Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease.

BACKGROUND: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. METHOD: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. MAIN RESULTS: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. CONCLUSIONS: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent.

Recent studies have related mitochondrial impairment with peritoneal membrane damage during peritoneal dialysis (PD) therapy. Here, we assessed the involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells, a hallmark in the pathogenesis of PD-related peritoneal membrane damage. Our ex vivo studies showed that IL-1ß causes a drop in the mitochondrial membrane potential in cells from peritoneal effluent. Moreover, when mitochondrial damage was induced by inhibitors of mitochondrial function, a low-grade inflammatory response was generated. Interestingly, mitochondrial damage sensitized mesothelial cells, causing a significant increase in the inflammatory response induced by cytokines, in which ROS generation and NF-κB activation appear to be involved, since inflammation was counteracted by both mitoTEMPO (mitochondrial ROS scavenger) and BAY-117085 (NF-κB inhibitor). Furthermore, the natural anti-inflammatory antioxidant resveratrol significantly attenuated the inflammatory response, by reversing the decline in mitochondrial membrane potential and decreasing the expression of IL-8, COX-2 and PGE2 caused by IL-1ß. These findings suggest that IL-1ß regulates mitochondrial function in mesothelial cells and that mitochondrial dysfunction could induce an inflammatory scenario that sensitizes these cells, causing significant amplification of the inflammatory response induced by cytokines. Resveratrol may represent a promising strategy in controlling the mesothelial inflammatory response to PD.

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis.

Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.

Does Prior Abdominal Surgery Influence Peritoneal Transport Characteristics or Technique Survival of Peritoneal Dialysis Patients?

INTRODUCTION: Prior abdominal surgery may result in peritoneal membrane adhesions and fibrosis, compromising the success of peritoneal dialysis (PD). The impact of this factor on peritoneal membrane function and PD technique survival has not been adequately investigated. METHODS: Following an observational, retrospective design, we studied 171 incident PD patients, with the main objective of analyzing the influence of prior abdominal surgical procedures (main study variable) on baseline and evolutionary peritoneal transport characteristics (main outcome) and PD patient and technique survival (secondary outcomes). Abdominal surgeries were categorized according to the degree of presumed injury to the peritoneal membrane. We also considered the additive effect of aggressions to the membrane during the first year on PD therapy. RESULTS: All patients had a baseline peritoneal equilibration test with complete drainage at 60', and 113 patients had a second study at the end of the first year. Sixty-one patients (35.7%) had a record of prior abdominal surgery, including 29 patients with at least one major intraperitoneal surgery, 22 having undergone minor intraperitoneal procedures, and 21 with a background of major abdominopelvic extraperitoneal surgery. We did not observe differences, at baseline or after 1 year, among patients with or without previous abdominal procedures regarding small solute transport, overall capacity of ultrafiltration, free water transport, small pore ultrafiltration, or peritoneal protein excretion. Stratified analysis, considering prior and first-year-on-PD peritoneal aggressions, did not reveal any differences, although in this case our analysis was hampered by a limited statistical power. Abdominal surgical events did not influence patient or PD technique survival. CONCLUSION: Prior abdominal surgical procedures do not appear to compromise peritoneal membrane function or technique survival in patients successfully started on PD.

Long-term trends in the incidence of peritoneal dialysis-related peritonitis disclose an increasing relevance of streptococcal infections: A longitudinal study.

BACKGROUND: The selective impact of strategies for prevention of PD-related peritonitis (PDrP) may have modified, in the long term, the causal spectrum, clinical presentation and outcomes of these infections. OBJECTIVES: To compare trends in the incidence of PDrP by different microorganisms during a 30-year period, with a particular focus on streptococcal infections. To analyze the clinical presentation and outcomes of these infections. Secondarily, to investigate how the isolation of different species of streptococci can influence the clinical course of PDrP by this genus of bacteria. METHOD: Following a retrospective, observational design we investigated 1061 PDrP (1990-2019). We used joinpoint regression analysis to explore trends in the incidence of PDrP by different microorganisms, and compared the risk profile (Cox), clinical presentation and outcomes (logistic regression) of these infections. MAIN RESULTS: Our data showed a progressive decline in the incidence of PDrP by staphylococci and Gram negative bacteria, while the absolute rates of streptococcal (average annual percent change +1.6%, 95% CI -0.1/+3.2) and polymicrobial (+1.8%, +0.1/+3.5) infections tended to increase, during the same period. Remarkably, streptococci were isolated in 58.6% of polymicrobial infections, and patients who suffered a streptococcal PDrP had a 35.8% chance of presenting at least one other infection by the same genus. The risk profile for streptococcal infections was comparable to that observed for PDrP overall. Streptococcal PDrP were associated with a severe initial inflammatory response, but their clinical course was generally nonaggressive thereafter. We did not observe a differential effect of different groups of streptococci on the clinical presentation or outcome of PDrP. CONCLUSIONS: Time trends in the incidence of PDrP by different microorganisms have granted streptococci an increasing relevance as causative agents of these infections, during the last three decades. This behaviour suggests that current measures of prevention of PDrP may not be sufficiently effective, in the case of this genus of microorganisms.

[SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN)]. / Situación de la infección por SARS-CoV-2 en pacientes en tratamiento renal sustitutivo. Informe del Registro COVID-19 de la Sociedad Española de Nefrología (SEN).

INTRODUCTION: The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. MATERIAL AND METHODS: The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an online registry. Patients were diagnosed with SARS-CoV-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contact acquainted with another patient. RESULTS: As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of RRT is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. CONCLUSIONS: SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality.

Analysis of Factors Influencing the Prognostic Significance of Hyponatremia in Peritoneal Dialysis Patients.

BACKGROUND: The evidence linking low serum sodium levels with the risk of mortality in peritoneal dialysis (PD) patients is controversial. Considering the different mechanisms contributing to hyponatremia in these patients, it is conceivable that the prognostic significance of this factor may vary, according to the clinical setting. METHODS: Following a retrospective, observational design, we analyzed the association between hyponatremia and mortality in 748 patients incident on PD. We applied multivariate strategies of analysis, with the main objective of identifying subgroups of patients in whom hyponatremia could sustain different degrees of association with mortality (main outcome variable). For this purpose, we performed preliminary analyses to: (1) disclose predictors of serum sodium levels before and after (mean of first 3 months) initiation of PD (main study variable) and (2) investigate the overall prognostic significance of hyponatremia, in our patients. RESULTS: Comorbidity, hypoalbuminemia, and lower glomerular filtration rate (GFR) were main predictors of hyponatremia. Use of icodextrin was another inverse correlate of serum sodium, and the only consistent predictor of a decline of natremia, once PD was started. Multivariate analysis confirmed early hyponatremia as an independent marker of survival. However, stratified analyses showed that this association was most apparent in specific subsets, namely, hypoalbuminemic, more anemic patients with higher baseline levels of GFR and C-reactive protein and faster peritoneal solute transport rates. Other factors potentially reinforcing the prognostic significance of hyponatremia included lower lean body mass levels, nonprescription of renin-angiotensin-aldosterone system antagonists, and use of icodextrin-based PD solution. On the contrary, baseline overhydration or categorization by classic predictors of mortality (age, comorbidity, diabetes) did not appear to influence the risk pattern associated with lower serum sodium levels. CONCLUSIONS: Our results suggest that hyponatremia performs as a consistent correlate of the risk of mortality mainly in PD patients manifesting direct or indirect signs of inflammation and wasting, while this association is not apparently linked to the presence of overhydration or nominal, preexisting comorbid conditions.

Persistent overhydration is associated with a significant risk of peritoneal infection by enteric pathogens in patients treated with peritoneal dialysis. / La sobrehidratación persistente asocia un riesgo significativo de infección peritoneal por gérmenes entéricos en pacientes tratados con diálisis peritoneal.

BACKGROUND: Overhydration (OH) complicates frequently the clinical course of Peritoneal Dialysis (PD) patients, and keeps a controversial association with the risk of peritoneal infection. The main objective of this study was to disclose an association between persistent OH and the risk of enteric peritonitis in a relatively large sample of patients undergoing PD. METHOD: Following a prospective design, we monitorized systematically body composition of patients treated with PD in our unit (2011-2016), searching for a correlation with the ensuing risk of peritonitis, with an emphasis on the association between persistent OH (main study variable) and the risk of infection by enteric pathogens (main outcome). Essential demographic, clinical and laboratory variables with a potential influence on the risk of peritonitis were recorded. We used multivariate survival analysis to clarify the specific effect of different body composition parameters on the main outcome. MAIN RESULTS: We included 139 patients for analysis (mean follow-up 24 months). Sixty-three patients suffered at least one peritonitis, and 17 had at least one diagnosis of enteric peritonitis. Univariate analysis disclosed a general trend to an increased risk of enteric peritonitis in overhydrated patients, as evidenced by associations of this outcome with mean extracellular water/intracellular water (ECW/ICW) (p=.007), OH/ECW (p=.033) and ECW/total body water (ECW/TBW) (p=.004) ratios, but not with absolute OH values. Multivariate analysis confirmed similar associations or trends (RR: 3.48, 95% CI: 1.03-14.59; p=.046, highest versus lowest tertile of ECW/ICW, RR: 2.31, 95% CI: 0.98-6.56; p=.061, highest versus lowest tertile of OH/ECW, and RR: 6.33, 95% CI: 1.37-19.37; p=.011, highest versus lowest tertile of ECW/TBW). On the contrary, no apparent association was detected between OH and the overall risk of peritoneal infection. CONCLUSION: Persistent overhydration portends a significant risk of peritoneal infection by enteric pathogens, among patients undergoing chronic PD.

High rates of protein intake are associated with an accelerated rate of decline of residual kidney function in incident peritoneal dialysis patients.

BACKGROUND: Preservation of residual kidney function (RKF) is a relevant objective in peritoneal dialysis (PD) patients. The influence of dietary protein intake (PI) on this variable has not been adequately investigated. METHODS: Following an observational design, we studied 336 patients incident on PD, with a minimum follow-up of 6 months. The main study variable was the mean PI [normalized rate of protein nitrogen appearance (nPNA)] during the first 4 months on PD. The main outcome variables were the absolute rate of decline of RKF and the proportion of patients presenting a >50% decay of their RKF during the first year of follow-up. We applied univariate and multivariate strategies of analysis, taking into consideration the main control variables bearing a correlation with nPNA and/or RKF. RESULTS: Mean nPNA (first 4 months) was 1.23 ± 0.33 g/kg/day, while the overall rate of decline of RKF was -0.13 ± 0.29 mL/min/month; 69 patients (25.1%) had lost >50% of their initial RKF by the end of the first year. Univariate analysis disclosed consistent associations between the main study variable on one hand and baseline RKF (r = 0.32, P < 0.0005) and its rate of decline (r = -0.23, P < 0.0005) on the other. The latter two variables were also significantly correlated (r = -0.36, P < 0.0005). Multivariate analysis identified mean nPNA as an independent predictor of the rate of decline of RKF [odds ratio 1.09 per 0.10 g/kg/day, 95% confidence interval (CI) 0.99-1.19, P = 0.058] and, in particular, of the probability of losing >50% of the baseline RKF during the first year of treatment (odds ratio 1.15 per 0.10 g/kg/day, 95% CI 1.04-1.27, P = 0.006). CONCLUSION: Higher rates of PI during the first months of therapy are associated with a faster decline of RKF among patients incident on PD. Our results underline the convenience of keeping an adequate balance between sufficient protein ingestion, to prevent malnutrition and wasting, and sensible restriction in stable, adequately nourished individuals with rates of intake in the higher range or above-recommended allowances.

The Spanish Society of Nephrology (SENEFRO) commentary to the Spain GBD 2016 report: Keeping chronic kidney disease out of sight of health authorities will only magnify the problem.

The Global Burden of Disease (GBD) study measures the health of populations worldwide and by country on an annual basis and aims at helping guide public policy on health issues. The GBD estimates for Spain in 2016 and recent trends in mortality and morbidity from 2006 to 2016 were recently published. According to these estimates, chronic kidney disease was the 8th cause of death in Spain in 2016. Among the top ten causes of death, chronic kidney disease was the fastest growing from 2006 to 2016, after Alzheimer disease. At the current pace of growth, chronic kidney disease is set to become the second cause of death in Spain, after Alzheimer disease, by 2100. Additionally, among major causes of death, chronic kidney disease also ranked second only to Alzheimer as the fastest growing cause of Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). Public resources devoted to prevention, care and research on kidney disease should be in line with both its current and future burden.

Peritoneal Dialysis Is an Independent Factor Associated to Lower Intima Media Thickness in Dialysis Patients Free From Previous Cardiovascular Disease.

Carotid intima media thickness (cIMT) displays prognostic value as a marker of cardiovascular risk in dialysis patients. However, few data are available regarding the impact of dialysis modality on cIMT. The aim of this study is to determine whether the modality of dialysis influences cIMT values. We compared 237 peritoneal dialysis (PD) and 451 hemodialysis (HD) patients without previous cardiovascular disease included in NEFRONA, a prospective, observational and multicenter study. This cross sectional study included the determination of cIMT in 6 carotid territories by arterial ultrasound. cIMT was determined in territories without atheroma plaque and averaged. A second analysis was performed using all territories, giving a truncated cIMT value of 1,5 mm to territories presenting with atheroma plaque. Age and plaque presence at baseline were the clinical variables more closely associated to cIMT in dialysis patients. The evaluation of the impact of the modality of dialysis on cIMT showed that PD patients had lower cIMT than HD patients, both in territories with no plaques and when using truncated cIMT values. No differences were found between right and left sides, neither in cIMT or truncated cIMT values. Lineal multivariate analysis adjusted by several clinical variables showed a statistically significant association of PD with a lower cIMT (slope -0.036; SD 0.010). These results were also confirmed when truncated cIMT values were used. We conclude that the modality of dialysis has an impact on cITM. HD patients have greater global cIMT than PD patients, and PD is and independent factor associated with a lower cIMT.

Correction: The modality of dialysis does not influence atheromatous vascular disease progression or cardiovascular outcomes in dialysis patients without previous cardiovascular disease.

[This corrects the article DOI: 10.1371/journal.pone.0186921.].

Comprehensive Approach to Peritoneal Dialysis-Related Peritonitis by Enteric Microorganisms. Comparison Between Single Organism and Polymicrobial Infections.

BACKGROUND: Peritoneal infections of enteric origin (EntP) have been classically investigated using partial strategies, focused on particular subgroups of microorganisms. A more comprehensive approach may facilitate the definition of the nomenclature and clinical presentation of these infections. OBJECTIVES: To investigate the clinical presentation and outcomes of a full spectrum of EntP, with a particular interest in the comparison between single-organism and polymicrobial infections. METHOD: Following an observational design, we investigated 165 single-organism and 83 polymicrobial peritonitis episodes with isolation of at least 1 enteric bacteria (Enterobacteriaceae, Enterococcus spp. and/or intestinal anaerobics). We compared the risk of treatment failure for these 2 types of infection and explored the significance of the isolation of specific microorganisms and of their antibacterial susceptibility patterns. RESULTS: Polymicrobial EntP was associated with higher rates of hospitalization, more changes to initial antibiotic therapy, more surgical explorations, and higher mortality and treatment failure rates than monobacterial EntP. However, stratified and multivariate analyses revealed that the burden of these differences rested on the isolation of intestinal anaerobics (odds ratio [OR] 12.05, 95% confidence interval [CI] 2.53-31.09, p < 0.001) and/or Enterococcus faecium (OR 3.37, 95% CI 1.02-11.30, p = 0.046), while other polymicrobial infections were more comparable with single-organism peritonitis, except for even higher mortality rates in the former group. Lower antibiotic susceptibility of the isolations (OR 1.18, 95% CI 0.51-2.70, p = 0.70) did not perform as a predictor of treatment failure. CONCLUSION: A comprehensive approach to peritoneal infections by intestinal microorganisms may provide a focused perspective of the clinical presentation and outcomes of these complications of peritoneal dialysis.

The modality of dialysis does not influence atheromatous vascular disease progression or cardiovascular outcomes in dialysis patients without previous cardiovascular disease.

BACKGROUND: There is limited and inconclusive information regarding the influence of the modality of renal replacement therapy on the atherosclerotic burden of patients on dialysis. The aim of this study was to compare the prevalence of asymptomatic atheromatous carotid disease, as also its rate of progression and cardiovascular outcomes, in two matched populations of patients treated with hemodialysis (HD) and peritoneal dialysis (PD). METHODS: Following a prospective, observational and multicenter design, we compared 237 PD and 237 HD patients without previous cardiovascular disease, included in the NEFRONA study, and matched for age, sex, diabetes and time on dialysis. Carotid ultrasound study was performed at baseline and after two years of follow-up in 6 carotid territories. Atheromatous vascular disease (AVD) progression was defined as any increase in the number of territories with plaques after 2 years. Fatal and non fatal cardiovascular events were also recorded during 36-month of follow-up. MAIN RESULTS: At baseline, PD patients presented a worse general cardiovascular risk profile than HD patients. On the contrary, some markers of prevalent atherosclerotic disease (common carotid intima-media thickness and ankle-brachial index) were more favorable in PD patients. During follow-up, we observed no differences either in the rate of progression of atheromatous vascular disease (OR 1.78, 95% CI 0.80-4.06, p = 0.161) or in the incidence of cardiovascular events (OR 1.51, 95% CI 0.85-2.66, p = 0.159), according to the modality of dialysis. CONCLUSION: Dialysis modality did not impact on atherosclerotic carotid disease progression or cardiovascular outcomes, in two groups of patients treated with PD or HD.

Peritoneal Water Transport Characteristics of Diabetic Patients Undergoing Peritoneal Dialysis: A Longitudinal Study.

BACKGROUND: Volume overload is frequent in diabetics undergoing peritoneal dialysis (PD), and may play a significant role in the excess mortality observed in these patients. The characteristics of peritoneal water transport in this population have not been studied sufficiently. METHOD: Following a prospective, single-center design we made cross-sectional and longitudinal comparisons of peritoneal water transport in 2 relatively large samples of diabetic and nondiabetic PD patients. We used 3.86/4.25% glucose-based peritoneal equilibration tests (PET) with complete drainage at 60 min, for these purposes. MAIN RESULTS: We scrutinized 59 diabetic and 120 nondiabetic PD patients. Both samples showed relatively similar characteristics, although diabetics were significantly more overhydrated than nondiabetics. The baseline PET disclosed lower ultrafiltration (mean 439 mL diabetics vs. 532 mL nondiabetics, p = 0.033) and sodium removal (41 vs. 53 mM, p = 0.014) rates in diabetics. One hundred and nine patients (36 diabetics) underwent a second PET after 12 months, and 45 (14 diabetics) underwent a third one after 24 months. Longitudinal analyses disclosed an essential stability of water transport in both groups, although nondiabetic patients showed a trend where an increase in free water transport (p = 0.033) was observed, which was not the case in diabetics. CONCLUSIONS: Diabetic patients undergoing PD present lower capacities of ultrafiltration and sodium removal than their nondiabetic counterparts. Longitudinal analyses disclose an essential stability of water transport capacities, both in diabetics and nondiabetics. The clinical significance of these differences deserves further analysis.

Low Serum Levels of Vitamin D are Associated with Progression of Subclinical Atherosclerotic Vascular Disease in Peritoneal Dialysis Patients: A Prospective, Multicenter Study.

BACKGROUND: The prevalence of subclinical atherosclerosis and the main predictors of progression of this condition in patients undergoing peritoneal dialysis (PD) have been insufficiently investigated. OBJECTIVES AND METHOD: Following a prospective, multicenter, observational design, we studied 237 patients who were treated with PD for ≥3 months, without any clinical background of cardiovascular (CV) disease. Our objectives were the following: (1) to investigate the prevalence of subclinical atherosclerosis, as compared to a control group of age- and sex-matched healthy individuals, and (2) to disclose PD technique-related predictors of progression of disease during a 24-month follow-up period. We used vascular ultrasound for characterization of subclinical atherosclerotic disease. MAIN RESULTS: A total of 123 patients (51.9%) vs. 79 controls (33.5%) presented ≥1 carotid plaque, and 114 patients (48.3%) vs. 72 controls (30.5%) ≥1 femoral plaque, at baseline evaluation (p < 0.0005). Progression of disease, either in clinical or ultrasound (new plaques) terms, affected 62.6% of patients. Multivariate analysis identified age, carotid intima-media thickness, presence of ≥1 carotid plaque, and serum levels of 25OH vitamin D and C-reactive protein (CRP) at baseline as independent correlates of progression of atherosclerotic disease. On the contrary, PD technique-related variables did not show any association with this outcome. CONCLUSIONS: Atherosclerotic vascular disease is frequent among asymptomatic patients undergoing PD. Older age, pre-existent disease (assessed by vascular ultrasound), and serum levels of 25OH vitamin D and CRP are independent markers of the progression of this condition. These findings may contribute to improve identification of subpopulations with a high risk of CV events, deserving intensified measures of prevention.

Serum levels of the adipomyokine irisin in patients with chronic kidney disease. / Niveles séricos de la adipomioquina irisina en pacientes con enfermedad renal crónica.

BACKGROUND: Irisin is an adipomyokine with claimed anti-obesity and anti-diabetic effects. This hormone has been insufficiently studied in patients with advanced chronic kidney disease (CKD). OBJECTIVE: To perform an exploratory analysis of serum irisin levels in patients undergoing different CKD treatments. METHOD: Following a cross-sectional design, we estimated serum levels of irisin in 95 patients with CKD managed conservatively (advanced CKD), with peritoneal dialysis (PD) or with haemodialysis, and compared our findings with a control group of 40 healthy individuals. We investigated the correlations between serum irisin and demographic, clinical, body composition and metabolic variables. RESULTS: Irisin levels were lower in all the CKD groups than in the control group. The univariate analysis revealed limited correlations between irisin, on the one hand, and fat (but not lean) mass, glomerular filtration rate (GFR) and plasma albumin and bicarbonate, on the other. The multivariate analysis confirmed that advanced CKD patients managed conservatively (difference 111.1ng/ml), with PD (25.9ng/ml) or haemodialysis (61.4ng/ml) (all P<.0005) presented lower irisin levels than the control group. Furthermore, PD patients presented higher serum levels of irisin than those on haemodialysis (difference 39.4ng/ml, P=.002) or those managed conservatively (24.4 ng/ml, P=.036). The multivariate analysis also identified plasma bicarbonate (B=3.90 per mM/l, P=.001) and GFR (B=1.89 per ml/minute, P=.003) as independent predictors of irisin levels. Conversely, no adjusted correlation between irisin and body composition markers was found. CONCLUSIONS: Serum irisin levels are low in patients with CKD and show a consistent correlation with GFR and plasma bicarbonate levels. PD patients present higher levels of irisin than those managed conservatively or with haemodialysis. Our study confirms a general inconsistency of the association between serum irisin levels, on the one hand, and body composition and metabolic markers, on the other.

Baseline Residual Kidney Function and Its Ensuing Rate of Decline Interact to Predict Mortality of Peritoneal Dialysis Patients.

BACKGROUND: Baseline residual kidney function (RKF) and its rate of decline during follow-up are purported to be reliable outcome predictors of patients undergoing Peritoneal Dialysis (PD). The independent contribution of each of these factors has not been elucidated. METHOD: We report a multicenter, longitudinal study of 493 patients incident on PD and satisfying two conditions: a glomerular filtration rate (GFR) ≥1 mL/minute and a daily diuresis ≥300 mL. The main variables were the GFR (mean of urea and creatinine clearances) at PD inception and the GFR rate of decline during follow-up. The main outcome variable was patient mortality. The secondary outcome variables were: PD technique failure and risk of peritoneal infection. The statistical analysis was based on a multivariate approach, placing an emphasis on the interactions between the two main study variables. MAIN RESULTS: Baseline GFR and its rate of decline performed well as independent predictors of both patient mortality and risk of peritoneal infection. These two main study variables maintained a moderate correlation with each other (r2 = 0.12, p<0.0005), and interacted clearly, as predictors of patient mortality. A low baseline GFR followed by a fast decline portended the worst survival outcome (adjusted HR 3.84, 95%CI 1.81-8.14, p<0.0005)(Ref. baseline GFR above median plus rate of decline below median). In general, the rate of decline of RKF had a greater effect on mortality than baseline GFR, which had no detectable effect on survival when the decline of RKF was slow (HR 1.17, 95% CI 0.81-2.22, p = 0.22). Conversely, a relatively high GFR at the start of PD still carried a significant risk of mortality, when RKF declined rapidly (HR 1.89, 95% CI 1.05-3.72, p = 0.028). CONCLUSION: The risk-benefit balance of an early versus late start of PD cannot be evaluated without taking into consideration the rate of decline of RKF. This circumstance may contribute to explain the controversial results observed at the time of evaluating the potential benefits of an early initiation of PD.

Circulating Levels of Irisin in Hypopituitary and Normal Subjects.

CONTEXT: The recently identified myokine irisin conveys some of the benefits of exercise. Hypopituitarism with adult growth hormone deficiency (HP) is a situation characterized by decreased GH secretion and an altered body composition. OBJECTIVE: Our aim was to study the skeletal muscle hormone irisin in HP, and compare the results with a similar group of normal subjects. PARTICIPANTS AND METHODS: Seventeen HP patients and fifty-one normal subjects of similar age and sex were studied. The diagnosis of GH deficiency was confirmed by the presence of pituitary disease and a peak GH secretion below 3 µg/L after an insulin tolerance test. The patients were adequately treated for all pituitary hormone deficits, except for GH. Fasting serum irisin was measured with an enzyme immunoassay, and HOMA-IR, QUICKI and HOMA-ß were calculated. RESULTS: Fasting irisin levels (ng/ml) were similar in normal [208.42 (168.44-249.23)] and HP patients [195.13 (178.44-241.44)]. In the control group there were moderate significant positive correlations between irisin and BMI, waist circumference, leptin, fasting insulin, HOMA-IR, HOMA-ß, triglycerides, and cholesterol. In the control group there were moderate significant negative correlations between irisin and IGF-I and QUICKI. In the hypopituitary group there were moderate significant positive correlations between irisin and body fat and HOMA-ß. CONCLUSIONS: We found similar irisin levels in GH deficiency hypopituitary patients when compared with normal subjects. The correlation between irisin and adiposity related factors suggests that that in the case of this clinical model, irisin is regulated by adiposity and not by GH.

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis.

BACKGROUND: Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD). METHOD: Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses. MAIN RESULTS: The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08-2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other. CONCLUSIONS: Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients.