Asymmetric dimethylarginine: a cardiovascular risk factor in renal disease?

Endothelial dysfunction due to reduced availability of nitric oxide (NO) is an early step in the course of atherosclerotic vascular disease. NO is synthesized from the amino acid L-arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). In laboratory animals, administration of ADMA significantly reduces NO generation, and causes an increase of blood pressure and renal vascular resistance. In clinical studies, a strong correlation between increased ADMA blood levels and impaired endothelial-dependent vasodilatation, and cardiovascular morbidity and mortality has been documented in different populations, including in patients with renal disease. Thus, ADMA seems to be the culprit, and not just an innocent biochemical bystander, of the atherosclerotic disease process. Moreover, reduced NO availability is involved in the progression of renal disease, and increased ADMA blood levels may contribute to this process. Interventions that lower ADMA blood levels in renal patients could, therefore, modulate their atherogenic profile and interfere with progression of renal failure.     

Asymmetric dimethylarginine in end-stage renal disease patients: a biomarker modifiable by calcium blockade and angiotensin II antagonism?

The nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an emerging risk biomarker in cardiovascular and renal diseases. Apparently amlodipine and valsartan produce substantial reductions in the plasma concentration of this methylarginine in hemodialysis patients. These findings are of relevance for designing studies aimed at testing the etiologic relevance of ADMA to the high cardiovascular risk of ESRD.     

Asymmetrical dimethylarginine in renal disease: limits of variation or variation limits? A systematic review

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is increasingly recognized as a putative biomarker in cardiovascular and renal disease. Elevated plasma levels of ADMA are the consequence of increased synthesis, reduced renal clearance or reduced enzymatic degradation. Based upon the metabolic fate the highest plasma concentrations of ADMA have been reported in patients with renal failure in whom this molecule accumulates. However, the range of published ADMA levels in patients with chronic renal failure as well as in patients with end-stage renal failure undergoing maintenance hemodialysis, peritoneal dialysis or kidney transplant recipients is widely scattered and overlaps with the levels reported in healthy individuals. This wide distribution can in part be explained by different bioanalytical techniques and the lack of standardization of such assays. This review summarizes available literature on ADMA in patients with kidney disease and stresses the urgent need for a consensus regarding reference values for different analytical methods in order to appreciate the prognostic significance of elevated ADMA levels. At present, one cannot advocate this molecule for risk assessment or individual patient prognosis in the clinical work-up of patients with renal impairment.     

Kidney organogenesis and regeneration: a new era in the treatment of chronic renal failure?

The recent development of a strategy to establish human inducible pluripotent stem (iPS) cells has created a second surge in the field of regenerative research, which had been slowed by restrictions on the use of pluripotent embryonic stem cells. Research on regenerative nephrology offers hope for patients on dialysis. However, due to its anatomic complexity, the kidney is the most difficult organ for the application of regenerative medicine. Very recently, the establishment of a functional whole kidney has been attempted using various stem cells, which may lead to clinical applications. We review recent progress in the field of regenerative nephrology, focusing on the de novo establishment of a whole kidney.     

Interleukin-33: a novel player in osteonecrosis of the femoral head?

Osteonecrosis of the femoral head (ONFH) is a disabling disease affecting young adults, which usually leads to the destruction of the hip joint. It is mainly due to an inadequate blood supply that causes the death of osteocytes and bone marrow cells. Joint salvaging procedures are numerous but relatively inefficient, justifying the need for new therapeutic strategies. In this regard, the recently discovered interleukin (IL)-33 alarmin appears as a possible target. Indeed, IL-33 seems to be specifically released by necrotic cells, and interestingly, is constitutively expressed in human bone, in particular by osteocytes, osteoblasts and marrow adipocytes. Moreover, recent reports suggesting that IL-33 modulates angiogenesis, vascular permeability, osteoclastogenesis and bone resorption, indicate that IL-33 may play a role in ONFH.     

Immune complex: does it have a role in pathogenesis of renal failure in dengue infection?

Dengue infection is a major public health problem. When acute renal failure complicates dengue infection, it is usually associated with severe disease as in dengue hemorrhagic fever or dengue shock syndrome. The role of immune complex in development of renal failure in dengue infection is still unclear. Here, the author used a computational medicine technology to study the property of the dengue virus-immunoglobulin complex. According to this study, the diameter of derived complex is much smaller, compared with the diameter of glomerulus. Entrapment of the immune complex is believed to occur when a previous glomerular lesion causes narrowing of the glomerulus's diameter. Therefore, the immune complex should not have a significant role in pathogenesis of renal failure in dengue infection.     

Role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Peyronie's disease:a new diagnostic approach to predict the stage of the disease?

Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)have been associated with multiple entities and several types of cancers.They can be ass...     

Autophagy: A new player in skeletal maintenance?

Imbalances between bone resorption and formation lie at the root of disorders such as osteoporosis, Paget's disease of bone (PDB), and osteopetrosis. Recently, genetic and functional studies have implicated proteins involved in autophagic protein degradation as important mediators of bone cell function in normal physiology and in pathology. Autophagy is the conserved process whereby aggregated proteins, intracellular pathogens, and damaged organelles are degraded and recycled. This process is important both for normal cellular quality control and in response to environmental or internal stressors, particularly in terminally‐differentiated cells. Autophagic structures can also act as hubs for the spatial organization of recycling and synthetic process in secretory cells. Alterations to autophagy (reduction, hyperactivation, or impairment) are associated with a number of disorders, including neurodegenerative diseases and cancers, and are now being implicated in maintenance of skeletal homoeostasis. Here, we introduce the topic of autophagy, describe the new findings that are starting to emerge from the bone field, and consider the therapeutic potential of modifying this pathway for the treatment of age‐related bone disorders. © 2012 American Society for Bone and Mineral Research.     

Kienbock��s disease in a varsity football player: a case report and review of the literature

Objective:

To present the diagnostic, clinical features, and management of Kienbock’s disease and create awareness of the differential diagnosis of this condition in patients presenting with insidious, progressive dorsal wrist pain.

Clinical Features:

A 23-year old male varsity football player presented with insidious progressive dorsal sided wrist pain with reduced wrist flexion and extension. A diagnosis of Kienbock’s disease was made based on radiographs and magnetic resonance imaging.

Intervention and Outcome:

A 3mm ulnar-minus variance was found and a joint leveling procedure to shorten the radius was performed. Conservative therapy was provided pre and post surgical management.

Summary:

This case report demonstrates the importance of findings on radiographs, MRI, and clinical examination in the accurate diagnosis and management of a patient with wrist pain.     

Discordant Hirschsprung's disease in monozygotic twins: a clue to pathogenesis?

Presented is a case of discordant aganglionosis in monozygous twins that supports the "post migration" destruction mechanism in Hirschsprung's disease.     

Is there a deleterious effect of erythropoietin in end-stage renal disease?

The use of erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease has declined as randomized controlled trials have demonstrated increased risk of cardiovascular complications and mortality without a marked benefit in quality of life. Several studies have suggested that exposure to high dosages of ESA, rather than raising of the hemoglobin concentration, explains this increased risk. Cotter and colleagues report that exposure to high dosages of ESA in patients with diabetes is associated with increased risk.     

Crystal retention in renal stone disease: a crucial role for the glycosaminoglycan hyaluronan?

The mechanisms that are involved in renal stone disease are not entirely clear. In this article, the various concepts that have been proposed during the past century are reviewed briefly and integrated into current insights. Much attention is dedicated to hyaluronan (HA), an extremely large glycosaminoglycan that may play a central role in renal stone disease. The precipitation of poorly soluble calcium salts (crystal formation) in the kidney is the inevitable consequence of producing concentrated urine. HA is a major constituent of the extracellular matrix in the renal medullary interstitium and the pericellular matrix of mitogen/stress-activated renal tubular cells. HA is an excellent crystal-binding molecule because of its size, negative ionic charge, and ability to form hydrated gel-like matrices. Crystal binding to HA leads to crystal retention in the renal tubules (nephrocalcinosis) and to the formation of calcified plaques in the renal interstitium (Randall's plaques). It remains to be determined whether one or both forms of renal crystal retention are involved in the development of kidney stones (nephrolithiasis).     

Legionnaires' disease in a renal transplant recipient: nosocomial or home-grown?

Legionnaires' disease is a community-acquired or hospital-acquired pneumonia, and the immunocompromised patient is at particular risk. We report a case of serogroup 1 pneumonia in a renal transplant patient shortly after grafting. No source of infection was identified in the hospital unit, but an extended investigation located patient exposure to a shower during a weekend home stay. Sampling at the hospital, in the patient's flat, other flats, and the laundry of the same building returned only one positive result from the patient's showerhead. Strain identity was confirmed by pulsed-field electrophoresis and amplified fragment length polymorphism. Guidelines recommend -free water for transplant units, but further epidemiologic evidence is required before extending this preventive approach to the patient's home.     

Resolution of renal disease: mission impossible?

Several studies have extensively shown that both dietary and pharmacological intervention can prevent the progression of renal damage. The best results may be obtained by optimizing blood pressure control, reducing proteinuria levels in non diabetic nephropathies, and further achieving a good glycemic control in diabetic nephropathies. The earlier the treatment is started, the better the results. Since slowing progression of renal disease has been established, the challenge of the future seems to be the resolution of an established renal damage. Few studies have suggested that this process of regression is possible. Experimental animal studies, based on repeated renal morphological investigations, showed resolution of glomerular lesions in 40% of animals treated with either ACEI or AIIRA. Resolution of renal lesions (62%) has been claimed in a single study and in a small number of patients with diabetic nephropathy after 10-year pancreas transplantation. Confirmation studies are awaited.