Liposomal iron in moderate chronic kidney disease

Introduction and objective: The optimal iron supplementation route of administration (intravenous vs. oral) in patients with chronic kidney disease (CKD) not on dialysis is a hot topic of debate. An oral preparation (liposomal iron, FeSu) has recently been developed with high bioavailability and low incidence of side effects. The objective was to evaluate the efficacy of FeSu in patients with stage 3 CKD and gastrointestinal intolerance to conventional oral iron therapy. Material and methods: Prospective observational study of patients with stable stage 3 CKD and gastrointestinal intolerance to conventional oral iron therapy. An oral 30 mg/day dose of FeSu was administered for 12 months. The primary outcome measure was hemoglobin increase at 6 and 12 months. Treatment adherence and adverse effects were also evaluated. Results: 37 patients aged 72.6 ± 14.7 years and with an estimated glomerular filtration rate (eGFR) of 42 ± 10 mL/min/1.73 m2 were included. 32 patients had received previous treatment with conventional oral formulations, 73% of which exhibited gastrointestinal intolerance with treatment adherence of 9.4%. After 6 months with FeSu, an increase in hemoglobin was observed versus baseline, which was sustained at 12 months (0.49 ± 0.19 and 0.36 ± 0.19 g/dL, respectively, p < 0.05), despite a significant eGFR decrease of 3.16 ± 1.16 and 4.20 ± 1.28 mL/min/1.73 m2 at 6 and 12 months, respectively. None of the patients experienced adverse reactions that required the treatment to be suspended. Adherence was 100% at both 6 and 12 months. Conclusions: FeSu is effective in a cohort of patients with stage 3 CKD with similar characteristics to the general population of moderate CKD patients, with a low rate of adverse reactions and excellent tolerability

High cut-off membrane for in- vivo dialysis of free plasma hemoglobin in a patient with massive hemolysis

Background: The possibility of clearing Cell-free Plasma Hemoglobin (CPH) from human plasma may appear attractive, especially when considering the noxious effects that CPH has on the immune function and the renal damage caused by its filtration. The existence of the so-called High Cut-Off (HCO) filters, possessing pores as big as 60 kDa, could potentially allow the clearance of the αβ dimers (31.3 kDa), the form in which the α2β2 hemoglobin tetramers (62.6 kDa) physiologically dissociate in plasma. We present herein the first reported case in which such an attempt was made. Case presentation: The patient was a 51-year-old man with hemolytic crisis due to glucose-6-phosphate dehydrogenase deficiency, further complicated by pigment-induced nephropathy. He underwent a 48-h CVVHD session, in which a HCO filter was used. The Sieving Coefficient (SC) for CPH was initially 0.08 and decreased to 0.02 after 24 h. This unexpected low SC was due to the initial high concentration of CPH (4.24 g/L). At such concentrations, the α2β2 tetramer poorly dissociates into the αβ dimer; but increases exponentially at concentrations lower than 1 g/L. Conclusions: Clearance of CPH through a HCO filter is technically feasible but its performance markedly relies on the initial concentration of CPH. Critically ill patients with smoldering hemolysis, as it happens during septic shock or ECMO treatment, may benefit the most from the use of this membrane in order to clear CPH

Rol de la resonancia magnética renal en la monitorización del aclaramiento de los depósitos de hemosiderina en la hemoglobinuria paroxística nocturna

La hemoglobinuria paroxística nocturna (HPN) es un trastorno secundario a la deficiencia de CD55 y CD59, proteínas de superficie reguladoras del complemento, resultando en hemólisis crónica mediada por el complemento1. La afectación renal oscila entre la lesión renal aguda durante las crisis hemolíticas, la disfunción tubular proximal (DTP) y la enfermedad renal crónica (ERC)2. La hemoglobinuria solo ocurre en el 25% de los pacientes3, en series recientes se ha reportado una incidencia del 64% de ERC, con hasta un 20% de ERC estadio 3-54. Se presentan 2 casos de HPN en el que los depósitos de hemosiderina visualizadas por resonancia magnética (IRM) parecen ser los primeros signos de afectación renal

Thrombotic microangiopathies assessment: mind the complement.

When faced withmicroangiopathic haemolytic anaemia, thrombocytopenia and organ dysfunction, clinicians should suspect thrombotic microangiopathy (TMA). The endothelial damage that leads to this histological lesion can be triggered by several conditions or diseases, hindering an early diagnosis and aetiological treatment. However, due to systemic involvement in TMA and its lowincidence, an accurate early diagnosis is often troublesome. In the last few decades,major improvements have been made in the pathophysiological knowledge of TMAs such as thrombotic thrombocytopenic purpura [TTP, caused by ADAMTS-13 (a disintegrin andmetalloproteinase with a thrombospondin Type 1motif,member 13) deficiency] and atypical haemolytic uraemic syndrome (aHUS, associated with dysregulation of the alternative complement pathway), together with enhancements in patientmanagement due to newdiagnostic tools and treatments. However, diagnosis of aHUS requires the exclusion of all the other entities that can cause TMA, delaying the introduction of terminal complement blockers, which have shown high efficacy in haemolysis control and especially in avoiding organ damage if used early. Importantly, there is increasing evidence that other forms of TMA could present overactivation of the complement system, worsening their clinical progression. This review addresses the diagnostic and therapeutic approach when there is clinical suspicion of TMA, emphasizing complement evaluation as a potential tool for the inclusive diagnosis of aHUS, as well as for the improvement of current knowledge of its pathophysiological involvement in other TMAs. The development of both new complement activation biomarkers and inhibitory treatments will probably improve themanagement of TMA patients in the near future, reducing response times and improving patient outcomes

The Renal Range of the κ/λ sFLC Ratio: Best Strategy to Evaluate Multiple Myeloma in Patients With Chronic Kidney Disease

Background: Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD. Methods: Serum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90). Results: In the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/ min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82-3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84-0.97) compared with the current ranges proposed by Katzmann and Hutchinson. Conclusions: This study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82-3,6) for eGFR ≤55 ml/ min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies

Risk Factors for Acute Kidney Injury Following Cardiac Surgery and Performance of Leicester Score in a Spanish Cohort

The incidence of acute kidney injury following cardiac surgery (CSA-AKI) is up to 30%, and it places patients at an increased risk of death. The Leicester score (LS) is a new score that predicts CSA-AKI of any stage with better discrimination compared to previous scores. The aim of this study was to identify risk factors for CSA-AKI and to assess the performance of LS. A unicentric retrospective study of patients that required cardiac surgery with cardio-pulmonary bypass (CPB) in 2015 was performed. The inclusion criteria were patients over 18 years old who were operated on for cardiac surgery (valve substitution (VS), Coronary Artery Bypass Graft (CABG), or a combination of both procedures and requiring CPB). CSA-AKI was defined with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. In the multivariate analysis, hypertension (odds ratio 1.883), estimated glomerular filtration rate (EGFR) <60 mL/min (2.365), and peripheral vascular disease (4.66) were associated with the outcome. Both discrimination and calibration were better when the LS was used compared to the Cleveland Clinic Score and Euroscore II, with an area under the curve (AUC) of 0.721. In conclusion, preoperative hypertension in patients with CKD with or without peripheral vasculopathy can identify patients who are at risk of CSA-AKI. The LS was proven to be a valid score that could be used to identify patients who are at risk and who could benefit from intervention studies

Tratamiento de la hiponatremia secundaria al síndrome de secreción inadecuada de la hormona antidiurética: algoritmo multidisciplinar

Introducción: El síndrome de secreción inadecuada de la hormona antidiurética (SIADH) es la causa más frecuente de hiponatremia en el paciente hospitalizado. Sin embargo, faltan protocolos y algoritmos concretos que faciliten su abordaje terapéutico. Nuestro objetivo fue el desarrollo de dos algoritmos de tratamiento de la hiponatremia secundaria al SIADH en el paciente ingresado. Material y método: Un grupo multidisciplinar español compuesto por 2 especialistas en Endocrinología, 1 en Farmacia Hospitalaria, 2 en Medicina Interna y 2 en Nefrología se reunieron durante un año, bajo la tutela del grupo español del European Hyponatremia Network, y de las respectivas sociedades científicas españolas. Las pautas terapéuticas propuestas fueron basadas en recomendacio- nes ampliamente aceptadas, la práctica de expertos, guías de consenso, así como en la experiencia clínica de los autores. Resultados: Se elaboraron dos algoritmos de tratamiento. El Algoritmo 1 se dirige al tratamiento de la hiponatremia aguda como urgencia médica de abordaje inmediato, y es de aplicación al tratamiento de la hiponatremia grave tanto de tipo euvolémico como hipovolémico. Se basa en el uso de sueros salinos hipertónicos al 3 % i.v., con pautas de infusión y monitorización. Se expone cómo evitar la hipercorrección de la natremia y cómo corregirla en su caso. El Algoritmo 2 aborda el tratamiento de la hiponatremia no aguda leve o moderada asociada al SIADH. Expone cómo y cuándo usar la restricción hídrica, solutos, furosemida y tolvaptán, para alcanzar eunatremia en el paciente con SIADH. Conclusiones: Se han elaborado dos estrategias complementarias para el tratamiento de la hiponatremia inducida por SIADH, en un intento de fomentar la toma de conciencia acerca de esa patología, simplificar su abordaje y su tratamiento y, así, mejorar su pronóstico

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. Methods: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Results: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). Conclusion: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). We pre­sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components