scholarly journals Risk Factors for Nephrotoxicity Associated with Cisplatin

2017 ◽  
Vol 70 (2) ◽  
Author(s):  
Karine Almanric ◽  
Nathalie Marceau ◽  
Ariane Cantin ◽  
Émilie Bertin
Keyword(s):  
Risk Factors ◽  
Serum Creatinine ◽  
National Cancer Institute ◽  
Enzyme Inhibitor ◽  
Facteurs De Risque ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Increased Risk ◽  
Premier Cycle ◽  
Concomitant Medications

<p><strong>ABSTRACT</strong></p><p><strong>Background:</strong> Cisplatin-induced nephrotoxicity occurs in about one-third of patients who receive this chemotherapy drug. In late 2012, the study institution began measuring serum creatinine on day 7 after administration of cisplatin to identify patients with acute renal failure.</p><p><strong>Objective:</strong> To evaluate the extent of nephrotoxicity associated with cisplatin and the influence of risk factors for nephrotoxicity.</p><p><strong>Methods:</strong> This retrospective study involved patients who received a first cycle of cisplatin-based chemotherapy between November 1, 2012, and November 1, 2013. Patients’ medical records were reviewed to determine the increase in creatinine level (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events) and the influence of certain prespecified risk factors, such as age, concomitant medications, initial dose of cisplatin, and related medical conditions.</p><p><strong>Results:</strong> Among the 80 patients evaluated, 14 (17%) experienced no increase in the level of serum creatinine (grade 0), 44 (55%) experienced a grade 1 increase, 19 (24%) a grade 2 increase, and 3 (4%) a grade 3 increase; no patients experienced a grade 4 increase. Patients with the greatest risk of a grade 2 or 3 increase were those treated with hydrochlorothiazide (odds ratio [OR] 9.35, 95% confidence interval [CI] 2.49 to 35.14) or an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 5.02, 95% CI 1.76 to 14.32). After adjustment, only hydrochlorothiazide was associated with an increased risk of nephrotoxicity (OR 5.39, 95% CI 1.04 to 28.07). Among patients taking hydrochlorothiazide, the average incremental increase in serum creatinine was 59.9 μmol/L (95% CI 34.3 to 85.4 μmol/L).</p><p><strong>Conclusions:</strong> Taking hydrochlorothiazide was associated with a significant increase in serum creatinine following cisplatin therapy. On the basis of these results, patients should stop taking hydrochlorothiazide before undergoing cisplatin-based chemotherapy.</p><p><strong>RÉSUMÉ</strong></p><p><strong>Contexte :</strong> La néphrotoxicité associée au cisplatine se produit chez environ le tiers des patients qui reçoivent ce médicament de chimiothérapie. À la fin de 2012, l’établissement de santé des auteurs a commencé à mesurer la créatinine sérique au jour 7 après l’administration de cisplatine afin de repérer les patients atteints d’insuffisance rénale aiguë.</p><p><strong>Objectif :</strong> Évaluer le degré de la néphrotoxicité associée au cisplatine et déterminer si des facteurs de risque favorisent cette néphrotoxicité. Méthodes : Cette étude rétrospective a été menée auprès de patients ayant subi un premier cycle de chimiothérapie à base de cisplatine entre le premier novembre 2012 et le premier novembre 2013. Les dossiers médicaux<br />des patients ont été examinés afin de détecter les cas d’augmentation de créatinine sérique (qui ont été classés selon les critères pour une terminologie commune des événements indésirables du National Cancer Institute) et l’influence de facteurs de risque préétablis (âge, médicaments concomitants, dose initiale de cisplatine et pathologies associées).</p><p><strong>Résultats :</strong> Parmi les 80 patients analysés, 14 (17 %) n’affichaient aucune augmentation du taux de créatinine sérique (degré 0), 44 (55 %) présentaient une augmentation de degré 1, 19 (24 %) affichaient une augmentation de degré 2 et 3 (4 %) présentaient une augmentation de degré 3; aucun ne présentait une augmentation de degré 4. Les patients qui couraient le plus grand risque de connaître une augmentation de degré 2 ou 3 étaient ceux traités avec l’hydrochlorothiazide (risque relatif approché [RRA] de 9,35, intervalle de confiance [IC] à 95 % de 2,49 à 35,14) ou d’un inhibiteur de l’enzyme de conversion de l’angiotensine ou d’un bloqueur des récepteurs de l’angiotensine II (RRA de 5,02, IC à 95 % de 1,76 à 14,32). Après ajustement, seul l’hydrochlorothiazide était associé à une augmentation du risque de néphrotoxicité (RRA de 5,39, IC à 95 % de 1,04 à 28,07). Parmi les patients qui prenaient de l’hydrochlorothiazide, l’augmentation différentielle moyenne de créatinine sérique était de 59,9 μmol/L (IC à 95 % de 34,3 à 85,4 μmol/L).</p><p><strong>Conclusions :</strong> La prise concomitante d’hydrochlorothiazide a été associée à une augmentation significative de la créatinine sérique après un traitement de cisplatine. Considérant ces résultats, les patients devraient cesser de prendre de l’hydrochlorothiazide avant de recevoir une chimiothérapie à base de cisplatine.</p>

scholarly journals Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258684
Author(s):  
Sebastian Cremer ◽  
Lisa Pilgram ◽  
Alexander Berkowitsch ◽  
Melanie Stecher ◽  
Siegbert Rieg ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Disease Severity ◽  
Enzyme Inhibitor ◽  
Receptor Blocker ◽  
Angiotensin Ii Receptor Blocker ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Cardiovascular Comorbidities ◽  
Increased Risk

Aims Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. Methods and results We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators. Conclusion These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

Landscape of Combination Therapy – Which Way Forward? Proceedings of the Satellite Symposium Held at the ESH European Meeting on Hypertension and Cardiovascular Protection, 27 April 2012, London

2012 ◽  
Vol 8 (3) ◽  
pp. 192
Author(s):  
Patricia Fonseca ◽  
Anna F Dominiczak ◽  
Stephen Harrap ◽  
◽  
◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Risk ◽  
Combination Therapy ◽  
Enzyme Inhibitor ◽  
Synergistic Effects ◽  
Term Treatment ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Patients ◽  
Long Term Treatment

Early combination therapy is more effective for hypertension control in high-risk patients than monotherapy, and current guidelines recommend the use of either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for first-line therapy in patients younger than 55 years. Recent evidence shows that ACEIs reduce mortality, whereas ARBs show no apparent benefit despite their blood pressure lowering action. However, it is important to consider which blood pressure parameters should be targeted given that different drugs have distinct effects on key parameters. Remarkably, a high percentage of hypertensive patients whose treatment has brought these parameters within target ranges still remain at high risk of cardiovascular disease due to additional risk factors. Combination therapy with synergistic effects on blood pressure and metabolic control should thus be considered for the long-term treatment of hypertensive patients with co-morbid conditions.

scholarly journals Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: A prospective observational Brazilian study

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244532
Author(s):  
Rodrigo A. Brandão Neto ◽  
Julio F. Marchini ◽  
Lucas O. Marino ◽  
Julio C. G. Alencar ◽  
Felippe Lazar Neto ◽  
...  
Keyword(s):  
Emergency Department ◽  
Multivariate Analysis ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Converting Enzyme Inhibitor ◽  
Enzyme Inhibitor ◽  
Angiotensin Ii Receptor Blocker ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
All Cause Mortality

Background The first cases of coronavirus disease (COVID-19) in Brazil were diagnosed in February 2020. Our Emergency Department (ED) was designated as a COVID-19 exclusive service. We report our first 500 confirmed COVID-19 pneumonia patients. Methods From 14 March to 16 May 2020, we enrolled all patients admitted to our ED that had a diagnosis of COVID-19 pneumonia. Infection was confirmed via nasopharyngeal swabs or tracheal aspirate PCR. The outcomes included hospital discharge, invasive mechanical ventilation, and in-hospital death, among others. Results From 2219 patients received in the ED, we included 506 with confirmed COVID-19 pneumonia. We found that 333 patients were discharged home (65.9%), 153 died (30.2%), and 20 (3.9%) remained in the hospital. A total of 300 patients (59.3%) required ICU admission, and 227 (44.9%) needed invasive ventilation. The multivariate analysis found age, number of comorbidities, extension of ground glass opacities on chest CT and troponin with a direct relationship with all-cause mortality, whereas dysgeusia, use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker and number of lymphocytes with an inverse relationship with all-cause mortality Conclusions This was a sample of severe patients with COVID-19, with 59.2% admitted to the ICU and 41.5% requiring mechanical ventilator support. We were able to ascertain the outcome in majority (96%) of patients. While the overall mortality was 30.2%, mortality for intubated patients was 55.9%. Multivariate analysis agreed with data found in other studies although the use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker as a protective factor could be promising but would need further studies. Trial registration The study was registered in the Brazilian registry of clinical trials: RBR-5d4dj5.

Mineralocorticoid receptor blockade with spironolactone has no direct effect on plasma IL-17A and injury markers in urine from kidney transplant patients

2021 ◽  
Author(s):  
Sai Sindhu Thangaraj ◽  
Helle Charlotte Thiesson ◽  
Per Svenningsen ◽  
Jane Stubbe ◽  
Yaseelan Palarasah ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Mineralocorticoid Receptor ◽  
Enzyme Inhibitor ◽  
Plasma Concentrations ◽  
Transplant Recipients ◽  
Angiotensin Ii Receptor ◽  
Kidney Transplant Recipients ◽  
Double Blind ◽  
Plasma Aldosterone Concentration ◽  
Increased Risk

Kidney transplantation is associated with increased risk of cardiovascular morbidity. Interleukin-17A (IL-17A) mediates kidney injury. Aldosterone promotes T-helper-17 (Th-17) lymphocyte differentiation and IL-17A production through the mineralocorticoid receptor (MR). In this exploratory, post-hoc substudy, it was hypothesized that 1-year intervention with the MR antagonist spironolactone lowers IL-17A and related cytokines and reduces epithelial injury in kidney transplant recipients. Plasma and urine samples were obtained from kidney transplant recipients from a double-blind randomized clinical trial testing spironolactone (n=39) versus placebo (n=41). Plasma concentrations of cytokines IFN-γ, IL-17A, TNF-α, IL-6, IL-1β, and IL-10 were determined before and after 1-year treatment. Urine calbindin, clusterin, KIM-1, osteoactivin, TFF3, and VEGF/creatinine ratios were analyzed. Blood pressure and plasma aldosterone concentration at inclusion did not relate to plasma cytokines and injury markers. None of the cytokines changed in plasma after spironolactone intervention. Plasma IL-17A increased in the placebo group. Spironolactone induced an increase in plasma K+ (0.4 ± 0.4 mmol/L). This increase did not correlate with plasma IL-17A or urine calbindin and TFF3 changes. Ongoing treatment at inclusion with angiotensin-converting-enzyme inhibitor and/or angiotensin II receptor blockers was not associated with changed levels of IL-17A and injury markers and had no effect on the response to spironolactone. Urinary calbindin and TFF3 decreased in the spironolactone group with no difference in between-group analyses. In conclusion, irrespective of ongoing ANGII inhibition, spironolactone has no effect on plasma IL-17A and related cytokines or urinary injury markers in kidney transplant recipients.

scholarly journals Continued In-Hospital Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use in Hypertensive COVID-19 Patients Is Associated With Positive Clinical Outcome

2020 ◽  
Vol 222 (8) ◽  
pp. 1256-1264 ◽  
Author(s):  
Katherine W Lam ◽  
Kenneth W Chow ◽  
Jonathan Vo ◽  
Wei Hou ◽  
Haifang Li ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Odds Ratio ◽  
Enzyme Inhibitor ◽  
Laboratory Data ◽  
Admission Rate ◽  
Angiotensin Ii Receptor Blocker ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Icu Admission

Abstract Background This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients. Methods Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed. To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization. Results Mortality (22% vs 17%, P &gt; .05) and intensive care unit (ICU) admission (26% vs 12%, P &gt; .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups. However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187–.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101–.455) compared to patients who discontinued ACEi/ARB. The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI. Conclusions These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.

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