survival among patients with ESRD receiving peritoneal dialysis (PD) or hemodialysis (HD), we conducted a prospective cohort study in a single center from April 1995 to March 2005. During that period, 454 patients (161 women, 293 men; mean age: 61.7 +/- 14.4 years; 46.6% with diabetic nephropathy) were started on HD therapy, and 120 patients (40 women, 80 men; mean age: 54.5 +/- 11.3 years; 16.7% with diabetic nephropathy) were started on PD therapy; all patients were followed for at least 3 years. The 3-year survival rates were 65% for the HD patients and 81% for the PD patients (p < 0.05). The causes of death in patients undergoing HD were 52% cardiovascular 25% infectious diseases, and 12% cancer; in patients undergoing PD, the causes were 36% infectious diseases, 24% cardiovascular, and 6% cancer Median time from initiation of dialysis to study enrollment was 90 days for HD patients and 180 days for PD patients. Although patients in this study were not randomly assigned to their initial type of dialysis therapy, survival rate was found to be dependent on dialysis type. Moreover, this study suggests the importance of early referral and evaluation of risk factors in individual patients before they are started on dialysis therapy.
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PMID:Comparison and survival of patients receiving hemodialysis and peritoneal dialysis in a single center. 1788 22

This review briefly handles the use of (1)H NMR spectroscopy in lipoprotein subclass analytics. Potential diagnostic uses of (1)H NMR metabonomics of human serum for coronary heart disease, diabetic nephropathy and cancer are also discussed. In addition, miscellaneous recent applications of NMR metabonomics (e.g., a pharmacometabonomic tactic to personalize drug treatment) as well as multi-organ, multispecies and multi-omics approaches to molecular systems biology are featured. Some related experimental and data analysis methodologies are briefly introduced with respect to the biochemical rationales. Critical considerations on the potential diagnostic value of in vitro (1)H NMR are presented together with optimism toward the usage of body fluid (1)H NMR metabonomics in disease risk assessment and as an aid for personalized medicine.
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PMID:Potential role of body fluid 1H NMR metabonomics as a prognostic and diagnostic tool. 1802 Sep 6

Nephrotic syndrome (NS) is an essential clinical problem in the elderly. It may be difficult to recognize NS in the elderly because its symptoms are frequently missed with congestive heart failure or venous insufficiency. Glomerular diseases are not most common in elderly population but they play important role in renal pathology in this group of patients. Many structural and functional changes occur in the kidney with an increasing age. These changes may make, at least in part, the interpretation of renal lesions difficult. Glomerular pathology in this group of patients may be secondary to neoplastic diseases, and, therefore before the kidney biopsy screening for malignancies should be performed. The occurrence of particular forms of glomerular diseases differs between the older and young population. The most common forms of primary glomerular diseases in elderly are membranous nephropathy and focal-segmental glomerulosclerosis, whereas diabetic nephropathy and amyloidosis are common causes of secondary nephropathies. Kidney biopsy in the elderly gives valuable information, just as it is in the other age groups. It is a reasonably safe procedure, although associated with an increased risk of bleedings, when compared to younger population.
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PMID:[Nephrotic syndrome in the elderly. The most frequent causes of the nephrotic syndrome in the elderly (part I)]. 1836 26

Urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) is an excellent marker of oxidative DNA damage. Until now, urinary 8OHdG has been measured by high-performance liquid chromatography with electrochemical detection. A simple and sensitive method for the analysis of urinary 8OHdG by capillary electrophoresis with end-column amperometric detection has been developed and is described in this chapter. A single-step solid-phase extraction procedure was optimized and used for extracting 8OHdG from human urine. To improve the sensitivity of this method, a new focusing technique based on a dynamic pH junction was used. In the end, the urinary concentration of 8OHdG in healthy persons, patients with cancer, patients with diabetic nephropathy, and smokers was determined. Emphasis is focused on the establishment and application of the methods.
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PMID:Capillary electrophoresis of oxidative DNA damage. 1839 78

Members of the CCN (CYR61/CTGF/NOV) family have emerged as dynamically expressed, extracellular matrix-associated proteins that play critical roles in cardiovascular and skeletal development, injury repair, fibrotic diseases and cancer. The synthesis of CCN proteins is highly inducible by serum growth factors, cytokines, and environmental stresses such as hypoxia, UV exposure, and mechanical stretch. Consisting of six secreted proteins in vertebrate species, CCNs are typically comprised of four conserved cysteine-rich modular domains. They function primarily through direct binding to specific integrin receptors and heparan sulfate proteoglycans, thereby triggering signal transduction events that culminate in the regulation of cell adhesion, migration, proliferation, gene expression, differentiation, and survival. CCN proteins can also modulate the activities of several growth factors and cytokines, including TGF-beta, TNFalpha, VEGF, BMPs, and Wnt proteins, and may thereby regulate a broad array of biological processes. Recent studies have uncovered novel CCN activities unexpected for matricellular proteins, including their ability to induce apoptosis as cell adhesion substrates, to dictate the cytotoxicity of inflammatory cytokines such as TNFalpha, and to promote hematopoietic stem cell self-renewal. As potent regulators of angiogenesis and chondrogenesis, CCNs are essential for successful cardiovascular and skeletal development during embryogenesis. In the adult, the expression of CCN proteins is associated with injury repair and inflammation, and has been proposed as diagnostic or prognostic markers for diabetic nephropathy, hepatic fibrosis, systemic sclerosis, and several types of cancer. Targeting CCN signaling pathways may hold promise as a strategy of rational therapeutic design.
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PMID:Functions and mechanisms of action of CCN matricellular proteins. 1877 91

Previous reports have shown that DNA methylation profiles within primary human malignant tissues are altered when these cells are transformed into cancer cell lines. However, it is unclear if similar differences in DNA methylation profiles exist between DNA derived from peripheral blood leukocytes (PBLs) and corresponding Epstein-Barr Virus transformed lymphoblastoid cell lines (LCLs). To assess the utility of LCLs as a resource for methylation studies we have compared DNA methylation profiles in promoter and 5' regions of 318 genes in PBL and LCL sample pairs from patients with type 1 diabetes with or without nephropathy. We identified a total of 27 (approximately 8%) genes that revealed different DNA methylation profiles in PBL compared with LCL-derived DNA samples. In conclusion, although the profiles for most promoter regions were similar between PBL-LCL pairs, our results indicate that LCL-derived DNA may not be suitable for DNA methylation studies at least in diabetic nephropathy.
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PMID:Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines. 1944 41

Vascular endothelial growth factor (VEGF) is a main regulator of blood vessel growth and plays an important role in promoting endothelial survival and maintaining the microvasculature. The kidney is a highly vascularized organ and has two important microvasculatures; glomerular and peritubular capillaries. Loss of these capillaries is strongly associated with the progression of chronic kidney disease (CKD) to end-stage renal disease. In several kidney disease animal models, VEGF expression in the kidney is decreased and administration of VEGF is protective. Recent clinical observations revealed that blocking VEGF by endogenous inhibitor (soluble Flt-1) in preeclampsia and monoclonal antibody against VEGF in cancer patients cause proteinuria and renal dysfunction. However, plasma VEGF levels in diabetic nephropathy patients are increased and blocking VEGF improved diabetic nephropathy in animal models. Increased plasma VEGF levels have been reported in CKD patients. Deleterious effects of VEGF have been demonstrated in atherosclerosis and sepsis, which are frequent complications in CKD patients. Although administrating VEGF or novel drugs that activate VEGF pathway may improve the progression of CKD, careful monitoring will be required when CKD patients have complications of diabetes, atherosclerosis or sepsis.
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PMID:Role of vascular endothelial growth factor in kidney disease. 1948 13

While anemia is common in patients on chronic hemodialysis (HD), spontaneous erythrocytosis is rare and can be caused by either the same conditions causing erythrocytosis in the general population or any condition specific to chronic renal failure. We present a patient illustrating this latter circumstance. A 53-year-old man with diabetic nephropathy, with no known disease causing hypoxemia started HD in April 2001. Blood hemoglobin (Hgb) level was 13.7 +/- 2.8 g/dL while his kidney function was normal (1993-1996) and after 1997, with the development of chronic kidney disease, decreased progressively to a low of 10.2 g/dL in March 2001 when erythropoietin (EPO) injections were started. Erythropoietin requirements progressively decreased because of rising Hgb. Erythropoietin was discontinued in mid-2005. Blood hemoglobin continued to rise, however, to a high value of 17.6 g/dL in February 2006. At the same time, endogenous blood EPO level was 3.6 mIU/mL, a value consistent with primary polycythemia. White blood cell and platelet counts were normal. Several small renal cysts, including 1 complex cyst, were detected by ultrasonography and computer tomography in April 2006. He refused surgical treatment. He was treated with small phlebotomies (not returning the blood in the dialyzer at the end of dialysis) and monitoring of Hgb, which decreased toward the desired range. Repeated computer tomographic scans showed a slow increase in the size of the complex cyst and several other cysts. In late 2007 Hgb started rising again, and in February 2008, while the Hgb level was 16.4 g/dL, the endogenous serum EPO level was 726 mIU/mL (upper normal limit 31.5 mIU/mL). Intermittent phlebotomies were reinstituted. He subsequently developed multiple vascular catastrophes and expired from ischemic bowel disease in September 2008. Acquired cystic disease of the kidneys should be considered in HD patients who develop spontaneous erythrocytosis. The risks of acquired cystic disease include, in addition to the development of malignancy, vascular events from elevated Hgb.
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PMID:Spontaneous erythrocytosis in a patient on chronic hemodialysis. 1977 22


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