Acute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome.

Acute kidney injury (AKI) in patients with cirrhosis is a diagnostic challenge due to multiple and sometimes overlapping possible etiologies. Many times, diagnosis cannot be made based on case history, physical examination or laboratory data, especially when the nephrologist is faced with AKI with a hemodynamic basis, such as hepatorenal syndrome. In addition, the guidelines still include generalized recommendations regarding withdrawal of diuretics and plasma volume expansion with albumin for 48 h, which may be ineffective and counterproductive and may have iatrogenic effects, such as fluid overload and acute cardiogenic pulmonary edema. For this reason, the use of new tools, such as hemodynamic point-of-care ultrasound (PoCUS), allows us to phenotype volume status more accurately and ultimately guide medical treatment in a noninvasive, rapid and individualized manner.

Medicina de precisión: «Point of Care Ultrasound» (PoCUS) en el abordaje diagnóstico del paciente con hiponatremia / Precision medicine: “Point of Care Ultrasound” (PoCUS) in the diagnostic approach to the patient with hyponatremia

La hiponatremia es un trastorno multifactorial definido como una disminución en la concentración plasmática de sodio. Su diagnóstico diferencial requiere una evaluación adecuada del volumen extracelular. Sin embargo, la determinación del volumen extracelular, simplemente basada en la historia clínica, las constantes vitales, el examen físico y los hallazgos de laboratorio, conducen en ocasiones a un diagnóstico erróneo por lo que el enfoque terapéutico puede ser equivocado. El empleo de ecografía a pie de cama (Point-of-Care Ultrasound [PoCUS]), mediante la combinación de ecografía pulmonar (Lung Ultrasound [LUS]), Venous Excess UltraSound (VExUS) y la ecocardioscopia (Focused Cardiac Ultrasound [FoCUS]) permiten, en combinación con el resto de los parámetros, una valoración holística mucho más precisa del estado del volumen extracelular del paciente.(AU)

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume. However, extracellular volume determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (PoCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's extracellular volume status in combination with the other parameters.(AU)

Urinary cell cycle arrest biomarkers and diuretic efficiency in acute heart failure.

Introduction This study aimed to evaluate the association between the NephroCheck ® Test AKIRisk® Score, diuretic efficiency (DE) and the odds of worsening kidney function (WKF) within the first 72 hours of admission in patients hospitalized for acute heart failure (AHF). Methods The study prospectively enrolled 125 patients admitted with AHF. NephroCheck ® Test was obtained within the first 24 of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents. Results The median AKIRisk® Score was 0.11 (IQR 0.06-0.34) and 38 (30.4%) patients had an AKIRisk® Score >0.3. The median cumulative DE at 72 hours was 1963 mL (IQR 1317-3239 ml). At 72 hours, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariate setting, there was an inverse association between the AKIRisk® Score and DE within the first 72 hours. In fact, the highest the AKIRisk® Score (centered at 0.3) the higher the likelihood of poor diuretic efficiency (below the median) and WKF at 72 hours (Odds Ratio [OR] 2.04; 95%; CI 1.02-4.07; p=0.043, and OR 3.31, 95% CI 1.30-8.43; p = 0.012, respectively). Conclusion In patients with AHF, a higher NephroCheck ® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 hours. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario.

Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

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.

Trajectories of Kidney Function in Heart Failure Over a 15-Year Follow-Up: Clinical Profiling and Mortality.

BACKGROUND: Limited data are available on the long-term trajectory of estimated glomerular filtration rate (eGFR) in patients with chronic heart failure. OBJECTIVES: The authors evaluated eGFR dynamics using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation and its prognostic significance in a real-world cohort over a 15-year follow-up. METHODS: A prospective observational registry of ambulatory heart failure outpatients was conducted, with regular eGFR assessments at baseline and on a 3-month schedule for ≤15 years. Urgent kidney function assessments were excluded. Locally weighted error sum of squares curves were plotted for predefined subgroups. Multivariable longitudinal Cox regression analyses were conducted to assess associations with all-cause and cardiovascular death. RESULTS: A total of 2,672 patients were enrolled consecutively between August 2001 and December 2021. The average age was 66.8 ± 12.6 years, and 69.8% were men. Among 40,970 creatinine measurements, 28,634 were used for eGFR analysis, averaging 10.7 ± 8.5 per patient. Over the study period, a significant decline in eGFR was observed in the entire cohort, with a slope of -1.70 mL/min/1.73 m2 per year (95% CI: -1.75 to -1.66 mL/min/1.73 m2 per year). Older patients, those with diabetes, a preserved ejection fraction, a higher baseline eGFR, elevated hospitalization rates, and those who died during follow-up experienced more pronounced decreases in the eGFR. Moreover, the decrease in kidney function correlated independently with all-cause mortality and cardiovascular death. CONCLUSIONS: These findings highlight the sustained decline in eGFR over 15 years in patients with heart failure, with variations based on clinical characteristics, and emphasize the importance of regular eGFR monitoring in this population.

Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk.

Kidneys have an amazing ability to adapt to adverse situations, both acute and chronic. In the presence of injury, the kidney is able to activate mechanisms such as autoregulation or glomerular hyperfiltration to maintain the glomerular filtration rate (GFR). While these adaptive mechanisms can occur in physiological situations such as pregnancy or high protein intake, they can also occur as an early manifestation of diseases such as diabetes mellitus or as an adaptive response to nephron loss. Although over-activation of these mechanisms can lead to intraglomerular hypertension and albuminuria, other associated mechanisms related to the activation of inflammasome pathways, including endothelial and tubular damage, and the hemodynamic effects of increased activity of the renin-angiotensin-aldosterone system, among others, are recognized pathways for the development of albuminuria. While the role of albuminuria in the progression of chronic kidney disease (CKD) is well known, there is increasing evidence of its negative association with cardiovascular events. For example, the presence of albuminuria is associated with an increased likelihood of developing heart failure (HF), even in patients with normal GFR, and the role of albuminuria in atherosclerosis has recently been described. Albuminuria is associated with adverse outcomes such as mortality and HF hospitalization. On the other hand, it is increasingly known that the systemic effects of congestion are mainly preceded by increased central venous pressure and transmitted retrogradely to organs such as the liver or kidney. With regard to the latter, a new entity called congestive nephropathy is emerging, in which increased renal venous pressure can lead to albuminuria. Fortunately, the presence of albuminuria is modifiable and new treatments are now available to reverse this common risk factor in the cardiorenal interaction.

Effect on Kidney Function Recovery Guiding Decongestion with VExUS in Patients with Cardiorenal Syndrome 1: A Randomized Control Trial.

INTRODUCTION: In cardiorenal syndrome type 1 (CRS1), vascular congestion is central to the pathophysiology of heart failure and thus a key target for management. The venous evaluation by ultrasound (VExUS) system could guide decongestion effectively and thereby improve outcomes. METHODS: In this randomized clinical trial, patients with CRS1 (i.e., increase in creatinine ≥0.3 mg/dL) were randomized to guide decongestion with VExUS compared to usual clinical evaluation. The primary endpoint was to assess kidney function recovery (KFR), and the key secondary endpoint was decongestion evaluated by physical examination and changes in brain natriuretic peptide (BNP) and CA-125. Exploratory endpoints included days of hospitalization and mortality. RESULTS: From March 2022 to February 2023, a total of 140 patients were randomized 1:1 (70 in the VExUS and 70 in the control group). KFR was not statistically different between groups. However, VExUS improved more than twice the odds to achieve decongestion (odds ratio [OR]: 2.6, 95% CI: 1.9-3.0, p = 0.01) and the odds to reach a decrease of BNP >30% (OR: 2.4, 95% CI: 1.3-4.1, p = 0.01). The survival at 90 days, recongestion, and CA-125 were similar between groups. CONCLUSION: In patients with CRS1, we observed that VExUS-guided decongestion did not improve the probability of KFR but improved the odds to achieve decongestion.

Bedside Ultrasound in the Management of Cardiorenal Syndromes: An Updated Review.

BACKGROUND: Cardiorenal syndromes constitute a spectrum of disorders involving heart and kidney dysfunction modulated by a complex interplay of neurohormonal, inflammatory, and hemodynamic derangements. The management of such patients often poses a diagnostic and therapeutic challenge to physicians owing to gaps in understanding of pathophysiology, paucity of objective bedside diagnostic tools, and individual biases. SUMMARY: In this narrative review, we discuss the role of clinician who performed bedside ultrasound in the management of patients with cardiorenal syndromes. Novel sonographic applications such as venous excess ultrasound score (VExUS) are reviewed in addition to the lung and focused cardiac ultrasound. Further, underrecognized causes of heart failure such as high-flow arteriovenous fistula are discussed. KEY MESSAGE: Bedside ultrasound allows a comprehensive hemodynamic characterization of cardiorenal syndromes.

Kidney function changes in acute heart failure: a practical approach to interpretation and management.

Worsening kidney function (WKF) is common in patients with acute heart failure (AHF) syndromes. Although WKF has traditionally been associated with worse outcomes on a population level, serum creatinine concentrations vary greatly during episodes of worsening heart failure, with substantial individual heterogeneity in terms of their clinical meaning. Consequently, interpreting such changes within the appropriate clinical context is essential to unravel the pathophysiology of kidney function changes and appropriately interpret their clinical meaning. This article aims to provide a critical overview of WKF in AHF, aiming to provide physicians with some tips and tricks to appropriately interpret kidney function changes in the context of AHF.

Is there a role in acute kidney injury for FGF23 and Klotho?

Cardio-renal syndrome is a clinical condition that has recently been well defined. In acute kidney disease, this interaction might trigger chronic processes determining the onset of cardiovascular events and the progression of chronic kidney disease. Moreover, the high mortality rate of acute kidney injury (AKI) is also linked to the fact that this condition is often complicated by dysfunctions of other organs such as lungs or heart, or is associated with septic episodes. In this context the role and the potential link between bone, heart and kidney is becoming an important topic of research. The aim of this review is to describe the cardiac alterations in the presence of AKI (cardiorenal syndrome type 3) and explore how bone can interact with heart and kidney in determining and influencing the trend of AKI in the short and long term. The main anomalies of mineral metabolism in patients with AKI will be reported, with specific reference to the alterations of fibroblast growth factor 23 and Klotho as a link between the bone-kidney-heart axis.

Changes in Doppler-Derived Kidney Venous Flow and Adverse Cardiorenal Outcomes in Patients With Heart Failure.

Background The impact of changes in Doppler-derived kidney venous flow in heart failure (HF) is not well studied. We aimed to investigate the association of Doppler-derived kidney venous stasis index (KVSI) and intrakidney venous-flow (IKVF) patterns with adverse cardiorenal outcomes in patients with HF. Methods and Results In this observational cohort study, consecutive inpatients with HF referred to a nephrologist because of a history of diuretic resistance and abnormal kidney function (n=216) underwent spectral kidney assessments after admission (Doppler 1) and 25 to 35 days later (Doppler 2) to identify IKVF patterns (continuous/pulsatile/biphasic/monophasic) and KVSI levels. Cox proportional hazard regression models were used to evaluate the associations between KVSI/IKVF patterns at Doppler 1 as well as changes from Doppler 1 to Doppler 2 and risk of cardiorenal events up to 18 months after admission. Worsening HF or death occurred in 126 patients. Both baseline KVSI (hazard ratio [HR], 1.49 [95% CI, 1.37-1.61] per 0.1-unit increase) and baseline IKVF pattern (HR, 2.47 [95% CI, 2.01-3.04] per 1 pattern severity increase) were significantly associated with worsening HF/death. Increases in both KVSI and IKVF pattern severity from Doppler 1 to 2 were also associated with an increased risk of worsening HF/death (HR, 3.00 [95% CI, 2.08-4.32] per 0.1-unit increase change; and HR, 6.73 [95% CI, 3.27-13.86] per 1 pattern increase in severity change, respectively). Similar results were observed for kidney outcomes. Conclusions Baseline kidney venous flow predicted adverse cardiorenal events, and inclusion of serial kidney venous flow in cardiorenal risk stratification could facilitate clinical decision-making for patients with HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03039959.

Valvular heart disease in patients on kidney replacement therapy: "opening Pandora's box".

Valvular heart disease (VHD) is highly prevalent among dialysis patients, affecting up to 30%-40% of the population. Aortic and mitral valves are the most frequently affected and commonly lead to valvular stenosis and regurgitation. Although it is well established that VHD is associated with a high morbimortality burden, the optimal management strategy remains unclear, and treatment options are limited due to the high risk of complications and mortality after surgical and transcatheter interventions. In this issue of Clinical Kidney Journal, Elewa et al. provide new evidence in this field by reporting the prevalence and associated outcomes of VHD in patients with kidney failure on renal replacement therapy.

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines.

Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

PoCUS in nephrology: a new tool to improve our diagnostic skills.

Point-of-Care Ultrasonography (PoCUS) aims to include a fifth pillar (insonation) in the classical physical examination in order to obtain images to answer specific questions by the clinician at the patient's bedside, allowing rapid identification of structural or functional abnormalities, enabling more accurate volume assessment and supporting diagnosis, as well as guiding procedures. In recent years, PoCUS has started becoming a valuable tool in day-to-day clinical practice, adopted by healthcare professionals from various medical specialties, never replacing physical examination but improving patient and medical care and experience. Renal patients represent a wide range of diseases, which lends PoCUS a special role as a valuable tool in different scenarios, not only for volume-related information but also for the assessment of a wide range of acute and chronic conditions, enhancing the sensitivity of conventional physical examination in nephrology. PoCUS in the hands of a nephrologist is a precision medicine tool.

Doppler-based evaluation of intrarenal venous flow as a new tool to predict acute kidney injury: A systematic review and meta-analysis.

Congestion is a common complication in the critical care setting, these patients are at increased risk of developing acute kidney injury (AKI). Congestive nephropathy (CN) has recently been described as a mechanism of worsening renal function, and evaluation of renal venous flow by pulsed Doppler (PD) is a useful tool to assess the presence of renal vein congestion. We comprehensively explore the ability of the PD in the evaluation of the intrarenal venous flow (IRVF) to predict the development of AKI in critically ill patients. We searched Pubmed-MEDLINE, Scopus, Embase, and Cochrane Library of Systematic Reviews (to 31th December 2021). We evaluated the association between Doppler-based Intrarenal venous flow demodulation and AKI. CN was defined as the presence of a pulsatile pattern (biphasic or monophasic) in the PD. A total of 4 articles (660 patients) were included in our systematic review, three of these in the metanalysis (413 patients): one study was excluded because its data were inadequate for pooling. Two studies originated in Europe and the other two in the United States. AKI occurrence ranged between 34 and 68%. Patients who developed AKI had a significant difference in PD pattern (continuous vs. pulsatile) in the IRVF (RR=0.46; 95% CI 0.28-0.76). Nevertheless, a large heterogeneity was observed among the studies (I2=68.7%; p=0.04). Albeit preliminary, these findings suggest that the presence of a pulsatile pattern in the PD of the IRVF may be involved in the development of AKI in the critically ill patient. The effect of alterations in the IRVF and renal function warrant further investigation.