ABSTRACT
Asymmetric dimethylarginine (ADMA) and its enantiomer, Symmetric dimethylarginine (SDMA), are naturally occurring amino acids that were first isolated and characterized in human urine in 1970. ADMA is the most potent endogenous inhibitor of nitric oxide synthase (NOS), with higher levels in patients with end-stage renal disease (ESRD). ADMA has shown to be a significant predictor of cardiovascular outcome and mortality among dialysis patients. On the other hand, although initially SDMA was thought to be an innocuous molecule, we now know that it is an outstanding marker of renal function both in human and in animal models, with ESRD patients on dialysis showing the highest SDMA levels. Today, we know that ADMA and SDMA are not only uremic toxins but also independent risk markers for mortality and cardiovascular disease (CVD). In this review, we summarize the role of both ADMA and SDMA in chronic kidney disease along with other cardiovascular risk factors.
Subject(s)
Arginine/analogs & derivatives , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/metabolism , Aging/metabolism , Animals , Arginine/metabolism , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Humans , Metabolic Networks and Pathways/drug effects , Molecular Targeted Therapy , Prognosis , Renal Dialysis , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/therapyABSTRACT
BACKGROUND: Various factors can lead to inadequate nephrology referral decisions being taken by clinicians, but a major cause is unawareness of guidelines, recommendations and indications, or of appropriate timing. Today, tools such as smartphone applications (Apps) can make this knowledge more accessible to non-nephrologist clinicians. Our study aim is to determine the effectiveness of a purpose-built app in this respect. METHODS: In a retrospective study, nephrology referrals were compared before and after the introduction of the app in clinical practice. The initial study population consisted of first visits by patients referred to our department in 2015, before the introduction of the app. In 2016, the smartphone app NefroConsultor began to be implemented in our hospital. We compared the initial study population with the results obtained for patients referred in 2017, when the app was in use, taking into account clinical features considered, such as urinalysis, proteinuria or kidney ultrasound, to determine whether these patients met currently recommended criteria for referral. RESULTS: The total study population consisted of 628 patients, of whom 333 were examined before the introduction of the app (in 2015) and 295 when it was in use (in 2017). Among the first group, 132 (39.6%) met established KDIGO criteria for nephrology referral and were considered to be correctly referred. Among the second group, 200 (67.8%) met the criteria and were considered to be properly referred (P = 0.001). The increase in the rate of intervention success (before-after app) was 28.8% with a binomial effect size display (Cohen's d effect size) of 0.751. Before the introduction of the app, data for albuminuria were included in 62.5% of nephrology referrals; in 2017, the corresponding value was 87.5% (P = 0.001). In the same line, referrals including urinalysis rose from 68.5% to 85.8% (P = 0.001). Multivariate regression analysis, using referrals meeting KDIGO criteria as the dependent variable and adjusting for age, sex and referring department, showed that the 2017 group (after the introduction of NefroConsultor) was associated with an odds ratio of 3.57 (95% confidence interval 2.52-5.05) for correct referrals, compared with the 2015 group (P = 0.001). References to proteinuria as the reason for nephrology referral also increased from 23.7% to 34.2% (P = 0.004). CONCLUSIONS: Use of the app is associated with more frequent studies of albuminuria at the time of referral and a greater likelihood of proteinuria being cited as the reason for referral. The smartphone app considered can improve the accessibility of information concerning nephrology referrals and related studies.
ABSTRACT
INTRODUCTION: Low pre-hemodialysis (pre-HD) serum sodium or hyponatremia is associated with higher mortality. Pre-HD serum sodium can be more stable over time with low fluctuation compared to other serum parameters. MATERIALS AND METHODS: We examined variation of pre-HD serum sodium in 24 months and after this point examined all-cause mortality in a cohort of 261 patients followed-up for 48.8 (standard deviation (SD) = 19.1) months. 6,221 determinations of pre-HD serum sodium were made and corrected for glucose concentrations. Serum sodium was measured pre-HD monthly, and the variability was calculated using the coefficient of variation (CV). RESULTS: The mean age was of 60 ± 14.1 years, 60.9% were men, 48% had diabetes mellitus, and diabetic nephropathy was the most frequent cause of end-stage renal disease. Median CV of sodium in 24 months was 1.7% with a mean of 1.78% (95% CI 1.73 - 1.83). Patients with CV > 1.7% had a higher mortality (53 patients a 36.8%) compared to CV < 1.7% (22 patients a 18.8%) (p = 0.002). In Kaplan-Meier analysis, patients with CV > 1.7% had significantly worse overall survival (log rank = 6.395, p = 0.011). We also stratified the sample in serum sodium tertiles (< 138 mEq/L; 138 - 140 mEq/L; > 140 mEq/L) and made a Kaplan-Meier analysis which showed persistent worse survival outcomes in patients with CV > 1.7% (log rank Mantel-Cox 7.64; p = 0.006). Cox regression multivariate model showed that CV of sodium was significantly associated with overall mortality after adjusting for confounder variables (hazard ratio 2.16, 95% CI 1.37 - 3.41; p = 0.001). CONCLUSION: Variation of pre-HD serum sodium in 2 years is less than a 2%. With the limitations of our study, a higher variability of pre-HD serum sodium in 2 years of treatment (CV > 1.7%) is associated with increased mortality.â©.
