Impact of Chronic Kidney Disease on the Outcomes of Patients Undergoing Percutaneous Left Atrial Appendage Occlusion: Insights from a Large National Database.

BACKGROUND: Studies exploring the effectiveness and safety of percutaneous left atrial appendage occlusion (pLAAO) in patients with chronic kidney disease (CKD) are limited. OBJECTIVES: We aimed to analyze trends and outcomes following pLAAO in patients with CKD. METHODS: We utilized the National Inpatient Sample (NIS) to identify hospitalizations for pLAAO from 2016-2020 and further identified cases with concomitant CKD. The primary outcome was mortality, and secondary outcomes were cerebrovascular accidents, major bleeding, vasopressor requirements, percutaneous coronary intervention, cardiac arrest, acute respiratory failure, transfusion, length of stay (LOS), and total hospital charges. Multivariable logistic regression was performed to further adjust for covariates. RESULTS: A total of 89,309 pLAAO procedures from 2016 to 2020 were identified, of which 21,559 (24.1%) reported concomitant CKD, with males comprising the majority (62.2%). An increasing trend in pLAAO procedures was seen from 2.24 to 13.9 per 10,000 patients from 2016 to 2020. Despite patients with CKD having a higher rate of most comorbidities, there was no difference in mortality (non-CKD vs. CKD, 0.07% vs. 0.42%; aOR: 1.3, 95% CI: 0.4 - 4.4, p=0.686) and complications for CKD and non-CKD patients, while CKD patients had longer LOS and higher total hospital charge. No significant sex differences in outcomes among CKD patients were observed except for a longer LOS in females. CONCLUSION: Despite generally having more comorbidities, outcomes of patients with CKD following pLAAO are similar to those without CKD, suggesting that pLAAO can be offered as a safe option for the treatment of AF in eligible patients with CKD.

Unlocking the Potential of VExUS in Assessing Venous Congestion: The Art of Doing It Right.

BACKGROUND: Congestion, marked by elevated cardiac filling pressures and their repercussions, is a contributing factor to morbidity and mortality in heart failure and critical illness. Relying on traditional methods for bedside evaluation often leads to inadequate decongestion and increased hospital readmissions. Point-of-care ultrasound (POCUS), particularly multi-organ POCUS, including the Venous Excess Ultrasound (VExUS) score, offers a promising approach in this scenario. VExUS enables the quantification of systemic venous congestion, aiding in fluid overload states by assessing inferior vena cava and venous Doppler waveforms. SUMMARY: This comprehensive review delves into the latest developments in comprehending and evaluating congestion, shedding light on technical intricacies to enhance the effective application of VExUS. Recent studies emphasize the importance of evaluating signs of hemodynamic congestion before administering intravenous fluids, highlighting the concept of "fluid tolerance." Moreover, VExUS-guided decongestion significantly improves decongestion rates in acute decompensated heart failure patients with acute kidney injury. Newer studies also highlight the prognostic implications of VExUS in the general ICU cohorts not confining to cardiac surgery patients. However, performing VExUS without understanding technical pitfalls may lead to clinical errors. Technical considerations in performing VExUS include nuances related to inferior vena cava and internal jugular vein ultrasound and familiarity with Doppler principles, optimal settings, and artifacts. Additionally, local structural alterations such as those seen in liver and kidney disease impact Doppler waveforms, emphasizing the need for careful interpretation. KEY MESSAGE: Overall, VExUS presents a valuable tool for assessing congestion and guiding management, provided clinicians are familiar with its technical complexities and interpret findings judiciously.

Contemporary Decongestive Strategies in Acute Heart Failure.

Congestion is the primary driver of hospital admissions in patients with heart failure and the key determinant of their outcome. Although intravenous loop diuretics remain the predominant agents used in the setting of acute heart failure, the therapeutic response is known to be variable, with a significant subset of patients discharged from the hospital with residual hypervolemia. In this context, urinary sodium excretion has gained attention both as a marker of response to loop diuretics and as a marker of prognosis that may be a useful clinical tool to guide therapy. Several decongestive strategies have been explored to improve diuretic responsiveness and removal of excess fluid. Sequential nephron blockade through combination diuretic therapy is one of the most used methods to enhance natriuresis and counter diuretic resistance. In this article, I provide an overview of the contemporary decongestive approaches and discuss the clinical data on the use of add-on diuretic therapy. I also discuss mechanical removal of excess fluid through extracorporeal ultrafiltration with a brief review of the results of landmark studies. Finally, I provide a short overview of the strategies that are currently under investigation and may prove helpful in this setting.

Hepato-Cardio-Renal Syndrome.

Hepatorenal syndrome has conventionally been regarded as a multisystem syndrome in which pathophysiologic pathways that link cirrhosis with impairment in kidney function are followed by dysfunction of several organs such as the heart. The advances in cardiac studies have helped diagnose more subtle cardiac abnormalities that would have otherwise remained unnoticed in a significant subset of patients with advanced liver disease and cirrhosis. Accumulating data suggests that in many instances, the cardiac dysfunction precedes and predicts development of kidney disease in such patients. These observations point to the heart as a key player in hepatorenal syndrome and challenge the notion that the cardiac abnormalities are either the consequence of aberrancies in hepatorenal interactions or have only minor effects. As such, the disturbances traditionally bundled within hepatorenal syndrome may indeed represent a hepatic form of cardiorenal syndrome whereby the liver affects the kidney in part through cardiorenal pathways (that is, hepato-cardio-renal syndrome).

Cardiorenal Interactions in Acute Heart Failure: Renal Proximal Tubules in the Spotlight.

BACKGROUND: The maladaptive neurohormonal activation, an integral mechanism in the pathophysiology of heart failure (HF) and cardiorenal syndrome, has a profound impact on renal sodium handling. Congestion is the primary reason for hospitalization of patients with HF and the main target of therapy. As sodium is the main determinant of extracellular volume, the goal is to enhance urinary sodium excretion in order to address excess fluid. The interventions to increase natriuresis have conventionally focused on distal nephron as the primary segment that counterbalances the effects of loop diuretics. SUMMARY: Recent developments in the field of cardiorenal medicine have resulted in a shift of attention to renal proximal tubules (e.g., emerging evidence on proximal tubular dysfunction beyond handling of sodium). Herein, we discuss the three main mechanisms of sodium transport in the proximal tubules with emphasis on their intrinsic links to one another as well as to more distal transporters of sodium. Then, we provide an overview of the findings of the most recent clinical studies that have tried to enhance the conventional decongestive strategies through simultaneous blockade of these mechanisms. KEY MESSAGE: Interventions aiming at renal proximal tubules have the potential to significantly improve our ability to decongest patients with acute HF.

Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis.

Background: In patients with heart failure (HF), randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing the primary composite outcome of cardiovascular death and hospitalizations for HF. A recently published meta-analysis showed that the use of SGLT-2is among women with diabetes resulted in less reduction in primary composite outcomes compared with men. This study aims to explore potential sex differences in primary composite outcomes among patients with HF treated with SGLT-2is. Methods: We systematically searched the medical database from 2017 to 2022 and retrieved all the RCTs using SGLT-2is with specified cardiovascular outcomes. We used the PRISMA (Preferred Reporting Items for a Review and Meta-analysis) method to screen for eligibility. We evaluated the quality of studies using the Cochrane Risk of Bias tool. We pooled the hazard ratio (HR) of the primary composite outcomes in both sexes, performed a meta-analysis, and calculated the odds ratio (OR) of the primary composite outcomes based on sex. Results: We included 5 RCTs with a total number of 21,947 patients. Of these, 7837 (35.7 %) were females. Primary composite outcomes were significantly lower in males and females taking SGLT-2is compared to placebo (males - HR 0.77; 95 % CI 0.72 to 0.84; p = 0.00001; females - HR 0.75; 95 % CI 0.67 to 0.84; p = 0.00001). Pooled data from four of the RCTs (n = 20,725) revealed a greater occurrence of the primary composite outcomes in females compared with males (OR 1.32; 95 % CI 1.17 to 1.48; p = 0.0002). Conclusion: SGLT-2is reduce the risk of primary composite outcomes in patients with HF, regardless of sex; however, the benefits were less pronounced in women. Further research needs to be done to better explain these observed differences in outcomes.

Prognostic models to predict complete resolution of hypertension after adrenalectomy in primary aldosteronism: A systematic review and meta-analysis.

Complete resolution of hypertension (CRH) after adrenalectomy for primary aldosteronism is far from a certainty. Although several prognostic models have been proposed to predict outcome after adrenalectomy, studies have not clarified which of the available models can be used reliably in clinical practice. To identify, describe and appraise all prognostic models developed to predict CRH, and meta-analyse their predictive performances. We searched MEDLINE, Embase and Web of Science for development and validation studies of prognostic models. After selection, we extracted descriptive statistics and aggregated area under the receiver operator curve (AUC) using meta-analysis. From 25 eligible studies, we identified 12 prognostic models used for predicting CRH after total adrenalectomy in primary aldosteronism. We report the results for 3 models that had available data from at least 3 external validation studies: the primary aldosteronism surgical outcome (PASO) score (AUC: 0.81; 95% confidence interval [CI]: 0.74-0.86; 95% predictive interval [PI]: 0.04-1.00), Utsumi nomogram (AUC: 0.79; 95% CI: 0.72-0.85; 95% PI: 0.03-1.00) and the aldosteronoma resolution score (ARS) model (AUC: 0.77; 95% CI: 0.74-0.80; 95% PI: 0.59-0.86 for all studies and AUC: 0.80; 95% CI: 0.75-0.85; 95% PI: 0.57-0.93 for the studies with the same adrenal vein sampling-guided adrenalectomy rate compared to the models meta-analysed). The PASO score, Utsumi nomogram and ARS model showed comparable discrimination performance to predict CRH in primary aldosteronism. Unlike the ARS model, the number of external validation studies for the PASO score and the Utsumi nomogram was relatively low to draw definite conclusions.

Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure: Trials and Tribulations.

In contrast to significant advances in the management of patients with chronic heart failure over the past few years, there has been little change in how patients with acute heart failure are treated. Symptoms and signs of fluid overload are the primary reason for hospitalization of patients who experience acute decompensation of heart failure. Intravenous loop diuretics remain the mainstay of therapy in this patient population, with a significant subset of them showing suboptimal response to these agents leading to incomplete decongestion at the time of discharge. Combination diuretic therapy, that is, using loop diuretics along with an add-on agent, is a widely applied strategy to counter renal sodium avidity through sequential blockade of sodium absorption within renal tubules. The choice of the second diuretic is affected by several factors, including the site of action, the anticipated secondary effects, and the available evidence on their efficacy and safety. While the current guidelines recommend combination diuretic therapy as a viable option to overcome suboptimal response to loop diuretics, it is also acknowledged that this strategy is not supported by strong evidence and remains an area of uncertainty. The recent publication of landmark studies has regenerated the interest in sequential nephron blockade. In this article, we provide an overview of the results of the key studies on combination diuretic therapy in the setting of acute heart failure and discuss their findings primarily with regard to the effect on renal sodium avidity and cardiorenal outcomes.

Gross Hematuria following SARS-CoV-2 Vaccination.

In the setting of the rapid development of currently available vaccines for coronavirus disease of 2019 (COVID-19), little is known about their less frequent potential side effects. Raising the awareness of clinicians and front-line healthcare workers about the less well-known potential side effects of vaccination is important. We describe the self-limited occurrence of gross hematuria in two elderly men on a combination of aspirin and another antiplatelet or anticoagulant following their second dose of the Moderna COVID-19 vaccination. While the bleeding seems to be self-limited, the long-term course currently remains elusive.

Pregnancy in end-stage kidney disease: Great news that needs to be handled carefully.

Compared to women with normal kidney function, women with end-stage kidney disease (ESKD) are much less likely to become pregnant, but more likely to have a complicated pregnancy. While renal transplantation remains the best option for women who desire to have a child, pregnancy on dialysis should be considered an option for those who may not receive a transplant during their reproductive years. Many physicians do not encounter a pregnant patient with ESKD during their nephrology training, and may not feel prepared to provide care for such patients in a busy practice. In this paper, we briefly provide an overview of the most significant practical points related to management of a pregnant patient with ESKD through a real-life case with twin pregnancy. The two key elements in management of these patients would be an intensified hemodialysis regimen and a multidisciplinary team that can provide frequent, regular, and multifaceted assessments.

The Science of Extracorporeal Ultrafiltration: Introducing a Novel Miniaturized Device.

INTRODUCTION: Fluid overload has been associated with untoward outcomes in a variety of clinical settings. Isolated extracorporeal ultrafiltration (UF) allows for mechanical extraction of excess fluid and optimization of volume status without the established risks associated with use of high-dose diuretics. Conventional machines for renal replacement therapy can be used to perform isolated UF. However, they typically need high blood flow rates with high circuit volumes and the therapy has to be performed by trained nurses. Herein, we describe a novel device, the Artificial Diuresis-1, or AD 1 (Medica S.p.A., Medolla, Italy), which is a portable technology designed to perform extracorporeal UF at bedside. MATERIALS AND METHODS: The AD 1 uses a polysulfone mini-filter to generate ultrafiltrate with the help of two forces: blood flow (Qb) and gravity (based on the height at which the ultrafiltrate collection bag is placed). In vitro experiments were performed using human blood to evaluate vascular access pressures and ultrafiltrate volumes using various central venous catheters (CVCs; 12 Fr bilume, 10 Fr with 2 separate lumens, pediatric catheter 7 Fr). A variety of combinations were tested with Qb of 20, 35, 50 mL/min and collection bag height at 20, 40, 60 cm, measuring the UF rate per minute while monitoring the pressures in the venous and arterial lines and filtration fraction. RESULTS: The device's performance was as expected. Regarding the pediatric CVC, it was possible to perform measurements only with a Qb of 20 mL/min due to increased venous pressure. UF rates when lines were directly connected to the blood container as well as for CVC Tesio ranged from 3.7 to 11 mL/min, for the CVC Niagara™ from 4.5 to 12.5 mL/min, and for the CVC 7 Fr from 8.5 to 10 mL/min. The pressures of the vascular accesses were kept within a range of -5/-40 mm Hg for the artery and +10/+70 mm Hg for the vein. The highest venous pressure values were found with the CVC 7 Fr (+80/+100 mm Hg). CONCLUSIONS: This novel device allows to treat patients with fluid overload in a variety of settings, from low-intensity department such as long-term care facilities to the intensive care unit. The device is small and portable, has a simple design, and is user friendly. Future studies will be needed to evaluate whether gentle UF and treatment of volume overload will translate into improvement in clinical outcomes such as a reduction in congestion-related hospital admissions.

Tackling Congestion in Acute Heart Failure: Is It the Primetime for "Combo Diuretic Therapy?"

Symptoms and signs of congestion are the primary reason for hospitalization of patients with acute heart failure. Efficient fluid and sodium removal remain the main goals of therapy, and loop diuretics are the recommended agents in this setting. However, the therapeutic response to these medications is known to be variable, and a significant subset of patients is discharged from the hospital with residual fluid overload. Therefore, sequential blockade of the nephron has been proposed as a more effective decongestive strategy. Pilot studies have suggested significant increase in diuresis and natriuresis with combination diuretic therapy. Recently, two groups of investigators examined this hypothesis on a larger scale in randomized placebo-controlled trials; one targeted the proximal tubules upstream of the loop of Henle (Acetazolamide in Decompensated Heart Failure with Volume Overload - ADVOR), while the other one blocked sodium-chloride cotransporters in the distal convoluted tubules (Combination of Loop with Thiazide Diuretics for Decompensated Heart Failure - CLOROTIC). Herein, we discuss the results of these two trials with special focus on their impact on extraction of sodium, i.e., the main determinant of extracellular volume, and put them in the context of previous studies of combination diuretic therapy as well as extracorporeal ultrafiltration.

Point of Care Ultrasound Training in Nephrology: Twitter Poll as a Modern Tool for Development of an Effective Curriculum.

INTRODUCTION: Point of care ultrasonography (POCUS) is being increasingly recognized as an adjunct to physical examination in the field of nephrology. However, paucity of trained faculty and standardized curricula remain key barriers to widespread adoption of this skill as well as development of reliable quality assessment programs at the institutional level. Herein, we sought to explore the utility of Twitter polls to gain insights into knowledge deficits of the learners for making curricular improvements while simultaneously disseminating POCUS pearls and pitfalls. METHODS: A series of 57 single-question polls were tweeted over a 12-month period, each containing an ultrasound image or a video asking for correct interpretation. These were sent out from the Twitter handle of NephroPOCUS.com (@NephroP), an online POCUS education tool. The answer and a brief explanation were shared in a subsequent tweet at the end of the voting period. Information on the percentage of correct answers, Tweet impressions, and engagements was collected and analyzed by the pre-determined difficulty level (I-III) and the organ/learning objective being tested. RESULTS: The number of responses per poll was 228 ± 94.6 (mean ± SD), and the percentage of correct responses was 57.9 ± 17.5 (mean ± SD). 16 (of 57) polls received less than 50% correct responses, of which 8 belonged to level III difficulty. The learning objectives that received the least number of correct responses in the kidney, cardiac, lung, vascular, and other categories were identification of end-stage kidney (16.2% correct answers), right pleural effusion on the parasternal short axis view of the heart (29%), right pleural effusion from the subxiphoid window (39%), grading of systemic venous congestion (27.3%), and identification of ascites on the right lateral chest window (15%), respectively. The overall engagement rate was 6.96%, which was above the median for health and higher education-related tweets on Twitter. Targeted didactic material was developed based on these results, published on various open-access nephrology education platforms. CONCLUSIONS: Twitter polls aid in identifying the knowledge gaps among POCUS learners. Information obtained from the polls can be used to improve POCUS-related curricula and develop targeted educational material to facilitate remote learning.

Aortic Stenosis and Aortic Valve Replacement among Patients with Chronic Kidney Disease: A Narrative Review.

BACKGROUND: Aortic stenosis (AS) can present with dyspnea, angina, syncope, and palpitations, and this presents a diagnostic challenge as chronic kidney disease (CKD) and other commonly found comorbid conditions may present similarly. While medical optimization is an important aspect in management, aortic valve replacement (AVR) by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) is the definitive treatment. Patients with concomitant CKD and AS require special consideration as it is known that CKD is associated with progression of AS and poor long-term outcomes. AIMS AND OBJECTIVES: The aim of the study was to summarize and review the current existing literature on patients with both CKD and AS regarding disease progression, dialysis methods, surgical intervention, and postoperative outcomes. CONCLUSION: The incidence of AS increases with age but has also been independently associated with CKD and furthermore with hemodialysis (HD). Regular dialysis with HD versus peritoneal dialysis (PD) and female gender have been associated with progression of AS. Management of AS is multidisciplinary and requires planning and interventions by the heart-kidney team to decrease the risk of further inducing kidney injury among high-risk population. Both TAVR and SAVR are effective interventions for patients with severe symptomatic AS, but TAVR has been associated with better short-term renal and cardiovascular outcomes. IMPLICATIONS FOR PRACTICE: Special consideration must be given to patients with both CKD and AS. The choice of whether to undergo HD versus PD among patients with CKD is multifactorial, but studies have shown benefit regarding AS progression among those who undergo PD. The choice regarding AVR approach is likewise the same. TAVR has been associated with decreased complications among CKD patients, but the decision is multifactorial and requires a comprehensive discussion with the heart-kidney team as many other factors play a role in the decision including preference, prognosis, and other risk factors.

HIV-Associated Nephropathy in 2022.

Background: HIV-associated nephropathy (HIVAN) is a renal parenchymal disease that occurs exclusively in people living with HIV. It is a serious kidney condition that may possibly lead to end-stage kidney disease, particularly in the HIV-1 seropositive patients. Summary: The African-American population has increased susceptibility to this comorbidity due to a strong association found in the APOL1 gene, specifically two missense mutations in the G1 allele and a frameshift deletion in the G2 allele, although a "second-hit" event is postulated to have a role in the development of HIVAN. HIVAN presents with proteinuria, particularly in the nephrotic range, as with other kidney diseases. The diagnosis requires biopsy and typically presents with collapsing subtype focal segmental glomerulosclerosis and microcyst formation in the tubulointerstitial region. Gaps still exist in the definitive treatment of HIVAN - concurrent use of antiretroviral therapy and adjunctive management with like renal-angiotensin-aldosterone system inhibitors, steroids, or renal replacement therapy showed benefits. Key Message: This study reviews the current understanding of HIVAN including its epidemiology, mechanism of disease, related genetic factors, clinical profile, and pathophysiologic effects of management options for patients.

Chloride and Cardiorenal Interactions in Heart Failure.

The cardiorenal literature has long been dominated by a sodium-centric view. However, mechanisms affecting sodium homeostasis in patients with heart failure (HF) commonly lead to concurrent changes in the serum levels of chloride as well. There is a growing body of evidence on a strong link between low serum chloride levels and adverse outcomes in HF, which might be even more potent than that of sodium. Maladaptive neurohormonal activation and unresponsiveness to diuretics have been proposed as potential mechanisms to explain this phenomenon. In parallel with accumulating evidence on the predictive value of chloride in various HF populations, the limited available interventional studies that were aimed at increasing serum chloride levels have also shown promising results. Ongoing studies are designed to elucidate the role of chloride as a key cardiorenal connector and whether hypochloremia represents a modifiable risk factor (i.e., target of therapy) or a mere marker of disease severity and poor prognosis.