Genetic Etiologies for Chronic Kidney Disease Revealed through Next-Generation Renal Gene Panel.

INTRODUCTION: Chronic kidney disease (CKD) is a major public health issue in the USA. Identification of monogenic causes of CKD, which are present in ∼10% of adult cases, can impact prognosis and patient management. Broad gene panels can provide unbiased testing approaches, which are advantageous in phenotypically heterogeneous diseases. However, the use and yield of broad genetic panels by nephrologists in clinical practice is not yet well characterized. METHODS: Renal genetic testing, ordered exclusively for clinical purposes, predominantly by general and transplant nephrologists within the USA, was performed on 1,007 consecutive unique patient samples. Testing was performed using a commercially available next-generation sequencing-based 382 gene kidney disease panel. Pathogenic (P) and likely pathogenic (LP) variants were reported. Positive findings included a monoallelic P/LP variant in an autosomal dominant or X-linked gene and biallelic P/LP variants in autosomal recessive genes. RESULTS: Positive genetic findings were identified in 21.1% (212/1,007) of cases. A total of 220 positive results were identified across 48 genes. Positive results occurred most frequently in the PKD1 (34.1%), COL4A5 (10.9%), PKD2 (10.0%), COL4A4 (6.4%), COL4A3 (5.9%), and TTR (4.1%) genes. Variants identified in the remaining 42 genes comprised 28.6% of the total positive findings, including single positive results in 26 genes. Positive results in >1 gene were identified in 7.5% (16/212) of cases. CONCLUSIONS: Use of broad panel genetic testing by clinical nephrologists had a high success rate, similar to results obtained by academic centers specializing in genetics.

Practical Considerations and Implementation of Sodium-Glucose Co-Transporter-2 Inhibitors in Chronic Kidney Disease: Who, When, and How? A Position Statement by Nephrologists.

INTRODUCTION: There remains an unmet need to reduce kidney and cardiovascular risk in patients with chronic kidney disease (CKD). This report is therefore intended to provide real-world clinical guidance to primary care providers on sodium-glucose co-transporter-2 (SGLT2) inhibitor use in patients with CKD, focusing on practical considerations. Initially developed as glucose-lowering drugs, SGLT2 inhibitors preserve kidney function and reduce risks of cardiovascular events and mortality. Clinical benefits of SGLT2 inhibitors in CKD have been demonstrated in multiple clinical trials, yet utilization in practice remains relatively low, likely due to the complexity of labeled indications (past and present) and misconceptions about SGLT2 inhibitors as a class. METHODS: A panel of 8 US-based nephrologists convened in August 2022 to develop consensus guidance for the primary care community surrounding risk assessment as well as initiation and implementation of SGLT2 inhibitors in patients with CKD. Here, we provide an adapted version of the Kidney Disease: Improving Global Outcomes (KDIGO) heatmap and a treatment-decision algorithm. CONCLUSIONS: We advocate SGLT2 inhibitors as co-first-line therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors, where RAAS inhibitor dose titration need not be completed before initiation of an SGLT2 inhibitor. In fact, SGLT2 inhibitor therapy may facilitate up-titration or maintenance of optimal RAAS inhibitor dosing. We describe potential strategies to aid implementation of an SGLT2 inhibitor in clinical practice, including improving education and awareness among care providers and patients and dispelling misconceptions about the safety of SGLT2 inhibitors. In summary, we support the use of SGLT2 inhibitors with RAAS inhibitors as co-first-line therapy in most patients with CKD.

Patients' Perspectives on the Acceptability and Effectiveness of a Community Health Worker-Led Intervention to Increase Chronic Kidney Disease Knowledge and Screening among Underserved Latine Adults: The CARE 2.0 Study.

In the United States, Chronic Kidney Disease (CKD) affects approximately 1 in 7 adults. Despite its significant impact, CKD awareness, education, and screening are often lacking among underserved Latine populations, leading to poorer health outcomes and higher mortality rates. Various studies highlight the crucial role of Community Health Workers (CHWs) in improving health outcomes within minority communities both domestically and globally. However, there remains a gap in research on the acceptance and effectiveness of CHW-led interventions targeting CKD. This prospective intervention study employed a pre-post quasi-experimental design to evaluate a CHW-led educational program aimed at enhancing CKD knowledge, screening, and monitoring among Latines with low health literacy and English proficiency. CHWs utilized a culturally tailored CKD Flipchart, and 100 underserved patients received the intervention. Feedback from 85 participants who completed post-intervention surveys indicated high satisfaction with the program's relevance and the professionalism of the CHWs. Importantly, 85% expressed a positive intention to seek kidney care following the intervention. Preliminary analysis of medical records before and after the intervention showed improvements in glycemic control (median change = -18.0, p = 0.014) and triglyceride levels (median change = -29.0, p = 0.035), suggesting the program's effectiveness in managing CKD risk factors. These findings highlight the potential of CHW-led interventions to reduce kidney health disparities among underserved communities.

Analysis of Survival Modification by Furosemide Use in a Cohort of Hospitalized COVID-19 Patients with Severe or Critical Disease in Mexico: Due to Its Chemical Structure, Furosemide Is More than Just a Diuretic.

In the ongoing fight against Coronavirus Disease 2019 (COVID-19), researchers are exploring potential treatments to improve outcomes, especially in severe cases. This includes investigating the repurposing of existing medications, such as furosemide, which is widely available. This study aimed to evaluate the impact of furosemide on mortality rates among COVID-19 patients with severe or critical illness. We assessed a cohort of 515 hospitalized adults who experienced a high mortality rate of 43.9%. Using a multivariate analysis with adjusted risk ratios (AdRRs), factors like smoking (AdRR 2.48, 95% CI 1.53-4.01, p < 0.001), a high Pneumonia Severity Index (PSI) score (AdRR 7.89, 95% CI 5.82-10.70, p < 0.001), mechanical ventilation (AdRR 23.12, 95% CI 17.28-30.92, p < 0.001), neutrophilia (AdRR 2.12, 95% CI 1.52-2.95, p < 0.001), and an elevated neutrophil-to-lymphocyte ratio (NLR) (AdRR 2.39, 95% CI 1.72-3.32, p < 0.001) were found to increase mortality risk. In contrast, vaccination and furosemide use were associated with reduced mortality risk (AdRR 0.58, p = 0.001 and 0.60, p = 0.008; respectively). Furosemide showed a pronounced survival benefit in patients with less severe disease (PSI < 120) and those not on hemodialysis, with mortality rates significantly lower in furosemide users (3.7% vs. 25.7%). A Kaplan-Meier analysis confirmed longer survival and better oxygenation levels in patients treated with furosemide. Furthermore, a Structure-Activity Relationship analysis revealed that furosemide's sulfonamide groups may interact with cytokine sites such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), potentially explaining its beneficial effects in COVID-19 management. These findings suggest that furosemide could be a beneficial treatment option in certain COVID-19 patient groups, enhancing survival and improving oxygenation.

Community-Engaged Research (CEnR) to Address Gaps in Chronic Kidney Disease Education among Underserved Latines-The CARE Study.

Ensuring equitable chronic kidney disease (CKD) education for Latine patients with low health literacy and low English proficiency stands as a critical challenge, and the "Caridad Awareness and Education" (CARE) initiative represents our ongoing effort to address this imperative issue. In collaboration with twenty-three patients living with CKD, diabetes and/or hypertension and twelve trained Community Health Workers (CHWs) from diverse Latine subgroups, we conducted a research initiative funded by the National Kidney Foundation. Our primary objective was to co-design and test culturally tailored patient education materials (PEMs) for underserved Latine adults at risk for or diagnosed with CKD. We effectively integrated Community-Engaged Research (CEnR) principles with a Human-Centered Design (HCD) approach to create a range of CKD-PEM prototypes in Spanish. Patient preferences for printed educational materials were clear. They favored printed materials that incorporated visual content with concise text over digital, email, texts, or online resources and personalized phone outreach and the involvement of CHWs. Additionally, patients identified their unwavering commitment to their families as a forceful motivator for caring for their kidney health. Currently, a culturally and linguistically tailored CKD flipchart for one-on-one education, led by CHWs, is undergoing a pilot testing phase involving a sample of one hundred Latine patients at risk for or diagnosed with CKD. This innovative approach signifies a commitment to amplifying the insights and expertise of the Latine community afflicted by kidney health disparities, effectively embracing a CEnR to forge meaningful and impactful CKD-PEMs.

Urgent-start peritoneal dialysis: report from a U.S. private nephrology practice.

Urgent-start peritoneal dialysis (PD) can be defined as initiation of PD within 2 weeks of catheter insertion. Urgent-start PD can be offered to patients who are referred late to a nephrologist and who would typically be initiated on hemodialysis with a temporary vascular access. An urgent-start PD capability requires expedited options education, catheter placement, unique change in the PD unit infrastructure, and new processes of care. This report describes the urgent-start PD program established by a nephrology private practice in the United States. Operational aspects of the program and initial clinical results are described.

Association of decreased quality of life and erectile dysfunction in hemodialysis patients.

BACKGROUND: Quality of life in hemodialysis patients has been associated with treatment outcomes. We explored the impact of erectile dysfunction on quality of life in a cohort of hemodialysis subjects. METHODS: A random sample of 302 Philadelphia area hemodialysis (HD) subjects was enrolled using a cross-sectional design. Subjects completed a self-administered questionnaire including items on sexual function, past medical history, and quality of life. Linear regression (accounting for sampling design by weighted estimation methods) was used to examine the associations between various measures of quality of life (the dependent variables) and erectile dysfunction (ED) and other variables (the predictor variables). RESULTS: We found the emotional domains of the SF-36, a multi-purpose, short-form health survey with 36 questions, to be more profoundly associated with ED than the physical domains. Using the physical and mental components of the SF-12, a new 12-item short form health survey as predictors of ED, only the mental composite score (MCS) was statistically significant after adjusting for age and diabetes (P = 0.008). Subjects with ED had significantly lower quality of life mean scores. In particular, ED was associated with poorer social interaction (mean score difference, -10.3, adjusted P < 0.001), decreased emotional well-being (-12.9, adjusted P = 0.005), more role limitations due to emotional problems (-22.9, adjusted P = 0.01), and poorer social function (-17.8, P = 0.001). CONCLUSION: Recent advances in therapies for ED warrant that the diagnosis and treatment of erectile dysfunction be included in the global health assessment by the nephrologists and primary care providers of patients with renal insufficiency, as it may improve the quality of life of patients.