Asymmetric dimethylarginine: a new player in the pathogenesis of renal disease?

PURPOSE OF REVIEW: This review summarizes current knowledge on asymmetric dimethylarginine, renal function in health and disease, and renal disease progression and examines interventions that may modify the plasma concentration of this methylarginine. RECENT FINDINGS: Nitric oxide deficiency may occur in patients with chronic kidney disease and may contribute to accelerate progression of chronic kidney disease, hypertension and cardiovascular complications. An increase of endogenous nitric oxide inhibitors like asymmetric dimethylarginine seems to play a major role in this process. The kidneys are crucial in both, in re-absorbing and generating L-arginine as well as in eliminating asymmetric dimethylarginine primarily by the enzyme dimethylarginine dimethylaminohydrolase and to a minor degree by urinary excretion. Asymmetric dimethylarginine accumulation predicts both accelerated renal function loss and death in patients with chronic kidney disease and incident cardiovascular complications in patients with end stage renal disease. SUMMARY: Asymmetric dimethylarginine is a new risk factor potentially implicated in the progression of renal insufficiency and in the high rate of cardiovascular complications of patients with chronic kidney disease.     

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.     

Mini-percutaneous nephrolithotomy for pediatric complex renal calculus disease: one-stage or two-stage?

International Urology and Nephrology - To compare two different treatment strategies, one-stage and two-stage multi-tract mini-percutaneous nephrolithotomy (mt-mPCNL), for pediatric complex renal...     

Screening for renal disease using serum creatinine: who are we missing?

BACKGROUND: Appropriate management and timely referral of patients with early renal disease often depend on the identification of renal insufficiency by primary care physicians. Serum creatinine (SCr) levels are frequently used as a screening test for renal dysfunction; however, patients can have significantly decreased glomerular filtration rates (GFR) with normal range SCr values, making the recognition of renal dysfunction more difficult. This study was designed to estimate the prevalence of patients who have significantly reduced GFR as calculated by the Cockcroft-Gault (C-G) formula, but normal-range SCR: METHODS: The study included 2781 outpatients referred by community physicians to an urban laboratory network for SCr measurement. GFR was estimated using the C-G formula. Patients were grouped according to the concordance of SCr level abnormalities (abnormal >130 micromol/l) with significantly abnormal C-G values (abnormal or =70 years old, 12.6% 60-69 years old, and 1.2% 40-59 years old. Analysis of historical available laboratory data for patients with abnormal SCr and abnormal C-G values showed that 2 years prior to the study period, 72% of this group had abnormal SCr, while 18% had normal SCr with abnormal C-G values, and 10% had normal SCr with normal C-G values. CONCLUSIONS: This study documents the substantial prevalence of significantly abnormal renal function among patients identified by laboratories as having normal-range SCR: Including calculated estimates of GFR in routine laboratory reporting may help to facilitate the early identification of patients with renal impairment.     

Continent jejunal reservoir dialysis for end-stage renal disease: is it possible?

With limited organs available for renal transplantation in comparison with the number of patients on the waiting list, and with the drawbacks of dialysis, other forms of treatment for end-stage renal disease (ESRD) need to be investigated. We propose that using a reconfigured segment of bowel as a reservoir in which dialysate of various compositions can be instilled to remove metabolic wastes usually handled by the kidney may augment or replace renal function in a uremic patient. We have chosen the jejunum and have documented our preliminary findings using hyperosmotic dialysate along with the unique characteristics of continent jejunal reservoir dialysis (CJRD). With further refinements, CJRD may eventually be offered as an alternative treatment for ESRD.     

Early prostate cancer: is there a need for new treatment options?

Improvements in diagnostic techniques have led to prostate cancer being diagnosed in younger patients and at an earlier stage of disease. The question therefore arises as to what is the best treatment for early prostate cancer. The main issues to be considered are whether the cancer is likely to progress quicker if these patients do not receive early treatment and what the quality of life implications are for patients receiving early treatment. As yet, due to the lack of valid comparisons of treatments, there is no clear "best treatment" for early prostate cancer. A number of clinical trials, comparing current treatments or investigating potential new treatment options for early prostate cancer, are in progress. The results of these should clarify the relative benefits of currently available treatments. This article reviews the latest information on the incidence, prognosis and current treatments for early prostate cancer and discusses the need for new treatments. Potential clinical benefits and cost implications of new treatments for early prostate cancer, such as improved surgical and radiotherapy techniques and adjuvant medical therapy, are also evaluated.     

Variable renal disease progression in autosomal dominant polycystic kidney disease: a role for nitric oxide?

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a variable renal disease progression, which is primarily due to genetic heterogeneity (PKD1 vs. PKD2). Evidence obtained in murine models and studies of variability in siblings and twins suggest that modifier genes influence renal disease progression in ADPKD. These modifier loci could affect cystogenesis and/or cyst progression, but also more general factors, i.e. endothelial dysfunction. The demonstration of endothelial dysfunction in Pkd1(+/-) mice and ADPKD patients, and the effect of the frequent Glu298Asp polymorphism of ENOS on renal disease progression in ADPKD suggest that an impaired release of nitric oxide (NO) by endothelial cells can accelerate renal function degradation. These results also suggest that polycystins can participate in the regulation of endothelial NO synthase (eNOS) and that addressing endothelial dysfunction in ADPKD can offer a new perspective to slow renal disease progression.     

Metformin: effective and safe in renal disease?

There is good evidence supporting more extensive use of metformin in type 2 diabetes, in reducing morbidity and mortality. The evidence for a real problem from metformin-induced lactic acidosis is weak, and the risks of alternative agents are often overlooked. We have examined the available data regarding metformin that might cause concern in patients with kidney disease, and find it to be extremely limited. There is no good data on which to offer guidance, but it seems likely that metformin can be used in patients with GFR 60–90 ml/min but at reduced dose at lower levels of GFR, and can probably be safely used at GFRs from 30–60 ml/min but with the same caution as with any renally excreted drug. The risks (often overlooked) and benefits of alternative hypoglycaemic agents should be considered carefully. The overall evidence that metformin causes major harm is poor.     

Ischemic acute renal failure: an inflammatory disease?

Inflammation plays a major role in the pathophysiology of acute renal failure resulting from ischemia. In this review, we discuss the contribution of endothelial and epithelial cells and leukocytes to this inflammatory response. The roles of cytokines/chemokines in the injury and recovery phase are reviewed. The ability of the mouse kidney to be protected by prior exposure to ischemia or urinary tract obstruction is discussed as a potential model to emulate as we search for pharmacologic agents that will serve to protect the kidney against injury. Understanding the inflammatory response prevalent in ischemic kidney injury will facilitate identification of molecular targets for therapeutic intervention.     

Incidental renal artery stenosis in peripheral vascular disease: a case for treatment?

BACKGROUND: Renal artery stenosis (RAS) is frequently encountered as an incidental finding in peripheral vascular disease. We assessed whether revascularization is indicated to prevent the practical consequences of end-stage renal failure, that is, the need for renal replacement therapy. METHODS: In a retrospective study, a cohort of consecutive patients was followed who had undergone angiography 8 to 10 years previously for peripheral artery disease. Patients with untreated incidental RAS of > or =50% diameter stenosis (68.8 +/- 9.8 years, mean +/- SD) were compared with regard to the prevalence of renal replacement therapy to controls without RAS who were matched for age and gender. RESULTS: RAS was present in 126 of 386 evaluable patients (33%). None of these patients required renal replacement therapy during the 10-year follow-up. Serum creatinine values remained stable during follow-up. CONCLUSIONS: Incidental RAS is frequently seen in patients with peripheral vascular disease. If left untreated, incidental RAS seems not to result in end-stage renal failure or in a need for renal replacement therapy. Revascularization with the aim to prevent end-stage renal failure seems less indicated, and further prospective studies are indicated to elucidate this issue.     

Can pentoxifylline prevent renal disease?

The characteristics of pentoxifylline(Trental) suggest that it is an ideal agent to be used as adjunct in the therapy of chronic proliferative glomerulonephritides. Theoretical considerations suggest that pentoxifylline should also protect against and even ameliorate tubulo-interstitial fibrosis of affected kidneys.     

Is double renal transplantation a risk factor for cytomegalovirus disease?

We performed a retrospective study to identify the risk factors for cytomegalovirus (CMV) disease among 570 renal transplant recipients. By means of a multivariate analysis we identified antilymphocyte antibody therapy (odds ratio [OR]: 4.6; 95% confidence interval [CI]: 2.0 to 10.6), high doses of corticosteroids (OR: 3.4; 95% CI: 1.2 to 10.1), and double renal transplant (OR: 4.1; 95% CI: 1.5 to 11.5). To the best of our knowledge, this is the first study to suggest that in addition to other well-known risk factors for CMV disease (ie, therapy with anti-lymphocyte antibodies or high doses of corticosteroids), the use of double renal transplantation appears to increase the risk of CMV disease in this population.