Anisodamine for the prevention of contrast-induced nephropathy in patients with acute coronary syndrome: a pilot systematic review and meta-analysis of randomized controlled trials.

Introduction: Contrast-induced nephropathy (CIN) is a common post-procedural complication of percutaneous coronary intervention for acute myocardial infarction (AMI). Anisodamine hydrobromide is an alkaloid that has demonstrated efficacy in improving microcirculation. This meta-analysis aims to evaluate the reno-protective effects of Anisodamine in patients undergoing percutaneous coronary intervention (PCI) for AMI. Methods: PubMed, Embase, Cochrane Library, Scopus, and clinicaltrials.gov were searched from inception to January 2024 for randomized controlled trials (RCTs) comparing the efficacy of Anisodamine in preventing the development of CIN. Outcomes of interest included the incidence of CIN, serum creatinine levels, and estimated glomerular filtration rate (eGFR). A random-effects model was used for pooling standard mean differences (SMDs) and odds ratios (ORs) with a 95% CI. Statistical significance was considered at a P less than 0.05. Results: Three RCTs involving 563 patients were included. Anisodamine was associated with a reduction in the incidence of CIN [OR: 0.44; 95% CI: 0.28, 0.69; P=0.0003], a reduction in serum creatinine levels at 48 [SMD: -6.78; 95% CI: -10.54,-3.02; P=0.0004] and 72 h [SMD: -6.74; 95% CI: -13.33,-0.15; P=0.03], and a higher eGFR at 24 [SMD: 5.77; 95% CI: 0.39, 11.14; P=0.03], and 48 h [SMD: 4.70; 95% CI: 2.03,7.38; P=0.0006]. The levels of serum creatinine at 24 h and eGFR value at 72 h were comparable between both groups. Conclusions: Anisodamine has demonstrated clinical efficacy in ameliorating the development of CIN post-PCI in AMI patients. Large, multi-centric RCTs are warranted to evaluate the robustness of these findings.

Association between Pan-Immune-Inflammation Value and Contrast-Induced Nephropathy with Coronary Angiography.

Background: Contrast-induced nephropathy (CIN) is one of the most important complications after invasive cardiovascular procedures. Considering the pivotal role of inflammation in CIN development, the use of peripheral blood-based indexes may be an easily available biomarker to predict CIN risk. Therefore, in the present study, we evaluated the association between the pan-immune-inflammation value (PIV) and the risk of CIN. Patients and Methods: A total of 1343 patients undergoing coronary angiography (CAG) were included. The PIV was calculated with the following equation: (neutrophil count × platelet count × monocyte count)/lymphocyte count. Multivariable regression analyses were used to determine the association between clinical and laboratory parameters and CIN development. Results: The median age of the cohort was 58 (IQR 50-67), and 48.2% of the patients were female. CIN developed in 202 patients (15%) in follow-up. In multivariate analyses, older age (OR: 1.015, 95% CI: 1.002-1.028, p = 0.020) and higher PIV levels (OR: 1.016, 95% CI: 1.004-1.028, p = 0.008) were associated with a higher CIN risk, while the use of antiplatelet agents was associated with a lower risk of CIN (OR: 0.670, 95% CI: 0.475-0.945, p = 0.022). Conclusions: We demonstrated that the risk of CIN was significantly higher in patients with higher PIV and older patients in a large cohort of patients undergoing CAG for stable ischemic heart disease. If supported with prospective evidence, PIV levels could be used as a minimally invasive reflector of CIN.

Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy.

BACKGROUND: Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl2) can protect renal tubules, the protective effect and potential mechanism of action of CoCl2 on contrast-induced nephropathy (CIN) warrant investigation. METHODS: A CIN mouse model was established to determine the protective effect of CoCl2 on renal injury in vivo. Then, TMT-based proteomics was performed to determine the differentially expressed proteins (DEPs), following which, enrichment analyses of gene ontology and the KEGG pathway were performed. In vitro, a CIN model was constructed with renal tubular epithelial cells (HK-2) to determine the effect of CoCl2 on potential targets and the role of the key protein identified from the in vivo experiments. RESULTS: CoCl2 treatment decreased the levels of BUN and serum creatinine (sCr), while increasing the levels of urea and creatinine (Cr) in the urine of mice after CIN injury. Damage to the renal tubules in the CoCl2 treatment group was significantly less than in the CIN model group. We identified 79 DEPs after treating the in vivo model with CoCl2, and frequently observed ferroptosis-related GO and KEGG pathway terms. Of these, Hp (haptoglobin) was selected and found to have a strong renoprotective effect, even though its expression level in kidney tissue decreased after CoCl2 treatment. In HK-2 cells, overexpression of Hp reduced the ferroptosis caused by erastin, while knocking down Hp negated the attenuation effect of CoCl2 on HK-2 cell ferroptosis. CONCLUSION: CoCl2 attenuated kidney damage in the CIN model, and this effect was associated with the decrease in ferroptosis mediated by Hp.

Association between Systolic Pulmonary Artery Pressure and Contrast-Induced Nephropathy in Patients with ST-Segment Elevation Myocardial Infarction.

Introduction: The objective of this study was to examine whether there is an elevated risk of developing contrast induced nephropathy (CIN) in patients with high systolic pulmonary artery pressure (SPAP) in ST-segment elevation myocardial infarction (STEMI). Methods: A total of 213 patients diagnosed with STEMI and who underwent primary percutaneous coronary intervention were enrolled in the study. The patients were stratified into two groups based on the presence of CIN. Comparisons between these groups included an assessment of demographic characteristics, laboratory findings, and risk factors. SPAP was calculated for each patient upon admission through echocardiography, and subsequent comparisons were performed between the groups. Results: The distribution of the study population was as follows: 33 (15.5%) were CIN(+) and 180 (84.5%) were CIN(-). SPAP [odds ratio (OR) = 1.295, 95% confidence interval (CI): 1.157-1.451, p < 0.001], and diabetes (OR = 1.241, 95% CI: 1.194-1.287, p = 0.013) were identified as independent factors associated with CIN development. In receiver operating characteristic curve analysis, SPAP above a cut-off level of 31.5 mmHg could determine the presence of CIN with a sensitivity of 91.0% and specificity of 90.0% (p < 0.001). Conclusions: SPAP on echocardiography is an independent predictor of the development of CIN in patients with STEMI. Its ease of calculation renders it a valuable tool for predicting CIN among STEMI patients.

The Effect of Contrast Rationing on the Development of Acute Kidney Injury During the Global Contrast Shortage.

BACKGROUND: In April of 2022, the COVID-19 pandemic resulted in a global shortage of intravenous contrast media (ICM), which led our health care system to implement rationing measures. STUDY OBJECTIVES: We set out to determine if the reduction in ICM use was associated with a change in the incidence of acute kidney injury (AKI). METHODS: We conducted a multicenter retrospective cohort analysis to compare the incidence of AKI in patients who presented before and after ICM rationing. Adult patients who had a CT of the abdomen performed who had at least 2 creatinine measurements, at least 24 h apart, were included. The maximum increase in creatinine was determined by subtracting the maximal creatinine obtained within 7 days with the initial creatinine. The primary outcome was the development of AKI. RESULTS: A total of 2168 patients met inclusion criteria (1082 before; 1086 after). There was no significant difference in age, gender, comorbid conditions, disposition, or initial estimated glomerular filtration rate between groups. In the prerationing group, 87.7% of patients received ICM compared to 42.7% after. There was no significant difference in the development of AKI between groups (11.1% vs. 11.0%), including when stratified by baseline renal function and adjusted for age, sex, race, comorbid conditions, and emergency severity index. CONCLUSIONS: The dramatic reduction in ICM use that resulted from the global shortage was not associated with a change in the incidence of AKI. This reinforces the results of previous studies which have failed to find evidence of a relationship between ICM administration and AKI.

Safety of ultra-low contrast coronary angiography in patients with acute kidney injury.

BACKGROUND: Ultra-low contrast administration during coronary angiography has been previously shown to be feasible and safe among patients with stable chronic kidney disease. In the present study, we investigate the safety of ultra-low contrast coronary angiography in patients with pre-existing acute kidney injury (AKI). METHODS: The study was a retrospective single-center evaluation of hospitalized patients who had AKI and required coronary angiography. Ultra-low contrast use was defined as ≤18 mL of contrast media. RESULTS: The cohort consisted of a case series of eight inpatients with AKI who required coronary angiography. The mean age was 57 (±16) years and half were females. All patients had chronic kidney disease with a mean baseline estimated glomerular filtration rate of 34 (±17) mL/min/1.73 m2. The mean creatinine before angiography was 3 (±1) mg/dL and volume of contrast administered was 14 (±4) mL. One patient had a 0.1 mg/dL increase in creatinine during admission, and no patients had further AKI up to 1-week postprocedure. CONCLUSIONS: The current data suggest that ultra-low contrast coronary angiography can be safely performed in patients with pre-existing AKI The study should be viewed as hypothesis-generating due to its small sample size. A larger cohort is required to validate the results.

Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy / La desregulación de ferroptosis puede participar en el efecto mitigador de CoCl2 en la nefropatía inducida por contraste

Background: Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl2) can protect renal tubules, the protective effect and potential mechanism of action of CoCl2 on contrast-induced nephropathy (CIN) warrant investigation. Methods: A CIN mouse model was established to determine the protective effect of CoCl2 on renal injury in vivo. Then, TMT-based proteomics was performed to determine the differentially expressed proteins (DEPs), following which, enrichment analyses of gene ontology and the KEGG pathway were performed. In vitro, a CIN model was constructed with renal tubular epithelial cells (HK-2) to determine the effect of CoCl2 on potential targets and the role of the key protein identified from the in vivo experiments. Results: CoCl2 treatment decreased the levels of BUN and serum creatinine (sCr), while increasing the levels of urea and creatinine (Cr) in the urine of mice after CIN injury. Damage to the renal tubules in the CoCl2 treatment group was significantly less than in the CIN model group. We identified 79 DEPs after treating the in vivo model with CoCl2, and frequently observed ferroptosis-related GO and KEGG pathway terms. Of these, Hp (haptoglobin) was selected and found to have a strong renoprotective effect, even though its expression level in kidney tissue decreased after CoCl2 treatment. In HK-2 cells, overexpression of Hp reduced the ferroptosis caused by erastin, while knocking down Hp negated the attenuation effect of CoCl2 on HK-2 cell ferroptosis. Conclusion: CoCl2 attenuated kidney damage in the CIN model, and this effect was associated with the decrease in ferroptosis mediated by Hp.(AU)

Antecedentes: Los agentes de contraste pueden inducir isquemia tubular renal y daño hipóxico de manera directa o indirecta. Dado que el cloruro de cobalto (CoCl2) puede proteger los túbulos renales, el efecto protector y el mecanismo de acción potencial de CoCl2 en la nefropatía inducida por contraste (NIC) merecen ser investigados. Métodos: Se estableció un modelo de NIC en ratones para determinar el efecto protector de CoCl2 en la nefropatía in vivo. Seguidamente, se realizó un análisis proteómico por TMT para determinar las proteínas diferencialmente expresadas (DEP) y, a continuación, un análisis de enriquecimiento de ontología genética y vía KEGG. In vitro, se construyó un modelo NIC en células epiteliales de túbulos renales (HK-2) para determinar el efecto de CoCl2 en los objetivos potenciales y el rol de la proteína clave identificada en los experimentos in vivo. Resultados: El tratamiento con CoCl2 redujo los niveles de BUN y de creatinina sérica e incrementó, a la vez, los de urea y creatinina en la orina de los ratones, tras la lesión NIC. El daño a los túbulos renales en el grupo de tratamiento con CoCl2 fue significativamente menor que en el grupo de modelo NIC. Identificamos 79 DEP tras el tratamiento en el modelo in vivo con CoCl2 y observamos con frecuencia ontología genética relacionada con ferroptosis y términos de vías KEGG. De ellos, se seleccionó la haptoglobina (Hp) y se encontró que tenía un fuerte efecto renoprotector, aun cuando su nivel de expresión en el tejido renal se redujo tras el tratamiento con CoCl2. En las células HK-2, la sobreexpresión de Hp redujo la ferroptosis causada por erastina, a pesar de que el descenso de Hp negó el efecto atenuador de CoCl2 en la ferroptosis de las células HK-2. Conclusión: El CoCl2 atenuó el daño renal en el modelo NIC y se asoció este efecto al descenso de ferroptosis mediada por Hp.(AU)

Evaluating biomarkers for contrast-induced nephropathy following coronary interventions: an umbrella review on meta-analyses.

BACKGROUND: Contrast-induced nephropathy (CIN) is a form of acute kidney injury (AKI) occurring in patients undergoing cardiac catheterization, such as coronary angiography (CAG) or percutaneous coronary intervention (PCI). Although the conventional criterion for CIN detection involves a rise in creatinine levels within 72 h after contrast media injection, several limitations exist in this definition. Up to now, various meta-analyses have been undertaken to assess the accuracy of different biomarkers of CIN prediction. However, the existing body of research lacks a cohesive overview. To address this gap, a comprehensive umbrella review was necessary to consolidate and summarize the outcomes of prior meta-analyses. This umbrella study aimed to offer a current, evidence-based understanding of the prognostic value of biomarkers in predicting CIN. METHODS: A systematic search of international databases, including PubMed, Scopus, and Web of Science, from inception to December 12, 2023, was conducted to identify meta-analyses assessing biomarkers for CIN prediction. Our own meta-analysis was performed by extracting data from the included studies. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were assessed using Meta-Disc and CMA softwares. RESULTS: Twelve studies were ultimately included in the umbrella review. The results revealed that neutrophil gelatinase-associated lipocalin (NGAL) exhibited the highest area under the curve (AUC), followed by cystatin-C, urinary kidney injury molecule-1 (uKIM-1), and brain natriuretic peptide (BNP) with AUCs of 0.91, 0.89, 0.85, and 0.80, respectively. NGAL also demonstrated the highest positive likelihood ratio [effect size (ES): 6.02, 95% CI 3.86-9.40], followed by cystatin-C, uKIM-1, and BNP [ES: 4.35 (95% CI 2.85-6.65), 3.58 (95% CI 2.75-4.66), and 2.85 (95% CI 2.13-3.82), respectively]. uKIM-1 and cystatin-C had the lowest negative likelihood ratio, followed by NGAL and BNP [ES: 0.25 (95% CI 0.17-0.37), ES: 0.25 (95% CI 0.13-0.50), ES: 0.26 (95% CI 0.17-0.41), and ES: 0.39 (0.28-0.53) respectively]. NGAL emerged as the biomarker with the highest diagnostic odds ratio for CIN, followed by cystatin-C, uKIM-1, BNP, gamma-glutamyl transferase, hypoalbuminemia, contrast media volume to creatinine clearance ratio, preprocedural hyperglycemia, red cell distribution width (RDW), hyperuricemia, neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), high-sensitivity CRP, and low hematocrit (P < 0.05). CONCLUSION: NGAL demonstrated superior diagnostic performance, exhibiting the highest AUC, positive likelihood ratio, and diagnostic odds ratio among biomarkers for CIN, followed by cystatin-C, and uKIM-1. These findings underscore the potential clinical utility of NGAL, cystatin-C and uKIM-1 in predicting and assessing CIN.

Spironolactone for Preventing Contrast-Induced Nephropathy After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction and Chronic Kidney Disease.

Patients with acute myocardial infarction (AMI) and chronic kidney disease (CKD) are at high risk of contrast-induced nephropathy (CIN), which can subsequently worsen the overall prognosis. To evaluate the efficacy of spironolactone for CIN prevention, 410 patients with AMI and CKD receiving percutaneous coronary intervention (PCI) were retrospectively analyzed. Among them, 240 and 170 patients were enrolled in the standard treatment and spironolactone groups (spironolactone was administered 2 days before and 3 days after PCI), respectively. The primary endpoint of CIN was defined as a 0.5 mg/dL or >25% increase from the baseline serum creatinine level within 48-72 h post-PCI. CIN incidence was significantly lower in the spironolactone group than in the standard treatment group (11.2 vs 26.7%, P < .001). Further, cardiac re-hospitalization (hazard ratio [HR]: 0.515; 95% CI: 0.382-0.694; P < .001) and cardiac death (HR: 0.612; 95% CI: 0.429-0.872; P = .007) risks were significantly lower in patients who received long-term spironolactone with a median treatment duration of 42 months after discharge. Spironolactone might lower the risk of CIN, and long-term use of spironolactone reduces the risk of cardiac re-hospitalization and cardiac death in patients with AMI and CKD undergoing PCI.

Evaluating the Differential Risk of Contrast-Induced Nephropathy Among Diabetic and Non-diabetic Patients Following Percutaneous Coronary Intervention.

Background Contrast-induced nephropathy (CIN) significantly complicates percutaneous coronary intervention (PCI), with a higher prevalence in diabetic patients. This study compares the incidence of CIN in diabetic and non-diabetic patients undergoing PCI. Material and methods Conducted at Lady Reading Hospital, Peshawar, PAK, from January to December 2023, this observational study involved 450 adult patients with coronary artery disease (CAD) undergoing PCI. The cohort was categorized based on diabetes status, excluding patients with chronic kidney disease and those on renal replacement therapy. Baseline characteristics documented included age, gender, blood pressure, creatinine levels, and the presence of acute coronary syndrome (ACS). CIN was defined as a ≥25% increase in serum creatinine from baseline within 48-72 hours post-PCI. Data analysis was performed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 25.0, Armonk, NY), incorporating descriptive statistics, Chi-square tests, and independent t-tests, with a significance level of p<0.05. Results The median age of the study population was 55 years. The cohort comprised 52% male (n=234) and 48% female (n=216). Notably, 33% (n=149) had ACS. Diabetic patients exhibited a significantly higher incidence of CIN post-PCI compared to non-diabetics. The highest incidence of CIN (17%, n=77) occurred in the 70+ age group. The findings highlight the criticality of renal function monitoring and procedural adjustments for diabetic patients. Conclusion Diabetic patients demonstrate an increased risk of CIN following PCI. This necessitates the development of tailored prevention strategies for this high-risk subgroup.

Prognostic Role of Neutrophil to Lymphocyte Ratio in Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.

This meta-analysis assessed the use of the neutrophil-to-lymphocyte ratio (NLR) as a means of early detection of contrast-induced nephropathy (CIN) following diagnostic or therapeutic procedures. We used Web of Science, PubMed, and Scopus to conduct a systematic search. There was no limitation regarding language or date of publication. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Due to high heterogeneity, a random-effects model was used, and the Newcastle-Ottawa scale was used for quality assessment. Thirty-one articles were included in the analysis. Patients in the CIN group had elevated levels of NLR compared with those in the non-CIN group (SMD = 0.78, 95% CI = 0.52-1.04, P < .001). Similar results were observed in either prospective (SMD = 1.03, 95% CI = 0.13-1.93, P = .02) or retrospective studies (SMD = 0.70, 95% CI = 0.45-0.96, P < .001). The pooled sensitivity of NLR was 74.02% (95% CI = 66.54%-81.02%), and the pooled specificity was 60.58% (95% CI = 53.94%-66.84%). NLR shows potential as a cost-effective biomarker for predicting CIN associated with contrast-involved treatments. This could help implement timely interventions to mitigate CIN and improve outcomes.

Does metabolic syndrome increase contrast-induced nephropathy in patients with normal renal function?

Background: Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention. This study aimed to compare the incidence of CIN in two groups of patients with and without metabolic syndrome (Mets) with baseline normal renal function. Materials and Methods: In this case - control study, 260 patient candidates for CAG, 130 patients with Mets and 130 patients without Mets participated, and their serum creatinine (Cr) level before and the 48 and 72 h after the angiography was measured. The incidence of CIN was compared in two groups. Two-way analysis of variance with repeated measures and univariate and multivariate logistic regression models. Results: The results showed a higher chance of being Mets with raising in triglyceride (adjusted odds ratio = 1.05, 95% confidence interval = (1.03-1.06), P < 0.001), Fasting blood glucose (1.010 [1.001-1.019], P = 0.025), and diastolic blood pressure (1.07 [1.07-1.20], P < 0.001), but declining in high-density lipoprotein-cholesterol (HDL-C) (0.91 [0.85-0.98], P = 0.008). Furthermore, blood urea nitrogen (BUN) and Cr level was raised in 48 and 72 h after contrast injection in both groups (All P < 0.001). Furthermore, in 48 h (3.11 [1.12-9.93], P = 0.016) and 72 h (2.82 [1.07-8.28], P = 0.021) after injection, a total of 25 patients had an increased Cr level and a significant difference between Mets and without Mets groups. The developing Mets had a significant association with the increased risk of AKI, which increased the chance of developing nephropathy (7.14 [2.27-22.5], P = 0.001). Conclusion: Mets, together with other risk factors, increased the overall risk of CIN development. Therefore, the incidence of CIN in patients Mets is significantly higher than that of patients without Mets, indicating a more important CIN risk factor.

Contrast-Free Endovascular Aneurysm Repair Combined With Fibrin Sealant Filling for Treating Abdominal Aortic Aneurysm: Technical Note.

INTRODUCTION: Endovascular aneurysm repair using iodinated contrast agents risks contrast-induced nephropathy, especially in high-risk patients. This technical note describes a contrast-free endovascular aneurysm repair (EVAR) protocol using preoperative imaging measurement and fibrin sealant (FS) filling. TECHNIQUE: Preoperative imaging measurement and intraoperative guidewire manipulation facilitated anatomical identification without contrast. After endograft deployment, the aneurysm sac was filled with FS if endoleak was indicated by pressure fluctuations. RESULT: Between 2017 and 2020, 6 high-risk patients underwent contrast-free EVAR with FS filling. Complete exclusion was achieved in all cases. Over follow-up, no endoleaks, deterioration in renal function, or other complications were observed. CONCLUSION: Contrast-free EVAR with FS filling shows early feasibility as an alternative technique for contrast-induced nephropathy (CIN) high-risk patients, while larger studies with long-term monitoring are imperative to validate outcomes. CLINICAL IMPACT: This study showcases a contrast-free EVAR technique with fibrin sealant filling for high-risk CIN patients. It offers a safer approach for those with renal challenges, reducing CIN risk. The technique's feasibility in a small cohort suggests its utility in treating AAA without iodinated contrast, crucial for patients with specific health risks. For clinicians, it introduces a method that decreases nephrotoxic risks, potentially changing practice for vulnerable patients.

The effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery.

BACKGROUND: Craniocerebral interventional surgery is a common and essential treatment for cerebrovascular diseases. Despite continuous progress in interventional diagnosis and treatment technology, there is no effective method to alleviate contrast-induced kidney injuries. In this retrospective cohort study, we investigated the effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery. METHODS: We identified 228 cases of patients underwent craniocerebral interventional surgery from January 2018 to March 2022. Patients who used DEX during general anesthesia were in the DEX group (DEX group) or that did not use dexmedetomidine as the control group (CON group). The markers of kidney injury were recorded before and within 48 h after surgery. RESULTS: Compared with CON group, the urea nitrogen (BUN) of the DEX group decreased significantly on the first day and the second day after surgery (p < 0.05). The serum cystatin-C and the blood urea nitrogen/creatinine ratio (BUN/Cr) was significantly lower than that in CON group on the second day (p < 0.05). The urine output in the DEX group increased significantly, and the mean arterial pressure (MAP) was higher than the CON group (p < 0.01). There was no difference in postoperative complications, ICU stay time and hospitalization time between the two groups. CONCLUSION: The combined use of dexmedetomidine in general anesthesia for craniocerebral interventional surgery can reduce BUN levels within 48 h after surgery, significantly increase intraoperative urine volume, maintain intraoperative circulation stability.

Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. METHODS: NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. RESULTS: Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. CONCLUSIONS: In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

The Treatment of Coronary Artery Disease in Patients with Chronic Kidney Disease: Gaps, Challenges, and Solutions.

Background: Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease (CAD), which remains the leading cause of death in CKD patients. Despite the high cardiovascular risk, ACS patients with renal dysfunction are less commonly treated with guideline-based medical therapy and are less frequently referred for coronary revascularization. Summary: The management of CAD is more challenging in patients with CKD than in the general population due to concerns regarding side effects and renal toxicity, as well as uncertainty regarding clinical benefit of guideline-based medical therapy and interventions. Patients with advanced CKD and especially those receiving dialysis have not traditionally been represented in randomized trials evaluating either medical or revascularization therapies. Thus, only scant data from small prospective studies or retrospective analyses are available. Recently published studies suggest that there are significant opportunities to substantially improve both cardiovascular and renal outcomes of patients with CAD and CKD, including new medications and interventions. Thus, the objective of this review is to summarize the current evidence regarding the management of CAD in CKD patients, in particular with respect to improvement of both cardiovascular and renal outcomes. Key Messages: Adequate medical therapy and coronary interventions using evidence-based strategies can improve both cardiac and renal outcomes in patients with CAD and CKD.