[Multiplex analysis of post-Covid cardiorenal complications in patients with type 1 and type 2 diabetes mellitus according to the mobile diagnostic and treatment center (Diamobil)].

BACKGROUND: Patients with diabetes mellitus (DM) are at risk for a higher incidence and severity of COVID-19, as well as its adverse outcomes, including post-Covid syndrome. AIM: to assess the incidence of cardiorenal complications in patients with type 1 and type 2 diabetes (T1DM/T2DM) who have had COVID-19, and to analyze the structure and severity of disorders according to examination data at the Diamobil mobile medical diagnostic and treatment center. MATERIALS AND METHODS: a cohort of T1DM and T2DM patients examined in Diamobil (n=318), with a confirmed anamnesis of COVID-19 (n=236). The time interval between COVID-19 and the visit to Diamobil was 8.7/8.2 months for T1DM/T2DM. The parameters of the last visit before COVID-19 recorded in the Federal Register of Diabetes (FRD) were used as initial data. RESULTS: Clinical characteristics of patients with T1DM/T2DM: age - 49.2/64.5 years, duration of DM - 22/11 years, proportion of women - 64/73%, respectively. After analysis the data from visits before and after COVID-19 there weren't statistically significant differences in HbA1c levels for both types of DM (before 9.0/8.3%; after 8.4/8.2%, respectively), there was the intensification of glucose lowering therapy (the proportion of patients with T2DM on 2 and 3 component therapy increased by 4.3% and 1.6%, the proportion of patients on insulin therapy by 16%). After COVID-19, there was a statistically significant decrease in glomerular filtration rate (GFR) in T1DM from 88.1 to 62 ml/min/1.73 m2; with T2DM from 74.7 to 54.1 ml/min/1.73 m2. When assessing acute diabetic complications, there was an increase in the frequency of coma in T1DM by 1.5 times, severe hypoglycemia in T1DM by 3 times, and in T2DM by 1.7 times. Analysis of the frequency of cardiorenal complications before and after COVID-19 showed a total increase of 8.5% in T1DM, by 13.2% in T2DM, of which myocardial infarction, ischemic heart disease, and CHF increased in T1DM in the range from 1.5 to 5 times, with T2DM by 1.3 times, the frequency of CKD with T1DM by 1.5 times, with T2DM by 5.6 times. CONCLUSION: There was a decline of kidney filtration function (decrease in GFR) and an increase in the frequency of cardiovascular complications in both types of diabetes in post-Covid period while patients achieved a stable HbA1c levels by intensifying therapy during the COVID-19 infection. This fact reflects combined damage to the kidney and cardiovascular system as a part of the post-Covid syndrome and determines a key set of measures for the development of preventive strategies.

A new animal model of cardiorenal syndrome could be established by inducing heart failure through coronary artery ligation in spontaneously hypertensive rats.

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin-angiotensin-aldosterone system.

Biomarker for cardiorenal syndrome risk in patients with liver cirrhosis and type 2 diabetes in Saudi Arabia.

OBJECTIVES: To evaluate the correlation between different attributes, levels of biomarkers, and the probability of developing cardiorenal syndrome (CRS) in patients who have been diagnosed with type 2 diabetes mellitus (T2DM) and liver cirrhosis (LC). The hypothesis suggests that liver illness may be linked to renal impairment, cardiac dysfunction, and the development of cardiorenal syndrome METHODS: The current study retrospectively assessed the medical records of patients who had LC and T2DM diagnoses and were hospitalized at Al Madina Al Munwara hospitals in 2022 and 2023. RESULTS: This research investigated T2DM patients with physician-confirmed to have LC. Poor glycemic control is indicated by high blood glucose and glycated hemoglobin (HbA1c) readings in research participants. High blood pressure, atherogenic plasma indicator (AIP), and obesity plagued most of these individuals. High creatinine, moderate estimated Glomerular Filtration Rate (eGFR) decline, and a modest urinary albumin-to-creatinine (UACR) rise were the most prevalent variables in LC and T2DM patients. Cardiorenal syndrome risk factors, including elevated blood pressure, triglyceride levels, body mass index (BMI), and high-sensitivity C-reactive protein (hs-CRP) concentrations, were identified through logistic regression. It has been demonstrated that the prevalence of these risk factors increases with age; women may be at a greater risk for developing CRS. Specific biomarker evaluations classified 108 (22.6%) LC and T2DM patients at high risk for chronic kidney disease (CKD), 100 (20%) at risk for cardiovascular disease (CVD), and 91 (18.2%) at risk for CRS. CONCLUSION: The current assessment included 500 patients with T2DM and LC. The risk factors for CRS identified in this study included elevated cholesterol and triglyceride levels, high BMI, and elevated blood pressure, with age being a significant factor, particularly in female patients. Early identification of these characteristics in patients with LC and T2DM could aid in mitigating the progression of chronic illnesses and their associated complications.

Risk factors and early prediction of cardiorenal syndrome type 3 among acute kidney injury patients: a cohort study.

BACKGROUND: Type 3 cardiorenal syndrome (CRS type 3) triggers acute cardiac injury from acute kidney injury (AKI), raising mortality in AKI patients. We aimed to identify risk factors for CRS type 3 and develop a predictive nomogram. METHODS: In this retrospective study, 805 AKI patients admitted at the Department of Nephrology, Second Hospital of Shanxi Medical University from 1 January 2017, to 31 December 2021, were categorized into a study cohort (406 patients from 2017.1.1-2021.6.30, with 63 CRS type 3 cases) and a validation cohort (126 patients from 1 July 2021 to 31 Dec 2021, with 22 CRS type 3 cases). Risk factors for CRS type 3, identified by logistic regression, informed the construction of a predictive nomogram. Its performance and accuracy were evaluated by the area under the curve (AUC), calibration curve and decision curve analysis, with further validation through a validation cohort. RESULTS: The nomogram included 6 risk factors: age (OR = 1.03; 95%CI = 1.009-1.052; p = 0.006), cardiovascular disease (CVD) history (OR = 2.802; 95%CI = 1.193-6.582; p = 0.018), mean artery pressure (MAP) (OR = 1.033; 95%CI = 1.012-1.054; p = 0.002), hemoglobin (OR = 0.973; 95%CI = 0.96--0.987; p < 0.001), homocysteine (OR = 1.05; 95%CI = 1.03-1.069; p < 0.001), AKI stage [(stage 1: reference), (stage 2: OR = 5.427; 95%CI = 1.781-16.534; p = 0.003), (stage 3: OR = 5.554; 95%CI = 2.234-13.805; p < 0.001)]. The nomogram exhibited excellent predictive performance with an AUC of 0.907 in the study cohort and 0.892 in the validation cohort. Calibration and decision curve analyses upheld its accuracy and clinical utility. CONCLUSIONS: We developed a nomogram predicting CRS type 3 in AKI patients, incorporating 6 risk factors: age, CVD history, MAP, hemoglobin, homocysteine, and AKI stage, enhancing early risk identification and patient management.

Rat Models of Cardiorenal Syndrome and Methods for Functional Assessment.

Cardiorenal syndrome (CRS) is a clinical disorder involving combined heart and kidney dysfunction, which leads to poor clinical outcomes. To understand the complex pathophysiology and mechanisms that lie behind this disease setting, and design/evaluate appropriate treatment strategies, suitable animal models are required. Described here are the protocols for establishing surgically induced animal models of CRS including important methods to determine clinically relevant measures of cardiac and renal function, commonly used to assess the degree of organ dysfunction in the model and treatment efficacy when evaluating novel therapeutic strategies.

Pulmonary hypertension without heart failure causes cardiorenal syndrome in a porcine model.

Cardiorenal syndromes type 1 and 2 are complex disorders in which cardiac dysfunction leads to kidney dysfunction. However, the mechanisms remain incompletely explained, during pulmonary hypertension in particular. The objective of this study is to develop an original preclinical model of cardiorenal syndrome secondary to a pulmonary hypertension in piglets. Twelve 2-month-old Large White piglets were randomized in two groups: (1) induction of pulmonary hypertension by ligation of the left pulmonary artery and iterative embolizations of the right lower pulmonary artery, or (2) Sham interventions. We evaluated the cardiac function using right heart catheterization, echocardiography and measurement of biochemistry markers). Kidney was characterized using laboratory blood and urine tests, histological evaluation, immunostainings for renal damage and repair, and a longitudinal weekly assessment of the glomerular filtration rate using creatinine-based estimation and intravenous injection of an exogenous tracer on one piglet. At the end of the protocol (6 weeks), the mean pulmonary artery pressure (32 ± 10 vs. 13 ± 2 mmHg; p = 0.001), pulmonary vascular resistance (9.3 ± 4.7 vs. 2.5 ± 0.4 WU; p = 0.004) and central venous pressure were significantly higher in the pulmonary hypertension group while the cardiac index was not different. Piglets with pulmonary hypertension had higher troponin I. We found significant tubular damage and an increase in albuminuria in the pulmonary hypertension group and negative correlation between pulmonary hypertension and renal function. We report here the first porcine model of cardiorenal syndrome secondary to pulmonary hypertension.

Syringaresinol inhibits cardiorenal fibrosis through HSP90 in a cardiorenal syndrome type 2.

BACKGROUND: Syringaresinol processes anti-inflammatory and antioxidative activity. However, the effects of syringaresinol on cardiorenal fibrosis caused by cardiorenal syndrome type 2 (CRS2) are unclear. METHODS: Molecular docking predicted binding activity of syringaresinol to heat shock protein 90 (HSP90). The toxicity of a 4-weeks treatment with 20 mg/kg of syringaresinol was observed by measuring serum pro-inflammatory cytokines levels and by cardiorenal pathology. A CRS2 rad model was established by myocardial infarction using ligation over an 8 week-period. Rats were divided into five groups, including sham, CRS2, pimitespib, syringaresinol, and HSP90 + syringaresinol. Rats were received a 4-weeks daily treatment with 10 mg/kg pimitespib (a HSP90 inhibitor) or 20 mg/kg syringaresinol. Recombinant adeno-associated virus (rAAV) carrying a periostin (PE) promoter driving the expression of wild-type HSP90 (rAAV9-PE-HSP90, 1 × 1011 µg) was treated intravenously once in CRS2 model rats. Cardiorenal function and pathology were assessed. Expressions of HSP90 and TGF-ß1 in the myocardium and kidney were measured by immunohistochemistry and western blotting. RESULTS: Syringaresinol showed good binding activity with HSP90, and no signs of toxicity in rats following treatment. Pimitespib or syringaresinol significantly improved the cardiorenal function and fibrosis in rats with CRS2. Meanwhile, the rAAV9-PE-HSP90 injection obviously blocked the effects of syringaresinol. CONCLUSIONS: Syringaresinol targets HSP90 to suppress CRS2-induced cardiorenal fibrosis, providing a promising therapeutic drug for CRS2.

The impact of preoperative kidney replacement therapy on kidney outcome and survival in patients with left ventricular assist device.

Left ventricular assist device (LVAD) has been highlighted as a new treatment option in the end-stage heart failure (HF). Kidney outcome after LVAD in severe cardiorenal syndrome (CRS) patients requiring kidney replacement therapy (KRT) is unclear. We investigated the impact of preoperative KRT on kidney function and survival in LVAD patients with severe CRS. A total of 50 patients followed up for at least 1 year after LVAD implantation was analyzed. The primary outcomes were estimated glomerular filtration rate and survival rate. Patients were divided into two groups depending on in-hospital KRT before LVAD implantation: the control group (n = 33) and the KRT group (n = 17). Postoperative KRT was performed for 76.5% of patients in the KRT group, and all of them discontinued KRT before discharge. There were no statistically significant differences in the degree of eGFR decline in survivors according to preoperative KRT. Although there were no statistically significant differences in the degree of eGFR decline in survivors regardless of preoperative KRT, old age (ß -0.94, p < 0.01), preexisting chronic kidney disease (ß -21.89, p < 0.01), and high serum creatinine (ß -13.95, p < 0.01) were identified as independent predictors of post-LVAD eGFR decline. Mortality rate was higher, and more patients progressed to end-stage kidney disease in KRT group than control group. However, LVAD still can be considered as the treatment option in end-stage HF patients with severe CRS requiring KRT, especially in those with young age and previous normal kidney function.

Recent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review.

Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.

[Italian Society of Cardiology-Italian Society of Nephrology Consensus document: The cardio-renal interaction in the prevention and treatment of cardiovascular diseases - Part I: From cardiovascular risk factors to the mechanisms of cardio-renal syndrome]. / Documento di consenso Società Italiana di Cardiologia- Società Italiana di Nefrologia: Ruolo dell'asse cardio-renale nella prevenzione e trattamento delle patologie cardiovascolari ­ Parte I: Dai fattori di rischio cardiovascolare ai meccanismi di danno cardio-renale.

Chronic kidney disease (CKD) and cardiovascular (CV) disease are highly prevalent conditions in the general population and are strictly connected to each other with a bidirectional interaction. In patients affected by CKD, the leading cause of morbidity and mortality is represented by CV disease, since CKD promotes the atherosclerotic process increasing inflammation, and modifying lipid and bone mineral metabolism. On the other side, a strict relationship exists between CKD and CV risk factors, which are prevalent in nephropathic patients and impose a stringent assessment of the risk of CV events in this population together with an optimized pharmacological approach, complicated by the coexistence of the two pathological conditions. The first part of this consensus document focuses on the mechanisms of cardio-renal damage and on the impact, as well as the management, of the main CV risk factors in the context of CKD.

Modulation of cardiometabolic risk and CardioRenal syndrome by oral vitamin D3 supplementation in Black and White Southern Sahara residents with chronic kidney disease Stage 3: focus on racial and ethnic disparities.

OBJECTIVES: Several studies have shown that cholecalciferol supplementation (25OHD-S) in chronic kidney disease (CKD) improves kidney injury by reducing fibrosis-related vascular calcification and declining apoptosis-linked nephron damage. METHODS: The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/d/24 weeks in CKD Stage 3 with serum 25OHD level < 20 ng/mL. The study was undertaken on 156 black subjects and 150 white subjects Southern Sahara (SS). All biomarkers of cardiometabolic (CMet) and cardiorenal (CRenal) syndrome, Renin-angiotensin-aldosterone system (RAAS) profile, secondary hyperparathyroidism (SHPT), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin T (cTnT) and atherogenicity risk were assessed by biochemical methods. Estimate glomerular filtration rate (eGFR) by chronic CKD-EPI equation formula. Total serum vitamin D by liquid chromatography-tandem mass spectrometry (MS). RESULTS: Vitamin D deficiency alters in the same manner CMet, CRenal, and others biomarkers in both groups SS; however, these disorders are more acute in blacks compared to whites SS. Oral 25OHD-S a highlighted improvement of eGFR drop, SHPT decrease, decline proteinuria, and cardiac failure risk (NT-proBNP and cTnT) attenuation. Concomitantly, 25OHD-S normalizes Renin, Aldosterone, and Angiotensin System (RAAS) activity. Nevertheless, homocysteine and Lp (a) do not modulate by 25OHD-S. CONCLUSIONS: The oral vitamin D3 supplementation, according the dose, and the treatment duration does not like in black-skinned people versus to white-skinned inhabitants, while the 02 groups are native to the same Saharan environment. It emerge that a high intermittent dose through an extensive supplementation (60,000 IU/36 weeks) was more effective in black subjects. At opposite, a lower dose during a short period supplementation is sufficient (2000 IU/24 weeks) in white subjects.

Long-term impact of cardiorenal syndromes on major outcomes based on their chronology: a comprehensive French nationwide cohort study.

BACKGROUND: Cardiorenal syndromes (CRSs) are reputed to result in worse prognosis than isolated heart failure (HF) and chronic kidney disease (CKD). Whether it is true for all major outcomes over the long-term regardless of CRS chronology (simultaneous, cardiorenal and renocardiac CRS) is unknown. METHODS: The 5-year adjusted risk of major outcomes was assessed in this nationwide retrospective cohort study in all 385 687 with either CKD or HF (out of 5 123 193 patients who were admitted in a French hospital in 2012). RESULTS: Overall, 84.0% patients had HF and 8.9% had CKD (they had similar age, sex ratio, diabetes and hypertension prevalence), while 7.1% had CRS (cardiorenal: 44.6%, renocardiac: 14.5%, simultaneous CRS: 40.8%).The incidence of major outcomes was 57.3%, 53.0%, 79.2% for death; 18.8%, 10.9%, 27.5% for cardiovascular death; 52.6%, 34.7%, 64.3% for HF; 6.2%, 5.5%, 5.6% for myocardial infarction (MI); 6.1%, 5.8%, 5.3% for ischaemic stroke; and 23.1%, 4.8%, 16.1% for end-stage kidney disease (ESKD) for isolated CKD, isolated HF and CRS, respectively.As compared with isolated CKD or HF, the risk of death, cardiovascular death and HF was markedly increased in CRS, the worse phenotype being cardiorenal CRS, while the increased risk of MI and ischaemic stroke associated with CRS subtypes was statistically but not clinically significant. As compared with isolated CKD, the risk of ESKD was similar for cardiorenal CRS only and marginally increased for renocardiac and simultaneous CRS. We could not find a synergy between HF and CKD on major clinical outcomes in the whole population (n = 5 123 193 patients). CONCLUSIONS: The additional impact of CRS versus isolated HF or CKD on long-term kidney and cardiovascular risk is highly heterogenous, depending of the event considered and CRS chronology. No synergy between HF and CKD could be demonstrated.

Renal Compression in Heart Failure: The Renal Tamponade Hypothesis.

Renal dysfunction is one of the strongest predictors of outcome in heart failure. Several studies have revealed that both reduced perfusion and increased congestion (and central venous pressure) contribute to worsening renal function in heart failure. This paper proposes a novel factor in the link between cardiac and renal dysfunction: "renal tamponade" or compression of renal structures caused by the limited space for expansion. This space can be limited either by the rigid renal capsule that encloses the renal interstitial tissue or by the layer of fat around the kidneys or by the peritoneal space exerting pressure on the retroperitoneal kidneys. Renal decapsulation in animal models of heart failure and acute renal ischemia has been shown effective in alleviating pressure-related injury within the kidney itself, thus supporting this concept and making it a potentially interesting novel treatment in heart failure.

Murine models of uremic cardiomyopathy as a necessary tool to unravel mechanisms involved in cardiorenal syndrome.

Chronic kidney disease (CKD) and cardiovascular disease frequently run in parallel. Herein, Soppert et al. provide an interesting meta-analysis of the effects of CKD on cardiac remodeling and/or function in mice based on the model, strain, and duration. The authors sought to determine the most appropriate experimental model to unravel the specific underlying pathologic mechanisms involved in cardiac damage in CKD (single hit) or to investigate new strategies to prevent CKD-induced cardiovascular disease (multifactorial hits representing cardiovascular comorbidities of patients with CKD).

Arterial-renal Syndrome in Patients with ESRD, a New Disease Paradigm.

BACKGROUND: Patients with end-stage renal disease (ESRD) often present with an increased risk of cardiovascular disease. Conditions of compromised cardiovascular health such as atrial fibrillation (AFIB) and peripheral arterial disease (PAD) may alter biomarker levels in a way that reflects worsening ESRD. This study profiled biomarkers and laboratory parameters of endothelium dysfunction in patients with ESRD, categorized by additional AFIB and PAD conditions. METHODS: Citrated blood samples were collected from 95 patients with ESRD. Biomarker levels were measured from plasma samples using sandwich ELISAs, including tissue plasminogen activator (tPA), D-dimer, and nitrotyrosine. Lab parameters, including BUN, calcium, creatinine, parathyroid hormone, phosphate, alkaline phosphatase, ferritin, transferrin, and total iron capacity, and patient comorbidities were obtained from patient medical records. The comorbidities were determined through provider notes, and evidence of applicable testing. RESULTS: 14.89% of patients were found to have atrial fibrillation (n = 14), 30.85% of patients were found to have peripheral arterial disease (n = 29), and 6.38% of patients were found to have both peripheral arterial disease and atrial fibrillation (n = 6). When compared to patients with only ESRD, patients with ESRD and PAD showed elevated levels of D-Dimer (p = .0314) and nitrotyrosine (p = .0330). When compared to patients with only ESRD, patients with atrial fibrillation showed elevated levels of D-Dimer (p = .0372), nitrotyrosine (p = .0322), and tPA (p = .0198). CONCLUSION: When compared to patients with just ESRD, patients with concomitant PAD had elevated levels of Nitrotyrosine and D-dimer; while patients with concomitant Afib had elevated levels of nitrotyrosine, D-dimer, as well as tPA.

Relation of Cardiorenal Syndrome to Mitral and Tricuspid Regurgitation in Acute Decompensated Heart Failure.

This study aimed to investigate the role of secondary mitral regurgitation (MR) and tricuspid regurgitation (TR) in the pathogenesis of cardiorenal syndrome (CRS). Worsening renal function in patients with acute decompensated heart failure receiving diuretic therapy is defined as CRS and is related to central venous congestion. The role of secondary MR and TR is not well studied. We retrospectively reviewed the electronic medical records of 80 consecutive patients hospitalized with acute decompensated heart failure. Patients were divided into 2 groups: group 1 (CRS) if creatinine increased >0.3 mg/dl from baseline and group 2 (no CRS) if creatinine remained stable or improved with diuretic therapy. Admission creatinine was higher in group 1 compared with group 2 (1.5 vs 1.2 mg/dl, p = 0.033). The magnitude of MR and TR were higher by both visual assessment (moderate to severe [3+] or severe [4+] MR in 68% of patients in group 1 vs 3% in group 2, p <0.0001; 3+ or 4+ TR in 48% of patients in group 1 vs 10% in group 2, p = 0.0004) and by vena contracta (MR 0.6 ± 0.2 cm in group 1 vs 0.4 ± 0.1 cm in group 2, p <0.0001; TR 0.5 ± 0.2 cm in group 1 vs 0.4 ± 0.2 cm in group 2, p = 0.0013). By using receiver operating characteristic curves, MR and TR were the most sensitive parameters in predicting CRS. In conclusion, renal function on admission and moderate to severe or severe MR and TR are highly predictive of the risk of developing CRS.

Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure.

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.