Aluminum in renal disease

Biological Trace Element Research -     

Nuclear receptors in renal disease

Diabetes is the leading cause of end-stage renal disease in developed countries. In spite of excellent glucose and blood pressure control, including administration of angiotensin converting enzyme inhibitors and/or angiotensin II receptor blockers, diabetic nephropathy still develops and progresses. The development of additional protective therapeutic interventions is, therefore, a major priority. Nuclear hormone receptors regulate carbohydrate metabolism, lipid metabolism, the immune response, and inflammation. These receptors also modulate the development of fibrosis. As a result of their diverse biological effects, nuclear hormone receptors have become major pharmaceutical targets for the treatment of metabolic diseases. The increasing prevalence of diabetic nephropathy has led intense investigation into the role that nuclear hormone receptors may have in slowing or preventing the progression of renal disease. This role of nuclear hormone receptors would be associated with improvements in metabolism, the immune response, and inflammation. Several nuclear receptor activating ligands (agonists) have been shown to have a renal protective effect in the context of diabetic nephropathy. This review will discuss the evidence regarding the beneficial effects of the activation of several nuclear, especially the vitamin D receptor (VDR), farnesoid X receptor (FXR), and peroxisome-proliferator-associated receptors (PPARs) in preventing the progression of diabetic nephropathy and describe how the discovery and development of compounds that modulate the activity of nuclear hormone receptors may provide potential additional therapeutic approaches in the management of diabetic nephropathy. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.     

Drug dosing in renal disease

Renal disease alters the effects of many drugs, particularly when active drug moieties are renally cleared. Drug doses should usually be reduced in renal disease in proportion to the predicted reduction in clearance of the active drug moiety. Patient factors to consider in adjusting drug doses include the degree of renal impairment and patient size. Drug factors to consider in adjusting doses include the fraction of the drug excreted unchanged in urine and the drug's therapeutic index. Estimates of renal function are useful to guide dosing of renally cleared drugs with medium therapeutic indices, but are not precise enough to guide dosing of drugs with narrow therapeutic indices. This article discusses principles of drug dose adjustment in renal disease.     

Molecular mechanisms in renal degenerative disease

Chronic kidney disease (CKD) has become a major public health problem worldwide. Therefore, a considerable effort is currently directed to understand the molecular mechanisms of renal degenerative processes. Regardless of their initiating cause, all chronic kidney diseases (CKD) develop at some level organ fibrosis that interferes with kidney function. This is also true for the two most common inherited CKD syndromes, nephronophthitis and polycystic kidney disease, whose primary defects reside within the cilium of kidney epithelial cells. A cohort of elegant recent studies has elicited the role of the primary cilium as a versatile mechanosensory organelle that also might coordinate cross-talk between multiple signaling pathways. In addition, epigenetic mechanisms are now realized to be essential in the maintenance of adult renal architecture. In this review, we will discuss recent advances in our understanding of the signaling systems implicated in kidney homeostasis and repair.     

Antineutrophil cytoplasmic autoantibody in renal disease

ANCA are an important marker for identifying pauci-immune necrotizing and crescentic glomerulonephritis and systemic vasculitis. Patients with ANCA-associated renal disease have a spectrum of illness ranging from renal-limited disease to widespread vasculitis, including the clinicopathologic syndromes of polyarteritis nodosa and Wegener's granulomatosis. ANCA may be directly involved in the pathogenesis of pauci-immune glomerulonephritis and necrotizing systemic vasculitis.     

趋化因子ENA-78与肾脏疾病

体外实验中,各种肾脏细胞都能在特定刺激下表达趋化因子及受体。动物模型和人类肾脏疾病的肾组织中,炎症细胞浸润同时出现趋化因子及受体表达增多。ENA-78是一种来源广泛、生物功能多样的趋化因子,通过与其受体相互作用,引起中性粒细胞等白细胞的趋化、活化,参与肾脏疾病的发生、发展。     

Gender and human chronic renal disease

Background: Gender affects the incidence, prevalence, and progression of renal disease. In animal models of the disease, female sex appears to modify the course of progression. Hormonal manipulation by male or female castration also changes the course of renal disease progression, suggesting direct effects of sex hormones in influencing the course of these maladies.Objective: This review examines the pertinent animal and human studies assessing the role of gender, and strives to shed light on the possible physiologic mechanisms underlying the effect of gender, on renal disease progression.Methods: A summary and evaluation of past and recent studies describing the rate of renal disease progression in animal models and humans as it pertains to gender is provided. In addition, studies elucidating the factors involved in the more modest renal progression rate in females are reviewed and conclusions drawn. Relevant English-language publications were identified by searching the PubMed database from January 1990 until November 2007 using the search terms gender, sex, renal disease, and kidney.Results: In polycystic kidney disease, membranous nephropathy, immunoglobulin A nephropathy, and “chronic renal disease of unknown etiology,” men progress at a faster rate to end-stage renal failure than do women. In type 1 diabetes mellitus, there is evidence that males are more likely to manifest signs of renal disease, such as proteinuria. The factors involved in this gender disparity may include diet, kidney and glomerular size, differences in glomerular hemodynamics, and the direct effects of sex hormones. In many, but not all, animal models of renal disease, estrogens slow progression rate. Several studies have recently evaluated the effect of selective estrogen receptor modulators on renal function in humans.Conclusion: Further studies assessing the factors involved in the gender disparity in renal disease progression and the effects of hormonal treatments are warranted.     

整合素连接激酶与肾小球疾病

目前肾小球疾病系病因及发病机理尚不明确,许多细胞因子均参与了肾小球疾病的发生与发展.其中整合素连接激酶(integrin-linkedkinase,ILK)在肾脏疾病的发生发展过程起了一定的作用.它是一种丝氨酸/苏氨酸蛋白激酶,参与多种信号传导通路,在调节细胞凋亡、胚胎发生、肿瘤发生等过程中起重要作用,近期研究发现它与肾小球疾病密切相关.本文就ILK在肾小球疾病中的研究新进展作一综述.     

Ammonium chloride poisoning in chronic renal disease

A 58-year-old woman with a long history of renal stone disease and urinary tract infection presented to the emergency room with exhaustion and air hunger. Laboratory data confirmed profound metabolic acidosis. Unduly large quantities of bicarbonate and potassium were required for correction of the deficits. She had been taking 6 g daily of ammonium chloride as a urine-acidifying agent for a period of six months in addition to agents directed against urinary tract infection. The combination of impaired renal function and effective hydrogen ion loading resulted in profound systemic acidosis. The metabolic derangements associated with the administration of ammonium chloride and its use as a therapeutic agent are discussed.