Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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Insights into end-stage renal disease have emerged from many investigations but less is known about the epidemiology of chronic renal insufficiency (CRI) and its relationship to cardiovascular disease (CVD). The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for progression of CRI and CVD among CRI patients and develop models to identify high-risk subgroups, informing future treatment trials, and increasing application of preventive therapies. CRIC will enroll approximately 3000 individuals at seven sites and follow participants for up to 5 yr. CRIC will include a racially and ethnically diverse group of adults aged 21 to 74 yr with a broad spectrum of renal disease severity, half of whom have diagnosed diabetes mellitus. CRIC will exclude subjects with polycystic kidney disease and those on active immunosuppression for glomerulonephritis. Subjects will undergo extensive clinical evaluation at baseline and at annual clinic visits and via telephone at 6 mo intervals. Data on quality of life, dietary assessment, physical activity, health behaviors, depression, cognitive function, health care resource utilization, as well as blood and urine specimens will be collected annually. (125)I-iothalamate clearances and CVD evaluations including a 12-lead surface electrocardiogram, an echocardiogram, and coronary electron beam or spiral CT will be performed serially. Analyses planned in CRIC will provide important information on potential risk factors for progressive CRI and CVD. Insights from CRIC should lead to the formulation of hypotheses regarding therapy that will serve as the basis for targeted interventional trials focused on reducing the burden of CRI and CVD.
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PMID:The Chronic Renal Insufficiency Cohort (CRIC) Study: Design and Methods. 1281 21

In the nineties of the 20th century diabetic nephropathy has become the leading cause of regular dialysis treatment (RDT) in developed countries. In particular type 2 diabetics are involved. A similar trend can be observed also in the Czech Republic which holds in this respect the first place among countries of the former eastern block (33% patients with RDT) suffer from diabetes. The cause of the increase of patients with diabetic nephropathy and renal failure caused by diabetes is not only the rising prevalence and incidence of type 2 diabetes in the population but in particular the better care provided to patients with type 2 diabetes which enables them to survive macro- and microvascular complications incl. diabetic nephropathy. It is estimated that diabetic nephropathy affects 4-8% patients attending diabetic clinics. With regard to the increasing number of diabetics in RDT, moreover associated with their high polymorbidity, this is a serious medical and economic problem. The main factors which influence in the diabetic patients the risk of development of diabetic nephropathy are long-term control of glycaemia, genetic (ethnic) factors, age and sex. The decisive factor influencing in patients with diabetic nephropathy the progression of chronic renal insufficiency is control of the blood pressure. Including diabetics in RDT is not associated only with medical problems but also with socio-economic issues. The quality of life of diabetics is much lower and the survival of diabetics treated within the framework of RDT is still almost half as compared with the survival of non-diabetic patients. Decision on the selection of the dialysis method is not easy. Medical differences are well defined but should not be considered absolute. It is important to consider also which method is preferred by the patient. Optimally the decision is taken during the period of dispensarization. Both dialyzation methods have comparable results and survival although for diabetics under 50 years of age a more favourable prognosis of peritoneal dialysis is reported. However, the risk of "failure of the method" is in general higher in peritoneal dialysis.
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PMID:[Diabetes mellitus and chronic renal insufficiency]. 1290 75

Black Americans experience a disproportionate burden of ESRD compared with whites. Whether this is caused by the increased prevalence of chronic renal insufficiency (CRI) among blacks or by their increased progression from CRI to ESRD was investigated. A birth cohort analysis was performed using data from the Third National Health and Nutrition Examination Survey and the United States Renal Data System. It was assumed that those who developed ESRD in 1996 aged 25 to 79 yr came from the source population with CRI aged 20 to 74 yr that was sampled in the Third National Health and Nutrition Examination Survey (midpoint 1991). GFR was estimated using the Modification of Diet in Renal Disease study equation. The prevalence of CRI (GFR 15 to 59 ml/min per 1.73 m(2)) was not different among black compared with white adults (2060 versus 2520 per 100,000; P = 0.14). For each 100 blacks with CRI in 1991, five new cases of ESRD developed in 1996, whereas only one case of ESRD developed per 100 whites with CRI (risk ratio, 4.8; 95% confidence interval, 2.9 to 8.4). The increased risk for blacks compared with whites was only modestly affected by adjustment for age, gender, and diabetes. Blacks with CRI had higher systolic (147 versus 136 mmHg; P = 0.001) and diastolic (82 versus 77 mmHg; P = 0.02) BP and greater albuminuria (422 versus 158 micro g urine albumin/mg urine creatinine; P = 0.01). The higher incidence of ESRD among blacks is not due to a greater prevalence of CRI among blacks. The key to understanding black-white differences in ESRD incidence lies in understanding the extreme differences in their progression from CRI to ESRD.
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PMID:Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States. 1456

Drug-induced nephropathy is an important cause of renal injury which is reversible when detected early. Unfortunately, the clinical signs may not be apparent in the early phases and the nephropathy may become evident only at an advanced stage with an acute deterioration of the renal functions or chronic renal insufficiency. It is particularly important not only to know the nephrotoxic potential of the different drug groups, but especially to recognize the patient's risk factors that could be modified or that should preclude the use of these drugs. The presence of comorbid conditions such as older age, diabetes mellitus and congestive heart failure significantly influences the patient's ability to recover from the toxic effects. Many drugs can injure the kidneys, but they cause renal injury via only a few common mechanisms. The aim of the present review is to examine the main clinical presentations of drug-induced nephropathy.
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PMID:[Drug-induced nephropathy]. 1462 23

The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism has been associated with a decreased risk of type 2 diabetes and a lower albumin excretion rate (AER) in patients with established diabetes. We performed a case-control study aiming to evaluate the association between the Pro12Ala polymorphism and diabetic nephropathy. Genomic DNA was obtained from 104 type 2 diabetic patients (case subjects) with chronic renal insufficiency (78 on dialysis and 26 with proteinuria [AER >or=200 microg/min] and serum creatinine >or=2.0 mg/dl) and 212 normoalbuminuric patients (AER <20 microg/min) with known diabetes duration >or=10 years (control subjects). The genotypic distribution of the PPARgamma2 Pro12Ala polymorphism in these diabetic patients was in Hardy-Weinberg equilibrium, and the Ala allele frequency was 9%. The frequency of Ala carriers (Ala/Ala or Ala/Pro) was 20.3% in control subjects and 10.6% in case subjects (P = 0.031). The odds ratio of having diabetic nephropathy for Ala carriers was 0.465 (95% CI 0.229-0.945; P = 0.034). Carriers of the Ala allele were not different from noncarriers (Pro/Pro) regarding sex (38.9 vs. 44.1% males) or ethnicity (77.4 vs. 71.7% white) distribution, age (61 +/- 10 vs. 61 +/- 10 years), known diabetes duration (17 +/- 7 vs. 16 +/- 7 years), BMI (27 +/- 4 vs. 28 +/- 5 kg/m(2)), fasting plasma glucose (184 +/- 81 vs. 176 +/- 72 mg/dl), HbA(1c) (6.7 +/- 2.3 vs. 6.9 +/- 2.4%; high-performance liquid chromatography reference range: 2.7-4.3%), and systolic (145 +/- 27 vs. 0.144 +/- 24 mmHg) or diastolic (87 +/- 14 vs. 85 +/- 14 mmHg) blood pressure, respectively. In conclusion, the presence of the Ala allele may confer protection from diabetic nephropathy in patients with type 2 diabetes.
Diabetes 2003 Dec
PMID:The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes. 1463 65

This study provides extended follow-up of a nonrandomized series of symptomatic patients who underwent subclavian stent-supported angioplasty (SSA) with emphasis on preprocedure factors that may have influenced outcome. The endpoints of mortality and restenosis were analyzed using backward stepwise logistic regression with the following clinical variables: coronary artery disease, hypertension, hyperlipidemia, smoking, diabetes mellitus, chronic obstructive pulmonary disease, chronic renal insufficiency/failure, and hypothyroidism. Restenosis is reported based on prospective serial noninvasive studies and/or angiography. Mortality was evaluated by retrospective database review and inquiry to the State Department of Health and Human Services' statistical registry in patients who were lost to follow-up. Over a 9-year period (mean follow-up, 36.1 +/- 30.4 months; maximum observation, 109.5 months), 101 stents were placed in 91 consecutive patients (37 male, 54 female). The mean age at intervention was 62.03 +/- 9.3. The procedure was technically successful in 89 patients 97% (mean pre- and postoperative stenosis and pressure gradients were 90.2% +/- 9.4% vs. 3.7% +/- 6.6%, P < 0.001, and 59.9 +/- 35.2 vs. 0 mm Hg, P < 0.001, respectively), with 13 minor complications and no immediate major complications. One patient died of unrelated causes within 30 days. Per Kaplan-Meier method, for years 1 through 5, the rates of overall patency were 96%, 91%, 86%, 77%, and 72%; likewise, overall patient survival was 93%, 88%, 8%4, 81%, and 76%. No clear predictors for restenosis were discovered, although a trend toward higher recurrence was noted in women (18.5% in female vs. and 8.6% in male; P > 0.05), but the same were less likely to die during follow-up (P > 0.001). Also, the presence of hypothyroidism (P = 0.004) and increasing age (P = 0.068) were positively correlated with all-cause mortality. This study suggests that SSA is predictable, safe, and durable. The diagnosis of symptomatic subclavian disease is of prognostic importance, with age and male gender representing important predictors of all-cause long-term mortality. The strong association of increased mortality with hypothyroidism is difficult to discard and raises the question of a yet to be described thyroid steal phenomena.
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PMID:Subclavian artery stenting: factors influencing long-term outcome. 1469 51

Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important factors in the pathogenesis of type 2 diabetes and have a promising therapeutic potential. Alterations of their secretion, in vivo degradation, and elimination in patients with chronic renal insufficiency (CRI) have not yet been characterized. Ten patients with CRI (aged 47 +/- 15 years, BMI 24.5 +/- 2.2 kg/m(2), and serum creatinine 2.18 +/- 0.86 mg/dl) and 10 matched healthy control subjects (aged 44 +/- 12 years, BMI 24.9 +/- 3.4 kg/m(2), and serum creatinine 0.89 +/- 0.10 mg/dl) were included. On separate occasions, an oral glucose tolerance test (75 g), an intravenous infusion of GLP-1 (0.5 pmol. kg(-1). min(-1) over 30 min), and an intravenous infusion of GIP (1.0 pmol. kg(-1). min(-1) over 30 min) were performed. Venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1 (total and intact), and GIP (total and intact; specific immunoassays). Plasma levels of GIP (3-42) and GLP-1 (9-36 amide) were calculated. Statistics were performed using repeated-measures and one-way ANOVA. After the oral glucose load, plasma concentrations of intact GLP-1 and intact GIP reached similar levels in both groups (P = 0.31 and P = 0.87, respectively). The concentrations of GIP (3-42) and GLP-1 (9-36 amide) were significantly higher in the patients than in the control subjects (P = 0.0021 and P = 0.027, respectively). During and after the exogenous infusion, GLP-1 (9-36 amide) and GIP (3-42) reached higher plasma concentrations in the CRI patients than in the control subjects (P < 0.001 and P = 0.0033, respectively), whereas the plasma levels of intact GLP-1 and GIP were not different between the groups (P = 0.29 and P = 0.27, respectively). Plasma half-lives were 3.4 +/- 0.6 and 2.3 +/- 0.4 min for intact GLP-1 (P = 0.13) and 5.3 +/- 0.8 and 3.3 +/- 0.4 min for the GLP-1 metabolite (P = 0.029) for CRI patients vs. healthy control subjects, respectively. Plasma half-lives of intact GIP were 6.9 +/- 1.4 and 5.0 +/- 1.2 min (P = 0.31) and 38.1 +/- 6.0 and 22.4 +/- 3.0 min for the GIP metabolite (P = 0.032) for CRI patients vs. healthy control subjects, respectively. Insulin concentrations tended to be lower in the patients during all experiments, whereas C-peptide levels tended to be elevated. These data underline the importance of the kidneys for the final elimination of GIP and GLP-1. The initial dipeptidyl peptidase IV-mediated degradation of both hormones is almost unaffected by impairments in renal function. Delayed elimination of GLP-1 and GIP in renal insufficiency may influence the pharmacokinetics and pharmacodynamics of dipeptidyl peptidase IV-resistant incretin derivatives to be used for the treatment of patients with type 2 diabetes.
Diabetes 2004 Mar
PMID:Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. 1498 49

Previous retrospective research suggests that low-level environmental lead exposure is associated with an acceleration of age-related impairment of renal function. For elucidating the long-term relationship between low-level environmental lead exposure and progression of chronic renal diseases in patients without diabetes, 121 patients who had chronic renal insufficiency, a normal body lead burden (BLB), and no history of exposure to lead were observed prospectively for 48 mo. Associations of both BLB and blood lead level (BLL) with renal function were evaluated, with reference to other covariates. The primary end point was an increase in the serum creatinine level to double the baseline value. Sixty-three patients had BLB > or =80 microg and < 600 microg (high-normal group), and 58 patients had BLB < 80 microg (low-normal group). The primary end point occurred in 17 patients. Fifteen of them had high-normal BLB, whereas two patients had low-normal BLB (hazard ratio [95% confidence interval]: 1.01 [1.00 to 1.01] for each increment of 1 microg; P = 0.002). The BLB and BLL at baseline were the most important risk factors to predict progression of renal insufficiency. Each increase of 10 microg in the BLB or 1 microg/dl in the BLL reduced the GFR by 1.3 (P = 0.002) or 4.0 ml/min (P = 0.01) during the study period. In conclusion, low-level environmental lead exposure is associated with accelerated deterioration of renal insufficiency. Even at levels far below the normal ranges, both increased BLL and BLB predict accelerated progression of chronic renal diseases.
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PMID:Environmental exposure to lead and progression of chronic renal diseases: a four-year prospective longitudinal study. 1503 4

Major non-cardiac surgery within 40 days of coronary angioplasty with stenting has high cardiac complication rates. We have performed a case-control study to determine whether the risk of vascular surgery might have increased in recent survivors of coronary artery bypass surgery (CABG). Using our vascular database from 1990 to 1999, we matched the cases who had vascular surgery within a month of CABG with controls by pre-operative comorbidities of diabetes mellitus, history of myocardial infarction (MI), history of congestive heart failure (CHF), and chronic renal insufficiency and compared the incidence of peri-operative MI, CHF, death, and other complications. Compared to case-matched controls, patients who underwent vascular surgery within a month of CABG suffered significantly greater mortality (20.6% vs. 3.9%, p < 0.005). The incidence of non-fatal cardiac complications was not significantly different between the groups. We conclude that the risk of mortality may be significantly greater in patients undergoing major vascular surgery within a month of CABG.
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PMID:Timing of high-risk vascular surgery following coronary artery bypass surgery: a 10-year experience from an academic medical centre. 1509 34

Cardiovascular calcification is a common consequence of aging, diabetes, hypercholesterolemia, mechanically abnormal valve function, and chronic renal insufficiency. Although vascular calcification may appear to be a uniform response to vascular insult, it is a heterogenous disorder, with overlapping yet distinct mechanisms of initiation and progression. A minimum of four histoanatomic variants-atherosclerotic (fibrotic) calcification, cardiac valve calcification, medial artery calcification, and vascular calciphylaxis-arise in response to metabolic, mechanical, infectious, and inflammatory injuries. Common to the first three variants is a variable degree of vascular infiltration by T cells and macrophages. Once thought benign, the deleterious clinical consequences of calcific vasculopathy are now becoming clear; stroke, amputation, ischemic heart disease, and increased mortality are portended by the anatomy and extent of calcific vasculopathy. Along with dystrophic calcium deposition in dying cells and lipoprotein deposits, active endochondral and intramembranous (nonendochondral) ossification processes contribute to vascular calcium load. Thus vascular calcification is subject to regulation by osteotropic hormones and skeletal morphogens in addition to key inhibitors of passive tissue mineralization. In response to oxidized lipids, inflammation, and mechanical injury, the microvascular smooth muscle cell becomes activated. Orthotopically, proliferating stromal myofibroblasts provide osteoprogenitors for skeletal growth and fracture repair; however, in valves and arteries, vascular myofibroblasts contribute to cardiovascular ossification. Current data suggest that paracrine signals are provided by bone morphogenetic protein-2, Wnts, parathyroid hormone-related polypeptide, osteopontin, osteoprotegerin, and matrix Gla protein, all entrained to endocrine, metabolic, inflammatory, and mechanical cues. In end-stage renal disease, a "perfect storm" of vascular calcification often occurs, with hyperglycemia, hyperphosphatemia, hypercholesterolemia, hypertension, parathyroid hormone resistance, and iatrogenic calcitriol excess contributing to severe calcific vasculopathy. This brief review recounts emerging themes in the pathobiology of vascular calcification and highlights some fundamental deficiencies in our understanding of vascular endocrinology and metabolism that are immediately relevant to human health and health care.
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PMID:Osteogenic regulation of vascular calcification: an early perspective. 1510 15


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