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In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.A cross-sectional study was performed in 71 patients affected by metabolic syndrome with CKD (stages 2–3) with normal serum P concentration. A 3-day dietary survey was performed to estimate the average daily amount and the source of P ingested. The daily intake ofPwas1086.5 ± 361.3mg/day; 64% contained in animal proteins, 22% in vegetable proteins, and 14% as inorganic P. The total amount of P ingested did not correlate with daily phosphaturia, but it did correlate with the P/UUN ratio (p < 0.018). Patients with the highest tertile of the P/UUN ratio >71.1 mg/g presented more abundant inorganic P intake (p < 0.038).The P/UUN ratio is suggested to be a marker of inorganic P intake. This finding might be useful in clinical practices to identify the source of dietary P and to make personalized dietary recommendations directed to reduce inorganic P intake.
María Pendón-Ruiz de Mier; Noemí Vergara; Cristian Rodelo-Haad; María López-Zamorano; Cristina Membrives-González; Rodrigo López-Baltanás; Juan Muñoz-Castañeda; Francisco Caravaca; Alejandro Martín-Malo; Arnold Felsenfeld; Eugenio De la Torre; Sagrario Soriano; Rafael Santamaría; Mariano Rodríguez. Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine. Nutrients 2021, 13, 292 .
AMA StyleMaría Pendón-Ruiz de Mier, Noemí Vergara, Cristian Rodelo-Haad, María López-Zamorano, Cristina Membrives-González, Rodrigo López-Baltanás, Juan Muñoz-Castañeda, Francisco Caravaca, Alejandro Martín-Malo, Arnold Felsenfeld, Eugenio De la Torre, Sagrario Soriano, Rafael Santamaría, Mariano Rodríguez. Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine. Nutrients. 2021; 13 (2):292.
Chicago/Turabian StyleMaría Pendón-Ruiz de Mier; Noemí Vergara; Cristian Rodelo-Haad; María López-Zamorano; Cristina Membrives-González; Rodrigo López-Baltanás; Juan Muñoz-Castañeda; Francisco Caravaca; Alejandro Martín-Malo; Arnold Felsenfeld; Eugenio De la Torre; Sagrario Soriano; Rafael Santamaría; Mariano Rodríguez. 2021. "Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine." Nutrients 13, no. 2: 292.
Background Besides the classic logistic regression analysis, non-parametric methods based on machine learning techniques such as random forest are presently used to generate predictive models. The aim of this study was to evaluate random forest mortality prediction models in haemodialysis patients. Methods Data were acquired from incident haemodialysis patients between 1995 and 2015. Prediction of mortality at 6 months, 1 year and 2 years of haemodialysis was calculated using random forest and the accuracy was compared with logistic regression. Baseline data were constructed with the information obtained during the initial period of regular haemodialysis. Aiming to increase accuracy concerning baseline information of each patient, the period of time used to collect data was set at 30, 60 and 90 days after the first haemodialysis session. Results There were 1571 incident haemodialysis patients included. The mean age was 62.3 years and the average Charlson comorbidity index was 5.99. The mortality prediction models obtained by random forest appear to be adequate in terms of accuracy [area under the curve (AUC) 0.68–0.73] and superior to logistic regression models (ΔAUC 0.007–0.046). Results indicate that both random forest and logistic regression develop mortality prediction models using different variables. Conclusions Random forest is an adequate method, and superior to logistic regression, to generate mortality prediction models in haemodialysis patients.
Victoria Garcia-Montemayor; Alejandro Martin-Malo; Carlo Barbieri; Francesco Bellocchio; Sagrario Soriano; Victoria Pendon-Ruiz de Mier; Ignacio R Molina; Pedro Aljama; Mariano Rodriguez. Predicting mortality in hemodialysis patients using machine learning analysis. Clinical Kidney Journal 2020, 14, 1388 -1395.
AMA StyleVictoria Garcia-Montemayor, Alejandro Martin-Malo, Carlo Barbieri, Francesco Bellocchio, Sagrario Soriano, Victoria Pendon-Ruiz de Mier, Ignacio R Molina, Pedro Aljama, Mariano Rodriguez. Predicting mortality in hemodialysis patients using machine learning analysis. Clinical Kidney Journal. 2020; 14 (5):1388-1395.
Chicago/Turabian StyleVictoria Garcia-Montemayor; Alejandro Martin-Malo; Carlo Barbieri; Francesco Bellocchio; Sagrario Soriano; Victoria Pendon-Ruiz de Mier; Ignacio R Molina; Pedro Aljama; Mariano Rodriguez. 2020. "Predicting mortality in hemodialysis patients using machine learning analysis." Clinical Kidney Journal 14, no. 5: 1388-1395.
Fibroblast Growth Factor 23 (FGF23) and Klotho play an essential role in the regulation of mineral metabolism, and both are altered as a consequence of renal failure. FGF23 increases to augment phosphaturia, which prevents phosphate accumulation at the early stages of chronic kidney disease (CKD). This effect of FGF23 requires the presence of Klotho in the renal tubules. However, Klotho expression is reduced as soon as renal function is starting to fail to generate a state of FGF23 resistance. Changes in these proteins directly affect to other mineral metabolism parameters; they may affect renal function and can produce damage in other organs such as bone, heart, or vessels. Some of the mechanisms responsible for the changes in FGF23 and Klotho levels are related to modifications in the Wnt signaling. This review examines the link between FGF23/Klotho and Wnt/β-catenin in different organs: kidney, heart, and bone. Activation of the canonical Wnt signaling produces changes in FGF23 and Klotho and vice versa; therefore, this pathway emerges as a potential therapeutic target that may help to prevent CKD-associated complications.
Juan Rafael Muñoz-Castañeda; Cristian Rodelo-Haad; Maria Victoria Pendon-Ruiz De Mier; Alejandro Martin-Malo; Rafael Santamaria; Mariano Rodriguez. Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease. Toxins 2020, 12, 185 .
AMA StyleJuan Rafael Muñoz-Castañeda, Cristian Rodelo-Haad, Maria Victoria Pendon-Ruiz De Mier, Alejandro Martin-Malo, Rafael Santamaria, Mariano Rodriguez. Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease. Toxins. 2020; 12 (3):185.
Chicago/Turabian StyleJuan Rafael Muñoz-Castañeda; Cristian Rodelo-Haad; Maria Victoria Pendon-Ruiz De Mier; Alejandro Martin-Malo; Rafael Santamaria; Mariano Rodriguez. 2020. "Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease." Toxins 12, no. 3: 185.
Fibroblast growth factor 23 (FGF23) plays a key role in the complex network between the bones and other organs. Initially, it was thought that FGF23 exclusively regulated phosphate and vitamin D metabolism; however, recent research has demonstrated that an excess of FGF23 has other effects that may be detrimental in some cases. The understanding of the signaling pathways through which FGF23 acts in different organs is crucial to develop strategies aiming to prevent the negative effects associated with high FGF23 levels. FGF23 has been described to have effects on the heart, promoting left ventricular hypertrophy (LVH); the liver, leading to production of inflammatory cytokines; the bones, inhibiting mineralization; and the bone marrow, by reducing the production of erythropoietin (EPO). The identification of FGF23 receptors will play a remarkable role in future research since its selective blockade might reduce the adverse effects of FGF23. Patients with chronic kidney disease (CKD) have very high levels of FGF23 and may be the population suffering from the most adverse FGF23-related effects. The general population, as well as kidney transplant recipients, may also be affected by high FGF23. Whether the association between FGF23 and clinical events is causal or casual remains controversial. The hypothesis that FGF23 could be considered a therapeutic target is gaining relevance and may become a promising field of investigation in the future.
Cristian Rodelo-Haad; Rafael Santamaria; Juan R. Muñoz-Castañeda; M. Victoria Pendón-Ruiz De Mier; Alejandro Martin-Malo; Mariano Rodriguez. FGF23, Biomarker or Target? Toxins 2019, 11, 175 .
AMA StyleCristian Rodelo-Haad, Rafael Santamaria, Juan R. Muñoz-Castañeda, M. Victoria Pendón-Ruiz De Mier, Alejandro Martin-Malo, Mariano Rodriguez. FGF23, Biomarker or Target? Toxins. 2019; 11 (3):175.
Chicago/Turabian StyleCristian Rodelo-Haad; Rafael Santamaria; Juan R. Muñoz-Castañeda; M. Victoria Pendón-Ruiz De Mier; Alejandro Martin-Malo; Mariano Rodriguez. 2019. "FGF23, Biomarker or Target?" Toxins 11, no. 3: 175.
Iron deficiency is the leading cause of anaemia and is highly prevalent in patients with chronic heart failure (CHF). Iron deficiency, with or without anaemia, can be corrected with intravenous (i.v.) iron therapy. In heart failure patients, iron status screening, diagnosis, and treatment of iron deficiency with ferric carboxymaltose are recommended by the 2016 European Society of Cardiology guidelines, based on results of two randomized controlled trials in CHF patients with iron deficiency. All i.v. iron complexes consist of a polynuclear Fe(III)‐oxyhydroxide/oxide core that is stabilized with a compound‐specific carbohydrate, which strongly influences their physico‐chemical properties (e.g. molecular weight distribution, complex stability, and labile iron content). Thus, the carbohydrate determines the metabolic fate of the complex, affecting its pharmacokinetic/pharmacodynamic profile and interactions with the innate immune system. Accordingly, i.v. iron products belong to the new class of non‐biological complex drugs for which regulatory authorities recognized the need for more detailed characterization by orthogonal methods, particularly when assessing generic/follow‐on products. Evaluation of published clinical and non‐clinical studies with different i.v. iron products in this review suggests that study results obtained with one i.v. iron product should not be assumed to be equivalent to other i.v. iron products that lack comparable study data in CHF. Without head‐to‐head clinical studies proving the therapeutic equivalence of other i.v. iron products with ferric carboxymaltose, in the highly vulnerable population of heart failure patients, extrapolation of results and substitution with a different i.v. iron product is not recommended.
Alejandro Martin-Malo; Gerrit Borchard; Beat Flühmann; Claudio Mori; Donald Silverberg; Ewa A. Jankowska. Differences between intravenous iron products: focus on treatment of iron deficiency in chronic heart failure patients. ESC Heart Failure 2019, 6, 241 -253.
AMA StyleAlejandro Martin-Malo, Gerrit Borchard, Beat Flühmann, Claudio Mori, Donald Silverberg, Ewa A. Jankowska. Differences between intravenous iron products: focus on treatment of iron deficiency in chronic heart failure patients. ESC Heart Failure. 2019; 6 (2):241-253.
Chicago/Turabian StyleAlejandro Martin-Malo; Gerrit Borchard; Beat Flühmann; Claudio Mori; Donald Silverberg; Ewa A. Jankowska. 2019. "Differences between intravenous iron products: focus on treatment of iron deficiency in chronic heart failure patients." ESC Heart Failure 6, no. 2: 241-253.
In hemodialysis patients, high levels of Fibroblast Growth Factor 23 (FGF23) predict mortality. Our study was designed to test whether the control of serum phosphate is associated with a reduction in serum FGF23 levels. Additionally other variables with a potential effect on FGF23 levels were evaluated. The effect of sustained (40-weeks) control of serum phosphate on FGF23 levels (intact and c-terminal) was evaluated in 21 stable hemodialysis patients that were not receiving calcimimetics or active vitamin D. Patients received non-calcium phosphate binders to maintain serum phosphate below 4.5 mg/dl. In an additional analysis, values of intact-FGF23 (iFGF23) and c-terminal FGF23 (cFGF23) from 150 hemodialysis patients were correlated with parameters of mineral metabolism and inflammation. Linear mixed models and linear regression were performed to evaluate longitudinal trajectories of variables and the association between FGF23 and the other variables examined. During the 40-week treatment, 12 of 21 patients achieved the target of serum phosphate 4.5 mg, iFGF23 and cFGF23 increased two and four-fold respectively as compared with baseline. Furthermore, changes in serum phosphate correlated with changes in C-reactive protein (hs-CRP). In our 150 hemodialysis patients, those in the higher tertile of serum phosphate also showed increased hs-CRP, iPTH, iFGF23 and cFGF23. Multiple regression analysis revealed that iFGF23 levels directly correlated with both serum phosphate and calcium, whereas cFGF23 correlated with serum phosphate and hs-CRP but not with calcium. The control of serum phosphate reduced iFGF23. This reduction was also associated with a decreased in inflammatory parameters. Considering the entire cohort of hemodialysis patients, iFGF23 levels correlated directly with serum phosphate levels and also correlated inversely with serum calcium concentration. The levels of cFGF23 were closely related to serum phosphate and parameters of inflammation.
Cristian Rodelo-Haad; Maria E. Rodríguez-Ortiz; Alejandro Martin-Malo; M. Victoria Pendon-Ruiz de Mier; M. Luisa Agüera; Juan R. Muñoz-Castañeda; Sagrario Soriano; Francisco Caravaca; M. Antonia Alvarez-Lara; Arnold Felsenfeld; Pedro Aljama; Mariano Rodriguez. Phosphate control in reducing FGF23 levels in hemodialysis patients. PLOS ONE 2018, 13, e0201537 .
AMA StyleCristian Rodelo-Haad, Maria E. Rodríguez-Ortiz, Alejandro Martin-Malo, M. Victoria Pendon-Ruiz de Mier, M. Luisa Agüera, Juan R. Muñoz-Castañeda, Sagrario Soriano, Francisco Caravaca, M. Antonia Alvarez-Lara, Arnold Felsenfeld, Pedro Aljama, Mariano Rodriguez. Phosphate control in reducing FGF23 levels in hemodialysis patients. PLOS ONE. 2018; 13 (8):e0201537.
Chicago/Turabian StyleCristian Rodelo-Haad; Maria E. Rodríguez-Ortiz; Alejandro Martin-Malo; M. Victoria Pendon-Ruiz de Mier; M. Luisa Agüera; Juan R. Muñoz-Castañeda; Sagrario Soriano; Francisco Caravaca; M. Antonia Alvarez-Lara; Arnold Felsenfeld; Pedro Aljama; Mariano Rodriguez. 2018. "Phosphate control in reducing FGF23 levels in hemodialysis patients." PLOS ONE 13, no. 8: e0201537.
Rafael Pérez-García, Javier Varas, Alejandro Cives, Alejandro Martín-Malo, Pedro Aljama, Rosa Ramos, Julio Pascual, Stefano Stuard, Bernard Canaud and José Ignacio Merello on behalf of the ORD group; Nephrol Dial Transplant 2017; gfx269. doi: 10.1093/ndt/gfx269
Rafael Pérez-García; Javier Varas; Alejandro Cives; Alejandro Martín-Malo; Pedro Aljama; Rosa Ramos; Julio Pascual; Stefano Stuard; Bernard Canaud; José Ignacio Merello. Erratum. Nephrology Dialysis Transplantation 2017, 33, 187 -187.
AMA StyleRafael Pérez-García, Javier Varas, Alejandro Cives, Alejandro Martín-Malo, Pedro Aljama, Rosa Ramos, Julio Pascual, Stefano Stuard, Bernard Canaud, José Ignacio Merello. Erratum. Nephrology Dialysis Transplantation. 2017; 33 (1):187-187.
Chicago/Turabian StyleRafael Pérez-García; Javier Varas; Alejandro Cives; Alejandro Martín-Malo; Pedro Aljama; Rosa Ramos; Julio Pascual; Stefano Stuard; Bernard Canaud; José Ignacio Merello. 2017. "Erratum." Nephrology Dialysis Transplantation 33, no. 1: 187-187.
Background: The majority of studies suggesting that online hemodiafiltration reduces the risk of mortality compared to hemodialysis (HD) have been performed in dialysis-prevalent populations. In this report, we conducted an epidemiologic study of mortality in incident dialysis patients, comparing post-dilution online hemodiafiltration and high-flux HD, with propensity score matching (PSM) used to correct indication bias. Methods: Our study cohort comprised 3,075 incident dialysis patients treated in 64 Spanish Fresenius Medical Care clinics between January 2009 and December 2012. The primary outcome of this study was to investigate the impact of the type of renal replacement on all-cause mortality. An analysis of cardiovascular mortality was defined as the secondary outcome. To achieve these objectives, patients were followed until December 2016. Patients were categorized as high-flux HD patients if they underwent this treatment exclusively. If >90% of their treatment was with online hemodiafiltration, then the patient was grouped to that modality. Results: After PSM, a total of 1,012 patients were matched. Compared with patients on high-flux HD, those on online hemodiafiltration received a median replacement volume of 23.45 (interquartile range 21.27–25.51) L/session and manifested 24 and 33% reductions in all-cause and cardiovascular mortality (all-cause mortality hazards ratio [HR] 0.76, 95% CI 0.62–0.94 [p = 0.01]; and cardiovascular mortality HR 0.67, 95% CI 0.50–0.90 [p = 0.008]). Conclusions: This study shows that post-dilution online hemodiafiltration reduces all-cause and cardiovascular mortality compared to high-flux HD in an incident HD population.
Francisco Maduell; Javier Varas; Rosa Ramos; Alejandro Martin-Malo; Rafael Pérez-Garcia; Isabel Berdud; Francesc Moreso; Bernard Canaud; Stefano Stuard; Adelheid Gauly; Pedro Aljama; Jose Ignacio Merello. Hemodiafiltration Reduces All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients: A Propensity-Matched Cohort Study. American Journal of Nephrology 2017, 46, 288 -297.
AMA StyleFrancisco Maduell, Javier Varas, Rosa Ramos, Alejandro Martin-Malo, Rafael Pérez-Garcia, Isabel Berdud, Francesc Moreso, Bernard Canaud, Stefano Stuard, Adelheid Gauly, Pedro Aljama, Jose Ignacio Merello. Hemodiafiltration Reduces All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients: A Propensity-Matched Cohort Study. American Journal of Nephrology. 2017; 46 (4):288-297.
Chicago/Turabian StyleFrancisco Maduell; Javier Varas; Rosa Ramos; Alejandro Martin-Malo; Rafael Pérez-Garcia; Isabel Berdud; Francesc Moreso; Bernard Canaud; Stefano Stuard; Adelheid Gauly; Pedro Aljama; Jose Ignacio Merello. 2017. "Hemodiafiltration Reduces All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients: A Propensity-Matched Cohort Study." American Journal of Nephrology 46, no. 4: 288-297.
Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Kaplan–Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations.
Javier Varas; Rosa Ramos; Pedro Aljama; Rafael Pérez-García; Francesc Moreso; Miguel Pinedo; José Ignacio Merello; Stefano Stuard; Bernard Canaud; Alejandro Martín-Malo; ORD Group. Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach. Nephrology Dialysis Transplantation 2017, 33, 160 -170.
AMA StyleJavier Varas, Rosa Ramos, Pedro Aljama, Rafael Pérez-García, Francesc Moreso, Miguel Pinedo, José Ignacio Merello, Stefano Stuard, Bernard Canaud, Alejandro Martín-Malo, ORD Group. Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach. Nephrology Dialysis Transplantation. 2017; 33 (1):160-170.
Chicago/Turabian StyleJavier Varas; Rosa Ramos; Pedro Aljama; Rafael Pérez-García; Francesc Moreso; Miguel Pinedo; José Ignacio Merello; Stefano Stuard; Bernard Canaud; Alejandro Martín-Malo; ORD Group. 2017. "Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach." Nephrology Dialysis Transplantation 33, no. 1: 160-170.
INTRODUCTION AND AIMS: High serum levels of both FGF23 and phosphate (P) are associated with increased mortality in dialysis (HD) patients; thus, control of these parameters should benefit the patients. Phosphate stimulates FGF23 production; in chronic kidney disease (CKD) patients, reductions in serum P concentration produce decreases in serum concentration of FGF23. However, this effect remains to be demonstrated in HD patients. The aim of the present study was to evaluate in HD patients whether a sustained reduction or elevation in serum P concentration is associated with changes in FGF23.
Cristian Rodelo-Haad; M Victoria Pendon-Ruiz De Mier; Maria L Agûera-Morales; Sagrario Soriano; Maria A Alvarez-Lara; Pedro Aljama; Maria E Rodrìguez-Ortìz; Alejandro Martin-Malo; Juan R Muñoz-Castañeda; Mariano Rodriguez. MP690SERUM PHOSPHATE MODIFICATIONS ARE ASSOCIATED WITH CHANGES IN SERUM FGF23 AND C-REACTIVE PROTEIN. Nephrology Dialysis Transplantation 2017, 32, iii684 -iii684.
AMA StyleCristian Rodelo-Haad, M Victoria Pendon-Ruiz De Mier, Maria L Agûera-Morales, Sagrario Soriano, Maria A Alvarez-Lara, Pedro Aljama, Maria E Rodrìguez-Ortìz, Alejandro Martin-Malo, Juan R Muñoz-Castañeda, Mariano Rodriguez. MP690SERUM PHOSPHATE MODIFICATIONS ARE ASSOCIATED WITH CHANGES IN SERUM FGF23 AND C-REACTIVE PROTEIN. Nephrology Dialysis Transplantation. 2017; 32 (suppl_3):iii684-iii684.
Chicago/Turabian StyleCristian Rodelo-Haad; M Victoria Pendon-Ruiz De Mier; Maria L Agûera-Morales; Sagrario Soriano; Maria A Alvarez-Lara; Pedro Aljama; Maria E Rodrìguez-Ortìz; Alejandro Martin-Malo; Juan R Muñoz-Castañeda; Mariano Rodriguez. 2017. "MP690SERUM PHOSPHATE MODIFICATIONS ARE ASSOCIATED WITH CHANGES IN SERUM FGF23 AND C-REACTIVE PROTEIN." Nephrology Dialysis Transplantation 32, no. suppl_3: iii684-iii684.
Achieving an adequate dialysis dose is one of the key goals for dialysis treatments. Here we assessed whether patients receiving the current cleared plasma volume (Kt), individualized for body surface area per recommendations, had improved survival and reduced hospitalizations at 2 years of follow-up. Additionally, we assessed whether patients receiving a greater dose gained more benefit. This prospective, observational, multicenter study included 6129 patients in 65 Fresenius Medical Care Spanish facilities. Patients were classified monthly into 1 of 10 risk groups based on the difference between achieved and target Kt. Patient groups with a more negative relationship were significantly older with a higher percentage of diabetes mellitus and catheter access. Treatment dialysis time, effective blood flow, and percentage of on-line hemodiafiltration were significantly higher in groups with a higher dose. The mortality risk profile showed a progressive increase when achieved minus target Kt became more negative but was significantly lower in the group with 1 to 3 L clearance above target Kt and in groups with greater increases above target Kt. Additionally, hospitalization risk appeared significantly reduced in groups receiving 9 L or more above the minimum target. Thus, prescribing an additional 3 L or more above the minimum Kt dose could potentially reduce mortality risk, and 9 L or more reduce hospitalization risk. As such, future prospective studies are required to confirm these dose effect findings
Francisco Maduell; Rosa Ramos; Javier Varas; Alejandro Martin-Malo; Manuel Molina; Rafael Pérez-Garcia; Daniele Marcelli; Francesc Moreso; Pedro Aljama; Jose Ignacio Merello. Hemodialysis patients receiving a greater Kt dose than recommended have reduced mortality and hospitalization risk. Kidney International 2016, 90, 1332 -1341.
AMA StyleFrancisco Maduell, Rosa Ramos, Javier Varas, Alejandro Martin-Malo, Manuel Molina, Rafael Pérez-Garcia, Daniele Marcelli, Francesc Moreso, Pedro Aljama, Jose Ignacio Merello. Hemodialysis patients receiving a greater Kt dose than recommended have reduced mortality and hospitalization risk. Kidney International. 2016; 90 (6):1332-1341.
Chicago/Turabian StyleFrancisco Maduell; Rosa Ramos; Javier Varas; Alejandro Martin-Malo; Manuel Molina; Rafael Pérez-Garcia; Daniele Marcelli; Francesc Moreso; Pedro Aljama; Jose Ignacio Merello. 2016. "Hemodialysis patients receiving a greater Kt dose than recommended have reduced mortality and hospitalization risk." Kidney International 90, no. 6: 1332-1341.
Hemodiafiltration with endogenous reinfusion (HFR) after ultrafiltrate passage through a resin cartridge combines adsorption, convection, and diffusion. Our prospective single-center crossover study compared HFR and online-hemodiafiltration (OLHDF) effects on two uremic toxins and 13 inflammatory, endothelial status, or oxidative stress markers. After an 8-week run-in period of high-flux hemodialysis, 17 eligible stable dialysis patients (median age 65 years, 10 male) without overt clinical inflammation were scheduled for four 8-week periods in the sequence: HFR/OLHDF/HFR/OLHDF. Relative to OLHDF, HFR was associated with greater indoxyl sulfate removal and lesser abnormalities in all other study variables, namely circulating interleukin-6, tumor necrosis factor-alpha, proportions of activated proinflammatory (CD14+CD16+, CD14++CD16+) monocytes, endothelial progenitor cells, apoptotic endothelial microparticles, vascular endothelial growth factor, vascular cellular adhesion molecule, angiopoietins 2 and 1, annexin V, and superoxide dismutase. Differences were significant (P < 0.05) in median values of 13/15 variables. Study period comparisons were generally consistent with dialysis technique comparisons, as were data from the subgroup completing all study periods (n = 9). Our investigation provides hypothesis-generating results suggesting that compared with OLHDF, HFR improves protein-bound toxin removal, inflammatory and endothelial status, and oxidative stress.
Elvira Esquivias-Motta; Alejandro Martín-Malo; Paula Buendia; Maria A Álvarez-Lara; Sagrario Soriano; Rodolfo Crespo; Julia Carracedo; Rafael Ramírez; Pedro Aljama. Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study. Artificial Organs 2016, 41, 88 -98.
AMA StyleElvira Esquivias-Motta, Alejandro Martín-Malo, Paula Buendia, Maria A Álvarez-Lara, Sagrario Soriano, Rodolfo Crespo, Julia Carracedo, Rafael Ramírez, Pedro Aljama. Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study. Artificial Organs. 2016; 41 (1):88-98.
Chicago/Turabian StyleElvira Esquivias-Motta; Alejandro Martín-Malo; Paula Buendia; Maria A Álvarez-Lara; Sagrario Soriano; Rodolfo Crespo; Julia Carracedo; Rafael Ramírez; Pedro Aljama. 2016. "Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study." Artificial Organs 41, no. 1: 88-98.
In patients with renal disease, uremia raises oxidative stress and senescence in endothelial cells, which can lead to endothelial dysfunction and cardiovascular disease. Klotho protein is a β-glucuronidase capable of hydrolyzing steroid β-glucuronides. This protein is recognized as an antiaging gene, that modulate both stress-induced senescence and functional response. The aim of the study was to investigate how senescence and oxidative stress induced by uremia in endothelial cells affects Klotho expression and whether intra or extracellular Klotho has effects on the response of these cells. Senescence and oxidative stress was obtained by exposure to uremic serum. Telomere length, the enzyme β-galactosidase, and oxidative stress were studied by flow cytometry. Nuclear factor kappa B activity was determined by electrophoretic mobility shift assay. The expression of Klotho decreased with the uremia and preceded the manifestations of cell aging. Levels of intracellular Klotho decreases associated to endothelial senescence, and exogenous Klotho prevents cellular senescence by inhibiting the increase in oxidative stress induced by uremia and diminished the nuclear factor kappa B–DNA binding ability.
Paula Buendía; Julia Carracedo; Sagrario Soriano; Juan Antonio Madueño; Alberto Ortiz; Alejandro Martín-Malo; Pedro Aljama; Rafael Ramírez. Klotho Prevents NFκB Translocation and Protects Endothelial Cell From Senescence Induced by Uremia. The Journals of Gerontology: Series A 2014, 70, 1198 -1209.
AMA StylePaula Buendía, Julia Carracedo, Sagrario Soriano, Juan Antonio Madueño, Alberto Ortiz, Alejandro Martín-Malo, Pedro Aljama, Rafael Ramírez. Klotho Prevents NFκB Translocation and Protects Endothelial Cell From Senescence Induced by Uremia. The Journals of Gerontology: Series A. 2014; 70 (10):1198-1209.
Chicago/Turabian StylePaula Buendía; Julia Carracedo; Sagrario Soriano; Juan Antonio Madueño; Alberto Ortiz; Alejandro Martín-Malo; Pedro Aljama; Rafael Ramírez. 2014. "Klotho Prevents NFκB Translocation and Protects Endothelial Cell From Senescence Induced by Uremia." The Journals of Gerontology: Series A 70, no. 10: 1198-1209.
Acute kidney failure in multiple myeloma (MM) occurs in 12%-20% of patients and is a poor prognostic factor for patient survival. Recent studies have shown that dialysis with a High-Cut-Off membrane (HCO) removes free light chains (FLC) effectively although with significant albumin loss. Other adsorption-based techniques, such as haemodiafiltration with ultrafiltrate regeneration by adsorption in resin (SUPRA-HFR), have not been studied. We present three cases of MM, all haemodialysis-dependent since diagnosis. Two cases were IgG kappa and one was IgA lambda. All patients were treated with chemotherapy and SUPRA-HFR. The aim of this study was to evaluate the effectiveness of SUPRA-HFR in the reduction of FLC and its effect on albumin. We collected blood samples pre- and post-dialysis, and ultrafiltrate (UF) samples pre- and post-resin 5 minutes into the session and 5 minutes from the end. The mean reduction rate of FLC in blood per session in the three patients was 53% and 63% (kappa) and 38% (lambda). In the UF, the mean FLC reduction rate was close to 99%, both at the start and at the end of dialysis, without the removal of albumin. With the results obtained we can conclude that this technique achieves an effective reduction of FLC, which is maintained throughout the session, without resin saturation and without albumin loss. Therefore, SUPRA-HFR is effective as an adjunctive therapy for MM.
M Victoria Pendonruiz De Mier; M Antonia Alvarezlara; Raquel Ojedalopez; Alejandro Martinmalo; Julia Carracedo; Javier Caballerovillarraso; Corona Alonso; Pedro Aljama. Eficacia de la hemodiafiltración con regeneración del ultrafiltrado en la reducción de cadenas ligeras en mieloma múltiple con insuficiencia renal. 2013, 33, 788 -96.
AMA StyleM Victoria Pendonruiz De Mier, M Antonia Alvarezlara, Raquel Ojedalopez, Alejandro Martinmalo, Julia Carracedo, Javier Caballerovillarraso, Corona Alonso, Pedro Aljama. Eficacia de la hemodiafiltración con regeneración del ultrafiltrado en la reducción de cadenas ligeras en mieloma múltiple con insuficiencia renal. . 2013; 33 (33):788-96.
Chicago/Turabian StyleM Victoria Pendonruiz De Mier; M Antonia Alvarezlara; Raquel Ojedalopez; Alejandro Martinmalo; Julia Carracedo; Javier Caballerovillarraso; Corona Alonso; Pedro Aljama. 2013. "Eficacia de la hemodiafiltración con regeneración del ultrafiltrado en la reducción de cadenas ligeras en mieloma múltiple con insuficiencia renal." 33, no. 33: 788-96.
Renal dysfunction is closely associated with endothelial damage leading to cardiovascular disease. However, the extent to which endothelial damage induced by uremia is modulated by aging is poorly known. Aging can render endothelial cells more susceptible to apoptosis through an oxidative stress-dependent pathway. We examined whether senescence-associated to oxidative stress determines the injury induced by the uremia in endothelial cells. Human umbilical vein endothelial cells (HUVEC) was incubated with human uremic serum and, in the animal model, endothelial cells were obtained from aortas of uremic and no uremic rats. Vitamin C was used to prevent oxidative stress. Senescence, assessed by telomere length and enzyme-betagalactosidase (β-gal), reactive oxygen species (ROS), mitochondrial depolarization (JC-1 probe), caspase 3, and apoptosis were determined by flow cytometry. NF-κB activity was determined by Western blot. Uremic serum increased ROS and NF-κB in young and aging HUVEC. However only in aging cells, uremic serum induced apoptosis (vs young HUVEC, p<0.01). The endothelial damage induced by uremia seems to be related with the increased oxidative stress, since in both HUVEC and in the experimental model of renal disease in rats, vitamin C prevents endothelial apoptosis. However, vitamin C did not decrease the oxidative stress associated to senescence. These results showed that as compared with young cells, senescent cells have high sensitivity to damage associated to the oxidative stress induced by the uremia. Consequently, protecting senescent endothelial cells from increased oxidative stress might be an effective therapeutic approach in the treatment of vascular disorders in chronic kidney diseases.
Julia Carracedo; Paula Buendía; Ana Merino; Sagrario Soriano; Elvira Esquivias; Alejandro Martín-Malo; Pedro Aljama; Rafael Ramírez. Cellular senescence determines endothelial cell damage induced by uremia. Experimental Gerontology 2013, 48, 766 -773.
AMA StyleJulia Carracedo, Paula Buendía, Ana Merino, Sagrario Soriano, Elvira Esquivias, Alejandro Martín-Malo, Pedro Aljama, Rafael Ramírez. Cellular senescence determines endothelial cell damage induced by uremia. Experimental Gerontology. 2013; 48 (8):766-773.
Chicago/Turabian StyleJulia Carracedo; Paula Buendía; Ana Merino; Sagrario Soriano; Elvira Esquivias; Alejandro Martín-Malo; Pedro Aljama; Rafael Ramírez. 2013. "Cellular senescence determines endothelial cell damage induced by uremia." Experimental Gerontology 48, no. 8: 766-773.
Recent publications show that elevation of FGF23 is independently associated with progression or renal disease, left ventricular hypertrophy and cardiovascular mortality. Dietary restriction of phosphate and phosphate binders are used for control phosphate balance and elevation of serum FGF23 levels. The aim of this study is to compare the effectiveness of calcium carbonate vs. lanthanum carbonate in reducing serum FGF23 levels in Chronic Kidney Disease (CKD) patients. 32 patients from the Nephrology outpatient clinic with CKD 4 - 5 non-dialysis were included. Patients receive a 4-month treatment period of calcium carbonate or lanthanum carbonate. Patients had normal serum calcium concentration, 25 (OH) levels >30 ng/ml and they were not on VDR activators or cinacalcet. As compared with calcium carbonate, patients on lanthanum carbonate had lower serum levels of FGF23 (226 ± 11 vs. 158 ± 9 pg/ml) and less urinary excretion of phosphate. No significant changes in serum calcium and PTH levels were observed in both groups. In conclusion, in CKD 4 - 5 patients lanthanum carbonate is effective in reducing phosphate load and FGF23 levels; this effect was not observed with calcium carbonate.
Sagrario Soriano; Raquel Ojeda; Mencarnación Rodríguez; Yolanda Almadén; Mariano Rodriguez; Alejandro Martín-Malo; Pedro Aljama. The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients. Clinical Nephrology 2013, 80, 17 -22.
AMA StyleSagrario Soriano, Raquel Ojeda, Mencarnación Rodríguez, Yolanda Almadén, Mariano Rodriguez, Alejandro Martín-Malo, Pedro Aljama. The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients. Clinical Nephrology. 2013; 80 (7):17-22.
Chicago/Turabian StyleSagrario Soriano; Raquel Ojeda; Mencarnación Rodríguez; Yolanda Almadén; Mariano Rodriguez; Alejandro Martín-Malo; Pedro Aljama. 2013. "The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients." Clinical Nephrology 80, no. 7: 17-22.
M Victoria Pendonruiz De Mier; Raquel Ojedalopez; M Antonia Alvarez De Larasanchez; Alejandro Martinmalo; Pedro Aljamagarcia. Eficacia de la hemodiafiltración con regeneración del ultrafiltrado en la insuficiencia renal por mieloma múltiple. 2013, 33, 426 -8.
AMA StyleM Victoria Pendonruiz De Mier, Raquel Ojedalopez, M Antonia Alvarez De Larasanchez, Alejandro Martinmalo, Pedro Aljamagarcia. Eficacia de la hemodiafiltración con regeneración del ultrafiltrado en la insuficiencia renal por mieloma múltiple. . 2013; 33 (33):426-8.
Chicago/Turabian StyleM Victoria Pendonruiz De Mier; Raquel Ojedalopez; M Antonia Alvarez De Larasanchez; Alejandro Martinmalo; Pedro Aljamagarcia. 2013. "Eficacia de la hemodiafiltración con regeneración del ultrafiltrado en la insuficiencia renal por mieloma múltiple." 33, no. 33: 426-8.
Background/Aims: The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. Methods: N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. Results: Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p Conclusions: NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.
Francesco Locatelli; Thierry Hannedouche; Alejandro Martin-Malo; Stefan H. Jacobson; Raymond Vanholder; Claudio Ronco; Vincenzo La Milia; Juan M. Lopez Gomez; Sergio Stefoni; Hervé Maheut; Marian Klinger; Thierry Krummel; Annemie Dhondt; Isabel Berdud; Adelheid Gauly; for the Membrane Permeability Outcome (MPO) Study Group. The Relationship of NT-proBNP and Dialysis Parameters with Outcome of Incident Haemodialysis Patients: Results from the Membrane Permeability Outcome Study. Blood Purification 2013, 35, 216 -223.
AMA StyleFrancesco Locatelli, Thierry Hannedouche, Alejandro Martin-Malo, Stefan H. Jacobson, Raymond Vanholder, Claudio Ronco, Vincenzo La Milia, Juan M. Lopez Gomez, Sergio Stefoni, Hervé Maheut, Marian Klinger, Thierry Krummel, Annemie Dhondt, Isabel Berdud, Adelheid Gauly, for the Membrane Permeability Outcome (MPO) Study Group. The Relationship of NT-proBNP and Dialysis Parameters with Outcome of Incident Haemodialysis Patients: Results from the Membrane Permeability Outcome Study. Blood Purification. 2013; 35 (1-3):216-223.
Chicago/Turabian StyleFrancesco Locatelli; Thierry Hannedouche; Alejandro Martin-Malo; Stefan H. Jacobson; Raymond Vanholder; Claudio Ronco; Vincenzo La Milia; Juan M. Lopez Gomez; Sergio Stefoni; Hervé Maheut; Marian Klinger; Thierry Krummel; Annemie Dhondt; Isabel Berdud; Adelheid Gauly; for the Membrane Permeability Outcome (MPO) Study Group. 2013. "The Relationship of NT-proBNP and Dialysis Parameters with Outcome of Incident Haemodialysis Patients: Results from the Membrane Permeability Outcome Study." Blood Purification 35, no. 1-3: 216-223.
Background/Aims: We examined the effects of different online hemodiafiltration techniques on microinflammation and endothelial damage/repair. Methods: The study was designed as a prospective crossover study. Flow cytometry was used to measure CD14+CD16+ monocytes, apoptotic endothelial microparticles (EMPs), and endothelial progenitor cells (EPCs). Results: Patients treated with high-flux hemodialysis showed a marked chronic inflammatory state (HF-HD 11 ± 2) versus healthy subjects (HS 3.9 ± 2.3; p < 0.05). High convective transport, independent of the technique used, improves microinflammatory parameters (OL-HDF 7.3 ± 2.1 or MID 6.5 ± 3.4; p < 0.05) and the endothelial damage/repair balance compared to HF-HD (EPCs HF-HD 0.3 ± 0.2), with no differences found between the two modalities (EPCs OL-HDF 0.6 ± 0.1, MID 0.6 ± 0.2; p < 0.05). Conclusion: An increase in convective transport improves the microinflammatory state and the endothelial damage/repair of these patients independently of the technique used.
Francisco Ariza; Ana Merino; Julia Carracedo; M.Antonia Alvarez De Lara; Rodolfo Crespo; Rafael Ramirez; Alejandro Martín-Malo; Pedro Aljama. Post-Dilution High Convective Transport Improves Microinflammation and Endothelial Dysfunction Independently of the Technique. Blood Purification 2013, 35, 270 -278.
AMA StyleFrancisco Ariza, Ana Merino, Julia Carracedo, M.Antonia Alvarez De Lara, Rodolfo Crespo, Rafael Ramirez, Alejandro Martín-Malo, Pedro Aljama. Post-Dilution High Convective Transport Improves Microinflammation and Endothelial Dysfunction Independently of the Technique. Blood Purification. 2013; 35 (4):270-278.
Chicago/Turabian StyleFrancisco Ariza; Ana Merino; Julia Carracedo; M.Antonia Alvarez De Lara; Rodolfo Crespo; Rafael Ramirez; Alejandro Martín-Malo; Pedro Aljama. 2013. "Post-Dilution High Convective Transport Improves Microinflammation and Endothelial Dysfunction Independently of the Technique." Blood Purification 35, no. 4: 270-278.
Geographical differences in disease prevalence and mortality have been described in the general population and in chronic kidney disease patients in Europe. In this secondary analysis of the Membrane Permeability Outcome (MPO) study, we addressed differences in patient and treatment patterns, and whether these affect patient outcomes.
Alejandro Martín-Malo; For the Membrane Permeability Outcome (MPO) Study Group*; Menelaos Papadimitriou; João Cruz; Jesus Bustamante; Dierik Verbeelen; Alain Nony; Raymond Vanholder; Stefan H. Jacobson; Jesús Montenegro; Thierry Hannedouche; Volker Wizemann; Francesco Locatelli. Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients. Journal of Nephrology 2012, 26, 119 -128.
AMA StyleAlejandro Martín-Malo, For the Membrane Permeability Outcome (MPO) Study Group*, Menelaos Papadimitriou, João Cruz, Jesus Bustamante, Dierik Verbeelen, Alain Nony, Raymond Vanholder, Stefan H. Jacobson, Jesús Montenegro, Thierry Hannedouche, Volker Wizemann, Francesco Locatelli. Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients. Journal of Nephrology. 2012; 26 (1):119-128.
Chicago/Turabian StyleAlejandro Martín-Malo; For the Membrane Permeability Outcome (MPO) Study Group*; Menelaos Papadimitriou; João Cruz; Jesus Bustamante; Dierik Verbeelen; Alain Nony; Raymond Vanholder; Stefan H. Jacobson; Jesús Montenegro; Thierry Hannedouche; Volker Wizemann; Francesco Locatelli. 2012. "Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients." Journal of Nephrology 26, no. 1: 119-128.