Advanced glycation end products and arterial stiffness in patients with diabetic nephropathy and patients with chronic kidney disease without diabetes.

INTRODUCTION:  Formation of advanced glycation end­products (AGEs) is increased in diabetic patients. Impaired renal function also elevates AGE accumulation. Pulse wave velocity (PWV) is a measure of arterial stiffness and a prognostic parameter. An association between AGEs and arterial stiffness was observed in hemodialyzed patients. OBJECTIVES:  We investigated the relationship between plasma AGE concentration and arterial stiffness in nondialyzed patients with diabetic nephropathy and those with chronic kidney disease (CKD) without diabetes. PATIENTS AND METHODS:  PWV measurement was performed in 24 patients with CKD and diabetic nephropathy (DN), 36 patients with CKD and without diabetes, and 19 controls. To assess AGE concentrations, plasma fluorescence spectra were recorded.  RESULTS:  Patients with and without diabetes did not differ with respect to the glomerular filtration rate (33 ±13 vs. 32 ±14 ml/min/1.73 m2, respectively). The AGE concentration was significantly higher in patients with DN compared with those without diabetes and controls (21.1 ±6.8 vs. 12.3 ±3.1 vs. 7.8 ±1.2 AU/ml, respectively; P <0.001). PWV was also significantly higher in patients with DN compared with those without diabetes and controls (13.7 ±4.3 vs. 10.1 ±2.4 vs. 8.4 ±1.6 m/s, respectively; P <0.05). A significant correlation was found between AGEs and PWV (r = 0.39, P <0.01) in patients with CKD. In a multiple regression analysis, PWV was independently associated with age, DN, and systolic blood pressure, but not with AGEs (R2 = 0.45).  CONCLUSIONS:  Accumulation of AGEs and arterial stiffness are increased in patients with CKD, particularly in those with DN; however, the results are not sufficient to confirm the causal role of AGE accumulation in arterial stiffening in CKD. AGEs should be considered as a potential therapeutic target in patients with CKD.

[Cardiovascular system in patients in different stages of chronic kidney disease]. / Stan ukladu sercowo-naczyniowego u pacjentów w róznych stadiach przewleklej choroby nerek.

The term "chronic kidney disease" (CKD) was introduced recently to nephrological literature. CKD is a growing epidemic problem, which affects 11% of adult US population. CKD, particularly with GFR below 60 ml/min/1, 73 m2 is associated with increased risk of cardiovascular morbidity and mortality. It is a result of coexistance of "traditional" cardiovascular risk factors cumulation such as hypertension, lipid and carbohydrate disorders but also "non-traditional" cardiovascular risk factors such as: anemia, calcium-phosphate metabolism disturbances, chronic inflammation and others. The paper discusses changes in left ventricle structure and function, arterial structure and function and cardiovascular calcifications in different stages of chronic kidney disease, and their prognostic significance. Result of the study in 31 CKD patients (GFR 39,4 +/- 14, 1 ml/min/m2) and 18 appearently healthy controls are also presented in the paper. Cardiovascular risk factors assessment, echocardiography, common carotid artery USG with diameter and intima-media thickness (IMT) measurement and aortic pulse wave velocity (PWV) measurement were performed in all participants. We found higher total cholersterol, LDL-cholesterol, triglicerides, CRP, advanced glycation end-products (AGE), and calcium x phosphorus product and lower hemoglobin concentration in CKD patients. Fasting glucose and insulin concentration did not differ between CKD patients and control group but insulin/glucose ratio was higher in CKD group. Abnormal left ventricular heart structure was found in 55% of CKD patients. Carotid artery internal diameter, intima-media thickness and aortic PWV--a marker of increased arterial stiffness - were higher in CKD patients. The study indicates that cardiovascular risk factors and cardiac and arterial abnormalities should be evaluated from the start of CKD.

[Advanced glycation end products (AGEs) and renal failure]. / Produkty zaawansowanej glikacji bialek (AGEs) a niewydolnosc nerek.

In the last decade a central role has been attributed to advanced glycation end products (AGE's) in the progression of accelerated atherosclerosis and progresion of chronic renal failure, especially in diabetic nephropathy. Deleterious effects of high AGE's concentration was observed mainly in diabetic hemodialyzed patients. D. M. type 2 is the most common cause of renal failure and renal replacement therapy in Poland and in the world. Diabetic complications are of huge medical and social interest. Therefore it is import ant to reveal all the mechanisms responsible for development of diabetic complications especially diabetic nephropatyhy. A significant role is also played by high cardiovascular mortality in hemodialysis patients, which is caused by atherosclerotic changes in vessels.

[Arterial stiffness--pathophysiological significance and practical aspects of assessment]. / Sztywnosc tetnic--znaczenie patofizjologiczne oraz praktyczne aspekty pomiaru.

Arterial stiffness is a dynamic property which depends on structure and function of arteries. Arterial stiffness progresses with age and it is an important factor leading to increase of systolic and pulse pressure and decrease in diastolic blood pressure. Increased arterial stiffness was also found in hypertension, chronic renal failure and diabetes. Arterial stiffness is an independent prognostic factor of mortality in hypertension and end-stage renal disease. Arterial stiffening leads to cardiovascular complications such as left ventricular hypertrophy. Many methods to assess different aspects of arterial stiffness: systemic, regional and local were developed. Various indicies of arterial stiffness were defined and are used in clinical investigations. Arterial stiffness is a dynamic parameter. Decrease in blood pressure leads to decrease of arterial stiffness. Many authors suggest, that angiotensin converting enzyme inhibitors may exert favourable effect, irrespective of blood pressure. Arterial stiffness assessment may become a cardiovascular risk parameter and a therapeutic goal.