Obesity, chronic kidney disease progression and the role of the adipokine C1q/TNF related protein-3.

INTRODUCTION AND AIMS: Obesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression. METHODS: Patients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered). RESULTS: 81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1±23.8 vs 84.5±6.2; p=0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4±24.7 vs 106±24.7;p<0.01). During a mean follow-up of 68 months, 15 patients had a renal event. Patients in the higher CTRP3 tertile had less events but without statistical significance (p=0.07). Obese patients in the higher CTRP3 tertile significantly had less renal events (p=0.049). By multiple regression analysis CTRP3 levels could not predict renal events (HR 0.98; CI95% 0.96-1.06). CONCLUSIONS: CTRP3 levels are higher in woman than men in patients with CKD, with similar levels between obese and non obese. Higher CTRP3 levels at baseline were associated with better renal outcomes in obese patients.

Development and validation of a nomogram to predict kidney survival at baseline in patients with C3 glomerulopathy.

Background: C3 glomerulopathy is a rare and heterogeneous complement-driven disease. It is often challenging to accurately predict in clinical practice the individual kidney prognosis at baseline. We herein sought to develop and validate a prognostic nomogram to predict long-term kidney survival. Methods: We conducted a retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. The dataset was randomly divided into a training group (n = 87) and a validation group (n = 28). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of kidney outcome and to build the nomogram. The accuracy of the nomogram was assessed by discrimination and risk calibration in the training and validation sets. Results: The study group comprised 115 patients, of whom 46 (40%) reached kidney failure in a median follow-up of 49 months (range 24-112). No significant differences were observed in baseline estimated glomerular filtration rate (eGFR), proteinuria or total chronicity score of kidney biopsies, between patients in the training versus those in the validation set. The selected variables by LASSO were eGFR, proteinuria and total chronicity score. Based on a Cox model, a nomogram was developed for the prediction of kidney survival at 1, 2, 5 and 10 years from diagnosis. The C-index of the nomogram was 0.860 (95% confidence interval 0.834-0.887) and calibration plots showed optimal agreement between predicted and observed outcomes. Conclusions: We constructed and validated a practical nomogram with good discrimination and calibration to predict the risk of kidney failure in C3 glomerulopathy patients at 1, 2, 5 and 10 years.

Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy.

INTRODUCTION: The association between a change in proteinuria over time and its impact on kidney prognosis has not been analysed in complement component 3 (C3) glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure. METHODS: This was a retrospective, multicentre observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modelling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure. RESULTS: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (hazard ratio 0.79; 95% confidence interval 0.56-0.97; P < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up. CONCLUSIONS: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.

Direct-acting antiviral therapy improves kidney survival in hepatitis C virus-associated cryoglobulinaemia: the RENALCRYOGLOBULINEMIC study.

BACKGROUND: Direct-acting antiviral agents (DAAs) have shown high rates of sustained virological response in chronic hepatitis C virus (HCV) infection. However, the influence of DAAs on the course of kidney involvement in HCV-associated mixed cryoglobulinaemia (HCV-MC) has been little studied. The aim of this study was to analyse the effects of antiviral treatment on kidney prognosis and evolution in patients diagnosed with HCV-MC. METHODS: The RENALCRYOGLOBULINEMIC study is an observational multicentre cohort study of 139 patients with HCV-MC from 14 Spanish centres. Clinical and laboratory parameters were measured before and after antiviral treatment. Primary endpoints were kidney survival and mortality after HCV-MC diagnosis. Secondary endpoints were clinical, immunological and virological responses after antiviral treatment. RESULTS: Patients were divided into three groups based on the treatment received: treatment with DAAs (n = 100) treatment with interferon (IFN) and ribavirin (RBV) (n = 24) and no treatment (n = 15). Patients were followed up for a median duration of 138 months (interquartile range 70-251. DAA treatment reduced overall mortality {hazard ratio [HR] 0.12 [95% confidence interval (CI) 0.04-0.40]; P < 0.001} and improved kidney survival [HR 0.10 ( 95% CI 0.04-0.33); P < 0.001]. CONCLUSIONS: Results from the RENALCRYOGLOBULINEMIC study indicated that DAA treatment in patients with HCV-MC improves kidney survival and reduces mortality.

Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease.

BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (n=81) or dense deposit disease (n=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure). RESULTS: The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse. CONCLUSIONS: The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.

COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

Obesity and chronic kidney disease progression-the role of a new adipocytokine: C1q/tumour necrosis factor-related protein-1.

BACKGROUND: Obesity is a risk factor for incident chronic kidney disease (CKD) in the general population. C1q/tumour necrosis factor-related protein 1 (CTRP1) is a new adipokine with multiple vascular and metabolic effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP1 levels and CKD progression. METHODS: Patients with Stages 3 and 4 CKD without previous cardiovascular events were enrolled and divided into two groups according to body mass index (BMI). Demographic, clinical and analytical data and CTRP1 levels were collected at baseline. During follow-up, renal events [defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate (Modification of Diet in Renal Disease)] were registered. RESULTS: A total of 71 patients with CKD were divided into two groups: 25 obese (BMI >30 kg/m2) and 46 non-obese. CTRP1 in plasma at baseline was higher in obese patients [median (interquartile range) 360 (148) versus 288 (188) ng/mL, P = 0.041]. No significant association was found between CTRP1 levels and CKD stage, presence of diabetes, aldosterone and renin levels, or blood pressure. Obese patients had higher systolic blood pressure (P = 0.018) and higher high-sensitivity C-reactive protein (P = 0.019) and uric acid (P = 0.003) levels, without significant differences in the percentage of diabetic patients or albuminuria. During a mean follow-up of 65 months, 14 patients had a renal event. Patients with CTRP1 in the lowest tertile had more renal events, both in the overall sample (log rank: 5.810, P = 0.016) and among obese patients (log rank: 5.405, P = 0.020). Higher CTRP1 levels were associated with slower renal progression (hazard ratio 0.992, 95% confidence interval 0.986-0.998; P = 0.001) in a model adjusted for obesity, aspirin, albuminuria and renal function. CONCLUSIONS: CTRP1 levels are higher in obese than in non-obese patients with CKD. High CTRP1 levels may have a renal protective role since they were associated with slower kidney disease progression. Interventional studies are needed to explore this hypothesis.

Impact of anticoagulation and platelet antiaggregation on anaemia and haemorragic events in patients with chronic kidney disease stages 3 and 4. / Impacto de la anticoagulación y antiagregación plaquetaria en la anemia y los eventos hemorrágicos y ateroscleróticos de pacientes con enfermedad renal crónica en estadios 3 y 4.

BACKGROUND AND OBJECTIVE: There is controversy concerning the risk/benefit of anticoagulation/antiaggregation in chronic kidney disease (CKD) patients. We analysed the impact of anticoagulation/antiaggregation on anaemia and haemorrhagic events in CKD patients. PATIENTS AND METHODS: A total of 232 CKD patients stages 3 and 4 were followed during a mean follow-up time of 36.7 ± 11.6 months: 81 patients did not receive any anticoagulation or antiaggregation treatment, 91 received anticoagulation treatment and 60 patients received platelet antiaggregation. Haemorrhagic and cardiovascular events were recorded. RESULTS: Haemoglobin and ferritine levels were significantly higher in patients who did not receive anticoagulation or antiaggregation (Hb 13.7 ± 1.6, 13.3 ± 1.8 and 12.7±1.9g/dl, p=0.004; ferritine 170 ± 145, 140 ± 138, 105 ± 99µg/l, p=0.023). During follow up, 36 haemorrhagic events were registered: 4in the control group, 23 in the anticoagulation group and 9in the antiaggregation group (log rank 12.5; p=0.002). In a Cox model adjusted by age, renal function and haemoglobin levels, the anticoagulation increased the risk of bleeding by 4times (HR 4.180, 1.955-8.937); p=0,001) and antiaggregation by almost 3times (HR 2.780, 1.257-6.149, p=0.012). A total of 64 cardiovascular events were registered, 21 of which were classified as atherosclerotic events: 10 in the antiaggregation group, 8in the control group and 3in the anticoagulation group (log rank: 8.351; p=0.015). Anticoagulation treatment showed a reduction in the risk of atherosclerotic events (HR 0.136, 0.033-0.551, p=0.005) while platelet antiaggregation did not modified this risk (HR 1,566, 0.569-4.308). CONCLUSIONS: Anticoagulation and antiaggregation increase haemorrhagic risk in patients with CKD and worsen anaemia. Anticoagulation reduces atherosclerotic events by more than 85% while platelet antiaggregation does not modify this risk.

Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass.

BACKGROUND AND OBJECTIVES: Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Retrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36-98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. RESULTS: One hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall -1.6ml/min/1.73m2/year (-3.0, -0.7)). Male gender, albuminuria>100mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p=0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06-2.63), p=0.023; 1.02 (1.01-1.03), p=0.001 and HR: 2.14 (1.26-3.64), p=0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p=0.006). CONCLUSIONS: Hyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass.

Cardiovascular risk prediction in chronic kidney disease patients. / Predicción del riesgo cardiovascular en pacientes con enfermedad renal crónica.

INTRODUCTION: Scores underestimate the prediction of cardiovascular risk (CVR) as they are not validated in patients with chronic kidney disease (CKD). Two of the most commonly used scores are the Framingham Risk Score (FRS-CVD) and the ASCVD (AHA/ACC 2013). The aim of this study is to evaluate the predictive ability of experiencing a cardiovascular event (CVE) via these 2scores in the CKD population. MATERIAL AND METHODS: Prospective, observational study of 400 prevalent patients with CKD (stages 4 and 5 according the KDOQI; not on dialysis). Cardiovascular risk was calculated according to the 2scores and the predictive capacity of cardiovascular events (atherosclerotic events: myocardial infarction, ischaemic and haemorrhagic stroke, peripheral vascular disease; and non-atherosclerotic events: heart failure) was analysed. RESULTS: Forty-nine atherosclerotic cardiovascular events occurred in 40.3±6.6 months of follow-up. Most of the patients were classified as high CVR by both scores (59% by the FRS-CVD and 75% by the ASCVD). All cardiovascular events occurred in the high CVR patients and both scores (FRS-CVD log-rank 12.2, P<.001, HR 3.1 [95% CI: 1.3-7.1] P: 0.006 and ASCVD log-rank 8.5 P<.001, HR 3.2 [95% CI: 1.1-9.4] P: 0.03) were independent predictors adjusted to renal function, albuminuria and previous cardiovascular events. CONCLUSION: The cardiovascular risk scores (FRS-CVD and ASCVD [AHA/ACC 2013]) can estimate the probability of atherosclerotic cardiovascular events in patients with CKD regardless of renal function, albuminuria and previous cardiovascular events.

Prevalence and characteristics of patients with resistant hypertension and chronic kidney disease. / Prevalencia y características de los pacientes con hipertensión arterial resistente y enfermedad renal crónica.

Resistant hypertension (RH) is a common problem in patients with chronic kidney disease (CKD). A decline in the glomerular filtration rate (GFR) and increased albuminuria are associated with RH; however, there are few published studies about the prevalence of this entity in patients with CKD. OBJECTIVE: To estimate the prevalence of RH in patients with different degrees of kidney disease and analyse the characteristics of this group of patients. METHODS: A total of 618 patients with hypertension and CKD stages i-iv were enrolled, of which 82 (13.3%) met the criteria for RH. RESULTS: RH prevalence increased significantly with age, the degree of CKD and albuminuria. The prevalence of RH was 3.2% in patients under 50 years, 13.8% between 50-79 years and peaked at 17.8% in patients older than 80 years. Renal function prevalence was 4, 15.8 and 18.1% in patients with an estimated glomerular filtration rate (GFR) of > 60, 30-59 and < 30ml/min/1.73 m2, respectively, and 8.9, 15.9 and 22.5% for a urine albumin to creatinine ratio (UACR) < 30, 30-299 and > 300mg/g respectively. In a logistic regression model, the characteristics associated with resistant hypertension were age, history of cardiovascular disease, GFR, albuminuria and diabetes mellitus. A total of 47.5% of patients with resistant hypertension had controlled BP (<140/90mmHg) with 4 or more antihypertensive drugs. These patients were younger, with better renal function, less albuminuria and received more aldosterone antagonists. CONCLUSION: RH prevalence increases with age, the degree of CKD and albuminuria. Strategies such as treatment with aldosterone receptor antagonists are associated with better blood pressure control in this group of patients, leading to reduced prevalence.

Fat tissue and inflammation in patients undergoing peritoneal dialysis.

BACKGROUND: Body weight has been increasing in the general population and is an established risk factor for hypertension, diabetes, and all-cause and cardiovascular mortality. Patients undergoing peritoneal dialysis (PD) gain weight, mainly during the first months of treatment. The aim of this study was to assess the relationship between body composition and metabolic and inflammatory status in patients undergoing PD. METHODS: This was a prospective, non-interventional study of prevalent patients receiving PD. Body composition was studied every 3 months using bioelectrical impedance (BCM(®)). We performed linear regression for each patient, including all BCM(®) measurements, to calculate annual changes in body composition. Thirty-one patients in our PD unit met the inclusion criteria. RESULTS: Median follow-up was 26 (range 17-27) months. Mean increase in weight was 1.8 ± 2.8 kg/year. However, BCM(®) analysis revealed a mean increase in fat mass of 3.0 ± 3.2 kg/year with a loss of lean mass of 2.3 ± 4.1 kg/year during follow-up. The increase in fat mass was associated with the conicity index, suggesting that increases in fat mass are based mainly on abdominal adipose tissue. Changes in fat mass were directly associated with inflammation parameters such as C-reactive protein (r = 0.382, P = 0.045) and inversely associated with high-density lipoprotein cholesterol (r=-0.50, P = 0.008). CONCLUSIONS: Follow-up of weight and body mass index can underestimate the fat mass increase and miss lean mass loss. The increase in fat mass is associated with proinflammatory state and alteration in lipid profile.

Management of resistant hypertension: aldosterone antagonists or intensification of diuretic therapy?

OBJECTIVE: No consensus has been established as to which is the best fourth-line agent in patients with resistant hypertension (RHT). The aim of the present study was to assess the effect of intensifying diuretic treatment with loop diuretic (furosemide) or aldosterone antagonist (spironolactone) on blood pressure (BP) control in RHT. METHODS: The study population comprised 30 patients with RHT who were divided into two treatment arms. Fifteen patients received furosemide 40 mg/day and 15 patients received spironolactone 25 mg/day. Ambulatory BP monitoring was performed baseline, 3 and 6 months. RESULTS: Baseline BP was 162 ± 8/90 ± 6 mmHg, 70% men, mean age 63.3 ± 9.1 years 56.1% diabetic and estimated glomerular filtration rate (eGFR) 55.8 ± 16.5 mL/min per 1.73 m(2) . There were no significant differences between groups at baseline in age, gender, percentage diabetics, eGFR, BP, number of antihypertensive drugs, or aldosterone levels. At 6 months, systolic BP decreased by 24 ± 9.2 mmHg (from 163.6 ± 8.6 to 139.6 ± 8.1 mmHg) in the spironolactone group, compared with 13.8 ± 2.8 mmHg (from 162 ± 7.9 to 148 ± 6.4 mmHg) in the furosemide group (P < 0.01). Diastolic BP fell 11 ± 8.1 mmHg in the spironolactone group compared with 5.2 ± 2.2 mmHg in the furosemide group (P < 0.01). Significant reduction in urinary albumin creatinine ratio (from 173 ± 268 to 14 ± 24 mg/g, P < 0.01) was observed in the spironolactone group at 6 months. Multiple regression analysis showed that only treatment with spironolactone was associated with control of BP < 140/90 mmHg at 6 months. No severe adverse events were recorded. CONCLUSION: Spironolactone is more effective than furosemide for control of BP in RHT patients, with a positive added effect on albuminuria. Spironolactone is safe in patients with mild kidney impairment, although serum potassium should be closely monitored, especially in diabetics.

Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial.

BACKGROUND: Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk. STUDY DESIGN: Post hoc analysis of a long-term follow-up after completion of the 2-year trial. SETTING & PARTICIPANTS: 113 participants (57 in the allopurinol group and 56 in the control group) initially followed up for 2 years and 107 participants followed up to 5 additional years. INTERVENTION: Continuation of allopurinol treatment, 100mg/d, or standard treatment. OUTCOME: Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥50% decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction, coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and peripheral vascular disease). RESULTS: During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up, an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus, during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P=0.004; adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the control group (HR, 0.43; 95% CI, 0.21-0.88; P=0.02; adjusted for age, sex, and baseline kidney function). LIMITATIONS: Small sample size, single center, not double blind, post hoc follow-up and analysis. CONCLUSIONS: Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk.

Response to comment on «Metabolic syndrome is associated with cardiovascular events in haemodialysis¼.

Nefrologia 2014;34(5):XXX. doi10.3265/Nefrologia.pre2014.Jun.12620 Reply to Esteve et al. Comment on Nefrologia 2014;34(4):xx. Nefrologia 2014;34(1):69-75.

The effect of replacing aluminium hydroxide with calcium acetate/magnesium carbonate on serum phosphorus control in haemodialysis patients.

INTRODUCTION: Calcium acetate/magnesium carbonate (MgCO3) is a phosphorus binder with advantages in terms of cost, safety and tolerance and it has a similar efficacy to other drugs. The objective of the study is to assess the effects of replacing aluminium hydroxide [Al(OH3)] with MgCO3 on phosphorus and calcium metabolism in a cohort of haemodialysis patients. MATERIALS AND METHODS: We included 21 patients with phosphorus <5mg/dl, with Al(OH3) as the only binder. The conversion to MgCO3 was carried out without changing the number of pills. We recorded clinical-demographic characteristics, treatment for secondary hyperparathyroidism and laboratory parameters before conversion and every month for four months. RESULTS: Phosphataemia decreased from 4.52 ± 0.99 to 4.02 ± 1.07 mg/dl (p=.027), and there was a decrease in the calcium-phosphorus product from 40.20 ± 10.44 to 35.16 ± 11.06 mg2/dl2 (p=.037). We did not observe significant changes in levels of calcium, parathyroid hormone or 25-OH-vitamin D3. The daily number of pills prescribed was reduced from 3.33 ± 2.29 to 2.15 ± 2.21 (p=.020). Concomitant treatments were not altered. We observed an initial significant increase in magnesaemia from 2.21 ± 0.24 to 2.43 ± 0.39 mg/dl (p=.001), which subsequently remained stable. We found a decrease in serum aluminium from 14.91 ± 8.55 to 8.47 ± 3.98 µg/l (p=.004), with levels within the recommended range in all patients. CONCLUSIONS: MgCO3 allowed good control of serum phosphorus in haemodialysis patients who were previously well controlled with Al(OH)3, using fewer daily pills. There was a slight increase in serum magnesium, without short-term clinical significance. We do not know the effects of this increase in the longer term.

[Metabolic syndrome is associated with cardiovascular events in haemodialysis]. / El síndrome metabólico se asocia con eventos cardiovasculares en hemodiálisis.

BACKGROUND: Metabolic syndrome (MS) is a cardiovascular risk factor and is associated with mortality in the general population and in patients with chronic kidney disease. However, few studies have been carried out in patients on haemodialysis (HD). OBJECTIVES: The objective of the study is to analyse the effect of MS on the occurrence of cardiovascular events in HD. The secondary objective is to determine the influence of the fat tissue index and conicity index on cardiovascular events. METHODS: A prospective study including 100 patients on HD. The follow-up period was 3 years. Cardiovascular events and mortality were recorded. MS was defined in accordance with ATPIII and IDF criteria. RESULTS: MS prevalence as defined by the ATPIII was 32%, and by the IDF, 29%. The concordance between the two definitions was high (kappa index 0.79, 95% confidence interval 0.65 to 0.92). The risk of cardiovascular events was higher in patients with MS (Log Rank 6.185, p = 0.013), with a fat tissue index greater than 11.5 kg/m(2) (log rank 10.220, p=.001) and a conicity index greater than 1.2 (log rank 6.393, p=.011). In the Cox analysis, adjusted for age and sex, patients with MS had twice the risk of being admitted due to a cardiovascular event (odds ratio 1.93, 1.022 to 3.6, p=.043). Mortality was 35% in the 3 year follow-up period with no differences between the groups with and without MS. CONCLUSIONS: MS is a very prevalent disease in HD patients and its presence doubles the risk of hospitalisation due to cardiovascular events in the short term.