[Vascular dysfunction in Cardiorenal Syndrome type 4].

The Cardiorenal Syndrome type 4 (CRS-4) defines a pathological condition in which a primary chronic kidney disease (CKD) leads to a chronic impairment of cardiac function. The pathophysiology of CRS-4 and the role of arterial stiffness remain only in part understood. Several uremic toxins, such as uric acid, phosphates, advanced glycation end-products, asymmetric dimethylarginine, and endothelin-1, are also vascular toxins. Their effect on the arterial wall may be direct or mediated by chronic inflammation and oxidative stress. Uremic toxins lead to endothelial dysfunction, intima-media thickening and arterial stiffening. In patients with CRS-4, the increased aortic stiffness results in an increase of cardiac workload and left ventricular hypertrophy whereas the loss of elasticity results in decreased coronary artery perfusion pressure during diastole and increased risk of myocardial infarction. Since the reduction of arterial stiffness is associated with an increased survival in patients with CKD, the understanding of the mechanisms that lead to arterial stiffening in patients with CRS4 may be useful to select potential approaches to improve their outcome. In this review we aim at discussing current understanding of the pathways that link uremic toxins, arterial stiffening and impaired cardiac function in patients with CRS-4.

Qiliqiangxin Protects against Renal Injury in Rat with Cardiorenal Syndrome Type I through Regulating the Inflammatory and Oxidative Stress Signaling.

Cardiorenal syndrome (CRS) is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. CRS remains a major global health problem. Qiliqiangxin (QLQX) is a traditional Chinese herbs medication, which can improve cardiac function, urine volume, and subjective symptoms in patients with chronic heart failure. In the present study, we aim to investigate the role of QLQX in the treatment of CRS type I and the possible mechanism through establishment of a rat model of myocardial infarction. Rats in CRS-Q group were orally treated with QLQX daily for 2 weeks or 4 weeks, while in sham group and CRS-C group were treated with saline at the same time. Enzyme-linked immunosorbent assay (ELISA) analysis showed that QLQX significantly reduced the levels of angiotensin II (AngII), brain natriuretic peptides (BNP), creatinine (CRE), cystatin C (CysC), tumor necrosis factor (TNF)-α, interleukin (IL)-6, microalbuminuria (MAU), and neutrophil gelatinase-associated lipocalin (NGAL) in plasma induced by myocardial infarction. Western blot analysis showed that QLQX significantly reduced the expressions of AngII, non-phagocytic cell oxidase (NOX)2, and B-cell lymphoma (Bcl)2 associated X protein (Bax), and increased the expressions of Bcl2 and Angiotensin II Type 1 receptor (ATR) in the kidney as compared with the CRS-C group. Fluorescence microscopy showed that the content of reactive oxygen species (ROS) was significantly reduced in the kidney as compared with the CRS-C group. We also examined the apoptosis level in kidney by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, and the result showed that QLQX significantly reduced the apoptosis level in kidney induced by myocardial infarction. Taken together, we suggest that QLQX may be a potentially effective drug for the treatment of CRS by regulating inflammatory/oxidative stress signaling.

Biochemical and electrocardiographic studies on the beneficial effects of gallic acid in cyclophosphamide-induced cardiorenal dysfunction.

Background Cardiac toxicity is one of the life-threatening complications of cancer therapy. Cyclophosphamide (CYP) is an alkylating agent with potent antineoplastic and immunosuppressive properties and possibly the most widely used antineoplastic agent. Chronic cardiotoxicity associated with CYP is characterized by progressive heart failure developing from weeks to years after therapy. Methods In this study, rats were administered with (60 mg/kg and 120 mg/kg) alone or in combination with single intraperitoneal (200 mg/kg) administration of CYP for 7 days. CYP was only administered on day 1. Results The administration of CYP led to a significant (p<0.05) increase in cardiac and renal malondialdehyde (MDA) contents and hydrogen peroxide (H2O2) generation. Also, the activities of catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) levels were significantly (p<0.05) reduced following CYP treatment. A significant (p<0.05) increase in serum myeloperoxidase (MPO) activity was recorded in rats administered CYP only. Electrocardiogram (ECG) showed a significant (p<0.05) increase in heart rate (HR) accompanied by transient decrease in QRS duration. Histologic examination revealed architectural anarchy of both heart and kidney of rats that received only CYP. Conclusions In this study, treatment with gallic acid (60 mg/kg and 120 mg/kg) restored the enzymic and non-enzymic antioxidants and also attenuated cardiotoxic and nephrotoxic effect of CYP through free radical scavenging activity, anti-inflammatory and improvement of antioxidant defence system.

[Magnesium: a kardio-renal viewpoint]. / Magnesiumstoffwechsel.

Disturbances in magnesium homeostasis are frequent clinical conditions, particularly the prevalence of hypomagnesaemia is high. However, it remains an open question which laboratory method is optimal to assess the magnesium level in the body. Most frequently physicians measure total magnesium in serum. Many associative data from observational studies point towards an association between low magnesium levels and increased cardiovascular risk as well as increased mortality. Vice versa, normal-to-high magnesium levels in patients with advanced renal failure translate to a better outcome. The present review summarizes our knowledge on protective effects of magnesium. Additionally, we address the limited evidence supporting targeted magnesium supplementation.

Mineral metabolism abnormalities and vitamin D receptor activation in cardiorenal syndromes.

Over the last decade, it has become increasingly clear that the cardiovascular and renal systems are interdependent. Primary disorders of either system have been shown to disturb the other system. As a result, a class of cardiorenal syndromes (CRS) has been identified wherein a vicious cycle is established as an acute/chronic dysfunction of either the kidney or the heart exacerbates the loss of function in the other organ. Progressive loss of kidney function observed in patients with CRS (mostly types 2 and 4) leads to reduced production of calcitriol (active vitamin D) and an imbalance in calcium and phosphorus levels, which are correlated with increased rates of cardiovascular events and mortality. In addition, hypocalcemia can lead to prolonged and excessive secretion of parathyroid hormone (PTH), eventually leading to development of secondary hyperparathyroidism. Therefore, based on this important mechanism of organ damage, one of the major goals of therapy for patients with CRS is to restore regulatory control of PTH. Although administration of calcitriol increases serum calcium levels and reduces PTH levels, it is also associated with elevated serum levels of calcium-phosphorus product. Therefore, compounds that selectively activate vitamin D receptors, potentially reducing calcium × phosphate toxicity, are likely to enhance cardiorenal protection and provide significant clinical benefit.