Background: Chronic kidney disease (CKD) is associated with a markedly increased risk of cardiovascular disease (CVD). Despite this, cardiovascular risk in patients with CKD is frequently underestimated and insufficiently treated in routine clinical practice. Summary: In this narrative review, we address ten concise and up-to-date questions focused on cardiovascular risk management in CKD. A panel of ten expert nephrologists provides evidence-based perspectives on key aspects including assessment of the arterial tree, cardiovascular risk estimation, identification of biomarkers for improved risk stratification, and both pharmacological and non-pharmacological interventions proven to reduce cardiovascular risk. Additional topics include blood pressure targets, optimal management of dyslipidemia, and cardiovascular risk management in patients receiving renal replacement therapy. Practical strategies to translate this evidence into everyday clinical care are also discussed. Key Message: A comprehensive and structured approach to cardiovascular risk assessment and management are essential in patients with CKD and should be systematically integrated into routine nephrology practice to improve cardiovascular outcomes.

The editors and Karger Publishers would like to thank the following reviewers for their ongoing support in reviewing manuscripts for Cardiorenal Medicine.Dmitry Abramov, Loma Linda, CA, USADeepak Acharya, Tucson, AZ, USAIbrahim Akin, Mannheim, GermanyGulali Aktas, Bolu, TurkeyAli AlSahow, Al Jahra, KuwaitEduardo R. Argaiz, Tlalpan, MexicoSudarshan Balla, Morgantown, WV, USAGiovanni Barbati, Vicenza, ItalyClemente Barron, Tlalpan, MexicoAmer Belal, Gainesville, FL, USAClaudia Benedetti, Vicenza, ItalyJiashen Cai, Singapore, SingaporeJesus Casado, Getafe, SpainVipanpreet Chahil, Modesto, CA, USAKristina Charaya, Moscow, RussiaJonathan S. Chavez Iñiguez, Guadalajara, MexicoMeihua Chen, Haikou, ChinaJi-dong Cheng, Xiamen, ChinaAna Cruz Solbes, Boston, MA, USAGianpiero Damico, Venice, ItalyRafael de la Espriella, Valencia, SpainPaul Der Mesropian, Alabany, NY, USAAbhishek Deshpande, Bengaluru, IndiaJavier Diez, Pamplona, SpainYiHong Du, Shanghai, ChinaRobert Ekart, Maribor, SloveniaGuido Filler, Toronto, ON, CanadaMatteo Floris, Cagliari, ItalyJara Gayán Ordás, Lleida, SpainJared Gollie, Washington, DC, USAMiguel González Rico, Valencia, SpainXiangchen Gu, Shanghai, ChinaGregor Guron, Gothenburg, SwedenAbiodun Idowu, Philadelphia, PA, USAVictor Issa, Antwerp, BelgiumJuan B. Ivey-Miranda, Mexico City, MexicoGuang Ji, Shanghai, ChinaGuanghong Jia, Columbia, MO, USAKyung An Kim, Seoul, Republic of KoreaBernd Krüger, Darmstadt, GermanyAlexander Kula, Chicago, IL, USALalathaksha Kumbar, Detroit, MI, USAPau Llacer, Madrid, SpainKunal Malhotra, St. Louis, MO, USAShreepriya Mangalgi, Columbia, MO, USAPedro Marques, Porto, PortugalMarco Mojoli, Pordenone, ItalyShan Mou, Shanghai, ChinaMelin Narayan, Loma Linda, CA, USAJacob Ninan, Olympia, WA, USARavi Nistala, Columbia, MO, USAGonzalo Núñez-Marin, Valencia, SpainJaume Padilla, Columbia, MO, USAAlberto Palazzuoli, Siena, ItalySuchita Pande, Boston, MA, USAXavier Fernando Parada, Worcester, MA, USAAlex Parker, Gainesville, FL, USAJose Angel Perez Rivera, Burgos, SpainAntonino Previti, Santorso, ItalyAbd Qannus, Tucson, AZ, USAAfif Ramadhan, Sleman, IndonesiaZaccaria Ricci, Florence, ItalyHongliang Rui, Beijing, ChinaCrina Claudia Rusu, Cluj-Napoca, RomaniaAbhishek Samprathi, Bengaluru, IndiaSarah Sanghavi, Seattle, WA, USANagaraju Sarabu, Cleveland, OH, USAKristin Schreiner, Heidelberg, GermanyDavid Selewski, Charleston, SC, USAYunfeng Shen, Shenzhen, ChinaRyann Sohaney, Ann Arbor, MI, USAKsenija Stach, Mannheim, GermanyCynthia Ann Stavish, Oak Ridge, TN, USAMingliang Tang, Nanjing, ChinaFei Tong, Xiamen, ChinaCundullah Torun, Istanbul, TurkeyJunior Uduman, Detroit, MI, USASerkan Ünlü, Ankara, TurkeyJorge Vazquez Lopez-Ibor, Madrid, SpainGiovanni Vescovo, Mestre, ItalyKrishnaswami Vijayaraghavan, Phoenix, AZ, USABenjamin Wagner, Detroit, MI, USAMatthew R. Weir, Baltimore, MD, USAR. Scott Wright, Rochester, NY, USAXiaohong Wu, Zhejiang, ChinaI-Wen Wu, Taipei, TaiwanPreethi Yerram, Columbia, MO, USADong-Dong Yu, Guangzhou, ChinaChen Yu, Shanghai, ChinaXiaohui Zhao, Chongqing, ChinaLiang Zheng, Shanghai, ChinaJiahua Zhou, Wenzhou, ChinaLara Zonneveld, Groningen, The Netherlands

Background: Pulse pressure (PP), the difference between systolic (SBP) and diastolic blood pressure (DBP), is an essential marker of cardiovascular (CV) health and arterial stiffness. Elevated PP is linked to a higher risk of CV events, a major cause of global mortality. This study examines its association with key electrolytes – sodium, potassium, calcium, magnesium, phosphate, and vitamin D – in blood-pressure regulation and vascular function. Methods: We analysed data from 3,316 LURIC participants who underwent coronary angiography and had a median follow-up of 9.9 years. Fasting blood samples were collected at baseline. Associations between PP and electrolyte levels were assessed using Spearman correlation. Logistic regression models were used to calculate odds ratios (ORs) per standard deviation (SD) of PP and electrolyte concentrations for four clinical outcomes: all-cause mortality, CV mortality, reduced estimate the glomerular filtration rate (eGFR), and type 2 diabetes mellitus. Results: The cohort’s average age was 62.7 years, with 70% of participants being male. Higher PP was significantly associated with older age, increased body mass index, and the prevalence of coronary artery disease (CAD), carotid stenosis, and peripheral arterial disease. Potassium, phosphate, renin, 25-OH, and 1,25-OH vitamin D concentrations decreased significantly as PP increased, while sodium remained unchanged. Sodium-potassium ratio and aldosterone-renin ratio increased with higher PP. Women had a higher risk of CV mortality per SD of PP (OR 1.57; 95% confidence interval [CI]: 1.33–1.86), while men showed a greater risk of reduced eGFR (OR 1.59; 95% CI: 1.40–1.80). Conclusion: Specific electrolyte imbalances are closely linked to increased PP and arterial stiffness. Our findings highlight sex-specific CV risk and support further research into nutrient-based and hormonal interventions targeting PP modulation.

Background: Diuretic resistance is commonly reported in acute heart failure (AHF), especially in patients presenting with impaired kidney function. Effective treatment strategies for promoting decongestion in this population remain unclear. Methods: A systematic review using MEDLINE/Cochrane databases was performed from inception to January 2024, identifying randomized clinical trials (RCTs) including patients with diuretic resistance or at risk of diuretic resistance based on the presence of kidney dysfunction at study enrollment. Trials testing different pharmacological or invasive modalities compared to standard of care, placebo or an active comparator were considered. Data on decongestion-related outcomes, safety outcomes, and clinical outcomes up to 90 days were collected. Results: Among the 22 RCTs included, 6 trials involved 529 patients with established diuretic resistance, while 16 trials enrolled 1,913 patients at risk of diuretic resistance. Diuretic resistance was differently defined across studies and most trials focused on interventions targeting different sites of action along the renal tubules. The different treatment strategies demonstrated efficacy in promoting decongestion while being associated with a mild increase in creatinine and cystatin C. The use of appropriately high doses of intravenous loop diuretics was able to promote decongestion across the spectrum of kidney dysfunction. The presence of baseline kidney dysfunction did not identify a population resistant to standard decongestive strategies. Conclusions: Diuretic resistance is not accurately defined in AHF but is uncommon in patients treated with appropriately high doses of intravenous loop diuretics. The main therapeutic goal in the acute setting should focus on promoting decongestion instead of overemphasizing on mild changes in kidney-related biomarkers.

Background: Recently, a large clinical trial found that treatment with semaglutide significantly reduced the risk of renal damage and cardiovascular death in patients with type 2 diabetes (T2D). To validate these findings and ensure the suitability of the drug, it is necessary to address the renal and cardiac safety of semaglutide in patients with T2D through real-world safety evidence. Methods: We examined post-marketing data on the use of semaglutide in patients with T2D using disproportionality analysis based on the FDA Adverse Event Reporting System database. We focused on the detection of positive signals for acute and chronic renal injury and cardiac adverse events associated with semaglutide therapy. Results: A total of 2,380 patients were enrolled in semaglutide therapy in T2D patients with no renal or cardiac positive signals in four algorithmic thresholds, including disproportionality analysis. Conclusions: In the current study, we observed no significant cardiac or renal safety signals in patients with T2D treated with semaglutide. Our results provide further support for its use as initial and combination therapy in relevant populations.

Introduction: Worsening renal function (WRF) is associated with poor prognosis in patients with heart failure (HF). Osteopontin (OPN) and matrix extracellular phosphoglycoprotein (MEPE) are expressed in the kidneys and are involved in bone mineralization processes. Higher OPN levels have been associated with a higher risk for adverse outcomes in patients with chronic kidney disease (CKD), and MEPE has been shown to promote renal phosphate excretion. Here, we explored if MEPE and OPN are associated with WRF and CKD in patients admitted for acute HF. Methods: WRF was defined as an increase in plasma creatinine of >26.5 mmol/L or 50% higher than admission concentration within 48 h of admission. OPN and MEPE were analyzed in 315 HF patients at baseline, and in 120 patients at 6-month follow-up. Associations between MEPE and OPN, and (a) WRF, (b) CKD stage 3–5, and (c) markers of kidney function were explored. Further, OPN and MEPE at baseline and at 6-month follow-up (delta [Δ] values) were related to CKD progression. Results: The study population had a mean age of 75 (±12) years and 31% were women. Higher levels of MEPE and OPN were associated with WRF (n = 30; OR 2.80; [1.49–5.25]; p = 0.001, and OR 1.84; [1.05–3.23]; p = 0.034, respectively). On admission, both MEPE and OPN were associated with CKD stage 3–5 (OR 5.27; [2.76–10.07]; p < 0.001, and OR 3.26; [1.90–5.60]; p < 0.001, respectively). At 6-month follow-up, progression in CKD stage was associated with ΔMEPE and ΔOPN (HR 2.53; [1.48–4.31]; p < 0.001, and HR 2.66; [1.51–4.71]; p < 0.001). Conclusion: Here, MEPE and OPN are for the first time shown to be independently associated with WRF and subsequent deterioration in CKD in a HF cohort. The mechanisms of these associations are currently largely unknown and need to be investigated further.

Background: The interaction between the heart and kidneys involves complex mechanisms, leading to a clinical condition known as cardiorenal syndrome (CRS), where dysfunction in one organ leads to impairment of the other. This syndrome can be acute or chronic, affecting both organs simultaneously. Summary: In 2008, the Acute Dialysis Quality Group classified CRS into two main categories: cardiorenal CRS and renocardiac CRS, based on the primary organ affected. Cardiorenal CRS includes two subtypes where heart failure causes kidney injury (types 1 and 2), while renocardiac CRS (types 3 and 4) refers to kidney injury leading to cardiac dysfunction, either from acute kidney injury or chronic kidney disease. Type 5 CRS is termed as secondary CRS which involves both organ dysfunction due to an acute systemic disease, such as sepsis, infections, or chronic conditions like diabetes mellitus. This review examines the cardiovascular involvement in various nephrological diseases commonly seen in clinical practice, with a focus on types 3–5 CRS in children from a nephrology perspective. Key Messages: CRS is common in pediatric patients with cardiac, renal, or systemic conditions and poses a significant risk of mortality. The lack of longitudinal studies or specific biomarkers for the diagnosis, treatment, and follow-up of CRS in children is evident. Aspects such as the development of new biomarkers, ongoing research into neurohormonal mechanisms, meta-analyses, and introduction of algorithms for the follow-up period may reshape patient management. Specific diagnostic tools or therapeutic interventions for CRS management in children should be implemented. Collaborative efforts among pediatricians, cardiologists, and nephrologists are essential for developing effective treatments. Large-scale studies are needed to better understand CRS and develop targeted therapies to improve outcomes for pediatric patients, reducing morbidity and mortality.