New Insights into Cardio-Renal Interactions: Novel Definitions, Pathophysiology and Management

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 10550

Special Issue Editor


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Guest Editor
1. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 39040, Israel
2. Cardiac Intensive Care Unit, Tel Aviv Sourasky Medical Center, Tel Aviv 62431, Israel
Interests: cardiorenal syndromes; acute renal damage; heart failure
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Special Issue Information

Dear Colleagues,

A large proportion of patients admitted to hospital have various degrees of heart and kidney dysfunction. A diseased heart has numerous negative effects on kidney function but, at the same time, renal insufficiency can significantly impair cardiac function.

Thus, direct and indirect effects of each organ that is dysfunctional can initiate and perpetuate the combined disorder of the two organs through a complex combination of neurohormonal feedback mechanisms.

Primary disorders of one of these two organs often result in secondary dysfunction or injury to the other. Such interactions represent the pathophysiological basis for a clinical entity called cardiorenal syndrome (CRS). Although generally defined as a condition characterized by the initiation and/or progression of renal insufficiency secondary to heart failure, the term CRS is also used to describe the negative effects of reduced renal function on the heart and circulation. Recent advances in basic and clinical sciences have improved our understanding of organ crosstalk and have demonstrated the efficacy of some therapies in attenuating both cardiac and renal injury.

The aim of this Special Issue is to present clinical and experimental scientific reports that improve our understanding of these complex and important organ interactions.

Dr. Yacov Shacham
Guest Editor

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Keywords

  • acute kidney injury
  • biomarkers
  • serum creatinine
  • tubular damage
  • glomerular filtration rate
  • heart failure

Published Papers (8 papers)

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Editorial

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2 pages, 156 KiB  
Editorial
Novel Biomarkers for the Assessment of the Cardio-Renal Syndrome—A Paradigm Shift
by Yacov Shacham
J. Clin. Med. 2023, 12(15), 5116; https://doi.org/10.3390/jcm12155116 - 04 Aug 2023
Viewed by 646
Abstract
Among patients admitted to medical wards, a growing number have various degrees of cardiac and renal dysfunction [...] Full article

Research

Jump to: Editorial

12 pages, 2069 KiB  
Article
Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Patients with ST-Elevation Myocardial Infarction and Its Association with Acute Kidney Injury and Mortality
by Mathias Alexander Højagergaard, Rasmus Paulin Beske, Christian Hassager, Lene Holmvang, Lisette Okkels Jensen, Yacov Shacham, Martin Abild Stengaard Meyer, Jacob Eifer Moeller, Ole Kristian Lerche Helgestad, Peter Dall Mark, Rasmus Møgelvang and Martin Frydland
J. Clin. Med. 2023, 12(11), 3681; https://doi.org/10.3390/jcm12113681 - 26 May 2023
Cited by 3 | Viewed by 1209
Abstract
Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker related to acute kidney injury (AKI). Including 1892 consecutive patients with ST-elevation myocardial infarction (STEMI), in which NGAL was measured in 1624 (86%) on admission and in a consecutive subgroup at 6–12 h (n = [...] Read more.
Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker related to acute kidney injury (AKI). Including 1892 consecutive patients with ST-elevation myocardial infarction (STEMI), in which NGAL was measured in 1624 (86%) on admission and in a consecutive subgroup at 6–12 h (n = 163) and 12–24 h (n = 222) after admission, this study aimed to evaluate the prognostic value of NGAL in predicting AKI and mortality. Patients were stratified based on whether their admission NGAL plasma concentration was greater than or equal to/less than the median. The primary endpoint was a composite of the first occurrence of AKI or all-cause death within 30 days. AKI was classified by the maximal plasma creatinine increase from baseline during index admission as KDIGO1 (<200% increase) or KDIGO23 (≥200% increase) according to the Kidney Disease Improving Global Outcomes (KDIGO) system. Admission NGAL > the median was independently associated with a higher risk of severe AKI (KDIGO2-3) and 30-day all-cause mortality when adjusted for age, admission systolic blood pressure and high-sensitivity C-reactive protein, left-ventricular ejection fraction, known kidney dysfunction, and cardiogenic shock with an odds ratio (95% confidence interval) of 2.26 (1.18–4.51), p = 0.014. Finally, we observed increasing predictive values in a subgroup during the first day of hospitalization suggesting that assessment of NGAL should be delayed for optimal prognostic purposes. Full article
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8 pages, 524 KiB  
Article
Relation of Gender to the Occurrence of AKI in STEMI Patients
by Shir Frydman, Ophir Freund, Ariel Banai, Lior Zornitzki, Shmuel Banai and Yacov Shacham
J. Clin. Med. 2022, 11(21), 6565; https://doi.org/10.3390/jcm11216565 - 05 Nov 2022
Cited by 8 | Viewed by 1461
Abstract
Patients undergoing percutaneous coronary interventions (PCIs) are prone to a wide range of complications; one complication that is constantly correlated with a worse prognosis is acute kidney injury (AKI). Gender as an independent risk factor for said complications has raised some interest; however, [...] Read more.
Patients undergoing percutaneous coronary interventions (PCIs) are prone to a wide range of complications; one complication that is constantly correlated with a worse prognosis is acute kidney injury (AKI). Gender as an independent risk factor for said complications has raised some interest; however, studies have shown conflicting results so far. We aimed to investigate the possible relation of gender to the occurrence of AKI in STEMI patients undergoing PCI. This retrospective observational study cohort included 2967 consecutive patients admitted with STEMI between the years 2008 and 2019. Their renal outcomes were assessed according to KDIGO criteria (AKI serum creatinine ≥ 0.3 mg/dL from baseline within 48 h from admission), and in-hospital complications and mortality were reviewed. Our main results show that female patients were older (69 vs. 60, p < 0.001) and had higher rates of diabetes (29.2% vs. 23%, p < 0.001), hypertension (62.9% vs. 41.3%, p < 0.001), and chronic kidney disease (26.7% vs. 19.3%, p < 0.001). Females also had a higher rate of AKI (12.7% vs. 7.8%, p < 0.001), and among patients with AKI, severe AKI was also more prevalent in females (26.1% vs. 14.5%, p = 0.03). However, in multivariate analyses, after adjusting for the baseline characteristics above, the female gender was a non-significant predictor for AKI (adjusted OR 1.01, 95% CI 0.73–1.4, p = 0.94) or severe AKI (adjusted OR 1.65, 95% CI 0.80–1.65, p = 0.18). In conclusion, while females had higher rates of AKI and severe AKI, gender was not independently associated with AKI after adjusting for other confounding variables. Other comorbidities that are more prevalent in females can account for the difference in AKI between genders. Full article
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11 pages, 564 KiB  
Article
BMI Modifies Increased Mortality Risk of Post-PCI STEMI Patients with AKI
by Reut Schvartz, Lior Lupu, Shir Frydman, Shmuel Banai, Yacov Shacham and Amir Gal-Oz
J. Clin. Med. 2022, 11(20), 6104; https://doi.org/10.3390/jcm11206104 - 17 Oct 2022
Cited by 4 | Viewed by 1221
Abstract
Mortality from acute ST elevation myocardial infarction (STEMI) was significantly reduced with the introduction of percutaneous catheterization intervention (PCI) but remains high in patients who develop acute kidney injury (AKI). Previous studies found overweight to be protective from mortality in patients suffering from [...] Read more.
Mortality from acute ST elevation myocardial infarction (STEMI) was significantly reduced with the introduction of percutaneous catheterization intervention (PCI) but remains high in patients who develop acute kidney injury (AKI). Previous studies found overweight to be protective from mortality in patients suffering from STEMI and AKI separately but not as they occur concurrently. This study aimed to establish the relationship between AKI and mortality in STEMI patients after PCI and whether body mass index (BMI) has a protective impact. Between January 2008 and June 2016, two thousand one hundred and forty-one patients with STEMI underwent PCI and were admitted to the Tel Aviv Medical Center Cardiac Intensive Care Unit. Their demographic, laboratory, and clinical data were collected and analyzed. We compared all-cause mortality in patients who developed AKI after PCI for STEMI and those who did not. In total, 178 patients (10%) developed AKI and had higher mortality (p < 0.001). Logistic regression analysis was performed to determine the relationship between AKI, BMI, and mortality. AKI was significantly associated with both 30-day and overall mortality, while BMI had a significant protective effect. Survival analysis found a significant difference in 30-day and overall survival between patients with and without AKI with a significant protective effect of BMI on survival at 30 days. AKI presents a major risk for mortality and poor survival after PCI for STEMI, yet a beneficial effect of increased BMI modifies it. Full article
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8 pages, 792 KiB  
Article
Biomarker-Guided Assessment of Acute Kidney Injury Phenotypes E among ST-Segment Elevation Myocardial Infarction Patients
by Ariel Banai, Shir Frydman, Hytham Abu Katash, Moshe Stark, Ilana Goldiner, Shmuel Banai and Yacov Shacham
J. Clin. Med. 2022, 11(18), 5402; https://doi.org/10.3390/jcm11185402 - 14 Sep 2022
Cited by 1 | Viewed by 1082
Abstract
Recent practice guidelines recommended the use of new stress, functional, and damage biomarkers in clinical practice to prevent and manage acute kidney injury (AKI). Biomarkers are one of the tools used to define various AKI phenotypes and provide prognostic information regardless of an [...] Read more.
Recent practice guidelines recommended the use of new stress, functional, and damage biomarkers in clinical practice to prevent and manage acute kidney injury (AKI). Biomarkers are one of the tools used to define various AKI phenotypes and provide prognostic information regardless of an acute decline in renal function. We investigated the incidence and possible implications of AKI phenotypes among ST elevation myocardial infarction patient treated with primary coronary intervention. We included 281 patients with STEMI treated with PCI. Neutrophil gelatinase associated lipocalin (NGAL) was utilized to determine structural renal damage and functional AKI was determined using the KDIGO criteria. Patients were stratified into four AKI phenotypes: no AKI, subclinical AKI, hemodynamic AKI, and severe AKI. Patients were assessed for in-hospital adverse events (MACE). A total of 46 patients (44%) had subclinical AKI, 17 (16%) had hemodynamic AKI, and 42 (40%) had severe AKI. We observed a gradual and significant increase in the occurrence of MACE between the groups being highest among patients with severe AKI (10% vs. 19% vs. 29% vs. 43%; p < 0.001). In a multivariable regression model, any AKI phenotype was independently associated with MACE with an odds ratio of 4.15 (95% CI 2.1–8.3, p < 0.001,) for subclinical AKI, 4.51 (95% CI 1.61–12.69; p = 0.004) for hemodynamic AKI, and 12.9 (95% CI 5.59–30.1, p < 0.001) for severe AKI. In conclusion, among STEMI patients, AKI is a heterogeneous condition consisting of distinct phenotypes, addition of novel biomarkers may overcome the limitations of sCr-based AKI definitions to improve AKI phenotyping and direct potential therapies. Full article
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9 pages, 542 KiB  
Article
Acute Kidney Injury Recovery Patterns in ST-Segment Elevation Myocardial Infarction Patients
by Tamar Itach, Ariel Banai, Yael Paran, David Zahler, Ilan Merdler, David Eliashiv, Shmuel Banai and Yacov Shacham
J. Clin. Med. 2022, 11(8), 2169; https://doi.org/10.3390/jcm11082169 - 13 Apr 2022
Viewed by 1363
Abstract
Background: Acute kidney injury (AKI) is a frequent complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Identification of different AKI recovery patterns may improve patient prognostic stratification. We investigated the clinical relevance of AKI recovery patterns among [...] Read more.
Background: Acute kidney injury (AKI) is a frequent complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Identification of different AKI recovery patterns may improve patient prognostic stratification. We investigated the clinical relevance of AKI recovery patterns among STEMI patients undergoing PCI. Methods: A retrospective study of 2943 STEMI patients undergoing PCI. The incidence of renal impairment, in-hospital complications, short and long-term mortality, were compared between patients without AKI, with early recovery defined as a return to baseline creatinine within 72 h, and no AKI recovery/delayed recovery defined as all other AKI cases. Results: A total of 255 (8.7%) patients developed AKI, of whom 124/255 (49%) patients had an early recovery, whereas 131/255 (51%) had no AKI recovery/delayed recovery. Patients without recovery were more likely to have in-hospital complications and higher long-term mortality (36.64% vs. 7.25%%; p < 0.001). In a multivariable regression model, the mortality hazard ratio (HR) for long term mortality remained significant for patients with no/delayed recovery AKI (HR 7.76, 95% CI 4.69 to 12.86, p < 0.001), and a strong trend among patients with resolving AKI (HR 2.09, 95% CI 0.933–4.687, p = 0.071). Conclusions: Among STEMI patients undergoing PCI, the recovery pattern of AKI is a valuable prognostic marker. Full article
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9 pages, 819 KiB  
Article
Predictive Value of Elevated Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels for Assessment of Cardio–Renal Interactions among ST-Segment Elevation Myocardial Infarction Patients
by David Zahler, Ilan Merdler, Ariel Banai, Eden Shusterman, Omri Feder, Tamar Itach, Leemor Robb, Shmuel Banai and Yacov Shacham
J. Clin. Med. 2022, 11(8), 2162; https://doi.org/10.3390/jcm11082162 - 13 Apr 2022
Cited by 9 | Viewed by 1476
Abstract
Background: Elevated serum neutrophil gelatinase-associated lipocalin (NGAL) levels reflect both inflammatory reactions and renal tubular injury. Recently, associations with endothelial dysfunction and plaque instability were also proposed. We investigated the prognostic utility of elevated NGAL levels for renal and clinical outcomes among ST-segment [...] Read more.
Background: Elevated serum neutrophil gelatinase-associated lipocalin (NGAL) levels reflect both inflammatory reactions and renal tubular injury. Recently, associations with endothelial dysfunction and plaque instability were also proposed. We investigated the prognostic utility of elevated NGAL levels for renal and clinical outcomes among ST-segment elevation myocardial infarction (STEMI) patients treated with primary coronary intervention (PCI). Methods: We performed a prospective, observational, open-label trial. High NGAL was defined as values within the third tertile (>66 percentile). Results: A total of 267 patients were included (mean age 66 ± 14 years, 81% males). Short-term adverse outcomes were consistently increased in the high NGAL group with more acute kidney injury, lower mean left ventricular ejection fraction, higher 30-day mortality, and higher incidence for the composite outcome of major adverse cardiac events (MACE). In a multivariate logistic regression model, high NGAL emerged as a strong and independent predictor for MACE (OR 2.07, 95% CI 1.15–3.73, p = 0.014). Conclusions: Among STEMI patients undergoing primary PCI, elevated NGAL levels are associated with adverse renal and cardiovascular outcomes, independent of traditional inflammatory markers. Further studies are needed to assess the potentially unique role of NGAL in cardio–renal interactions. Full article
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10 pages, 1413 KiB  
Article
Forced Diuresis with Matched Isotonic Intravenous Hydration Prevents Renal Contrast Media Accumulation
by Yael Ben-Haim, Ehud Chorin, Aviram Hochstadt, Merav Ingbir, Yaron Arbel, Shafik Khoury, Amir Halkin, Ariel Finkelstein, Shmuel Banai and Maayan Konigstein
J. Clin. Med. 2022, 11(3), 885; https://doi.org/10.3390/jcm11030885 - 08 Feb 2022
Cited by 2 | Viewed by 1530
Abstract
The accumulation of contrast media in the kidneys might lead to contrast-induced acute kidney injury. In this prospective, controlled observational study, we aimed to evaluate whether forced diuresis with matched isotonic intravenous hydration prevents the accumulation of contrast media in the kidneys of [...] Read more.
The accumulation of contrast media in the kidneys might lead to contrast-induced acute kidney injury. In this prospective, controlled observational study, we aimed to evaluate whether forced diuresis with matched isotonic intravenous hydration prevents the accumulation of contrast media in the kidneys of patients undergoing cardiac interventional procedures. We compared the intensity of contrast media accumulation as observed in nephrograms following these procedures, with and without peri-procedural controlled renal flushing. The study group consisted of 25 patients with impaired renal function treated with the RenalGuard system. The two control groups included 25 patients with normal kidney function and 8 patients with impaired renal function undergoing similar procedures with routine pre-procedural hydration, but without controlled renal flushing. Renal contrast media accumulation at the end of each procedure was scored by blinded cardiologists. The renal contrast accumulation score (CAS) in the study group was significantly lower, with a median score of 0 (IQR (0–0)) compared with 1.5 (IQR (1–2)) in the normal renal function control group and 1 (IQR (0.38–1.62)) in the impaired renal function control group (p < 0.001 and 0.003, respectively). In a multivariate analysis of CAS, RenalGuard treatment was independently associated with lower CAS compared to both control groups. In conclusion, RenalGuard use prevents renal contrast accumulation in patients with impaired renal function undergoing cardiac procedures with intra-arterial contrast media injection. Full article
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