Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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Serum cystatin C (CysC) has been proposed as a potentially superior marker for the evaluation of renal function because it was more sensitive and accurate for the estimation of glomerular filtration rate (GFR) than other markers. We evaluated the clinical usefulness of CysC in diabetic nephropathy. The study was performed on 414 Japanese diabetic patients. We compared serum CysC levels with serum creatinine levels, urinary concentrations of albumin, transferrin and type IV collagen, and creatinine clearance (Ccr). Then, the correlation between serum CysC levels and high-sensitivity C-reactive protein (H-CRP) levels were examined. When the patients were classified by renal function, 19% of the patients were free from nephropathy, 49% had microalbuminuria, 28% had persistent proteinuria, and 4% had end stage renal disease. The serum CysC levels increased with the progression of nephropathy, and significantly higher in overt nephropathy, but not significant in early nephropathy. Serum CysC levels were well-correlated with H-CRP levels in the patients without nephropathy. These results indicate that serum CysC would be practical for the evaluation of renal function in diabetic patients with overt nephropathy but not early nephropathy and might be related with a risk for cardiovascular events in patients without nephropathy.
Diabetes Res Clin Pract 2008 Feb
PMID:Serum cystatin C in diabetic patients. Not only an indicator for renal dysfunction in patients with overt nephropathy but also a predictor for cardiovascular events in patients without nephropathy. 1798 Sep 29

Renal dysfunction is associated with increased cardiovascular morbidity and mortality. The aim of this cross-sectional study was to investigate the relationship between the glomerular filtration marker cystatin C and other cardiovascular risk markers and morbidity in elderly males. Cystatin C was measured in a group of 77-year-old males (n=792) and compared cystatin C with other known risk markers for cardiovascular disease. Cystatin C values were significantly increased in individuals with diabetes (p=0.05) and cardiovascular diseases (p<0.0001). There were significant correlations between cystatin C values and body mass index, HbA1c, insulin, triglycerides and hsCRP.
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PMID:Serum cystatin C is associated with other cardiovascular risk markers and cardiovascular disease in elderly men. 1799 17

Because of incompatible reports about the renal impairment to abdominal aortic aneurysm (AAA) repair, we conducted a prospective study to determine the differences in renal response between open (OR) and endovascular (EVAR) aneurysm repair. In a prospective, nonrandomized, single-center study, we evaluated 485 patients with AAAs undergoing OR or EVAR between January 2000 and December 2005. Only electively performed procedures were analyzed in detail. The OR group included 229 patients (males/females 203/26, median age 69.8 [range 43-90] years, aneurysm diameter in median 57 [26-95] mm), and the EVAR group integrated 144 patients (males/females 129/15, 73.1 [49-90] years [p=.001], 55 [33-100] mm). Renal function was assessed by determinating the preoperative serum creatinine (SCr) level and SCr clearance according to Cockcroft-Gault. Postoperatively, SCr level and SCr clearance were determined at defined intervals, reported as highest postoperative SCr level, SCr level at time of discharge, lowest postoperative SCr clearance, and SCr clearance at time of discharge. The parameters of height, weight, diabetes, smoking habit, serum cholesterol level, and hemoglobin were not different between the groups. Significantly different were the American Society of Anesthesiologists classification, the Society for Vascular Surgery Comorbidity Score, and the exposure to contrast dye. Moreover, significantly different were intraoperatively measured median blood loss (1,200 vs. 400 mL) and the median time of operation (164 vs. 135 min). Although, the preoperative SCr levels between the groups were not statistically different (OR group 1.0 [0.87-1.23] mg/dL [median, interquartile range], EVAR group 1.0 [0.9-1.3]; p > 0.05), the SCr clearance was (OR group 72.8 [58.2-98.8] mL/min, EVAR group 67.6 [51.3-85.1] mL/min; p = 0.007). In the postoperative period, SCr level did not change significantly in the OR group but did in the EVAR group to a level of 1.08 (0.9-1.36) mg/dL (p = 0.007). Similarly, SCr clearance decreased significantly in the EVAR group to a level of 66.7 (49.9-81.4) mL/min. These results were influenced by the stent graft design (deployment under the renal arteries vs. covering the renals with bared stents). Mortality was 3/229 in the OR group and 4/144 in the EVAR group. Acute renal impairment occurred in a subset of patients with AAAs with regard to the type of repair. EVAR showed a slight deterioration of renal function, but the evaluated tests are insensitive and without prognostic value concerning mortality or hospitalization. More sensitive markers of the differentiated renal functions (cystatin C for renal glomerular function, N-acetyl-ss-d-glucosamidase for proximal tubular function) should be evaluated in future studies.
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PMID:Renal response to open and endovascular repair of abdominal aortic aneurysm: a prospective study. 1805 73

Pregnancy increases plasma cystatin C, but levels are much higher in preeclampsia. Previous studies have not quantified preeclampsia risk with varying cystatin C concentrations or adjusted for confounders. We performed a case-control study of 100 preeclampsia cases and 100 random pregnancies uncomplicated by hypertension (controls). All women were free of pre-existing hypertension, diabetes, and renal disease, and gave birth to singletons. Plasma cystatin C was measured at delivery. Adjusted odds ratios (OR) and 95% confidence intervals (CI) of preeclampsia by quartiles (based on control distribution) of maternal plasma cystatin C were estimated using multivariable logistic regression models. Mean cystatin C levels were elevated in preeclampsia cases compared with controls (1.38 +/- 0.04 vs. 1.22 +/- 0.03 mg/L, p < 0.01). Compared to the first quartile, the estimated risk of preeclampsia was increased by approximately 12-fold for the fourth quartile, after adjusting for maternal age, body mass index, physical inactivity, smoking, and gestational age. Increased plasma levels of cystatin C were independently associated with preeclampsia. Further studies are required to assess the role of cystatin C levels in preeclampsia severity and maternal and fetal outcomes.
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PMID:Cystatin C and preeclampsia: a case control study. 1819 49

Studies have indicated that matrix metalloproteinase-2 (MMP-2) is vital for the patient's condition after renal transplantation. Although the allograft survival rate has been improved, the relationships between various clinical parameters in stable graft function and serum MMP-2 still need to be clarified. In this study, gelatin zymography and enzyme-linked immunosorbent assay were employed to measure MMP-2 level in the plasma of 152 kidney transplant recipients, 41 chronic kidney disease patients, and 50 healthy control subjects. The creatinine and the MMP-2 levels in the transplant recipients were significantly greater (P < 0.001) than those of control subjects. Univariate and stepwise regression analysis demonstrated the MMP-2 level was associated with cystatin C level (P < 0.001), creatinine level (P = 0.036), proteinuria (P = 0.043), posttransplant days (P = 0.025), and posttransplant diabetes mellitus (P = 0.03). We conclude that circulating MMP-2 is associated with cystatin C, posttransplant duration, and diabetes mellitus in kidney transplant recipients and suggest that MMP-2 may be critical for graft survival.
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PMID:Circulating matrix metalloproteinase-2 is associated with cystatin C level, posttransplant duration, and diabetes mellitus in kidney transplant recipients. 1835 69

Acute and especially chronic renal failure (CRF) are relatively common and important risk factor for morbidity and mortality in patients after heart, lung, liver or intestine transplantation. Numerous factors contribute to the development of CRF in this group of patients, like treatment with calcineurin inhibitors and other nephrotoxic drugs in the perioperative period, hemodynamical changes during and after the surgery, preexistent renal disease, hypertension, diabetes mellitus, dyslipidemia and anemia. Pretransplant evaluation of renal function is mandatory to predict which patients have increased risk for development of CRF. In the posttransplantation course it is necessary to timely diagnose and treat renal failure, while patients with insufficient renal function have 4.55-fold increased risk of death compared to patients with normal renal function. Special problem is diagnostic approach to patients with suspected chronic renal disease who are candidates for transplantation of other parenhimatose organs. Diagnostic value of serum creatinine and estimation of renal function based on its value is very limited. Gold diagnostic standard is radioisotope estimation of glomerular filtration, but this method is not widely available. It seems that this problem may be solved with the use of cystatin C, but this approach needs to be validated in large studies. Numerous different immunosuppressive drugs available on the market enable individualization of immunosuppression. Different drugs combinations may have less nephrotoxic potential, but one must be careful because of the possible risk of organ rejection with the change of immunosuppression. Use of angiotensin convertase enzyme inhibitors and/or angiotensin receptor blockers, statins with drugs for control of hyperglycemia, may prevent or postpone development of CRF. Although technical advances of contemporary hemodialysis machines and peritoneal dialysis equipment enable well tolerated dialysis even in critically ill patients, renal transplantation remains the method of choice for treatment of patients with transplanted parenhimatous organ that developed CRF.
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PMID:[Chronic renal failure after heart, lung, liver, or intestine transplantation]. 1857 34

Genetic variants may increase susceptibility to both diabetes and kidney disease. Whether known diabetes-associated variants in the transcription factor 7-like 2 (TCF7L2) gene are associated with chronic kidney disease (CKD) progression and markers of kidney function is unknown. Participants of the Atherosclerosis Risk in Communities Study (ARIC; n = 11,061 self-identified white and n = 4014 black), Framingham Heart Offspring Cohort (FHS; n = 2468), and Heredity and Phenotype Intervention Heart Study (HAPI; n = 861) were genotyped at five (ARIC) and two (FHS) common TCF7L2 variants. The diabetes-conferring risk alleles at rs7903146 and rs7901695 were significantly associated with CKD progression among ARIC participants overall and among those without baseline diabetes. The overall adjusted hazard ratios per rs7903146 T allele were 1.17 (95% confidence interval [CI] 1.04 to 1.32) for white individuals and 1.20 (95% CI 1.03 to 1.41) for black individuals. Similarly, the overall hazard ratios per rs7901695 C allele were 1.19 (95% CI 1.06 to 1.34) for white individuals and 1.27 (95% CI 1.09 to 1.48) for black individuals. The FHS cohort supported these results: The rs7903146 T allele was significantly associated with lower estimated GFR (P = 0.01) and higher cystatin C (P = 0.004) in adjusted analyses overall and among those without diabetes. In the HAPI cohort, the rs7901695 C allele was significantly associated with lower estimated GFR in adjusted analyses (P = 0.049), as were several variants upstream and downstream of TCF7L2 (P < 0.003). No identified variant in the ARIC or FHS cohorts was associated with albuminuria. In conclusion, several population-based samples suggest that variants in the TCF7L2 gene are associated with reduced kidney function or CKD progression, overall and specifically among participants without diabetes.
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PMID:TCF7L2 variants associate with CKD progression and renal function in population-based cohorts. 1863 45

Peripheral arterial disease (PAD) is common, but often not diagnosed. A biomarker index would be useful to raise suspicion of PAD, so as to trigger appropriate vascular testing and management. The study comprised 540 individuals: 197 individuals with both coronary artery disease and peripheral arterial disease (CAD + PAD); 81 with CAD only; and 262 with no hemodynamically significant disease (NHSD) of the coronary or peripheral arteries. Multiple linear regression was performed to generate a biomarker panel score that could predict ankle-brachial index (ABI). Logistic regression was used to investigate the relationship between disease status and the panel score as well as other risk factors (e.g. age, diabetes status, smoking status). ROC analysis was performed to test the prediction power of the biomarker panel score. Among the plasma markers tested, beta 2 microglobulin (beta2M) and cystatin C had the highest correlation with ABI, and higher than any of the conventional risk factors of age, smoking status, and diabetes status. A biomarker panel score derived from beta2M, cystatin C, hsCRP, and glucose had an increased association with PAD status (OR = 12.4, 95% confidence interval (CI) 6.6-23.5 for highest vs lowest quartile), which was still significant after adjusting for known risk factors (OR = 7.3, 95% CI 3.6-14.9 for highest vs lowest quartile). In conclusion, after taking into account the traditional risk factors for PAD, a biomarker panel comprising beta2M, cystatin C, hsCRP, and glucose adds useful information to assess the risk of disease.
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PMID:A biomarker panel for peripheral arterial disease. 1868 58

The onset of diabetic nephropathy is characterised by a rise in albumin excretion rate (AER) and/or a transient rise in glomerular filtration rate (GFR) (hyperfiltration). Without intervention AER increases exponentially and there is a linear decrease in GFR after onset of overt nephropathy. In overt nephropathy, AER is a predictor of decline in GFR and the early AER response to antihypertensive therapy correlates with long-term decline in GFR. AER can be measured by immunoassay or by other techniques including HPLC. However, HPLC assays result in higher levels of AER in normal subjects compared with immunoassayable AER. Recent data suggest that there are distinct albuminuric and non-albuminuric pathways to renal impairment in type 1 and type 2 diabetes. In type 2 diabetes, the non-albuminuric pathway may explain a decline in GFR to <60 ml/min/1.73 m(2) in approximately one in four subjects after accounting for the use of renin angiotensin system inhibitors. In established nephropathy (chronic kidney disease (CKD) stages 3 and 4), plasma cystatin C based estimates of GFR are marginally superior to creatinine based estimates. However, cystatin C clearly outperforms creatinine based estimates of GFR decline at GFR levels >60 ml/min/1.73 m(2) (CKD stages 1 and 2). Other potential markers of progression of diabetic nephropathy include transforming growth factor beta (TGFbeta) and connective tissue growth factor (CTGF). However, long-term studies are needed to define their roles as markers of progression. Diabetic nephropathy is likely to be more susceptible to intervention at an early stage and accurate estimation of GFR is already possible with cystatin C. However, improved formulas for estimating GFR based on using creatinine or other markers are still required, because this may still provide the most cost effective approach applicable to existing clinical practice.
Diabetes Res Clin Pract 2008 Nov 13
PMID:New and old markers of progression of diabetic nephropathy. 1893 92

Today, eggs with an increased content of -3 fatty acids are available but there are few publications on the effects of consumption of such eggs on the lipoproteins and acute phase markers in humans. The aim of the present study was to evaluate the effects of consumption of standard eggs and -3 enriched eggs on lipoproteins, glucose and inflammation markers. Nineteen healthy volunteers consumed one extra egg per day of either standard eggs or omega-3 enriched eggs in a double-blind, cross-over study. The duration of each period was 1 month. The effects of the different egg diets on apolipoprotein A1 and B (Apo A1 and B), lipoprotein (a), creatinine, cystatin C, C-reactive protein, serum amyloid protein A, interleukin 6, triglycerides, glucose, total-, high-density lipoprotein and low-density lipo-protein cholesterol concentrations were analyzed. Addition of one regular egg per day to the normal diet had no negative impact on blood lipids or inflammation markers. Consumption of omega-3 enriched eggs resulted in higher levels of ApoA1, lower ApoB/ApoA1 ratio and lower plasma glucose. These effects have been associated in previous studies with a reduced risk for cardiovascular mortality and diabetes.
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PMID:Biochemical effects of consumption of eggs containing omega-3 polyunsaturated fatty acids. 1899 Dec 44


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