Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study.

RATIONALE & OBJECTIVE: Chronic kidney disease of unknown etiology (CKDUE) is one of the main global causes of kidney failure. Genetic studies may identify an etiology in these patients, but few studies have implemented genetic testing of CKDUE in a population-based series of patients, which was the focus of the GENSEN Study. STUDY DESIGN: Case series. SETTINGS & PARTICIPANTS: 818 patients aged≤45 years at 51 Spanish centers with CKDUE, and either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation. OBSERVATIONS: Genetic testing for 529 genes associated with inherited nephropathies using high-throughput sequencing (HTS). Pathogenic and/or likely pathogenic (P/LP) gene variants concordant with the inheritance pattern were detected in 203 patients (24.8%). Variants in type IV collagen genes were the most frequent (COL4A5, COL4A4, COL4A3; 35% of total gene variants), followed by NPHP1, PAX2, UMOD, MUC1, and INF2 (7.3%, 5.9%, 2.5%, 2.5%, and 2.5%, respectively). Overall, 87 novel variants classified as P/LP were identified. The top 5 most common previously undiagnosed diseases were Alport syndrome spectrum (35% of total positive reports), genetic podocytopathies (19%), nephronophthisis (11%), autosomal dominant tubulointerstitial kidney disease (7%), and congenital anomalies of the kidney and urinary tract (CAKUT, 5%). A family history of kidney disease was reported by 191 participants (23.3%) and by 65 of 203 patients (32.0%) with P/LP variants. LIMITATIONS: Missing data, and selection bias resulting from voluntary enrollment. CONCLUSIONS: Genomic testing with HTS identified a genetic cause of kidney disease in approximately one quarter of young patients with CKDUE and advanced kidney disease. These findings suggest that genetic studies are a potentially useful tool for the evaluation of people with CKDUE. PLAIN-LANGUAGE SUMMARY: The cause of kidney disease is unknown for 1 in 5 patients requiring kidney replacement therapy, reflecting possible prior missed treatment opportunities. We assessed the diagnostic utility of genetic testing in children and adults aged≤45 years with either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation. Genetic testing identified the cause of kidney disease in approximately 1 in 4 patients without a previously known cause of kidney disease, suggesting that genetic studies are a potentially useful tool for the evaluation of these patients.

The kidney-skeletal muscle-heart axis in chronic kidney disease: implications for myokines.

Myokines are signalling moieties released by the skeletal muscle in response to acute and/or chronic exercise, which exert their beneficial or detrimental effects through paracrine and/or autocrine pathways on the own muscle and through endocrine pathways in many other organs (e.g. the heart). Interestingly, alterations in myokines have been described in patients with heart failure (HF) that are associated with adverse structural and functional left ventricular remodelling and poor cardiac outcomes. Recent experimental and clinical studies have shown that the muscle regulation of a number of myokines is altered in chronic kidney disease (CKD) thus representing a new molecular aspect of the pathophysiology of skeletal myopathy present in patients with CKD. Muscle dysregulation of myokines may contribute to a number of disorders in non-dialysis and dialysis patients with CKD, including the high risk of developing HF. This possibility would translate into a range of new diagnostic and therapeutic options. In fact, the measurement of circulating myokines opens their possible usefulness as biomarkers to personalize exercise training and pharmacological therapies for the prevetion and treatment of HF in patients with CKD and skeletal myopathy. This review will analyze information on some myokines that target the heart and are altered at the level of skeletal muscle and circulation in patients with CKD.

Selective glomerular hypofiltration syndrome.

The estimated glomerular filtration rate (eGFR) provides insight into cardiovascular disease (CVD) risk stratification and proactive management. Accumulating evidence suggests that combining eGFR calculated from serum cystatin C (eGFRcys) and from serum creatinine (eGFRcrea) improves CVD risk stratification over eGFRcrea alone. The term selective glomerular hypofiltration syndrome (SGHS) or shrunken pore syndrome has been proposed to define an eGFRcys:eGFRcrea ratio <1, which is hypothesized to result from a reduced glomerular filtration of 5- to 30-kDa molecules as compared with smaller molecules. SGHS may be identified in people with normal or reduced measured GFR, but the prevalence depends on the cut-off value of the eGFRcys:eGFRcrea ratio used, which is not yet standardized. SGHS is strongly associated with increased CVD and mortality risks and it may offer an opportunity to expand our understanding of the mechanisms linking GFR disorders with CVD risk (e.g. an altered plasma proteome), which may guide treatment decisions. However, muscle wasting may also contribute to a reduced eGFRcys:eGFRcrea ratio and there are open questions regarding the pathophysiology of a reduced eGFRcys:eGFRcrea ratio, the reference cut-off values of the ratio to define the syndrome and its clinical implications. We now critically review the SGHS concept, its pathophysiological basis and links to CVD and the potential consequences for clinical practice and propose a research agenda.

Humoral response after the fourth dose of the SARS-CoV-2 vaccine in the CKD spectrum: a prespecified analysis of the SENCOVAC study.

BACKGROUND: There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity. RESULTS: Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titres in HD (P = .001) and ND-CKD (P = .014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titres at 12 months were independently associated with repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titres and not being a KT recipient. Breakthrough COVID-19 was registered in 137 (6%) patients, 5% of whom required admission. Admitted patients had prior titres <620 UI/ml and median values were lower (P = .020) than in non-admitted patients. CONCLUSIONS: A fourth vaccine dose increased anti-Spike antibody titres or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titres or KT recipients) derived the least benefit in terms of antibody titres. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titres.

Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients: the SENCOVAC study.

BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe coronavirus disease 2019 (COVID-19). The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in CKD patients. Safety and immediate humoral response results are reported here. METHODS: Four cohorts of patients were included: kidney transplant (KT) recipients, and haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on Day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analysed. RESULTS: A total of 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (P < 0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated with KT (odds ratio 20.56, P = 0.001) and with BNT162b2 vaccine (odds ratio 6.03, P = 0.023). CONCLUSION: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Potential differences between COVID-19 vaccines should be explored in prospective controlled studies.

Persistent kidney dysfunction after acute kidney injury predicts short-term outpatient mortality.

BACKGROUND: Acute kidney injury (AKI) during hospitalisation is frequent and associated with adverse outcomes. AIMS: To evaluate the association between renal function recovery after AKI and short-term post-discharge mortality. METHODS: This is a retrospective study of all AKI episodes codified in the electronic records of a single centre in 2013 and 2014. Epidemiological data and comorbidities at baseline and laboratory values at admission and discharge were collected. Persistent kidney dysfunction after AKI was defined as a last serum creatinine equal or above 1.2-fold over baseline level. Patients were followed for 30 days after discharge. RESULTS: Out of 1720 evaluated patients, 1541 (89%) were analysed. Of them, 869 (56%) recovered renal function. Independent predictors of renal function recovery after AKI were lower baseline estimated glomerular filtration rate (eGFR) (P < 0.001), higher admission eGFR (P < 0.001) and haemoglobin (P = 0.016), milder AKI (P = 0.037), absence of a history of heart failure (P < 0.001) and lower admission blood pressure (P < 0.001). After discharge, 46 (3%) patients died in the first 30 days. Persistent kidney dysfunction was associated (P = 0.01) with and independently predicted (odds ratio 2.6; 95% confidence interval 1.2-5.4; P = 0.01) short-term post-discharge mortality. CONCLUSIONS: Persistent kidney dysfunction after an AKI episode is an independent predictor of 30-day post-discharge mortality. This information might help select AKI patients who require closer follow up and monitoring after discharge.

Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease Progression in Chronic Kidney Disease Patients: a Multicenter Randomized Clinical Trial (AASER Study).

BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular events. However, limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression. STUDY DESIGN: Prospective, multicenter, open-label randomized controlled trial. SETTING AND PARTICIPANTS: One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73 m2 without previous cardiovascular events. INTERVENTION: Aspirin treatment (100 mg/day) (n = 50) or usual therapy (n = 61). Mean follow-up time was 64.8 ± 16.4 months. OUTCOMES: The primary endpoint was composed of cardiovascular death, acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral arterial disease. Secondary endpoints were fatal and nonfatal coronary events, renal events (defined as doubling of serum creatinine, ≥ 50% decrease in eGFR, or renal replacement therapy), and bleeding episodes. RESULTS: During follow-up, 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups, respectively. Aspirin did not significantly reduce primary composite endpoint (HR, 0.396 (0.146-1.076), p = 0.069. Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group. Aspirin significantly reduced the risk of coronary events (log-rank, 5.997; p = 0.014). Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group. Aspirin treatment decreased renal disease progression in a model adjusted for age, baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077-0.955; p = 0.043) but did not when adjusted for albuminuria. No differences were found in minor bleeding episodes between groups and no major bleeding was registered. LIMITATIONS: Small sample size and open-label trial. CONCLUSIONS: Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint; however, there were reductions in secondary endpoints with fewer coronary events and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.

Pulmonary Hypertension Is Associated with Mortality and Cardiovascular Events in Chronic Kidney Disease Patients.

BACKGROUND: We evaluated the prevalence, determinants and prognosis value of pulmonary hypertension (PH) in non-dialysis chronic kidney disease (CKD) patients. METHODS: This is a prospective study with stages 3-5 non-dialysis-dependent CKD patients. PH was estimated by Doppler echocardiography and defined as a pulmonary artery systolic pressure above 35 mm Hg. RESULTS: Three hundred fifty-three patients were recruited, of whom 94 (26.6%) had PH. Prevalence of PH increased with the decline of renal function: 21.6, 24.1, and 31.7% in stages 3, 4, and 5, respectively. Independent predictors of PH were age, estimated glomerular filtration rate (eGFR), history of cardiovascular (CV) events, the presence of an arteriovenous fistulae (AVF), and left ventricular (systolic and diastolic) dysfunction. Over a median follow-up of 22 months, 71 patients died (20%). After multivariate adjustment for age, gender, previous CV disease, diastolic and systolic dysfunction, PH remained as an independent predictor of all-cause mortality (hazards ratio [HR] 1.84, 95% CI 1.06-3.18, p = 0.02). One hundred patients (28%) had a new onset CV event. After adjustment for age, gender, previous CV disease, systolic and diastolic dysfunction, PH maintains its independent association with CV events (HR 2.77, 95% CI 2.00-3.25, p < 0.001). CONCLUSIONS: PH prevalence rises as kidney function declines. Main determinants of PH are age, eGFR, previous CV disease, the presence of an AVF and left ventricular systolic or diastolic dysfunction. PH is an independent predictor of all-cause mortality and CV events.

Cytomegalovirus encephalitis in a hemodialysis patient: a rare association.

Haemodialysis patients are at greater risk of infections than individuals not on dialysis due to their immunosuppressive state caused by several factors (uraemia, vascular access, inflammation, malnutrition). However, infections affecting the central nervous system are not frequent in this population. We present the case of a 77-year-old man with end-stage renal disease who was admitted to the emergency department for a decreased level of consciousness and fever. Although the initial clinical suspicion oriented to a urinary infection, the lack of improvement forced us to perform a lumbar puncture. Five days after cerebrospinal fluid was cultured, cytomegalovirus was isolated and ganciclovir initiated.

Pulmonary hypertension is an independent predictor of cardiovascular events and mortality in haemodialysis patients.

AIM: The evidence about prevalence, associated factors of pulmonary hypertension (PH) and its impact on patient's outcomes is limited. METHODS: We included 211 haemodialysis patients, we estimated the systolic pulmonary artery pressure (SPAP) by 2D Doppler echocardiography defining PH as a SPAP above 35 mmHg, the median follow-up was 39 (19-56) moths, and the primary endpoints were all cause mortality and cardiovascular events. RESULTS: We found PH in 91 patients (43.9%). Independent determinants of PH were age, previous cardiovascular disease, the Nt-pro-BNP level hs-TnT, the systolic dysfunction, diastolic dysfunction and left ventricular hypertrophy. Over the follow-up 94 cardiovascular events occurred, variables associated were: PH, age, history cardiovascular disease, dyslipidaemia, elevated concentration of Nt-pro-BNP and hs-TnT, systolic and diastolic dysfunction, in a multivariate model, the PH maintained its independent association. Mortality data: 88 patients died (41.7%); 35 (29.5%) in the no PH group and 53 (58.5%) in the PH group (P < 0.001). In the Cox survival analysis, we found an association between mortality and age, previous cardiovascular disease, history of peripheral vascular disease, Nt-pro-BNP levels. In a multivariate model the PH remains as independent predictor of mortality. CONCLUSIONS: Pulmonary hypertension is a common finding in HD patients and a valuable predictor of mortality and cardiovascular events. Prospective studies are needed to assess the effect of intervention on risk factors in improving patient's outcomes.

Interarm systolic blood pressure as a predictor of cardiovascular events in patients with chronic kidney disease.

BACKGROUND: Increased interarm systolic blood pressure difference (IASBPD) is associated with mortality and cardiovascular (CV) events both in the general population and in patients at high CV risk. The aim of the present study was to assess the value of IASBPD ≥ 10 mmHg for predicting CV events in patients with chronic kidney disease (CKD). METHODS: The study sample comprised 652 patients with CKD (age 67 ± 15 years, 58.1% men). Follow-up was 19 ± 5 months. We recorded increased IASBPD and related factors and assessed the predictive value of this variable for CV events. RESULTS: We recorded diabetes mellitus in 136 patients (20.8%), history of CV disease in 213 (32.6%) and dyslipidaemia in 327 (50.1%). The mean glomerular filtration rate was 45.9 ± 18.9 mL/min/1.73 m(2), and the median albumin/creatinine ratio was 26(0-151) mg/g. IASBPD was ≥10 mmHg in 184 patients (28.1%). The factors associated with IASBPD ≥10 mmHg were age, systolic blood pressure levels, history of congestive heart failure, lower levels of high-density lipid cholesterol and higher use of hypertensive drugs. Fifty-eight patients (8.5%) developed a CV event during the follow-up. IASBPD ≥10 mmHg [HR, 1.802, 95%CI (1.054-3.079); P = 0.031] was an independent predictor of CV events. CONCLUSIONS: Increased IASBPD is an independent predictor of CV events in CKD patients.

Body Composition Affects Urea Distribution Volume Estimated by Watson's Formula.

OBJECTIVE: Dialysis machines use the Watson formula (Vwatson) to estimate the urea distribution volume (UDV) to calculate the online Kt/V for each dialysis session. However, the equation could give rise to inaccuracies. The present study analyzes whether body composition affects UDV estimated by Vwatson in comparison to bioimpedance spectroscopy (Vbis) as the reference method. DESIGN: This is a transversal study performed in the setting of a hemodialysis unit. SUBJECTS: Prevalent hemodialysis patients. INTERVENTION: The same day, UDV was measured using Vwatson and Vbis. We compared their results. MAIN OUTCOME MEASURE: Differences between UDV using Watson equation and Vbis. RESULTS: We included 144 prevalent patients. Vwatson overestimated the volume with regard to Vbis (Vwatson - Vbis) by 2.5 L (1.8 L; P = .001). We found an excellent correlation between the 2 methods. A higher mean Vwatson - Vbis value was correlated to older age (P = .03), body mass index (P = .01), fat tissue index (P = .001), lower lean tissue index (P = .001), lower extracellular water (P = .01), and intracellular water (P = .001). CONCLUSION: Body composition affects UDV estimated by Vwatson, thus modifying the result of Kt/V. In young patients who present more lean tissue and less fat tissue, Kt/V is underestimated with Vwatson.

Body composition affects the response to erythropoiesis-stimulating agents in patients with chronic kidney disease in dialysis.

BACKGROUND: The response to erythropoiesis-stimulating agents (ESA) in patients with chronic kidney disease (CKD) is variable. The body mass index (BMI) variations can modify the response to ESA. The objective was to assess the effect of body composition on the response to ESA in dialysis patients. METHODS: This is an observational cross-sectional study. Prevalent hemodialysis and peritoneal dialysis (PD) patients were selected. In the same day, a single blood test, a body composition analysis using bioimpedance spectroscopy and anthropometric measurements were performed. We collected ESA doses. We analyzed erythropoietin resistance index (ERI). The ERI was calculated dividing the weekly weight-adjusted (kg) dose of ESA (IU) by the hemoglobin level (g/dL). RESULTS: The study was comprised of 218 patients (58% men; age 65 (16) years old; 80% hemodialysis, 20% PD). There was an inverse correlation between ERI and BMI (p=0.01), fat tissue index (FTI) (p=0.01) and prealbumin (p=0.04). We found an independent association between higher ERI levels and lower FTI and prealbumin values. CONCLUSION: Response to ESA is influenced by body composition. Fat tissue favors the body's response to ESA.

Strategies for prevention and treatment of SARS-COV-2 infection in patients with chronic kidney disease: Literature review.

COVID-19 has proven to be particularly aggressive in patients with chronic kidney disease (CKD). The lower immune response rate and the greater susceptibility to progress to severe forms of the disease have contributed to this phenomenon, which has persisted in the post-vaccination era of the pandemic. Paradoxically, CKD has been excluded from most clinical trials of the main therapeutic tools developed against SARS-CoV-2. However, experience in the use of these drugs has been accumulating in different stages of CKD, supporting their use with guarantees of efficacy and safety. The objective of this review is to gather all treatment indications for COVID-19 in the different phases of the disease, tailored to CKD in its various stages, including renal replacement therapy.

Genetic study in young patients with chronic kidney disease stage G5 from unknown etiology. The GENSEN study design.

INTRODUCTION: Chronic kidney disease (CKD) of non-inherited etiology is one of the main causes of renal replacement therapy in our setting. Previous studies in other territories suggest that hereditary diseases could be one of the potential causes of this pathology, especially in younger patients. The GENSEN study will evaluate the presence of pathogenic genetic variants in subjects who have developed CKD category G5 before the age of 46 years, of non-inherited etiology. METHODS: Observational, prospective, multicenter study, which evaluates the diagnostic utility of massive high-throughput sequencing (HTS) directed to a set of genes, in the identification of the cause of CKD. Patients from all over Spain will be included, from whom a blood or saliva sample will be taken and a panel of 529 genes associated with hereditary kidney disease will be analyzed. This publication communicates the study protocol. CONCLUSION: The GENSEN study will make it possible to evaluate the diagnostic performance of the gene panel study in young subjects in our setting with the development of CKD category G5 without a clear cause. An etiological diagnosis would offer potential benefits for patients and relatives (targeted therapies, clinical trials, detection of extrarenal manifestations, evaluation of relatives for live donation, estimation of the risk of recurrence in the renal graft, genetic counseling, among others) and would allow to apply this genetic study to the nephrology of our country.

AKI development is an independent predictor of mortality in infective endocarditis.

INTRODUCTION: Infective endocarditis presents a 25% mortality. Acute kidney injury (AKI) develops in up to 70% of the cases. The aim of this study is to evaluate the predictive value of AKI in mortality due to endocarditis and to assess its associated factors. METHODS: Unicentric and retrospective study including all patients with in-hospital diagnosis of endocarditis between 2015 and 2021. Epidemiological data and comorbidities were collected at baseline. During admission, renal function parameters, infection-related variables and mortality were collected. Using adjusted multivariate models, LRA predictive value was determined. RESULTS: One hundred and thirty-four patients (63% males, age 72±15 years) were included. Of them 94 (70%) developed AKI (50% AKIN-1, 29% AKIN-2 and 21% AKIN-3). Factors associated to AKI were age (p=0.03), hypertension (p=0.005), previous chronic kidney disease (p=0.001), heart failure (p=0.006), peripheral vascular disease (p=0.022) and glomerular filtration rate (GFR) at baseline (p<0.001). GFR at baseline was the only factor independently associated to AKI (OR 0.94, p=0.001). In-hospital deaths were registered in 46 (34%) patients. Of them, 45 (98%) patients had developed AKI. AKI was independently associated to mortality through diverse multivariate models. GFR loss (OR 1.054, p<0.001) and GFR at baseline (0.963, p=0.012) also predicted mortality during admission. CONCLUSIONS: AKI development and its severity (GFR loss and AKIN severity) impacts in in-hospital mortality due to infective endocarditis.

Practical Approaches to the Management of Cardiorenal Disease beyond Congestion.

BACKGROUND: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. SUMMARY: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. KEY MESSAGES: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.

Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).