Unresolved aspects in the management of renal anemia, a Delphi consensus of the Anemia Group of the S.E.N.

Anemia is a common complication of chronic kidney disease (CKD) and is associated with a decrease in quality of life and an increased risk of transfusions, morbidity and mortality, and progression of CKD. The Anemia Working Group of the Sociedad Española de Nefrología conducted a Delphi study among experts in anemia in CKD to agree on relevant unanswered questions by existing evidence. The RAND/UCLA consensus methodology was used. We defined 15 questions with a PICO structure, followed by a review in scientific literature databases. Statements to each question were developed based on that literature review. Nineteen experts evaluated them using an iterative Two-Round Delphi-like process. Sixteen statements were agreed in response to 8 questions related to iron deficiency and supplementation with Fe (impact and management of iron deficiency with or without anemia, iron deficiency markers, safety of i.v. iron) and 7 related to erythropoiesis stimulating agents (ESAs) and/or hypoxia-inducible factor stabilizers (HIF), reaching consensus on all of them (individualization of the Hb objective, impact and management of resistance to ESA, ESA in the immediate post-transplant period and HIF stabilizers: impact on ferrokinetics, interaction with inflammation and cardiovascular safety). There is a need for clinical studies addressing the effects of correction of iron deficiency independently of anemia and the impact of anemia treatment with various ESA on quality of life, progression of CKD and cardiovascular events.

Sarcopenia and Mortality in Older Hemodialysis Patients.

(1) Sarcopenia is a progressive loss of skeletal muscle mass and strength. The aim of this study was to determine the association of sarcopenia, defined according to the Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria, with mortality at 24 months in very elderly hemodialysis patients. (2) A prospective study was conducted in 60 patients on chronic hemodialysis who were older than 75 years. Sarcopenia was diagnosed according to EWGSOP2 criteria. Additionally, clinical, anthropometric and analytical variables and body composition by bioimpedance were assessed. The date and cause of death were recorded during 2 years of follow-up. (3) Among study participants, 41 (68%) were men, the mean age 81.85 ± 5.58 years and the dialysis vintage was 49.88 ± 40.29 months. The prevalence of probable sarcopenia was 75% to 97%, depending on the criteria employed: confirmed sarcopenia ranged from 37 to 40%, and severe sarcopenia ranged from 18 to 37%. A total of 30 (50%) patients died over 24 months. Sarcopenia probability variables were not related to mortality. In contrast, sarcopenia confirmation (appendicular skeletal muscle mass, ASM) and severity (gait speed, GS) variables were associated with mortality. In multivariate analysis, the hazard ratio (95% confidence interval) for all-cause death was 3.03 (1.14-8.08, p = 0.028) for patients fulfilling ASM sarcopenia criteria and 3.29 (1.04-10.39, p = 0.042) for patients fulfilling GS sarcopenia criteria. (4) The diagnosis of sarcopenia by EWGSOP2 criteria is associated with an increased risk of all-cause death in elderly dialysis patients. Specifically, ASM and GS criteria could be used as mortality risk markers in elderly hemodialysis patients. Future studies should address whether the early diagnosis and treatment of sarcopenia improve outcomes.

Estimated glomerular filtration rate by formulas in patients with cirrhosis: An unreliable procedure.

BACKGROUND & AIMS: In cirrhosis, the reliability of formulas that estimate renal function, either those specifically developed in this population or the classic equations, has not been properly quantified. We studied the agreement between estimated (eGFR) and measured glomerular filtration rate (mGFR) in cirrhosis. METHODS: Renal function was estimated with 56 formulas including specific equations: Glomerular Filtration Rate Assessment in Liver Disease (GRAIL), Royal Free Hospital Cirrhosis (RFHC) and Mindikoglu-eGFR, and measured with a gold standard procedure; plasma clearance of iohexol using dried blood spots sampling in a group of cirrhotics. The agreement eGFR-mGFR was evaluated with specific tests: total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). We defined acceptable agreement as values: TDI < 10%, CCC ≥ 0.9 and CP > 90%. RESULTS: A total of 146 patients (age 65 ± 9 years, 81% male) were evaluated; 61 (42%) Child A, 67 (46%) Child B and 18 (12%) Child C. Median MELD-Na was 14 (9-15). The agreement between eGFR and mGFR was poor: TDI averaged was of 73% (90% of the estimations ranged from ±73% of mGFR); CCC averaged was 0.7 indicating low concordance and CP averaged 22% indicating that 78% of the estimations have an error > 10%. Specific formulas showed also poor agreement: TDI was 82%, 70% and 37% for the GRAIL, RFHC and Mindikoglu equations, respectively. CONCLUSIONS: Overall, formulas poorly estimated renal function in cirrhotic patients. Specific formulas designed for cirrhosis did not outperform classic equations. eGFR must be considered with caution in cirrhotic patients.

Primary membranous nephropathy in the era of autoantibodies and biological therapies. / Nefropatía membranosa primaria en la era de los autoanticuerpos y de las terapias biológicas.

Primary membranous nephropathy is an autoimmune kidney disease and the most common cause of nephrotic syndrome in adults. About 70%-80% of cases are caused by anti-PLA2R antibodies. Its association with anti-THSD7A antibodies and other autoantibodies has also been described. Recent pilot studies and clinical trials have shown that several biological agents targeting autoantibody-producing cells are effective in controlling the disease with an acceptable safety profile. In this narrative review, we update key concepts about the pathogenesis, autoantibody-based diagnosis, and kidney biopsy findings in primary membranous nephropathy. In addition, we propose a diagnostic and therapeutic algorithm, including guidance on monitoring the response to therapy. We compare the efficacy and safety of currently available treatments, including rituximab and new biological agents, and identify unmet clinical needs.

[Teaching nephrology as part of a degree in medicine]. / La docencia de la nefrología en el grado de medicina.

The teaching of nephrology as part of a degree in medicine is potentially one of the most decisive factors when choosing a speciality. Until now, however, we have not had an overview of the teaching of nephrology in Spain. We have integrated information available in public databases with a survey and personal interviews with those responsible for teaching in Spanish medical faculties. In 2019, there were 44 universities offering a medicine degree in Spain, in 16 Autonomous Communities (34 of which were public and 10 private). For learning purposes, students have a number of hospital beds ranging from 0.2 to 4.7, and there are Autonomous Communities that have a higher proportion of students per inhabitant or per physician, such as Madrid or the Community of Navarra. In 16 universities there are tenured teaching staff (professors and lecturers), in 8 contracted medical lecturers, and in 2 assistant lecturers. In 21 medical faculties, theoretical and practical nephrology is taught by associate lecturers. The subject is taught between the third and fifth years of the degree, the median being the fourth year. It is usually integrated with another subject and only in the University of Navarra is it an independent subject, with 3 credits. The total number of hours devoted to theoretical teaching (both theoretical classes and seminars) is highly variable and ranges from 11 to 35, with a median of 17.5. Variability is observed in both the number of theoretical subjects (range 11 to 31) and seminars (range 0 to 9). Among the faculties that teach seminars, the ratio of theoretical topics to seminars ranges from 1.6 to 18. Most faculties evaluate clinical practices with various modalities and percentage of assessment. Knowledge is mostly assessed by a multiple choice exam. In conclusion, there is a high level of variability in the curriculum for the teaching of nephrology as part of a degree in medicine in Spain. Teaching staff who are tenured or who have a stable affiliation with universities make up just 23% of the total and, in many faculties, teaching depends exclusively on associate professors.

Teaching nephrology as part of a degree in medicine.

The teaching of nephrology as part of a degree in medicine is potentially one of the most decisive factors when choosing a speciality. Until now, however, we have not had an overview of the teaching of nephrology in Spain. We have integrated information available in public databases with a survey and personal interviews with those responsible for teaching in Spanish medical faculties. In 2019, there were 44 universities offering a medicine degree in Spain, in 16 Autonomous Communities (34 of which were public and 10 private). For learning purposes, students have a number of hospital beds ranging from 0.2 to 4.7, and there are Autonomous Communities that have a higher proportion of students per inhabitant or per physician, such as Madrid or the Community of Navarra. In 16 universities there are tenured teaching staff (professors and lecturers), in eight contracted medical lecturers, and in two assistant lecturers. In 21 medical faculties, theoretical and practical nephrology is taught by associate lecturers. The subject is taught between the third and fifth years of the degree, the median being the fourth year. It is usually integrated with another subject and only in the University of Navarra is it an independent subject, with three credits. The total number of hours devoted to theoretical teaching (both theoretical classes and seminars) is highly variable and ranges from 11 to 35, with a median of 17.5. Variability is observed in both the number of theoretical topics (range 11-31) and seminars (range 0-9). Among the faculties that teach seminars, the ratio of theoretical topics to seminars ranges from 1.6 to 18. Most faculties evaluate clinical practices with various modalities and percentage of assessment. Knowledge is mostly assessed by a multiple choice exam. In conclusion, there is a high level of variability in the curriculum for the teaching of nephrology as part of a degree in medicine in Spain. Teaching staff who are tenured or who have a stable affiliation with universities make up just 23% of the total and, in many faculties, teaching depends exclusively on associate professors.

Defining protein-energy wasting syndrome in chronic kidney disease: prevalence and clinical implications.

The presence of malnutrition in chronic kidney disease (CKD) is well-known. The discovery in the last 15 years of pathophysiological mechanisms that lead to this process, such as anorexia, the increase of protein catabolism and inflammation, has created the need for a new name by the International Society of Renal Nutrition and Metabolism (ISRNM): protein-energy wasting syndrome (PEW). This document's objectives are to propose the use of the term "desgaste proteico energético" (DPE) as a more accurate translation of the English term and to update the pathogenic mechanisms involved that are inherent to DPE (PEW). We simultaneously review the latest epidemiological evidence that highlight the relevance of malnutrition and its impact both on mortality and morbidity in CKD. Finally, we point out the need to redefine DPE (PEW) diagnostic criteria so that they are applicable to the Spanish population with CKD. We do not think that the criteria established by the ISRNM can be extrapolated to different populations, as is the case, for example, with interracial anthropometric differences.

Impact of implementing ISO 9001:2008 standard on the Spanish Renal Research Network biobank sample transfer process.

BACKGROUND: Biobank certification ISO 9001:2008 aims to improve the management of processes performed. This has two objectives: customer satisfaction and continuous improvement. This paper presents the impact of certification ISO 9001:2008 on the sample transfer process in a Spanish biobank specialising in kidney patient samples. The biobank experienced a large increase in the number of samples between 2009 (12,582 vials) and 2010 (37,042 vials). METHODS: The biobank of the Spanish Renal Research Network (REDinREN), located at the University of Alcalá, has implemented ISO standard 9001:2008 for the effective management of human material given to research centres. Using surveys, we analysed two periods in the “sample transfer” process. During the first period between 1-10-12 and 26-11-12 (8 weeks), minimal changes were made to correct isolated errors. In the second period, between 7-01-13 and 18-02-13 (6 weeks), we carried out general corrective actions. RESULTS: The identification of problems and implementation of corrective actions for certification allowed: a 70% reduction in the process execution time, a significant increase (200%) in the number of samples processed and a 25% improvement in the process. The increase in the number of samples processed was directly related to process improvement. CONCLUSION: The certification of ISO standard 9001:2008, obtained in July 2013, allowed an improvement of the REDinREN biobank processes to be achieved, which increased quality and customer satisfaction.

Vitamin D and proteinuria: a critical review of molecular bases and clinical experience.

Proteinuria is the main predictor of chronic kidney disease progression. Drugs that block the renin-angiotensin-aldosterone (RAA) system reduce proteinuria and slow down the progression of the disease. However, their effect is suboptimal, and residual proteinuria persists as an important predictor of renal impairment. Vitamin D has pleiotropic effects that could have an impact on these parameters. In this study, we critically review the molecular and experimental bases that suggest an antiproteinuric effect of vitamin D receptor (VDR) activation and the available evidence on its antiproteinuric effect in clinical practice. In animal models, we have observed the antiproteinuric effect of VDR activation, which could be due to direct protective action on the podocyte or other pleiotropic effects that slow down RAA system activation, inflammation and fibrosis. Clinical trials have generally been conducted in patients with a vitamin D deficiency or insufficiency and the main trial (VITAL) did not demonstrate that paricalcitol improved the study's primary endpoint (decrease in the urine albumin to creatinine ratio). In this sense, the information available is insufficient to advise the use of native vitamin D or VDR activators as renoprotective antiproteinuric drugs beyond the experimental level. Two Spanish clinical trials and one Italian trial attempted to determine the effect of paricalcitol and vitamin D on residual proteinuria in various clinical circumstances (PALIFE, NEFROVID and PROCEED).

Start-up of a clinical sample processing, storage and management platform: organisation and development of the REDinREN Biobank.

BACKGROUND: The creation of the Biobank, a resource pertaining to the Spanish Renal Research Network (REDinREN) promotes advances in clinical research on kidney disease in Spain. The Biobank's aims are to generate an archive of clinical samples and associated data, furnish those samples to research teams, and coordinate with European biobanks. METHOD: Applicable legislation had to be complied with in order to launch the Biobank project (Biomedical Research Law, Data Protection Law and Biological Sample Transport Regulations). A strict work protocol and a new database for the Network's clinical data were also implemented. RESULTS: Over time, the Biobank has acquired additional infrastructure and qualified personnel. In 2010, 2953 new patient samples were collected, giving a total of 37,043 stored vials containing different types of samples. Furthermore, the Biobank is currently participating in eleven research projects. DISCUSSION: Although the Biobank was originally designed for REDinREN use, we must take joint action to make this biological sample storage system and the many possibilities it offers available to the entire nephrological community with a view to promoting kidney disease research.

[Aging and inflammation: Klotho, diet and the kidney connection]. / Envejecimiento e inflamación: Klotho, dieta y la conexión renal.

Despite renal replacement therapy mortality among chronic kidney disease patients is 10-1000-fold higher than in age-matched controls. Klotho is a kidney protein with anti-ageing hormonal properties that is also a co-receptor for the FGF23 fosfatonin. There is a bidirectional relationship between Klotho and inflammation. Thus, inflammation decreases renal Klotho and Klotho has anti-inflammatory properties. Mice with genetic defects in Klotho suffer from accelerated aging and early death. Decreasing the phosphate load improves the phenotype and prolongs survival in these mice. Unraveling the Klotho-phosphate-inflammation interaction may open new avenues for research that may improve the outcomes of kidney patients as well as provide new tools to retard aging in the general population.

[Polycystic kidney disease: from genetics to dialysis]. / Poliquistosis renal: de la genética a la diálisis.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end stage renal disease. In addition, end-stage renal disease is complicated by acquired polycystic kidney disease. Recent advances in our understanding of the pathogenesis of ADPKD have identified the primary cilium as key to cystogenesis, and have defined the molecular, cellular and tissue pathogenesis of the disease, leading to the design of clinical trials that may ultimately lead to effective therapy of the disease. In 2012 a key trial has shown that blockade of vasopressin receptors with tolvaptan slows the rate of cyst growth and may slow the loss of renal function.

[Efficacy of oral supplementation during dialysis in patients with chronic renal failure]. / Eficacia de la suplementación oral intradiálisis en pacientes con insuficiencia renal crónica.

Protein-calorie malnutrition is common in hemodialysis patients and is a powerful predictor of morbidity and mortality. Nutritional supplementation, administered orally or parenterally, especially during dialysis, may compensate for the relatively inadequate protein and energy intake and improves net protein anabolism in chronic hemodialysis patients. Intradialytic oral nutrition seems preferable to intradialytic parenteral nutrition (IDPN) due to its lower cost and persistence of its anabolic effects after infusion is stopped, and because IDPN induces a higher increase in serum glucose and insulin levels and a greater reduction in serum ghrelin concentrations. Further larger scale randomized, controlled trials of nutritional interventions should be performed in maintenance dialysis patients to assess their efficacy regarding quality of life, morbidity, and mortality.