Olivier Phan

The pathogenesis of vascular calcification (VC) in diabetes mellitus (DM) has not been completely elucidated. VC often occur in patients with DM and chronic kidney disease (CKD). The incidence of VC in diabetic patients is more frequent than in nondiabetic patients, which is an important cause of cardiovascular (CV) morbidity and mortality. VC is a progressive transformation of the vascular wall; it results from an active and complex phenomenon affecting particularly the vascular smooth muscle cells (VSMCs). It leads to a change in the phenotype of the VSMCs towards an osteoblastic-like phenotype. DM is associated with specific risk factors in addition to hyperglycemia, such as increased oxidative stress, proinflammatory state, hypertension, and chronic kidney disease (CKD) promoting endothelial dysfunction. This article provides an overview and update of the pathophysiological data on the role of DM in VC progression.

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Hypertension is a frequent finding in patients with chronic kidney disease. Whether primary or secondary to renal disease, hypertension remains an important risk factory for the progression of chronic kidney disease and the occurrence of cardiovascular events. The objective of this paper is to review different treatment strategies in hypertensive CKD patients, with the exclusion of patients with renal replacement therapy such as dialysis or renal transplantation.

Hypertension contributes to the progression of kidney diseases as well as to the occurrence of cardiovascular events such as myocardial infarction, heart failure and stroke. The prevalence of hypertension is elevated in patients with kidney disease, and increases progressively as glomerular filtration rate falls. A better understanding of the mechanisms leading to hypertension in renal diseases has been gained in recent years; in this article we will review the pathogenesis of hypertension in chronic kidney disease (CKD) with a special focus on vascular calcification because calcification is associated with an increased incidence of cardiovascular morbidity in CKD patients. Although calcification of large arteries and blood pressure increase with age, few studies have specifically investigated a possible connection between these two factors as determinants of the severity of hypertension in CKD. Finally, we will review the trends in hypertension treatment in CKD patients. Expanded understanding of the role of CKD as both a cause and a target of hypertension highlights key points of pathophysiology of hypertension and may contribute to the identification of new strategies for its prevention and treatment.

Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based noncalcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5, 1.5, or 5% or CaCO3 3% in the diet for 4 weeks, and were compared with uremic and nonuremic control groups. After 4 weeks of phosphate binder treatment, serum calcium, creatinine, and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mM; P ≤ 0.001), PA21 1.5% (2.29 mM; P < 0.05), and PA21 5% (2.21 mM; P ≤ 0.001) versus CRF controls (2.91 mM). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml; both P ≤ 0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.

Le tabagisme reste un problème majeur de santé publique. Il est associé à un nombre considérable de décès dans la population mondiale. Fumer est au même titre que l’hypertension artérielle, un facteur indépendant de progression pour toute néphropathie primaire ainsi que chez le transplanté rénal. Il semble que l’arrêt du tabac ralentit la progression de l’insuffisance rénale chez les fumeurs. Les données de la littérature sont parfois à ce sujet contradictoires en raison de certaines faiblesses méthodologiques. En revanche, les modèles expérimentaux mettent en lumière les effets néfastes du tabac par des facteurs hémodynamiques et non hémodynamiques. La conclusion est qu’un effort important supplémentaire doit être produit par la communauté néphrologique afin de motiver nos patients de cesser de fumer. Smoking remains a major public health problem. It is associated with a considerable number of deaths in the world's population. Smoking is just like high blood pressure, an independent predictor of progression to any primary renal disease and renal transplant patients. It seems that smoking cessation slows the progression of kidney disease in smokers. The literature data are sometimes contradictory about it because of some methodological weaknesses. However, experimental models highlight the harmful effects of tobacco by hemodynamic and non-hemodynamic factors. The conclusion is that a major effort should be further produced by the nephrology community to motivate our patients to stop smoking.

Tobacco consumption is a major public health problem. More than 20 years ago smoking has been identified to contribute substantially to the degradation of renal function in patients suffering from diabetic nephropathy. Recently it has been shown that smoking alters renal hemodynamics and contributes to albuminuria. Smoking increases the risk of progression of renal failure in patients suffering from IgA nephropathy and polycystic kidney disease. Furthermore smoking has a deleterious effect on patients on hemodialysis and on the transplanted kidney. Nonetheless, it is important to realize that smoking not only is deleterious for the progression of vascular and pulmonary diseases, but also has a strong negative effect on kidney function.

Atherosclerotic renal artery stenosis is often associated with diffuse atherosclerotic disease and consequently an increased cardiovascular morbidity and mortality. Despite evidence of only moderate clinical benefit in comparison with medical treatment to control the blood pressure and to prevent renal failure, renal endovascular revascularisation has become more and more popular. The decision to treat an atherosclerotic renal stenosis by revascularisation should be taken only after a close examination of the hemodynamic impact of the stenosis, the renal function, the severity of hypertension and the quality of blood pressure control achieved by the medical treatment.

The renin-angiotensin system plays an important role in the regulation of blood pressure. Recent research in mouse indicates that 1,25(OH)2D interacts with the renin-angiotensin system by decreasing the expression of the gene encoding renin. Thus, an adequate vitamin D level may be important for decreasing the cardiovascular risk associated with a high blood pressure. In this article, the link between vitamin D and the cardiovascular system is discussed in the light of most recent scientific data.