The IMBG Test for Evaluating the Pharmacodynamic Response to Immunosuppressive Therapy in Kidney Transplant Patients: Current Evidence and Future Applications.

Immunosuppressive drugs are widely used to prevent rejection after kidney transplantation. However, the pharmacological response to a given immunosuppressant can vary markedly between individuals, with some showing poor treatment responses and/or experiencing serious side effects. There is an unmet need for diagnostic tools that allow clinicians to individually tailor immunosuppressive therapy to a patient's immunological profile. The Immunobiogram (IMBG) is a novel blood-based in vitro diagnostic test that provides a pharmacodynamic readout of the immune response of individual patients to a range of immunosuppressants commonly used in kidney transplant recipients. Here, we discuss the current approaches used to measure the pharmacodynamic responses of individual patients to specific immunosuppressive drugs in vitro, which can then be correlated with patient's clinical outcomes. We also describe the procedure of the IMBG assay, and summarize the results obtained using the IMBG in different kidney transplant populations. Finally, we outline future directions and other novel applications of the IMBG, both in kidney transplant patients and other autoimmune diseases.

Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19.

INTRODUCTION: Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. METHODS: This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, ß2 microglobulin and albumin levels pre/post-dialysis and on 1st-2nd week. We compared levels among both techniques and control group (HD without COVID-19). RESULTS: We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and ß2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. DISCUSSION: Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. CONCLUSION: HDx appears to provide better clearance for TNFα and ß2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

Derivation and external validation of the SIMPLICITY score as a simple immune-based risk score to predict infection in kidney transplant recipients.

Existing approaches for infection risk stratification in kidney transplant recipients are suboptimal. Here, we aimed to develop and validate a weighted score integrating non-pathogen-specific immune parameters and clinical variables to predict the occurrence of post-transplant infectious complications. To this end, we retrospectively analyzed a single-center derivation cohort of 410 patients undergoing kidney transplantation in 2008-2013 in Madrid. Peripheral blood lymphocyte subpopulations, serum immunoglobulin and complement levels were measured at one-month post-transplant. The primary and secondary outcomes were overall and bacterial infection through month six. A point score was derived from a logistic regression model and prospectively applied on a validation cohort of 522 patients undergoing kidney transplantation at 16 centers throughout Spain in 2014-2015. The SIMPLICITY score consisted of the following variables measured at month one after transplantation: C3 level, CD4+ T-cell count, CD8+ T-cell count, IgG level, glomerular filtration rate, recipient age, and infection within the first month. The discrimination capacity in the derivation and validation cohorts was good for overall (areas under the receiver operating curve of 0.774 and 0.730) and bacterial infection (0.767 and 0.734, respectively). The cumulative incidence of overall infection significantly increased across risk categories in the derivation (low-risk 13.7%; intermediate-risk, 35.9%; high-risk 77.6%) and validation datasets (10.2%, 28.9% and 50.4%, respectively). Thus, the SIMPLICITY score, based on easily available immune parameters, allows for stratification of kidney transplant recipients at month one according to their expected risk of subsequent infection.

Chronic kidney disease and acute kidney injury in the COVID-19 Spanish outbreak.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread, affecting >10 million cases worldwide. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and primarily manifesting as an acute respiratory failure with interstitial and alveolar pneumonia, it can also affect multiple organs. Kidney involvement was underestimated in early reports and its role remains controversial. The aim of this study was to analyse the role of kidney damage in COVID-19 outcome. METHODS: This is a prospective cohort study of 1603 consecutive patients admitted in a University Reference Hospital in the heart of the European outbreak. RESULTS: Median age was 64 years, 40.4% were female, 15.2% presented diabetes mellitus, 35.7% hypertension and 20.3% obesity. On admission, the prevalence of elevated serum creatinine (sCr), proteinuria, leucocyturia and haematuria were 21.0, 37.8, 31.8 and 45.6%, respectively. In total, 43.5% of those with an elevated sCr had previous chronic kidney disease (CKD) and 11.4% of those with normal sCr developed an in-hospital acute kidney injury (AKI); 17 patients needed acute haemodialysis; and 197 patients died during hospitalization. Cox proportional hazard regression confirmed that elevated baseline sCr [hazard ratio (95% confidence interval) 2.40 (1.79-3.22)], previous CKD [1.59 (1.06-2.37)], haematuria [1 + 1.68 (0.92-3.06), 2-3 + 2.69 (1.49-4.87)] and in-hospital AKI [1.50 (0.92-2.44)] were independent risk factors for in-hospital death after adjusting for age, sex and comorbidity. CONCLUSION: The prevalence of acute and chronic kidney disease on admission and in-hospital AKI is higher than previously reported in Wuhan, and is associated with high in-hospital mortality. We should increase our awareness towards kidney involvement and design specific strategies for management of COVID-19 in these patients.

Early outcomes of kidney transplantation from elderly donors after circulatory death (GEODAS study).

BACKGROUND: Spain has dramatically increased the number of controlled circulatory death donors (cDCD). The initial selection criteria for considering cDCD for kidney transplantation (KT) have been expanded progressively, with practically no limits in donor age during the last years. We aimed to analyze the early clinical outcomes using expanded (> 65 years) cDCD in comparison with standard ones. METHODS: Observational multicenter study including 19 transplant centers in Spain. We performed a systematic inclusion in a central database of every KT from expanded cDCD at each participant unit from January-2012 to January-2017. Surgical procedures and immunosuppressive protocols were based on local practices. Data was analyzed in the central office using logistic and Cox regression or competitive-risk models for multivariate analysis. Median time of follow-up was 18.1 months. RESULTS: 561 KT were performed with kidneys from cDCD, 135 from donors older than 65 years. As expected, recipients from older cDCD were also older (65.8 (SD 8.8) vs 53.7 (SD 11.4) years; p < 0.001) and with higher comorbidity. At 1 year, no differences were found amongst older and younger cDCD KT recipients in terms of serum creatinine (1.6 (SD 0.7) vs 1.5 (SD 0.8) mg/dl; p = 0.29). Non-death censored graft survival was inferior, but death-censored graft survival was not different (95.5 vs 98.2% respectively; p = 0.481). They also presented a trend towards higher delayed graft function (55.4 vs 46.7%; p = 0.09) but a similar rate of primary non-function (3.7 vs 3.1%; p = 0.71), and acute rejection (3.0 vs 6.3%; p = 0.135). In the multivariate analysis, in short follow-up, donor age was not related with worse survival or poor kidney function (eGFR < 30 ml/min). CONCLUSIONS: The use of kidneys from expanded cDCD is increasing for older and comorbid patients. Short-term graft outcomes are similar for expanded and standard cDCD, so they constitute a good-enough source of kidneys to improve the options of KT wait-listed patients.

A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome.

Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis. Identification of inherited complement abnormalities explained nine of the 22 cases, with CFH mutations and CFH to CFHR1 gene conversion events being the most prevalent genetic alterations associated with this disorder (66%). In thirteen of the cases, pregnancy complications were sufficient to trigger a thrombotic microangiopathy in the absence of genetic or acquired complement alterations. The postpartum period was the time with highest risk to develop the disease and the group shows an association of cesarean section with pregnancy-associated aHUS. Seventeen patients underwent plasma treatments with a positive renal response in only three cases. In contrast, ten patients received eculizumab with an excellent renal response in all, independent of carrying or not inherited complement abnormalities. Although the cohort is relatively small, the data suggest that pregnancy-associated aHUS is not different from other types of aHUS and suggest the efficacy of eculizumab treatment over plasma therapies. This study may be useful to improve prognosis in this group of aHUS patients.

[Anemia of chronic kidney disease: Protocol of study, management and referral to Nephrology]. / Anemia en la enfermedad renal crónica: protocolo de estudio, manejo y derivación a Nefrología.

The objective of this protocol is to know which test are needed to study an anaemia in a patient with chronic kidney disease, the differential diagnosis of renal anaemia, to know and correct other deficiency anaemias, and the criteria for referral to Nephrology or other specialties of the anaemic patient with chronic kidney disease.

Markers of endothelial damage in patients with chronic kidney disease on hemodialysis.

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

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 × 10 9 /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 condition.

Removing Beam Current Artifacts in Helium Ion Microscopy: A Comparison of Image Processing Techniques.

The development of the helium ion microscope (HIM) enables the imaging of both hard, inorganic materials and soft, organic or biological materials. Advantages include outstanding topographical contrast, superior resolution down to <0.5 nm at high magnification, high depth of field, and no need for conductive coatings. The instrument relies on helium atom adsorption and ionization at a cryogenically cooled tip that is atomically sharp. Under ideal conditions this arrangement provides a beam of ions that is stable for days to weeks, with beam currents in the order of picoamperes. Over time, however, this stability is lost as gaseous contamination builds up in the source region, leading to adsorbed atoms of species other than helium, which ultimately results in beam current fluctuations. This manifests itself as horizontal stripe artifacts in HIM images. We investigate post-processing methods to remove these artifacts from HIM images, such as median filtering, Gaussian blurring, fast Fourier transforms, and principal component analysis. We arrive at a simple method for completely removing beam current fluctuation effects from HIM images while maintaining the full integrity of the information within the image.

Risk Factors for Clostridium Difficile Diarrhea in Patients With Solid Organ Transplantation.

BACKGROUND: There is limited knowledge about specific risk factors for Clostridium difficile infection (CDI). METHOD: A retrospective study comparing cases of CDI in solid organ transplant (SOT) recipients with controls (SOT recipients who did not present CDI). RESULTS: Thirty patients with SOT from 1340 transplantation recipients had at least 1 episode of CDI (2.23%). The accumulated incidence was 3.06% in liver transplantation, 2.78% in lung transplantation, 2.36% in kidney transplantation, and 0.33% in heart transplantation. Seven (23%) cases occurred during the first 2 months. Fifteen (50%) cases were community acquired. Colonoscopy was performed in 6 (20%) cases, but pseudomembranes were observed in only 1 (16%) case. Independent variables found to be related to CDI were previous treatment with proton pump inhibitors (PPIs; odds ratio [OR] 5.5; 95% confidence interval [CI] 1.2-32.0), immunosuppressive regimen including mycophenolate (OR 5.2; 95%CI 1.1-18), hospitalization during the previous 3 months (OR 5.1; 95%CI 1.1-17), and antibiotic treatment during the previous month (OR 6.7; 95%CI 1.4-23). Five (16.7%) patients did not respond to the initial treatment. Recurrences were noted in 6 (20%) patients. CONCLUSIONS: Liver transplant recipients presented the highest incidence. Risk factors for CDI were previous treatment with PPIs, immunosuppressive regimen containing mycophenolate, prior hospitalization, and prior antibiotic treatment.

[Application of restriction fragment length polymorphism-polymerase chain reaction-flaA and resistotype to identify potential undiagnosed outbreaks of campylobacteriosis in Spain]. / Aplicación del análisis de los polimorfismos de los tamaños de los fragmentos de restricción del gen flaA amplificado por reacción en cadena de la polimerasa y resistotipo para identificar potenciales brotes de campilobacteriosis no diagnosticados en España.

INTRODUCTION: Outbreaks of campylobacteriosis are infrequent and usually involve a low number of patients, although it is estimated that many more remain undiagnosed. The most successful techniques for outbreak investigation in Campylobacter spp. (PFGE, MLST) have the drawback of being laborious and not available in many laboratories. METHODS: During the year 2008, 352 isolates of C. jejuni and C. coli from 16 hospitals were received in our laboratory. All strains were genotyped by RFLP-PCR-flaA (flaA type) and phenotyped with their resistotype. It was established that the strains of the same species from the same hospital, isolated over a period of up to 11 days, with MIC values of±1 dilution with the same flaA type could belong to an outbreak. Strains that met these criteria would be later subtyped by KpnI-PFGE and MLST. RESULTS: A total of 23 out of 352 isolates, distributed in 10 groups, met the criteria for being associated with putative undiagnosed outbreaks. The similarity of the PFGE-profiles in 8 groups was greater than 95% among the isolates from each group. In 7 of the groups, the sequence types (MLST) were coincident. CONCLUSIONS: The use of 2 easy markers (resistotype and RFLP-PCR-flaA) may detect isolates probably belonging to an undiagnosed outbreak of campylobacteriosis. Accurate diagnosis requires other molecular markers and epidemiological data of each isolate. The study suggests that, as in other countries, the number of outbreaks of campylobacteriosis in Spain is probably underestimated.

Efficacy and Safety in a Real-World Study of the New Oral Formulation of Semaglutide in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.

Background/Objectives: GLP-1 receptor agonists (GLP-1RAs) have emerged as fundamental components in the treatment of type 2 diabetic patients (T2DM) with chronic kidney disease (CKD). The oral formulation represents a novel therapeutic tool but may affect drug efficacy. This study sought to compare the effectiveness of subcutaneous versus oral semaglutide formulations in patients with CKD. Methods: A retrospective study in a real-world setting compared type 2 diabetes and chronic kidney disease patients, initiating oral semaglutide treatment to a historically matched control group treated with subcutaneous semaglutide. The matching considered factors such as estimated glomerular filtration rate (eGFR), age, and sex. Results: Nineteen patients were included in both groups, with a mean age of 68.0. Seventy-two percent were males with a CKD-EPI eGFR of 49.9 mL/min/1.73 m2 and a median urine albumin-to-creatinine ratio of 12.7 mg/g. Of the study participants, 94% and 79% of patients were on the maximum semaglutide sbc vs. oral dose, while 5.3% and 15.8% were on the sbc vs. oral low dose. Oral semaglutide significantly reduced HbA1C and BMI, identical to the control group (-0.9 and -1.4, p > 0.05). Renal function parameters and blood pressure remained stable throughout the follow-up in both groups. The main side effect was digestive intolerance (affecting three patients in the oral group and two patients in the subcutaneous group, p = 0.6), although the treatment abandonment percentage was similar. Conclusions: The oral formulation of semaglutide demonstrated equivalent effectiveness in glucose control and body weight management in patients with T2DM and CKD, even with a higher proportion of patients receiving low to medium doses. Gastrointestinal side effects were comparable between both oral and subcutaneous formulations.

The Uricosuric Effect of SGLT2 Inhibitors Is Maintained in the Long Term in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.

(1) Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) increase uric acid excretion. The intensity of uricosuria is linked to glycosuria. (2) Methods: We aim to analyze the effect of SGLT2 inhibitors on urinary fractional excretion (FE) of uric acid and glucose in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in a single-center retrospective study with patients with T2DM and CKD who started on treatment with SGLT2is. Patients on renal replacement therapy or with glucagon-like peptide-1 (GLP1) analogs were excluded. Subgroup analysis was performed according to the estimated glomerular filtration rate (eGFR), the SGLT2i molecule, the main comorbidities, and concomitant treatment. As a secondary objective, the study analyzed the effect of SGLT2 inhibitors on uricemia levels. (3) Results: Seventy-three patients were analyzed, with a mean follow-up of 1.2 years. Uric acid and glucose FE significantly increased after the initiation of SGLT2is. This increase remained stable during the follow-up without differences among eGFR groups. No significant reduction in uricemia was observed. However, a trend towards a decrease was observed. (4) Conclusion: The use of SGLT2is in patients with CKD and T2DM is associated with an increase in uric acid FE, which maintains stability irrespective of glomerular filtration loss at least during 24 months of follow-up.

Transitions and Long-Term Clinical Outcomes in Patients Admitted in Intensive Care Units Receiving Continuous Renal Replacement Therapy.

Introduction: Acute kidney injury (AKI) significantly disrupts vital renal functions and is a common and serious condition in intensive care units (ICUs). AKI leads to extended hospital stays, increases mortality rates, and often necessitates nephrology consultations. Continuous renal replacement therapy (CRRT) plays a central role in managing AKI, requiring a multidisciplinary approach involving nephrologists, intensivists, and anesthesiologists. This study examines the clinical profile and progression of AKI in ICU patients requiring CRRT, with a focus on CRRT indications and modalities. Materials and Methods: We conducted a single-center retrospective observational study on ICU patients with AKI requiring CRRT from January to December 2019. AKI diagnosis followed the RIFLE criteria, and patients who received CRRT for less than 36 h were excluded. Data collected included demographics, hemodynamic parameters, and renal function parameters, with follow-ups at 1 week, 1 month, 6 months, and 12 months. Statistical analyses evaluated outcomes and transitions between CRRT and other renal replacement therapies. Results: Among 123 evaluated patients, 95 met inclusion criteria. Fifteen patients received CRRT for less than 36 h, with an early mortality rate of 80%. The final cohort comprised 80 patients who underwent CRRT for over 36 h, with a mean age of 65.3 years (SD = 13.6) and a Charlson index of 6.4. Patients were categorized based on primary diagnosis into heart failure, cardiac surgery, sepsis, other surgeries, and miscellanea groups. Mortality rates were highest in the heart failure and miscellanea groups. Significant variability was observed in therapy transitions and long-term outcomes. Continuous venovenous hemodiafiltration (CVVHDF) was the most frequently used CRRT modality. Conclusions: This study highlights the variability in CRRT practices and the poor prognosis for critically ill patients with AKI requiring CRRT. Timely nephrology consultation and tailored treatment plans may improve patient outcomes and optimize CRRT utilization. Future research should focus on refining CRRT protocols and exploring preventive strategies for AKI.

Anaemia and quality of life in chronic kidney disease: a consensus document from the European Anaemia of CKD Alliance.

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD-specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD.

A compact torsional reference device for easy, accurate and traceable AFM piconewton calibration.

The invention of the atomic force microscope led directly to the possibility of carrying out nanomechanical tests with forces below the nanonewton and the ability to test nanomaterials and single molecules. As a result there is a pressing need for accurate and traceable force calibration of AFM measurements that is not satisfactorily met by existing calibration methods. Here we present a force reference device that makes it possible to calibrate the normal stiffness of typical AFM microcantilevers down to 90 pN nm(-1) with very high accuracy and repeatability and describe how it can be calibrated traceably to the International System of Units via the ampere and the metre, avoiding in that way the difficulties associated with traceability to the SI kilogram. We estimate the total uncertainty associated with cantilever calibration including traceability to be better than 3.5%, thus still offering room for future improvement.

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease.

BACKGROUND: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). METHODS: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. RESULTS: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. CONCLUSIONS: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patients.

Standardizing health outcomes for chronic kidney disease. Adaptation of the international consortium for health outcomes measurement standard set to the Spanish setting.

BACKGROUND AND OBJECTIVES: We aim to adapt the International Consortium for Health Outcomes Measurements standard set for chronic kidney disease (CKD) patients to the Spanish setting and supplement it with those variables agreed upon through initiatives proposed by the Spanish Society of Nephrologists (S.E.N.). MATERIAL AND METHODS: The working group defined a first standard set of variables based on a literature review. The S.E.N. members then assessed the suitability of each variable for inclusion (Consensus≥75%). A second draft of the standard set was generated and evaluated by the Patient advocacy group Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón (ALCER). Lastly, the working group established the final standard set of variables (Consensus≥75%). RESULTS: The standard set targets patients with very high-risk CKD (G3a/A3 and G3b/A2-G5) in pre-end-stage kidney disease (pre-ESKD), hemodialysis (HD), peritoneal dialysis (PD), kidney transplantation (KT) or conservative care (CC). The essential follow-up variables agreed for all patients (All) were patient survival, hospitalizations, cardiovascular events, smoking status, health-related quality of life, pain, fatigue, physical function, daily activities, depression, renal function and hemoglobin. Additionally, it was agreed to collect PD survival (in PD patients), peritonitis (PD), infection/bacteremia (PD, HD, KT), vascular access type (HD), vascular access survival (HD), acute rejection (KT), post-transplant cancer (KT), albuminuria (KT) and kidney allograft survival (KT). The optional variables agreed were phosphorus (All), potassium (All), diabetes control (All with diabetes), and albuminuria (pre-ESKD). CONCLUSIONS: This standard set may constitute a highly efficient tool allowing the evaluation of patient outcomes and helping to define strategies to enhance CKD patients' quality of care in the Spanish healthcare system.