Caracterización del síndrome del desgaste proteico energético en hemodialisis

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 28-11-201

Phosphorus and Nutrition in Chronic Kidney Disease

Patients with renal impairment progressively lose the ability to excrete phosphorus. Decreased glomerular filtration of phosphorus is initially compensated by decreased tubular reabsorption, regulated by PTH and FGF23, maintaining normal serum phosphorus concentrations. There is a close relationship between protein and phosphorus intake. In chronic renal disease, a low dietary protein content slows the progression of kidney disease, especially in patients with proteinuria and decreases the supply of phosphorus, which has been directly related with progression of kidney disease and with patient survival. However, not all animal proteins and vegetables have the same proportion of phosphorus in their composition. Adequate labeling of food requires showing the phosphorus-to-protein ratio. The diet in patients with advanced-stage CKD has been controversial, because a diet with too low protein content can favor malnutrition and increase morbidity and mortality. Phosphorus binders lower serum phosphorus and also FGF23 levels, without decreasing diet protein content. But the interaction between intestinal dysbacteriosis in dialysis patients, phosphate binder efficacy, and patient tolerance to the binder could reduce their efficiency

Reactions to synthetic membranes dialyzers: Is there an increase in incidence?

Background: Reactions to dialyzers used in dialysis have been reported more frequently in recent years. Evidence, however, shows that the reaction rate has remained stable for years. Summary: One explanation for the apparent increase in publication frequency could be the lack of knowledge that dialyzer reactions may well occur with biocompatible membranes. Studies showed that the cause of these reactions is very diverse and varied, involving multiple materials. However, polyvinylpyrrolidone continues to be the main suspect, but without conclusive results. There are no differences between the different fibers, and although polysulfone is the most described, it is also the most used. Key Messages: The change to cellulose triacetate continues to be the most appropriate form of treatment. The classification of these reactions into type A and B complicates the diagnosis, and its true usefulness is in doubtThe research presented in this article is supported by the grants from the Spanish Ministry of Economy and Competitiveness and European Regional Development Funds (ERDF/FEDER) through ISCIII/FIS grants PI16/01298, PI17/01495, CIBERDEM and REDINREN RD016/0019 and through the Madrid Renal Society (SOMANE) grant

Uso del sevelamer en la enfermedad renal crónica: Más allá del control del fósforo

Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis for hyperphosphataemia control. Several experimental, observational studies and clinical trials have shown that sevelamer has pleiotropic effects, beyond hyperphosphataemia control, including actions on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and the reduction of several uremic toxins. This is the biological basis for its global effect on cardiovascular morbidity and mortality in patients with chronic kidney disease. This review focuses on these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than ten years of clinical expertiseEl sevelamer es un captor no cálcico de fósforo que se utiliza en la ERC avanzada y en diálisis para el control de la hiperfosforemia. Varios estudios experimentales, observacionales y ensayos clínicos han mostrado que el sevelamer tiene efectos pleiotrópicos, más allá del control de la hiperfosforemia, incluyendo acciones sobre la inflamación, el estrés oxidativo, el perfil lipídico y la aterogénesis, la calcificación vascular, la disfunción endotelial y la disminución de diversas toxinas urémicas, todo lo cual sería la base biológica de su efecto global sobre la morbilidad y la mortalidad cardiovascular en pacientes con enfermedad renal crónica. En esta revisión, se hace énfasis en estas acciones pleiotrópicas del sevelamer y su impacto en la salud cardiovascular, con la experiencia publicada después de más de 10 años de experiencia clínicaInstituto de Salud Carlos III [Carlos III Health Institute] (PI10/00072), REDINREN (Red de Investigación Renal [Renal Research Network]) (RD012/0021

Clarifying the concept of chronic kidney disease for non-nephrologists

Chronic kidney disease (CKD) expands the prior concept of chronic renal insufficiency by including patients with relatively preserved renal function, as assessed by the estimated glomerular filtration rate (eGFR), as even these early CKD stages are associated with an increased risk for all-cause death and cardiovascular death, CKD progression and acute kidney injury. A decreased eGFR (3 months. However, when eGFR is 60 mL/min/1.73m2, an additional criterion is required to diagnose CKD. In a recent clinical trial published in The New England Journal of Medicine, all 6190 participants were reported to have CKD: 47% had Stages 1 and 2 CKD and 53% had Stage 3 CKD. This illustrates a widespread misunderstanding of the concept of CKD. Moreover, CKD categories in this study were assigned based on the estimated creatinine clearance. Since both estimated creatinine clearance and creatinine clearance overestimate eGFR, this illustrates another frequent misunderstanding: equating GFR with creatinine clearance. In this commentary, we clarify the concept of CKD and of CKD categories for non-nephrologists. Assigning a diagnosis of CKD to a patient with normal renal function and absence of other evidence of CKD may have negative consequences for the individual (e.g. insurance and others) as well as for the medical community at large by creating confusion about the concept.This research was supported by FIS PI16/02057, ISCIII-RETIC REDinREN RD016/0009 FEDER funds, Sociedad Española de Nefrología, Fundación Renal Iñigo Ávarez de Toledo (FRIAT), ISCIII Rio Hortega (MVPG) and Comunidad de Madrid Biomedicina B2017/BMD-3686 CIFRA2-CM

Diferencias entre los métodos de determinación de 2.a y 3.a generación de la parathormona sérica sobre la mortalidad en el paciente en hemodiálisis

Parathormone plays a key role in controlling mineral metabolism. PTH is considered a uremic toxin causing cardiovascular damage and cardiovascular mortality in dialysis patients. There are two different assays to measure PTH called 2nd generation or intact PTH (iPTH) and 3rd generation or bioPTH (PTHbio). Objective: To evaluate the differences in mortality of dialysis patients between both assays to measure PTH, as well as the possible prognostic role of the PTHbio/iPTH ratio. Methods: 145 haemodialysis patients were included with 2-year monitoring including baseline laboratory test and annually thereafter. Results: 21 patients died in the first year and 28 in the second. No correlation was found between PTH, PTHbio and PTHbio/iPTH ratio with mortality. Both PTH have a perfect correlation between them and correlate similarly with other molecules of the mineral metabolism. The extreme baseline values of PTH are those of higher mortality. In survival by iPTH intervals (according to guidelines and COSMOS study), a J curve is observed. When iPTH increases, the ratio decreases, possibly when increasing fragments no. 1–84. There is no greater prognostic approximation on mortality with PTHbio than PTHi. There was also no difference in mortality when progression ratio PTHbio/PTHi was analysed. Conclusions: We didn’t find any advantages to using bioPTH vs. PTHi as a marker of mortality. BioPTH limits of normality must be reevaluated because its relationship with iPTH is not consistent. Not knowing these limits affects its prognostic valueLa paratohormona tiene un papel fundamental en el control del metabolismo mineral. Además es considerada como una toxina urémica al originar dan˜ o cardiovascular e influir en la mortalidad cardiovascular del paciente en diálisis. Existen dos métodos de medición denominados de 2.a generación o PTH intacta (PTHi) y de 3.a generación o bioPTH (PTHbio). Objetivo: Evaluar las diferencias en la mortalidad del paciente en diálisis entre ambas formas de medición de PTH, así como el posible papel pronóstico de su cociente. Métodos: Se incluyeron 145 pacientes en hemodiálisis con un seguimiento de 2 an˜ os con determinación analítica basal y posteriormente de forma anual. Resultados: Veintiún pacientes fallecieron el primer an˜ o y 28 el segundo. No se encontró correlación entre PTHi, PTHbio y cociente PTHbio/PTHi con la mortalidad. Ambas PTH tienen una buena correlación entre ellas y correlacionan de manera similar con otras moléculas del metabolismo mineral. Los valores basales de PTH extremos son los de mayor mortalidad. En la supervivencia por tramos de PTHi (según guías y estudio COSMOS) se observa una curva en J. A mayor aumento de PTHi el cociente desciende, posiblemente al aumentar los fragmentos no 1-84. No existe una mayor aproximación pronóstica sobre mortalidad con PTHbio que con PTHi. No se observan diferencias en el valor predictivo del cociente sobre la mortalidad. Tampoco hubo diferencias en mortalidad cuando se analiza la progresión del cociente PTHbio/PTHi. Conclusiones: No encontramos ventajas en la utilización de PTHbio sobre la PTHi como marcador de mortalidad. Se deben reevaluar los límites de la PTHbio pues su relación con la PTHi no es constante. El no conocer esos límites condiciona su utilidad pronósticaOur thanks to Maribel Villarino for the help with the development of the study. L.R.-O. is a Health Professional on Research Training “Rio Hortega r” (CM13/00131), Ministry of Education, Government of Spain. R.V.B. is a professional with postdoctoral contract “Sara Borrell” (CD14/00198) and a project (SAF2014- 60699-JIN) of the Ministry of Economy (MINECO) and FEDER funds. PI14/00386. PI16/01298. FEDER funds ISCIII-RETIC REDinREN/ RD06/0016, RD12/002

Glomerulonefritis rápidamente progresiva asociada a endocarditis afebril y anca anti-proteinasa 3

Endocarditis associated with antiPR3 ANCA and acute kidney injure generates a challenge in its diagnosis and treatment. In order to make a review about that combination, we presented a patient with necrotizing glomerulonephritis produced by a Enterococcus faecalis´s subacute endocarditis and antiPR3 ANCA positive.Differential diagnosis is made between an acute kidney failure produced by ANCA´s vasculitis vs necrotizing glomerulonephritis by endocarditis. Frequently it is necessary to make a biopsy to get a diagnosis. Negative immunofluorescence will guide to vasculitis associated ANCA, while positive immune complexes will guide to poststreptococcal glomerulonephritis.Other challenge that generates the association of acute kidney disease, endocarditis and antiPR3 ANCA is the treatment. ANCA positive can prompt to start immunosuppressant treatments. However, in the context of endocarditis, it could be inadvisable and even dangerous to use it. For this reason, it is controversial the use of immunosuppressant in combination with antibiotics in the acute process, in contrast with the use of only antibiotics. In the current paper we collect the 19 reports in the literature about endocarditis associated with antiPR3 ANCA, the treatment and the renal evolution of each patient. We concluded, generally, a better improvement of kidney function in patients treated with only antibiotics than those patients treated with the combination of  antibiotics and corticoids. However, there are so few reports that we can´t consider significant the different between both treatment groups.La endocarditis asociada a ANCA anti-PR3 e insuficiencia renal plantea un dilema tanto en su diagnóstico como tratamiento. Para abordar una revisión de dicho tema, se presenta el caso de un paciente con glomerulonefritis rápidamente progresiva secundaria a endocarditis subaguda por Enterococcus faecalis y positividad para ANCA anti-PR3. El diagnóstico diferencial principal se establecería entre una afectación renal de una vasculitis asociada a ANCA no diagnosticada previamente vs una glomerulonefritis postinfecciosa secundaria a la endocarditis. En muchos casos es necesario disponer de una biopsia renal que esclarezca el diagnóstico, ya que una inmunofluorescencia negativa orientará hacia una vasculitis, mientras que una positividad para inmunocomplejos iría a favor de una glomerulonefritis postestreptocócica. El tratamiento a seguir es otro reto que se plantea en la coexistencia de insuficiencia renal aguda, endocarditis y ANCA anti-PR3 positivo. La positividad de ANCAs induce a valorar iniciar tratamiento con inmunosupresores, no obstante, en el lecho de una endocarditis puede resultar desaconsejado e incluso poner en riesgo la vida del paciente someterlo a un estado de inmunosupresión. Es, por tanto, controvertido el uso de inmunosupresión en combinación con antibioterapia en el proceso agudo en contraposición al uso de antibioterapia exclusivamente. En el actual artículo se recogen los 19 casos publicados en la literatura de endocarditis asociados a ANCA anti-PR3, así como el tratamiento que se realizó en cada uno de los casos y la evolución en la función renal de cada paciente, concluyendo, en general, una mejor recuperación de la función renal en los pacientes tratados con antibioterapia en exclusiva que en aquellos tratados con la combinación antibióticocorticoides. Sin embargo, dado el pequeño tamaño muestral, no se puede considerar significativa la diferencia entre ambos tratamientos

Evaluation of the impact of an intradialytic exercise programme on sarcopaenia in very elderly haemodialysis patients

Sarcopaenia is a highly prevalent condition in persons on haemodialysis (HD). In stable very elderly (75-95 years old) persons on chronic HD, we prospectively studied the European Working Group on Sarcopaenia in Older People (EWGSOP2) steps stability over time in 37 controls and their response to a 12-week intradialytic lower limb exercise programme in 23 persons. Overall dropout was 15% and the main cause for dropout was death (8%). Thus 33 controls and 18 exercise participants were evaluated at 12 weeks. In controls, comorbidity, nutrition, dependency and frailty scales, anthropometric assessments, EWGSOP2 step values and the prevalence of suspected, confirmed and severe sarcopaenia as assessed by EWGSOP2 remained stable. In contrast, in persons who completed the exercise programme, a significant improvement in the five times sit-to-stand (STS-5) test was noted at the end of the 12-week exercise programme (19.2 ± 4.9-15.9 ± 5.9 seconds; P =. 001), consistent with the lower limb nature of the exercise programme, that persisted 12 weeks after completion of the programme. Exercise also improved the Fried frailty scale (1.7 ± 1.0-1.1 ± 0.6; P =. 004). In conclusion, EWGSOP2 steps remain stable in stable very elderly persons on HD and STS-5 is responsive to a short-term intradialytic lower limb exercise programme. These results may help define EWGSOP2-based primary endpoints in future large-scale clinical trials assessing exercise interventionsThe authors would like to thank FRIAT for its support to the present study. The research groups of E.G.P., S.M.F. and A.O. are funded by the Ministerio de Economia, Industria y competitividad: FIS/Fondos FEDER (PI16/01298, PI18/01386, PI19/00588, PI19/00815, PI20/00487, PI21/01240, DTS18/00032), ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009) and Sociedad Española de Nefrología, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-C

Podocyte and tubular involvement in AngioJet-induced kidney injury

Altres ajuts: Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo and Comunidad de Madrid CIFRA2 B2017/BMD-3686.The AngioJet technique combines localized thrombolysis and percutaneous mechanical thrombectomy (PMT). However, PMT may cause acute kidney injury (AKI), which has been ascribed to severe mechanical haemolysis, although no renal biopsies have been reported. We now report the first renal biopsy in a patient with AKI following PMT. There is histological evidence of haemoglobin (Hb)-induced tubular injury and podocyte stress characterized by intracellular Hb and staining for ferritin and hemo-oxygenase-1, suggestive of an adaptive response to oxidative stress. This confirms that Hb is involved in kidney cell injury and supports the existence of several different kidney cellular targets

Eculizumab in secondary atypical haemolytic uraemic syndrome

Background. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods. We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 109/L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results. Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing conditionWork in this report was funded by the Instituto de Salud Carlos III: REDinREN (RD 016/009 Feder Funds), the Fondo de Investigaciones Sanitarias (13/02502 and ICI14/00350), the Ministerio de Economia y Competitividad (SAF2015-66287R) and the Autonomous Region of Madrid (S2010/BMD-2316; Grupo de Investigación Complemento-CM). SRdeC is funded by the Seventh Framework Programme European Union Project EURenOmics (305608