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1
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Montes D, Weerasiri SD, Suarez MG. 60-Year-Old Man With Low Hemoglobin and Elevated Creatinine Levels. Mayo Clin Proc 2025; 100:895-899. [PMID: 40202474 DOI: 10.1016/j.mayocp.2024.05.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/29/2024] [Accepted: 05/01/2024] [Indexed: 04/10/2025]
Affiliation(s)
- Daniel Montes
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Samiddhi D Weerasiri
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Maria Gonzalez Suarez
- Advisor to residents and Consultant in Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
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2
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Longo R, Savenkoff B, Ribal R, Dadoun A, Campitiello M, Plastino F, Legros P, Marcon N, Coppo P, Egea J. A Thrombocytopenic Thrombotic Purpura in a Patient With a Metastatic HER2+ Breast Cancer: Description of a Case Report. Clin Case Rep 2025; 13:e70395. [PMID: 40206570 PMCID: PMC11978524 DOI: 10.1002/ccr3.70395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 02/05/2025] [Accepted: 02/17/2025] [Indexed: 04/11/2025] Open
Abstract
Paraneoplastic (p) TTP is a rare syndrome characterized by an immune-induced, generalized microangiopathy associated with solid or hematological tumors. This case, reporting a patient with a metastatic HER2+ breast cancer and a pTTP, highlights the rarity of this entity, its difficult and challenging diagnosis, and the complexity of its management.
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Affiliation(s)
- Raffaele Longo
- Division of Medical Oncology“CHR Metz‐Thionville”Ars‐LaquenexyFrance
| | - Benjamin Savenkoff
- NephrologyDialysis and Apheresis Unit “CHR Metz‐Thionville”Ars‐LaquenexyFrance
| | - Romane Ribal
- Division of Medical Oncology“CHR Metz‐Thionville”Ars‐LaquenexyFrance
| | - Alexandre Dadoun
- Division of Medical Oncology“CHR Metz‐Thionville”Ars‐LaquenexyFrance
| | - Marco Campitiello
- Division of Medical Oncology“CHR Metz‐Thionville”Ars‐LaquenexyFrance
| | | | | | - Nathalie Marcon
- Department of Pathology“CHR Metz‐Thionville”Ars‐LaquenexyFrance
| | - Paul Coppo
- Department of HaematologyReference Centre for Thrombotic Microangiopathies, Saint‐Antoine University Hospital, Assistance Publique‐Hôpitaux de ParisParisFrance
| | - Julie Egea
- Division of Medical Oncology“CHR Metz‐Thionville”Ars‐LaquenexyFrance
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3
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Latcha S, Gutgarts V, Cespedes BN, Herrmann SM. Onconephrology. ADVANCES IN KIDNEY DISEASE AND HEALTH 2025; 32:69-78. [PMID: 40175032 DOI: 10.1053/j.akdh.2024.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 10/09/2024] [Accepted: 10/09/2024] [Indexed: 04/04/2025]
Abstract
Subspecialized training in the field of onconephrology offers a uniquely informed approach to the care of the patient with both cancer and kidney disease. There is a significant knowledge gap that has been created by the fact that patients with an estimated glomerular filtration rate <30 mL/min are generally excluded from clinical cancer trials. Thus, oncologists rely on the clinical experience and expertise of onconephrologists to dose cytotoxic chemotherapies, to recognize and manage complications of newer targeted drugs and immunotherapies, to become partners in establishing guidelines relating to the management of these complications, and to collaborate on the design of future clinical trials in this cohort. In this section, we provide a glimpse into some common clinical scenarios encountered by the onconephrologist and demonstrate how clinical data and observations inform decision-making in these situations.
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Affiliation(s)
- Sheron Latcha
- Memorial Sloan Kettering Cancer Center, New York, NY.
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4
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Vorobev A, Bitsadze V, Yagubova F, Khizroeva J, Solopova A, Tretyakova M, Gashimova N, Grigoreva K, Einullaeva S, Drozhzhina M, Hajiyeva A, Khalilulina E, Cherepanov A, Kapanadze D, Egorova E, Kuneshko N, Gris JC, Elalamy I, Ay C, Makatsariya A. The Phenomenon of Thrombotic Microangiopathy in Cancer Patients. Int J Mol Sci 2024; 25:9055. [PMID: 39201740 PMCID: PMC11354439 DOI: 10.3390/ijms25169055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 06/19/2024] [Accepted: 08/15/2024] [Indexed: 09/03/2024] Open
Abstract
Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes.
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Affiliation(s)
- Alexander Vorobev
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Victoria Bitsadze
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Fidan Yagubova
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Jamilya Khizroeva
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Antonina Solopova
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Maria Tretyakova
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Nilufar Gashimova
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Kristina Grigoreva
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Sabina Einullaeva
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Maria Drozhzhina
- Faculty of General Medicine, Russian University of Medicine, 4th Dolgorukovskaya Str., 127006 Moscow, Russia;
| | - Aygun Hajiyeva
- Faculty of General Medicine, I.M. Sechenov First State Moscow Medical University Baku Branch, Huseyn Javid, Yasamal, Baku AZ1141, Azerbaijan;
| | - Emilia Khalilulina
- Faculty of General Medicine, Pirogov Russian National Research Medical University, Ulitsa Ostrovityanova 1, 117997 Moscow, Russia;
| | - Alexander Cherepanov
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Daredzhan Kapanadze
- Center of Pathology of Pregnancy and Hemostasis «Medlabi», 340112 Tbilisi, Georgia;
| | - Elena Egorova
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
| | - Nart Kuneshko
- Moscow’s Region Odintsovo Maternity Hospital, 143003 Odintsovo, Russia;
| | - Jean-Christophe Gris
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
- Faculty of Pharmaceutical and Biological Sciences, Montpellier University, 34093 Montpellier, France
| | - Ismail Elalamy
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
- Department Hematology and Thrombosis Center, Medicine Sorbonne University, 75012 Paris, France
- Hospital Tenon, 4 Rue de la Chine, 75020 Paris, France
| | - Cihan Ay
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
- Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, 1080 Vienna, Austria
| | - Alexander Makatsariya
- Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia; (A.V.); (V.B.); (F.Y.); (J.K.); (A.S.); (M.T.); (K.G.); (S.E.); (A.C.); (E.E.); (J.-C.G.); (I.E.); (C.A.); (A.M.)
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Zhang W, Wang Y, Jiang X, Zhao H, Jia X, Wang Q, Chen Y, Jiang Y, Ma Z, Chang L, Wang X. Newly identified adverse events for gemcitabine using the Food and Drug Administration Adverse Event Reporting System. Expert Opin Drug Saf 2024; 23:917-923. [PMID: 37974405 DOI: 10.1080/14740338.2023.2284989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 10/31/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Our research aimed to identify previously undocumented adverse events (AEs) in the gemcitabine drug insert with the goal of informing clinical practice. METHODS We extracted adverse events associated with gemcitabine use through 2023 using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Four algorithms (Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayesian Geometric Mean) were employed to detect new AE signals. AEs were considered positive signals only if they were detected by all four algorithms. RESULTS From 2014 to 2023, a total of 42,360 AEs were reported in 14,905 individuals following gemcitabine use. These AEs totaled 437 preferred terms (PTs) across 20 system organ classes (SOCs). We identified unexpected AEs related to the ocular disorders, the nervous system, and the ear and the labyrinth. The ocular organ system will present with retinopathy, purtscher retinopathy, choroidal effusion, amaurosis, necrotizing scleritis, etc. The nervous system may experience reversible posterior encephalopathy syndrome, cerebellar syndrome, cauda equina syndrome, athetosis, transverse myelitis, etc. The ears and labyrinth may exhibit ototoxicity. CONCLUSION Our study identified previously undetected signals following gemcitabine treatment, thereby providing new insights for future medication guidance.
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Affiliation(s)
- Wei Zhang
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yuhong Wang
- Shanxi Medical Service Evaluation Center, Department of health management, Taiyuan, Shanxi, China
| | - Xin Jiang
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Hu Zhao
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xinli Jia
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Qiye Wang
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yue Chen
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yuanfang Jiang
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhifang Ma
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Lina Chang
- Shanxi Provincial Hospital of Traditional Chinese Medicine, Department of Physician Standardization Training Center, Taiyuan, Shanxi, China
| | - Xin Wang
- Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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Anil V, Alhujaily E, Grover D, Santos JP, Kanugula AK, Suleiman M, Singh S. Gemcitabine-Induced Thrombotic Microangiopathy in a Patient With Cholangiocarcinoma: An Atypical Case. Cureus 2024; 16:e63385. [PMID: 39070506 PMCID: PMC11283843 DOI: 10.7759/cureus.63385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2024] [Indexed: 07/30/2024] Open
Abstract
Gemcitabine-induced thrombotic microangiopathy (GITMA) is a rare but severe complication seen in cancer patients on gemcitabine therapy. This case report describes a 45-year-old female with metastatic cholangiocarcinoma on gemcitabine-capecitabine who developed acute kidney injury and hypertension without typical hematologic signs of thrombotic microangiopathy (TMA). Despite initial management targeting hypertensive urgency and acute kidney injury, renal function continued to decline and progressed to end-stage renal disease requiring hemodialysis. Laboratory tests revealed TMA features such as elevated lactate dehydrogenase (LDH), decreased haptoglobin, and schistocytes. Renal biopsy confirmed TMA with chronic features. This case highlights the challenge of diagnosing drug-induced TMA without typical hematologic findings.
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Affiliation(s)
- Vishwanath Anil
- Internal Medicine, Wellstar Spalding Medical Center, Griffin, USA
| | - Ensaf Alhujaily
- Internal Medicine, Wellstar Spalding Medical Center, Griffin, USA
| | - Deeksha Grover
- Internal Medicine, Wellstar Spalding Medical Center, Griffin, USA
| | | | | | - Moyosore Suleiman
- Hematology and Medical Oncology, Wellstar Spalding Medical Center, Griffin, USA
| | - Sonu Singh
- Nephrology, Wellstar Spalding Medical Center, Griffin, USA
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Mouillot P, Favrolt N, Khouri C, Grandvuillemin A, Chaumais MC, Schenesse D, Seferian A, Jais X, Savale L, Beltramo G, Sitbon O, Cracowski JL, Humbert M, Georges M, Bonniaud P, Montani D. Characteristics and outcomes of gemcitabine-associated pulmonary hypertension. ERJ Open Res 2024; 10:00654-2023. [PMID: 38770007 PMCID: PMC11103709 DOI: 10.1183/23120541.00654-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 12/18/2023] [Indexed: 05/22/2024] Open
Abstract
Background Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear. The objective of the present study was to assess the association between gemcitabine and PH. Methods We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 and December 2022. The aetiology, clinical, functional, radiological and haemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the World Health Organization (WHO) pharmacovigilance database. Results We identified nine cases of pulmonary arterial hypertension, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (range 26-47) mmHg, a cardiac index of 2.4 (1.6-3.9) L·min-1·m-2 and a pulmonary vascular resistance of 6.3 (3.1-12.6) Wood units. The median time from the initiation of gemcitabine to the onset of PH was 7 (4-50) months, with patients receiving a median of 16 (6-24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine. Conclusion Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnoea.
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Affiliation(s)
- Pierre Mouillot
- Department of Pneumology and Intensive Care, Reference Center for Rare Lung Diseases, François Mitterrand Hospital, Dijon, France
- Faculty of Medicine, INSERM 1231, University of Burgundy, Dijon, France
| | - Nicolas Favrolt
- Department of Pneumology and Intensive Care, Reference Center for Rare Lung Diseases, François Mitterrand Hospital, Dijon, France
- Faculty of Medicine, INSERM 1231, University of Burgundy, Dijon, France
| | - Charles Khouri
- Pharmacovigilance Unit, Grenoble Alpes University Hospital, Grenoble, France
- Clinical Pharmacology Department INSERM CIC1406, Grenoble Alpes University Hospital, Grenoble, France
- HP2 Laboratory, Inserm U1300, Grenoble Alpes University, Grenoble, France
| | | | - Marie-Camille Chaumais
- Faculty of Pharmacy, Université Paris-Saclay, Orsay, France
- Assistance Publique – Hôpitaux de Paris (AP-HP), Pharmacy Department, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hospital Marie Lannelongue, Le Plessis-Robinson, France
| | - Déborah Schenesse
- Department of Pneumology and Intensive Care, Reference Center for Rare Lung Diseases, François Mitterrand Hospital, Dijon, France
- Faculty of Medicine, INSERM 1231, University of Burgundy, Dijon, France
| | - Andrei Seferian
- INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hospital Marie Lannelongue, Le Plessis-Robinson, France
- Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France
- AP-HP, Department of Pneumology and Intensive Care, Pulmonary Hypertension Reference Centre, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Xavier Jais
- INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hospital Marie Lannelongue, Le Plessis-Robinson, France
- Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France
- AP-HP, Department of Pneumology and Intensive Care, Pulmonary Hypertension Reference Centre, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Laurent Savale
- INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hospital Marie Lannelongue, Le Plessis-Robinson, France
- Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France
- AP-HP, Department of Pneumology and Intensive Care, Pulmonary Hypertension Reference Centre, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Guillaume Beltramo
- Department of Pneumology and Intensive Care, Reference Center for Rare Lung Diseases, François Mitterrand Hospital, Dijon, France
- Faculty of Medicine, INSERM 1231, University of Burgundy, Dijon, France
| | - Olivier Sitbon
- INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hospital Marie Lannelongue, Le Plessis-Robinson, France
- Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France
- AP-HP, Department of Pneumology and Intensive Care, Pulmonary Hypertension Reference Centre, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Jean-Luc Cracowski
- Pharmacovigilance Unit, Grenoble Alpes University Hospital, Grenoble, France
- HP2 Laboratory, Inserm U1300, Grenoble Alpes University, Grenoble, France
| | - Marc Humbert
- INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hospital Marie Lannelongue, Le Plessis-Robinson, France
- Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France
- AP-HP, Department of Pneumology and Intensive Care, Pulmonary Hypertension Reference Centre, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Marjolaine Georges
- Department of Pneumology and Intensive Care, Reference Center for Rare Lung Diseases, François Mitterrand Hospital, Dijon, France
- Faculty of Medicine, INSERM 1231, University of Burgundy, Dijon, France
| | - Philippe Bonniaud
- Department of Pneumology and Intensive Care, Reference Center for Rare Lung Diseases, François Mitterrand Hospital, Dijon, France
- Faculty of Medicine, INSERM 1231, University of Burgundy, Dijon, France
- P. Bonniaud and D. Montani contributed equally
| | - David Montani
- INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hospital Marie Lannelongue, Le Plessis-Robinson, France
- Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France
- AP-HP, Department of Pneumology and Intensive Care, Pulmonary Hypertension Reference Centre, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
- P. Bonniaud and D. Montani contributed equally
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Kataoka S, Nishikawa Y, Funakoshi T, Horimatsu T, Sakuragi M, Uchino E, Hiragi S, Yamamoto S, Sakai K, Matsubara T, Yanagita M, Muto M. Proteinuria frequency and subsequent renal dysfunction in bevacizumab-treated patients: a single center, retrospective, observational study. Int J Clin Oncol 2024; 29:398-406. [PMID: 38351273 DOI: 10.1007/s10147-024-02474-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 01/09/2024] [Indexed: 03/26/2024]
Abstract
BACKGROUND Proteinuria is a common adverse event observed during treatment with antivascular endothelial growth factor (VEGF) antibodies. Proteinuria is a risk factor for renal dysfunction and cardiovascular complications in patients with chronic kidney disease. However, the association between anti-VEGF antibody-induced proteinuria and renal dysfunction or cardiovascular complications remains unclear. METHODS This retrospective, observational study included patients with cancer that were treated with bevacizumab (BV) at Kyoto University Hospital (Kyoto, Japan) between January 2006 and March 2018. Adverse event rates were compared between patients who developed qualitative ≥ 2 + proteinuria and those who developed < 1 + proteinuria. Adverse events were defined as renal dysfunction (i.e., ≥ 57% decrease in the eGFR, compared to the rate at the initial treatment) and hospitalization due to BV-associated cardiovascular complications and other adverse events. RESULTS In total, 734 patients were included in this analysis. Renal dysfunction was more common in patients with ≥ 2 + proteinuria than in those with < 1 + proteinuria (13/199, 6.5% vs. 12/535, 2.3%). Seven of these 13 patients with ≥ 2 + proteinuria had transient reversible renal dysfunction. Only four (2.0%) patients had BV-associated renal dysfunction. Of the 734 patients, six patients, 16 patients, and 13 patients were hospitalized because of the adverse events of cardiovascular complications, thromboembolisms, and cerebrovascular complications, respectively. No relationship was observed between these adverse events and proteinuria. CONCLUSION BV treatment-induced proteinuria was not associated with renal dysfunction or other adverse events. Continuing BV with caution is a possible treatment option, even after proteinuria develops, in patients with cancer and a limited prognosis.
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Affiliation(s)
- Shigeki Kataoka
- Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Yoshitaka Nishikawa
- Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Taro Funakoshi
- Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takahiro Horimatsu
- Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Minoru Sakuragi
- Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Eiichiro Uchino
- Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shusuke Hiragi
- Department of Medical Informatics, Medical Research Institute KITANO Hospital, PIIF Tazuke-Kofukai, Osaka, Japan
- Department of Nephrology, Medical Research Institute KITANO Hospital, PIIF Tazuke-Kofukai, Osaka, Japan
| | - Shinya Yamamoto
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kaoru Sakai
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takeshi Matsubara
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Motoko Yanagita
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Manabu Muto
- Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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9
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Pluchart H, Chanoine S, Moro-Sibilot D, Chouaid C, Frey G, Villa J, Degano B, Giaj Levra M, Bedouch P, Toffart AC. Lung cancer, comorbidities, and medication: the infernal trio. Front Pharmacol 2024; 14:1016976. [PMID: 38450055 PMCID: PMC10916800 DOI: 10.3389/fphar.2023.1016976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 09/25/2023] [Indexed: 03/08/2024] Open
Abstract
Most patients with lung cancer are smokers and are of advanced age. They are therefore at high risk of having age- and lifestyle-related comorbidities. These comorbidities are subject to treatment or even polypharmacy. There is growing evidence of a link between lung cancer, comorbidities and medications. The relationships between these entities are complex. The presence of comorbidities and their treatments influence the time of cancer diagnosis, as well as the diagnostic and treatment strategy. On the other hand, cancer treatment may have an impact on the patient's comorbidities such as renal failure, pneumonitis or endocrinopathies. This review highlights how some comorbidities may have an impact on lung cancer presentation and may require treatment adjustments. Reciprocal influences between the treatment of comorbidities and anticancer therapy will also be discussed.
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Affiliation(s)
- Hélène Pluchart
- Pôle Pharmacie, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France
- Université Grenoble Alpes, Grenoble, France
- Université Grenoble Alpes, CNRS, Grenoble INP, TIMC UMR5525, Grenoble, France
| | - Sébastien Chanoine
- Pôle Pharmacie, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France
- Université Grenoble Alpes, Grenoble, France
- Institut pour l’Avancée des Biosciences, UGA/INSERM U1209/CNRS 5309, Université Grenoble Alpes, La Tronche, France
| | - Denis Moro-Sibilot
- Université Grenoble Alpes, Grenoble, France
- Institut pour l’Avancée des Biosciences, UGA/INSERM U1209/CNRS 5309, Université Grenoble Alpes, La Tronche, France
- Service Hospitalier Universitaire de Pneumologie Physiologie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
| | - Christos Chouaid
- Service de Pneumologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France
- Inserm U955, UPEC, IMRB, équipe CEpiA, CréteilFrance
| | - Gil Frey
- Service de Chirurgie Thoracique, Vasculaire et Endocrinienne, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
| | - Julie Villa
- Service de Radiothérapie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
| | - Bruno Degano
- Université Grenoble Alpes, Grenoble, France
- Service Hospitalier Universitaire de Pneumologie Physiologie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
- Laboratoire HP2, INSERM U1042, Université Grenoble Alpes, Grenoble, France
| | - Matteo Giaj Levra
- Institut pour l’Avancée des Biosciences, UGA/INSERM U1209/CNRS 5309, Université Grenoble Alpes, La Tronche, France
- Service Hospitalier Universitaire de Pneumologie Physiologie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
| | - Pierrick Bedouch
- Pôle Pharmacie, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France
- Université Grenoble Alpes, Grenoble, France
- Université Grenoble Alpes, CNRS, Grenoble INP, TIMC UMR5525, Grenoble, France
| | - Anne-Claire Toffart
- Université Grenoble Alpes, Grenoble, France
- Institut pour l’Avancée des Biosciences, UGA/INSERM U1209/CNRS 5309, Université Grenoble Alpes, La Tronche, France
- Service Hospitalier Universitaire de Pneumologie Physiologie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
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10
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Nair SG, Benny S, Jose WM, Aneesh T P. Beta-blocker adjunct therapy as a prospective anti-metastatic with cardio-oncologic regulation. Clin Exp Metastasis 2024; 41:9-24. [PMID: 38177715 DOI: 10.1007/s10585-023-10258-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 12/12/2023] [Indexed: 01/06/2024]
Abstract
The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.
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Affiliation(s)
- Sachin G Nair
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682041, India
| | - Sonu Benny
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682041, India
| | - Wesley M Jose
- Department of Medical Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, AIMS PO, Kochi, Kerala, 682041, India.
| | - Aneesh T P
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682041, India.
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11
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Jha VK, Akal RS, Mahapatra D, Sharma A, Singh BP, Arora R. Nephrotic Syndrome and Posterior Reversible Encephalopathy Syndrome as Clinical Presentations of Gemcitabine-Induced Thrombotic Micro-Angiopathy. Indian J Nephrol 2024; 34:74-78. [PMID: 38645915 PMCID: PMC11003583 DOI: 10.4103/ijn.ijn_277_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/18/2022] [Indexed: 04/23/2024] Open
Abstract
Gemcitabine-induced thrombotic micro-angiopathy (GiTMA) is a very rare pathology of micro-vascular occlusion with a poor prognosis. In this case report, we present a young male with pancreatic carcinoma who received gemcitabine as adjuvant chemotherapy and developed thrombotic micro-angiopathy (TMA) manifesting as nephrotic syndrome with renal dysfunction and posterior reversible encephalopathy syndrome (PRES). The case was successfully managed with discontinuation of the drug and conservative management. The pathogenesis of GiTMA might be direct endothelial dysfunction with consequent activation of the clotting system. The role of plasma exchanges and monoclonal antibodies is unclear in drug-induced TMA.
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Affiliation(s)
- Vijoy Kumar Jha
- Department of Nephrology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | - Ramanjit Singh Akal
- Department of Nephrology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | - Debasish Mahapatra
- Department of Nephrology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | - Alok Sharma
- Department of Renal Pathology and Electron Microscopy, Lal PathLabs Limited, New Delhi, India
| | - Bhanu Pratap Singh
- Department of Radiology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | - Rahil Arora
- Department of Medicine, Command Hospital Air Force, Bengaluru, Karnataka, India
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12
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Pandey S, Kalaria A, Jhaveri KD, Herrmann SM, Kim AS. Management of hypertension in patients with cancer: challenges and considerations. Clin Kidney J 2023; 16:2336-2348. [PMID: 38046043 PMCID: PMC10689173 DOI: 10.1093/ckj/sfad195] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Indexed: 12/05/2023] Open
Abstract
The survival rates of many cancers have significantly improved due to recent advancements in cancer screening and therapeutics. Although better cancer outcomes are encouraging, additional health challenges have surfaced, the utmost of which is the burden imposed by various cardiovascular and renal toxicities of anticancer therapies. To improve the overall outcome of patients with cancer, it is essential to understand and manage these treatment-related adverse effects. The cardiovascular side effects of antineoplastic therapies are well-known and include left ventricular dysfunction, heart failure, myocardial ischaemia, QT prolongation, arrhythmia and hypertension. Among these, hypertension is the most common complication, prevalent in about 40% of all cancer patients, yet frequently overlooked and undertreated. This review explores the intricate connection between cancer and hypertension and provides distinct approaches to diagnosing, monitoring and managing hypertension in patients with cancer. We also outline the challenges and considerations that are relevant to the care of patients receiving anticancer drugs with prohypertensive potential.
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Affiliation(s)
- Shubhi Pandey
- Department of Internal Medicine, Calhoun Cardiology Center, University of Connecticut Health, Farmington, CT, USA
- University of Connecticut School of Medicine, Farmington, CT, USA
| | - Amar Kalaria
- University of Connecticut School of Medicine, Farmington, CT, USA
| | - Kenar D Jhaveri
- Division of Kidney Diseases and Hypertension, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
| | - Sandra M Herrmann
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Agnes S Kim
- Department of Internal Medicine, Calhoun Cardiology Center, University of Connecticut Health, Farmington, CT, USA
- University of Connecticut School of Medicine, Farmington, CT, USA
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13
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Muto S, Matsubara T, Inoue T, Kitamura H, Yamamoto K, Ishii T, Yazawa M, Yamamoto R, Okada N, Mori K, Yamada H, Kuwabara T, Yonezawa A, Fujimaru T, Kawano H, Yokoi H, Doi K, Hoshino J, Yanagita M. Chapter 1: Evaluation of kidney function in patients undergoing anticancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022. Int J Clin Oncol 2023; 28:1259-1297. [PMID: 37382749 DOI: 10.1007/s10147-023-02372-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 06/14/2023] [Indexed: 06/30/2023]
Abstract
The prevalence of CKD may be higher in patients with cancer than in those without due to the addition of cancer-specific risk factors to those already present for CKD. In this review, we describe the evaluation of kidney function in patients undergoing anticancer drug therapy. When anticancer drug therapy is administered, kidney function is evaluated to (1) set the dose of renally excretable drugs, (2) detect kidney disease associated with the cancer and its treatment, and (3) obtain baseline values for long-term monitoring. Owing to some requirements for use in clinical practice, a GFR estimation method such as the Cockcroft-Gault, MDRD, CKD-EPI, and the Japanese Society of Nephrology's GFR estimation formula has been developed that is simple, inexpensive, and provides rapid results. However, an important clinical question is whether they can be used as a method of GFR evaluation in patients with cancer. When designing a drug dosing regimen in consideration of kidney function, it is important to make a comprehensive judgment, recognizing that there are limitations regardless of which estimation formula is used or if GFR is directly measured. Although CTCAEs are commonly used as criteria for evaluating kidney disease-related adverse events that occur during anticancer drug therapy, a specialized approach using KDIGO criteria or other criteria is required when nephrologists intervene in treatment. Each drug is associated with the different disorders related to the kidney. And various risk factors for kidney disease associated with each anticancer drug therapy.
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Affiliation(s)
- Satoru Muto
- Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
| | - Takeshi Matsubara
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takamitsu Inoue
- Department of Renal and Urologic Surgery, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Hiroshi Kitamura
- Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | | | - Taisuke Ishii
- Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Masahiko Yazawa
- Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Ryohei Yamamoto
- Department of Urology, Akita University Graduate School of Medicine, Akita, Japan
| | - Naoto Okada
- Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan
- Pharmacy Department, Yamaguchi University Hospital, Yamaguchi, Japan
| | - Kiyoshi Mori
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
| | - Hiroyuki Yamada
- Department of Primary Care and Emergency Medicine, Kyoto University Hospital, Kyoto, Japan
| | - Takashige Kuwabara
- Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Atsushi Yonezawa
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan
| | - Takuya Fujimaru
- Department of Nephrology, St Luke's International Hospital, Tokyo, Japan
| | - Haruna Kawano
- Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Hideki Yokoi
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kent Doi
- Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Junichi Hoshino
- Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan
| | - Motoko Yanagita
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
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14
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Gudsoorkar P, Abudayyeh A, Tchakarov A, Hanna R. Onconephrology and Thrombotic Microangiopathy: Looking Beyond the Horizon. Semin Nephrol 2023; 42:151345. [PMID: 37196461 DOI: 10.1016/j.semnephrol.2023.151345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Thrombotic microangiopathies (TMAs) represent a complex interaction of endothelial and podocyte biology, nephron physiology, complement genetics, and oncologic therapies with host immunology. The complexity of various factors, such as molecular causes, genetic expressions, and immune system mimicking, along with incomplete penetrance, make it difficult to find a straightforward solution. As a result, there may be variations in diagnosis, study, and treatment approaches, and achieving a consensus can be challenging. Here, we review the molecular biology, pharmacology, immunology, molecular genetics, and pathology of the various TMA syndromes in the setting of cancer. Controversies in etiology, nomenclature, and points requiring further clinical, translational, and bench research are discussed. Complement-mediated TMAs, chemotherapy drug-mediated TMAs, TMAs in monoclonal gammopathy, and other TMAs central to onconephrology practice are reviewed in detail. In addition, established and emerging therapies within the US Food and Drug Administration pipeline subsequently are discussed. Finally, a comprehensive review of critical areas of onconephrology clinical practice is presented as practical value to the clinical practitioner and seeds of investigation to be sown among the community of atypical hemolytic uremic syndrome researchers.
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Affiliation(s)
- Prakash Gudsoorkar
- Division of Nephrology, Kidney C.A.R.E. Program, University of Cincinnati, Cincinnati, OH
| | - Ala Abudayyeh
- Section of Nephrology, The University of Texas, MD Anderson Cancer Center, Houston, TX
| | - Amanda Tchakarov
- Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, TX
| | - Ramy Hanna
- Division of Nephrology, Department of Medicine, University of California Irvine Medical Center, Orange, CA.
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15
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Moore M, Afolayan-Oloye O, Kroneman O, Li W, Kanaan HD, Zhang PL. Proteinuria in thrombotic microangiopathy is associated with partial podocytopathy. Ultrastruct Pathol 2023; 47:219-226. [PMID: 36906888 DOI: 10.1080/01913123.2023.2189341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/13/2023]
Abstract
BACKGROUND Thrombotic microangiopathy (TMA) results in acute kidney injury, but the cause of heavy proteinuria in this disorder is puzzling. The goal of this study was to determine if there were significant effacement of foot processes and CD133-positive hyperplastic podocytes in TMA to explain the proteinuria. METHODS The study included 12 negative controls (renal parenchyma removed from renal cell carcinoma) and 28 thrombotic microangiopathy due to different etiologies. The percent of foot process effacement was estimated, and proteinuria level was obtained for each TMA case. Both groups of cases were stained for CD133 by immunohistochemical method, and the number of positive CD133 in hyperplastic podocytes was counted and analyzed. RESULTS Nineteen (19) of 28 (68%) TMA cases had nephrotic range proteinuria (urine protein/creatinine >3). Twenty-one (21) of 28 (75%) TMA cases showed positive CD133 staining in scattered hyperplastic podocytes within Bowman's space but was absent in control cases. The percent of foot process effacement (56 ± 4%) correlated with proteinuria (protein/creatinine ratio 4.4 ± 0.6) (r = 0.46, p = .0237) in TMA group. CONCLUSION Our data indicate that the proteinuria in TMA can be associated with significant effacement of foot processes. CD133-positive hyperplastic podocytes can be seen in the majority of TMA cases of this cohort, indicating a partial podocytopathy.
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Affiliation(s)
- Megan Moore
- Oakland University William Beaumont School of Medicine, Rochester, MI, USA
| | | | - Olaf Kroneman
- Division of Nephrology, Beaumont Health, Royal Oak, MI, USA
| | - Wei Li
- Department of Pathology, Beaumont Labs, Royal Oak, MI, USA
| | | | - Ping L Zhang
- Department of Pathology, Beaumont Labs, Royal Oak, MI, USA
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16
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Aklilu AM, Shirali AC. Chemotherapy-Associated Thrombotic Microangiopathy. KIDNEY360 2023; 4:409-422. [PMID: 36706238 PMCID: PMC10103319 DOI: 10.34067/kid.0000000000000061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 12/22/2022] [Indexed: 01/28/2023]
Abstract
Thrombotic microangiopathy (TMA) is a syndrome of microangiopathic hemolytic anemia and thrombocytopenia with end-organ dysfunction. Although the advent of plasma exchange, immunosuppression, and complement inhibition has improved morbidity and mortality for primary TMAs, the management of secondary TMAs, particularly drug-induced TMA, remains less clear. TMA related to cancer drugs disrupts the antineoplastic treatment course, increasing the risk of cancer progression. Chemotherapeutic agents such as mitomycin-C, gemcitabine, and platinum-based drugs as well as targeted therapies such as antiangiogenesis agents and proteasome inhibitors have been implicated in oncotherapy-associated TMA. Among TMA subtypes, drug-induced TMA is less well-understood. Treatment generally involves withdrawal of the offending agent and supportive care targeting blood pressure and proteinuria reduction. Immunosuppression and therapeutic plasma exchange have not shown clear benefit. The terminal complement inhibitor, eculizumab, has shown promising results in some cases of chemotherapy-associated TMA including in re-exposure. However, the data are limited, and unlike in primary atypical hemolytic uremic syndrome, the role of complement in the pathogenesis of drug-induced TMA is unclear. Larger multicenter studies and unified definitions are needed to elucidate the extent of the problem and potential treatment strategies.
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Affiliation(s)
- Abinet M. Aklilu
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Anushree C. Shirali
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
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17
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Gunji M, Sawa C, Akiyama M, Mukai S, Takaki T, Kang D, Honda K. Gemcitabine alters sialic acid binding of the glycocalyx and induces inflammatory cytokine production in cultured endothelial cells. Med Mol Morphol 2023; 56:128-137. [PMID: 36622466 PMCID: PMC9828377 DOI: 10.1007/s00795-022-00347-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 12/30/2022] [Indexed: 01/10/2023]
Abstract
Gemcitabine (GEM) is an anticancer drug inhibiting DNA synthesis. Glomerular thrombotic microangiopathy (TMA) has been reported as an adverse effect. However, the precise mechanism of GEM-induced endothelial injury remains unknown. Cultured human umbilical vein endothelial cells (HUVECs) in the confluent phase were exposed to GEM (5-100 μM) for 48 h and evaluated cell viability and morphology, lectin binding concerning sialic acid of endothelial glycocalyx (GCX), and immunofluorescent staining of platelet-endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor receptor 2 (VEGFR2). The mRNA expression of α2,6-sialyltransferase (ST6Gal1), sialidase (neuraminidase-1: NEU-1), and interleukin (IL)-1β and IL-6 was also evaluated. GEM exposure at 5 μM induced cellular shrinkage and intercellular dissociation, accompanied by slight attenuation of PECAM and VEGFR2 immunostaining, although cell viability was still preserved. At this concentration, lectin binding showed a reduction of terminal sialic acids in endothelial GCX, probably associated with reduced ST6Gal1 mRNA expression. IL-1β and IL-6 mRNA expression was significantly increased after GEM exposure. GEM reduced terminal sialic acids in endothelial GCX through mRNA suppression of ST6Gal1 and induced inflammatory cytokine production in HUVECs. This phenomenon could be associated with the mechanism of GEM-induced TMA.
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Affiliation(s)
- Mariko Gunji
- Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan
| | - Chika Sawa
- Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan
| | - Minako Akiyama
- Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan
| | - Shumpei Mukai
- Department of Pathology, Showa University School of Medicine, Tokyo, Japan
| | - Takashi Takaki
- Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan ,Center for Electron Microscopy, Showa University, Tokyo, Japan
| | - Dedong Kang
- Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan
| | - Kazuho Honda
- Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan
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18
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Khan AM, Arjyal L, Shamaileh L, Simon M. Gemcitabine-induced digital ischaemia in a patient with metastatic breast cancer. BMJ Case Rep 2022; 15:e252083. [PMID: 36319039 PMCID: PMC9628528 DOI: 10.1136/bcr-2022-252083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2022] [Indexed: 12/05/2022] Open
Abstract
A woman in her 50s with HER2 (human epidermal growth factor receptor 2) positive, estrogen/progesterone receptor negative, metastatic invasive ductal carcinoma of the breast, presented with acral cyanosis and severe throbbing pain after recent administration of gemcitabine. She was treated with aspirin, heparin, amlodipine, topical nitroglycerin and analgesics. Gemcitabine was discontinued permanently. She had a gradual recovery except for a small necrotic area over the right 4th digit. However, surgical intervention was avoided.
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Affiliation(s)
- Abdul Moiz Khan
- Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA
| | - Lubina Arjyal
- Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA
| | - Lelas Shamaileh
- Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA
| | - Michael Simon
- Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA
- Oncology, Wayne State University, Detroit, Michigan, USA
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19
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Chuquin D, Abbate A, Bottinor W. Hypertension in Cancer Survivors: A Review of the Literature and Suggested Approach to Diagnosis and Treatment. J Cardiovasc Pharmacol 2022; 80:522-530. [PMID: 36027586 PMCID: PMC9547865 DOI: 10.1097/fjc.0000000000001342] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 06/28/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Hypertension, which is common among cancer survivors with a prevalence of greater than 70% by age 50, potentiates the risk for CVD in a more than additive fashion. For example, childhood cancer survivors who develop hypertension may have up to a 12 times higher risk for heart failure than survivors who remain normotensive. Studies have shown that mild valvular disease (28% incidence), cardiomyopathy (7.4%), arrhythmias (4.6%), and coronary artery disease (3.8%) are among the most common CVDs in childhood cancer survivors. Among adolescent and young adult cancer survivors, the most common reasons for cardiovascular-related hospital admission are venous/lymphatic disease (absolute excess risk 19%), cardiomyopathy and arrhythmia (15%), hypertension (13%), and ischemic heart disease (12%). In addition, cancer therapies can increase the risk for hypertension and CVD. Therefore, early detection and treatment of hypertension is essential to reducing cardiovascular morbidity and mortality among survivors. METHODS We present a literature review, which identified over 20 clinical trials, systemic reviews, and meta-analyses (13 clinical trials, 8 systemic reviews or meta-analyses) by searching PubMed, Google Scholar, and the Cochrane Library for relevant articles addressing hypertension in cancer survivors. RESULTS Although our understanding of the complex relationship between cancer therapies and CVD has grown significantly over the past 2 decades, there remain several gaps in knowledge when specifically addressing CVD in the survivor population. This review provides an up-to-date survivor-centered approach to the screening and treatment of hypertension, which considers survivor-specific cardiovascular risk, applies guideline directed therapies when appropriate, screens for survivor-specific factors that may influence antihypertensive medication selection, and finally considers the prohypertensive mechanisms of antineoplastic agents as a potential target for antihypertensive medications. CONCLUSIONS Screening for and treating hypertension among survivors can promote cardiovascular health in this vulnerable population.
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Affiliation(s)
- David Chuquin
- Pauley Heart Center, Virginia Commonwealth University, Richmond, VA
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20
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Garcia de Herreros M, Esposito F, Sauri T, Font C. Mild forms of thrombotic microangiopathy in patients with advanced pancreatic cancer receiving gemcitabine and nab-paclitaxel. J Oncol Pharm Pract 2022; 29:738-745. [PMID: 35876362 DOI: 10.1177/10781552221114653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Thrombotic microangiopathy (TMA) is an uncommon complication that may occur in cancer patients usually as an expression of cancer-associated coagulopathy or due to drug-related toxicity. The clinical spectrum of TMA may vary from an incidental laboratory finding in cancer outpatients to potentially severe life-threatening clinical forms with organ involvement requiring prompt recognition and multidisciplinary evaluation. CASE REPORTS We present the clinical characteristics and outcomes of four patients with advanced pancreatic cancer with acute non-immune intravascular haemolysis compatible with microangiopathic acute haemolytic anaemia associated with mild thrombocytopenia during long-term gemcitabine and nab-paclitaxel treatment. MANAGEMENT AND OUTCOMES Abnormal blood parameters (all four cases) and renal involvement (one case) were reversed with a conservative approach and chemotherapy discontinuation. One patient required a short hospitalization while the other three were managed as outpatients. The rapid reversibility of the blood abnormalities supported gemcitabine dose-related toxicity as the most likely aetiologic mechanism and demonstrates the current challenges in daily long-term cancer survivor care. DISCUSSION Clinicians must take into account TMA in the differential diagnosis of acute anaemia with or without thrombocytopenia and organ damage, since adequate recognition and early treatment discontinuation allow effective outpatient management and favourable patient outcomes.
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Affiliation(s)
| | - Francis Esposito
- Medical Oncology Department, 16493Hospital Clinic Barcelona, Barcelona, Spain
| | - Tamara Sauri
- Medical Oncology Department, 16493Hospital Clinic Barcelona, Barcelona, Spain
| | - Carme Font
- Medical Oncology Department, 16493Hospital Clinic Barcelona, Barcelona, Spain
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21
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Allard J, Bonnet M, Laurent L, Bouattour M, Gagaille MP, Leclerc V. Microangiopathy associated with gemcitabine: a drug interaction with nab-paclitaxel? A case series and literature review. Eur J Clin Pharmacol 2022; 78:1087-1093. [PMID: 35507073 DOI: 10.1007/s00228-022-03324-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 04/15/2022] [Indexed: 12/23/2022]
Abstract
PURPOSE Gemcitabine and nab-paclitaxel association can be used in first- or second-line treatment for metastatic pancreatic adenocarcinoma. Here, we report five cases of supposed gemcitabine-induced thrombotic microangiopathy (G-TMA), four of them with nab-paclitaxel. We assumed that nab-paclitaxel could be responsible for a potential drug interaction with gemcitabine, increasing the risk of thrombotic microangiopathy occurrence. METHODS Clinicians reported cases of supposed G-TMA that were declared to the Pharmacovigilance center. We collected the patients' data (clinical and biological characteristics), calculated an incidence rate of G-TMA in our center, and a Naranjo score for each patient. We also reviewed literature on a potential drug interaction between nab-paclitaxel and gemcitabine. RESULTS Four patients were treated with nab-paclitaxel/gemcitabine and one with gemcitabine alone. The time onset of supposed G-TMA was 2 to 11 months. Patients developed anemia, thrombocytopenia, and renal failure. The incidence rate of supposed G-TMA was 2.7% in our center compared to 0.31% (Meyler's Side Effect of Drugs) and 0.01% in the gemcitabine's summary of product characteristics. Literature review outlined an increase of gemcitabine's plasmatic concentrations induced by nab-paclitaxel (Drugs® website) and a potentiation of gemcitabine's effect by nab-paclitaxel in murine models. This study showed that nab-paclitaxel inhibits cytidine deaminase's activity (responsible for gemcitabine's metabolism) and increases gemcitabine's active metabolite concentrations (gemcitabine triphosphate) in tumor tissues. CONCLUSION High incidence rate of G-TMA was observed in our cohort due to a potential drug interaction between nab-paclitaxel and gemcitabine with an increased risk of developing G-TMA. Additional pharmacological and pharmaco-epidemiological investigations are mandatory to explore this hypothesis.
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Affiliation(s)
- Jeanne Allard
- Pharmacy Department, DMU PRISME, APHP, Beaujon Hospital, 92110, Clichy, France.
| | - Mathilde Bonnet
- Pharmacy Department, DMU PRISME, APHP, Beaujon Hospital, 92110, Clichy, France
| | - Lucie Laurent
- Department of Pancreatology, DMU DIGEST, APHP, Beaujon Hospital, 92110, Clichy, France
| | - Mohamed Bouattour
- Liver Cancer Unit, DMU DIGEST, APHP, Beaujon Hospital, 92110, Clichy, France
| | | | - Vincent Leclerc
- Pharmacy Department, DMU PRISME, APHP, Beaujon Hospital, 92110, Clichy, France
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22
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Thrombotic microangiopathy (TMA) in adult patients with solid tumors: a challenging complication in the era of emerging anticancer therapies. Support Care Cancer 2022; 30:8599-8609. [PMID: 35545722 PMCID: PMC9095052 DOI: 10.1007/s00520-022-06935-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 02/23/2022] [Indexed: 11/02/2022]
Abstract
Thrombotic microangiopathy (TMA) is a syndrome that encompasses a group of disorders defined by the presence of endothelial damage leading to abnormal activation of coagulation, microangiopathic hemolytic anemia and thrombocytopenia, occlusive (micro)vascular dysfunction, and organ damage. TMA may occur in patients with malignancy as a manifestation of cancer-related coagulopathy itself or tumor-induced TMA (Ti-TMA) as a paraneoplastic uncommon manifestation of Trousseau syndrome. TMA can also be triggered by other overlapping conditions such as infections or more frequently as an adverse effect of anticancer drugs (drug-induced TMA or Di-TMA) due to direct dose-dependent toxicity or a drug-dependent antibody reaction. The clinical spectrum of TMA may vary widely from asymptomatic abnormal laboratory tests to acute severe potentially life-threatening forms due to massive microvascular occlusion. While TMA is a rare condition, its incidence may progressively increase within the context of the great development of anticancer drugs and the emerging scenarios in supportive care in cancer. The objective of the present narrative review is to provide a general perspective of the main causes, the key work-up clues that allow clinicians to diagnose and manage TMA in patients with solid tumors who develop anemia and thrombocytopenia due to frequent overlapping causes.
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Ahlawat P, Gupta M, Upadhyay P, Gupta S, Kaur A. Gemcitabine-Induced Hemolytic Uremic Syndrome in Lung Cancer: A Case Report. Cureus 2022; 14:e20926. [PMID: 35145816 PMCID: PMC8812056 DOI: 10.7759/cureus.20926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2022] [Indexed: 11/20/2022] Open
Abstract
Gemcitabine is a broad-spectrum anti-metabolite drug that is widely used in the therapy of numerous advanced cancers such as pancreatic, breast, ovary, lung, and bladder cancer. Gemcitabine has been reported to cause hemolytic uremic syndrome (HUS), but the underlying mechanism is not elucidated. The outcome of gemcitabine-induced HUS is often poor and associated with high mortality. We present a case report of a patient who was on chemotherapy for lung cancer and presented with the concerns of decreased urine output and shortness of breath. He was investigated and found to have HUS. He was managed with plasmapheresis, which resulted in partial recovery. This case report describes HUS caused by gemcitabine in patients with lung carcinoma and the management implemented and also aims to highlight the importance of early and timely recognition and treatment to improve clinical outcomes in these patients.
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Aloy B, Janus N, Isnard-Bagnis C, Deray G, Launay-Vacher V. [Renal toxicity of anticancer drugs]. Nephrol Ther 2021; 17:553-563. [PMID: 34802974 DOI: 10.1016/j.nephro.2021.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The renal toxicity of anticancer drugs is a clinical challenge because of the intrinsic toxicity of some anticancer drugs and because the cancer itself. Indeed, cancer patients are exposed to all types of renal disorders (obstructive, functional, organic because of radiotherapy, paraneoplastic glomerulopathy, thrombotic microangiopathy…). The therapeutic index of anticancer drugs is often narrow and the doses used for optimal efficacy are high. Improving safety requires a better dose adjustment, which depends on the correct evaluation of the renal function. Prevention remains important as the mortality associated with acute renal failure is very high.
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Affiliation(s)
- Blandine Aloy
- Service de néphrologie, groupe hospitalier Pitié-Salpêtrière-Charles-Foix, 83, boulevard de l'Hôpital, 75013 Paris, France; Service information conseil adaptation rénale (Icar), cour des consultations porte 12, hôpital Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France.
| | - Nicolas Janus
- Service de néphrologie, groupe hospitalier Pitié-Salpêtrière-Charles-Foix, 83, boulevard de l'Hôpital, 75013 Paris, France; Service information conseil adaptation rénale (Icar), cour des consultations porte 12, hôpital Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France; Cancer and the Kidney International Network, boulevard du Souverain, 280, 1160 Bruxelles, Belgique
| | - Corine Isnard-Bagnis
- Service de néphrologie, groupe hospitalier Pitié-Salpêtrière-Charles-Foix, 83, boulevard de l'Hôpital, 75013 Paris, France; Campus Pierre-et-Marie-Curie, Sorbonne Université, 4, place Jussieu, 75005 Paris, France
| | - Gilbert Deray
- Service de néphrologie, groupe hospitalier Pitié-Salpêtrière-Charles-Foix, 83, boulevard de l'Hôpital, 75013 Paris, France; Service information conseil adaptation rénale (Icar), cour des consultations porte 12, hôpital Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France; Cancer and the Kidney International Network, boulevard du Souverain, 280, 1160 Bruxelles, Belgique; Campus Pierre-et-Marie-Curie, Sorbonne Université, 4, place Jussieu, 75005 Paris, France
| | - Vincent Launay-Vacher
- Service de néphrologie, groupe hospitalier Pitié-Salpêtrière-Charles-Foix, 83, boulevard de l'Hôpital, 75013 Paris, France; Service information conseil adaptation rénale (Icar), cour des consultations porte 12, hôpital Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France; Cancer and the Kidney International Network, boulevard du Souverain, 280, 1160 Bruxelles, Belgique
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25
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Kala J, Salman LA, Geara AS, Izzedine H. Nephrotoxicity From Molecularly Targeted Chemotherapeutic Agents. Adv Chronic Kidney Dis 2021; 28:415-428.e1. [PMID: 35190108 DOI: 10.1053/j.ackd.2021.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/16/2021] [Accepted: 09/01/2021] [Indexed: 11/11/2022]
Abstract
The introduction of novel molecularly targeted therapies in the last 2 decades has significantly improved the patient survival compared to standard conventional chemotherapies. However, this improvement has been accompanied by a whole new spectrum of kidney adverse events. Although known as "targeted," many of these agents lack specificity and selectivity, and they have a tendency to inhibit multiple targets including those in the kidneys. Early detection and correct management of kidney toxicities is crucial to preserve kidney functions. The knowledge of these toxicities helps guide optimal and continued utilization of these potent therapies. The incidence, severity, and pattern of nephrotoxicity may vary depending on the respective target of the drug. Here, we review the mechanism of action, clinical findings of kidney adverse events, and their proposed management strategies.
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26
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Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre JP, Pouteil-Noble C, Karras A, Guerrot D, François A, Benhamou Y, Veyradier A, Frémeaux-Bacchi V, Coppo P, Grangé S. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol 2021; 22:267. [PMID: 34284729 PMCID: PMC8293501 DOI: 10.1186/s12882-021-02470-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 07/01/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). METHODS This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. RESULTS Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4-44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2-22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0-10) before treatment vs 0 (range 0-1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group. CONCLUSIONS These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.
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Affiliation(s)
- Maximilien Grall
- Medical Intensive Care Unit, Rouen University Hospital, 37 boulevard Gambetta, 76031, Rouen Cedex, France
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
| | - Florence Daviet
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Nephrology, Conception University Hospital, APHM, Marseille, France
| | - Noémie Jourde Chiche
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Nephrology, Conception University Hospital, APHM, Marseille, France
| | - François Provot
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Nephrology, Lille University Hospital, Lille, France
| | - Claire Presne
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Nephrology, Amiens University Hospital, Amiens, France
| | - Jean-Philippe Coindre
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Nephrology, Le Mans General Hospital, Le Mans, France
| | - Claire Pouteil-Noble
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Nephrology, E. Herriot Hospital, Lyon I university, Lyon, France
| | - Alexandre Karras
- Department of Nephrology, Georges Pompidou Hospital, APHP, Paris, France
| | | | - Arnaud François
- Department of Pathology, Rouen University Hospital, Rouen, France
| | - Ygal Benhamou
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Internal Medicine, Rouen University Hospital, Rouen, France
| | - Agnès Veyradier
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Biological Hematology, Lariboisière University Hospital, APHP, Paris, France
| | - Véronique Frémeaux-Bacchi
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of immunology, Georges Pompidou Hospital, APHP, Paris, France
| | - Paul Coppo
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
- Department of Hematology, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
| | - Steven Grangé
- Medical Intensive Care Unit, Rouen University Hospital, 37 boulevard Gambetta, 76031, Rouen Cedex, France.
- French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.
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27
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Unravelling the tangled web of hypertension and cancer. Clin Sci (Lond) 2021; 135:1609-1625. [PMID: 34240734 DOI: 10.1042/cs20200307] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 01/11/2023]
Abstract
Cardiovascular disease remains the primary cause of mortality globally, being responsible for an estimated 17 million deaths every year. Cancer is the second leading cause of death on a global level with roughly 9 million deaths per year being attributed to neoplasms. The two share multiple common risk factors such as obesity, poor physical exercise, older age, smoking and there exists rare monogenic hypertension syndromes. Hypertension is the most important risk factor for cardiovascular disease and affects more than a billion people worldwide and may also be a risk factor for the development of certain types of cancer (e.g. renal cell carcinoma (RCC)). The interaction space of the two conditions becomes more complicated when the well-described hypertensive effect of certain antineoplastic drugs is considered along with the extensive amount of literature on the association of different classes of antihypertensive drugs with cancer risk/prevention. The cardiovascular risks associated with antineoplastic treatment calls for efficient management of relative adverse events and the development of practical strategies for efficient decision-making in the clinic. Pharmacogenetic interactions between cancer treatment and hypertension-related genes is not to be ruled out, but the evidence is not still ample to be incorporated in clinical practice. Precision Medicine has the potential to bridge the gap of knowledge regarding the full spectrum of interactions between cancer and hypertension (and cardiovascular disease) and provide novel solutions through the emerging field of cardio-oncology. In this review, we aimed to examine the bidirectional associations between cancer and hypertension including pharmacotherapy.
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28
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Valério P, Barreto JP, Ferreira H, Chuva T, Paiva A, Costa JM. Thrombotic microangiopathy in oncology - a review. Transl Oncol 2021; 14:101081. [PMID: 33862523 PMCID: PMC8065296 DOI: 10.1016/j.tranon.2021.101081] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 03/18/2021] [Indexed: 12/31/2022] Open
Abstract
Thrombotic microangiopathy is a syndrome triggered by a wide spectrum of situations, some of which are specific to the Oncology setting. It is characterized by a Coombs-negative microangiopathic haemolytic anemia, thrombocytopenia and organ injury, with characteristic pathological features, resulting from platelet microvascular occlusion. TMA is rare and its cancer-related subset even more so. TMA triggered by drugs is the most common within this group, including classic chemotherapy and the latest targeted therapies. The neoplastic disease itself and hematopoietic stem-cell transplantation could also be potential triggers. Evidence-based medical guidance in the management of cancer-related TMA is scarce and the previous knowledge about primary TMA is valuable to understand the disease mechanisms and the potential treatments. Given the wide spectrum of potential causes for TMA in cancer patients, the aim of this review is to gather the vast information available. For each entity, pathophysiology, clinical features, therapeutic approaches and prognosis will be covered.
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Affiliation(s)
- Patrícia Valério
- Nephrology Department, Setúbal Hospital Center, Portugal Rua Camilo Castelo Branco 175, 2910-549 Setúbal, Portugal.
| | - João Pedro Barreto
- Laboratory Diagnosis Department, Portuguese Oncology Institute of Porto, Portugal Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Hugo Ferreira
- Nephrology Department, Portuguese Oncology Institute of Porto, Portugal Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Teresa Chuva
- Nephrology Department, Portuguese Oncology Institute of Porto, Portugal Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Ana Paiva
- Nephrology Department, Portuguese Oncology Institute of Porto, Portugal Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - José Maximino Costa
- Nephrology Department, Portuguese Oncology Institute of Porto, Portugal Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
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Efe O, Goyal L, Galway A, Zhu AX, Niles JL, Zonozi R. Treatment of Gemcitabine-Induced Thrombotic Microangiopathy Followed by Gemcitabine Rechallenge With Eculizumab. Kidney Int Rep 2021; 6:1464-1468. [PMID: 34013127 PMCID: PMC8116759 DOI: 10.1016/j.ekir.2021.03.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/25/2021] [Accepted: 03/01/2021] [Indexed: 10/26/2022] Open
Affiliation(s)
- Orhan Efe
- Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Lipika Goyal
- Division of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aralee Galway
- Division of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Andrew X Zhu
- Division of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - John L Niles
- Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Reza Zonozi
- Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
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Iacopo F, Branch M, Cardinale D, Middeldorp M, Sanders P, Cohen JB, Achirica MC, Jaiswal S, Brown SA. Preventive Cardio-Oncology: Cardiovascular Disease Prevention in Cancer Patients and Survivors. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2021. [DOI: 10.1007/s11936-020-00883-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Hypertension management in cardio-oncology. J Hum Hypertens 2020; 34:673-681. [PMID: 32747676 PMCID: PMC7398285 DOI: 10.1038/s41371-020-0391-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/08/2020] [Accepted: 07/24/2020] [Indexed: 12/13/2022]
Abstract
Cancer is one of the leading causes of death worldwide. During the last few decades prognosis has improved dramatically and patients are living longer and suffering long-term cardiovascular consequences of chemotherapeutic agents. Cardiovascular disease is a leading cause of morbidity and mortality in cancer survivors second only to recurrent cancer. In some types of cancer, cardiovascular disease is a more common cause of death than the cancer itself. This has led to a new sub-specialty of cardiology coined cardio-oncology to manage this specific population. Hypertension is one of the most common cardiovascular disease seen in this cohort. The aetiology of hypertension in cardio-oncology is complex and multifactorial based on the type of chemotherapy, type of malignancy and intrinsic patient factors such as age and pre-existing comorbidities. A variety of different oncological treatments have been implicated in causing hypertension. The effect can be transient whilst undergoing treatment or can be delayed occurring decades after treatment. A tailored management plan is recommended given the plethora of agents and their differing underlying mechanisms and speed of this mechanism in causing hypertension. Management by a multidisciplinary team consisting of oncology, general practice and cardiology is advised. There are currently no trials comparing antihypertensives in this specific cohort of patients. In the absence of evidence demonstrating otherwise, hypertension in cardio-oncology should be managed utilising the same treatment guidelines for the general population.
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Piscitani L, Sirolli V, Di Liberato L, Morroni M, Bonomini M. Nephrotoxicity Associated with Novel Anticancer Agents (Aflibercept, Dasatinib, Nivolumab): Case Series and Nephrological Considerations. Int J Mol Sci 2020; 21:E4878. [PMID: 32664269 PMCID: PMC7402330 DOI: 10.3390/ijms21144878] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/07/2020] [Accepted: 07/08/2020] [Indexed: 12/16/2022] Open
Abstract
Cancer patients have an incidence of about 60% kidney disease development and are at elevated risk of acute renal damage. Kidney disease in these patients is frequently associated with nephrotoxicity from the ongoing oncological treatment. New anticancer therapeutic strategies, such as targeted therapies and immunotherapies, offer substantial benefits in the treatment of many neoplasms. However, their use is associated with significant nephrotoxicity, which qualitatively differs from that seen with traditional cytotoxic chemotherapy, while the underlying mechanisms are complex and still to be clearly defined. Nephrologists need to be knowledgeable about the array of such renal toxicities for effective collaboration with the oncologist in the prevention and management of kidney involvement. Renal adverse effects may range from asymptomatic proteinuria to renal failure, and their prompt identification and timely treatment is essential for optimal and safe care of the patient. In this article, after presenting clinical cases we discuss the differing renal toxicity of three novel anticancer agents (aflibercept, dasatinib, and nivolumab) and possible measures to counter it.
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Affiliation(s)
- Luca Piscitani
- Nephrology and Dialysis Unit, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy; (L.P.); (V.S.); (L.D.L.)
| | - Vittorio Sirolli
- Nephrology and Dialysis Unit, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy; (L.P.); (V.S.); (L.D.L.)
| | - Lorenzo Di Liberato
- Nephrology and Dialysis Unit, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy; (L.P.); (V.S.); (L.D.L.)
| | - Manrico Morroni
- Department of Experimental and Clinical Medicine-Neuroscience and Cell Biology, School of Medicine, Università Politecnica delle Marche, Via Tronto 10/A, 60126 Ancona, Italy;
| | - Mario Bonomini
- Nephrology and Dialysis Unit, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy; (L.P.); (V.S.); (L.D.L.)
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Chatzikonstantinou T, Gavriilaki M, Anagnostopoulos A, Gavriilaki E. An Update in Drug-Induced Thrombotic Microangiopathy. Front Med (Lausanne) 2020; 7:212. [PMID: 32528969 PMCID: PMC7256484 DOI: 10.3389/fmed.2020.00212] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 04/29/2020] [Indexed: 12/18/2022] Open
Affiliation(s)
| | - Maria Gavriilaki
- Laboratory of Clinical Neurophysiology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Eleni Gavriilaki
- BMT Unit, Hematology Department, G Papanicolaou Hospital, Thessaloniki, Greece
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Bamias A, Tzannis K, Dimitriadis I, Tsironis G, Papatheorodidi AM, Tsiara A, Fragkoulis C, Xirokosta A, Barbarousi D, Papadopoulos G, Zakopoulou R, Varkarakis I, Mitsogiannis I, Adamakis I, Alamanis C, Stravodimos K, Papatsoris AG, Dellis AE, Drivalos A, Ntoumas K, Matsouka H, Halvatsiotis P, Raptis A, Gerotziafas GT, Dimopoulos MA. Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy. Clin Genitourin Cancer 2020; 18:e457-e472. [PMID: 32007440 DOI: 10.1016/j.clgc.2019.12.021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 12/22/2019] [Accepted: 12/26/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. PATIENTS AND METHODS Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. RESULTS A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. CONCLUSION Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.
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Affiliation(s)
- Aristotelis Bamias
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece; 2nd Propaedeutic Dept of Internal Medicine, ATTIKON Hospital, National and Kapodistrian University of Athens, Athens, Greece.
| | - Kimon Tzannis
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Dimitriadis
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Tsironis
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Alkistis-Maria Papatheorodidi
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Anna Tsiara
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | | | | | | | - Roubini Zakopoulou
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Varkarakis
- 2nd Department of Urology, Sismanoglio General Hospital, University of Athens, Athens, Greece
| | - Iraklis Mitsogiannis
- 2nd Department of Urology, Sismanoglio General Hospital, University of Athens, Athens, Greece
| | - Ioannis Adamakis
- 1st University Urology Clinic, Laiko Hospital, University of Athens, Athens, Greece
| | - Christos Alamanis
- 1st University Urology Clinic, Laiko Hospital, University of Athens, Athens, Greece
| | | | - Athanasios G Papatsoris
- 2nd Department of Urology, Sismanoglio General Hospital, University of Athens, Athens, Greece
| | - Athanasios E Dellis
- 2nd Department of Surgery, Aretaieion Academic Hospital, University of Athens, Athens, Greece
| | | | | | | | - Panayiotis Halvatsiotis
- 2nd Propaedeutic Dept of Internal Medicine, ATTIKON Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Athanasios Raptis
- 2nd Propaedeutic Dept of Internal Medicine, ATTIKON Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Grigorios T Gerotziafas
- Cancer Biology and Therapeutics, INSERM U938, Institut Universitaire de Cancérologie (IUC), Faculté de Médecine Pierre et Marie Curie, Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France
| | - Meletios Athanasios Dimopoulos
- Hematology-Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Nicolaysen A. Nephrotoxic Chemotherapy Agents: Old and New. Adv Chronic Kidney Dis 2020; 27:38-49. [PMID: 32147000 DOI: 10.1053/j.ackd.2019.08.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 08/01/2019] [Indexed: 02/08/2023]
Abstract
In the last several decades, advancements in chemotherapy have improved the overall survival of cancer patients. These agents, however, are associated with adverse effects, including various kidney lesions. This review summarizes the nephrotoxic potential of chemotherapy agents, old and new, as well as the different factors that contribute to kidney injury. Provided for each class of chemotherapy agent is the associated kidney lesion and a brief discussion of clinical manifestation, mechanism of action, and possible treatment when available. Understanding the nephrotoxic potential of these agents have on the kidneys is imperative for both the oncologist and the nephrologist to properly care for cancer patients and ensure their best outcomes.
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Cohen JB, Geara AS, Hogan JJ, Townsend RR. Hypertension in Cancer Patients and Survivors: Epidemiology, Diagnosis, and Management. JACC CardioOncol 2019; 1:238-251. [PMID: 32206762 PMCID: PMC7089580 DOI: 10.1016/j.jaccao.2019.11.009] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 11/01/2019] [Accepted: 11/04/2019] [Indexed: 12/28/2022] Open
Abstract
Cancer patients and survivors of cancer have a greater burden of cardiovascular disease compared to the general population. Much of the elevated cardiovascular risk in these individuals is likely attributable to hypertension, as individuals with cancer have a particularly high incidence of hypertension following cancer diagnosis. Treatment with chemotherapy is an independent risk factor for hypertension due to direct effects of many agents on endothelial function, sympathetic activity, and renin-angiotensin system activity as well as nephrotoxicity. Diagnosis and management of hypertension in cancer patients requires accurate blood pressure measurement and consideration of potential confounding factors, such as adjuvant treatments and acute pain, that can temporarily elevate blood pressure readings. Home blood pressure monitoring can be a useful tool to facilitate longitudinal blood pressure monitoring for titration of antihypertensive medications. Selection of antihypertensive agents in cancer patients should account for treatment-specific morbidities and target organ injury.
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Affiliation(s)
- Jordana B. Cohen
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Abdallah S. Geara
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jonathan J. Hogan
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Raymond R. Townsend
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Summary of the International Conference on Onco-Nephrology: an emerging field in medicine. Kidney Int 2019; 96:555-567. [DOI: 10.1016/j.kint.2019.04.043] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 04/02/2019] [Accepted: 04/05/2019] [Indexed: 01/10/2023]
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Bassareo PP, Cocco D, Cadeddu C, Mercuro G. Multimodality Imaging Diagnosis of Multiple Ventricular Thrombosis and Massive Stroke after Gemcitabine and Cisplatin Chemotherapy for Urothelial Cancer. J Cardiovasc Echogr 2019; 29:71-74. [PMID: 31392124 PMCID: PMC6657469 DOI: 10.4103/jcecho.jcecho_12_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Cancer and chemotherapy are known to be risk factors for developing coagulative disorders, venous thrombosis, adverse cardiovascular events, and cardiotoxicity. Combined modality gemcitabine–cisplatin chemotherapy is often administered to treat a few solid tumors. We report the unusual case of a man suffering from urothelial cancer and admitted for chemotherapy, who developed an ischemic stroke after the last chemotherapeutical cycle. During his hospital stay, at echocardiographic examination, left ventricular transient hypokinesia and two intraventricular thrombi were detected, without evidence of acute coronary syndrome. Multimodality imaging approach (i.e., transthoracic echo, transoesophageal echo, computed tomography, and cardiac magnetic resonance imaging) played a pivotal role for a clear diagnosis and prompt decision-making. This is the first report of an intraventricular-related arterial thromboembolic event in a patient treated with the combination gemcitabine–cisplatin.
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Affiliation(s)
- Pier Paolo Bassareo
- Department of Cardiology, University College of Dublin, Mater Misericordiae University Hospital, Dublin, Republic of Ireland, Monserrato, Italy.,Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy
| | - Daniele Cocco
- Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy
| | - Christian Cadeddu
- Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy
| | - Giuseppe Mercuro
- Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy
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Martin K, Roberts V, Chong G, Goodman D, Hill P, Ierino F. Eculizumab therapy in gemcitabine-induced thrombotic microangiopathy in a renal transplant recipient. Oxf Med Case Reports 2019; 2019:omz048. [PMID: 31214360 DOI: 10.1093/omcr/omz048] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 03/11/2019] [Accepted: 04/13/2019] [Indexed: 11/14/2022] Open
Abstract
A renal transplant recipient 7 years post-transplantation, diagnosed with locally advanced pancreatic adenocarcinoma developed thrombotic microangiopathy (TMA) after treatment with gemcitabine and nab-paclitaxel. Gemcitabine was the most likely cause for TMA and was ceased. He received methylprednisolone and plasma exchange with fresh frozen plasma and albumin. Despite plasma exchange, his renal allograft function worsened, and he had persistent haematological evidence of haemolysis. Eculizumab was commenced with resolution-significant improvement in his renal and haematological markers. This case highlights an unusual occurrence of progressive gemcitabine-induced TMA in a renal allograft that had an excellent response to eculizumab. The clinical response also demonstrates involvement of complement dysregulation in gemcitabine-induced TNA.
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Affiliation(s)
- Kylie Martin
- Department of Nephrology, St Vincent's Hospital Melbourne, Fitzroy 3065 Victoria, Australia
| | - Veena Roberts
- Department of Nephrology, St Vincent's Hospital Melbourne, Fitzroy 3065 Victoria, Australia
| | - Geoff Chong
- Olivia-Newton John Cancer, Wellness and Research Centre, Austin Hospital, Heidelberg, Australia
| | - David Goodman
- Department of Nephrology, St Vincent's Hospital Melbourne, Fitzroy 3065 Victoria, Australia
| | - Prue Hill
- Department of Nephrology, St Vincent's Hospital Melbourne, Fitzroy 3065 Victoria, Australia
| | - Francesco Ierino
- Department of Nephrology, St Vincent's Hospital Melbourne, Fitzroy 3065 Victoria, Australia
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The footprints of mitochondrial impairment and cellular energy crisis in the pathogenesis of xenobiotics-induced nephrotoxicity, serum electrolytes imbalance, and Fanconi's syndrome: A comprehensive review. Toxicology 2019; 423:1-31. [PMID: 31095988 DOI: 10.1016/j.tox.2019.05.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 04/29/2019] [Accepted: 05/09/2019] [Indexed: 12/19/2022]
Abstract
Fanconi's Syndrome (FS) is a disorder characterized by impaired renal proximal tubule function. FS is associated with a vast defect in the renal reabsorption of several chemicals. Inherited and/or acquired conditions seem to be connected with FS. Several xenobiotics including many pharmaceuticals are capable of inducing FS and nephrotoxicity. Although the pathological state of FS is well described, the exact underlying etiology and cellular mechanism(s) of xenobiotics-induced nephrotoxicity, serum electrolytes imbalance, and FS are not elucidated. Constant and high dependence of the renal reabsorption process to energy (ATP) makes mitochondrial dysfunction as a pivotal mechanism which could be involved in the pathogenesis of FS. The current review focuses on the footprints of mitochondrial impairment in the etiology of xenobiotics-induced FS. Moreover, the importance of mitochondria protecting agents and their preventive/therapeutic capability against FS is highlighted. The information collected in this review may provide significant clues to new therapeutic interventions aimed at minimizing xenobiotics-induced renal injury, serum electrolytes imbalance, and FS.
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Cidon EU, Martinez PA, Hickish T. Gemcitabine-induced haemolytic uremic syndrome, although infrequent, can it be prevented: A case report and review of literature. World J Clin Cases 2018; 6:531-537. [PMID: 30397609 PMCID: PMC6212612 DOI: 10.12998/wjcc.v6.i12.531] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Revised: 09/08/2018] [Accepted: 10/09/2018] [Indexed: 02/05/2023] Open
Abstract
Gemcitabine is an antineoplastic used to treat several malignancies including pancreatic cancer. Its toxicity profile is well known with myelotoxicity, increased vascular permeability and peripheral oedema as most frequent adverse events. However, several cases of acute renal failure have been reported and haemolytic uremic syndrome (HUS) seems to be the underlying process. The cause of HUS remains unknown but its consequences can be lethal. Therefore, a high grade of suspicion is crucial to diagnose it and promptly treat it. This hopefully will reduce its morbidity. HUS is characterized by progressive renal failure associated with microangiopathic haemolytic anaemia and thrombocytopenia. The primary event is damage to endothelial cells and thrombotic microangiopathy (TMA) is the histopathological lesion. TMA affects mainly renal microvasculature. However, some cases evolve with central nervous or cardiovascular systems involvement. We present here a case of gemcitabine-induced HUS, with renal and cardiovascular system affected at the time of diagnosis which to our knowledge this is the first time of such case to be reported.
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Affiliation(s)
- Esther U Cidon
- Department of Medical Oncology, Royal Bournemouth and Christchurch Hospital NHS Foundation Trust, Bournemouth BH7 7DW, United Kingdom
| | - Pilar A Martinez
- Department of Oncology, Clinical University Hospital, Valladolid 47003, Spain
| | - Tamas Hickish
- Department of Medical Oncology, Royal Bournemouth and Christchurch Hospital NHS Foundation Trust and Bournemouth University, Bournemouth BH7 7DW, United Kingdom
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Hasan A, Jain AG, Naim H, Munaf A, Everett G. Drug-induced Thrombotic Microangiopathy Caused by Gemcitabine. Cureus 2018; 10:e3088. [PMID: 30324044 PMCID: PMC6171780 DOI: 10.7759/cureus.3088] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Hemolytic uremic syndrome (HUS) is the triad of nonimmune (Coombs negative) hemolytic anemia, low platelet count, and renal impairment. HUS has been associated with a variety of gastrointestinal malignancies and chemotherapeutic agents. We present a patient with pancreatic cancer treated with gemcitabine for palliation who developed gemcitabine-induced HUS (GiHUS) which responded to some extent to blood and platelet transfusions. With the increase in the use of gemcitabine therapy for pancreatic and other malignancies, it is essential to accurately and timely diagnose GiHUS to avoid the life-threatening complications.
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Affiliation(s)
| | - Akriti G Jain
- Internal Medicine Residency, Florida Hospital, Orlando, USA
| | - Huda Naim
- Internal Medicine, Dow University of Health Sciences (DUHS), Karachi, PAK
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Krishnappa V, Gupta M, Shah H, Das A, Tanphaichitr N, Novak R, Raina R. The use of eculizumab in gemcitabine induced thrombotic microangiopathy. BMC Nephrol 2018; 19:9. [PMID: 29329518 PMCID: PMC5767063 DOI: 10.1186/s12882-018-0812-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 01/01/2018] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure. Furthermore, a C5 inhibitor, eculizumab, has been successfully used in the treatment of GiTMA. CASE PRESENTATION A 64-year-old Caucasian female with history of pancreatic adenocarcinoma on gemcitabine chemotherapy presented with signs and symptoms of fluid overload and was found to have abnormal kidney function. Her BP was 195/110 mmHg, serum creatinine 4.48 mg/dl, hemoglobin 8.2 g/dl, platelets 53 × 103/cmm, lactate dehydrogenase 540 IU/L, and was found to have schistocytes on blood film. A diagnosis of TMA secondary to gemcitabine therapy was suspected. Hemodialysis for volume overload and daily plasmapheresis were initiated. After six days of plasmapheresis, renal function did not improve. Further work up revealed ADAMTS 13 activity >15%, low C3, and stool culture and Shiga-toxin PCR were negative. Renal biopsy was consistent with TMA. Gemcitabine was discontinued, but renal function failed to improve and eculizumab therapy was considered due to suspicion of aHUS. Serum creatinine >2.26 mg/dl and a platelet count of >/= 30 × 109/L is highly suggestive of aHUS, while TTP is more likely when creatinine is <2.26 mg/dl and platelet count of <30 × 109/L. She received intravenous eculizumab for eight months, which resulted in significant improvement of renal function. Other markers of hemolysis, namely LDH and bilirubin, also rapidly improved following eculizumab therapy. Plasmapheresis and hemodialysis were discontinued after two and eight weeks of initiation respectively. CONCLUSION Chemotherapy induced TMA is very rare and requires a high index of clinical suspicion for timely diagnosis. Discontinuation of the offending drug and supportive care is the main stay of treatment; however, eculizumab has been shown to be beneficial in GiTMA. Further research is required to validate this approach.
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Affiliation(s)
- Vinod Krishnappa
- Department of Internal Medicine and Nephrology, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307 USA
| | - Mohit Gupta
- Department of Internal Medicine and Nephrology, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307 USA
- Department of Nephrology, Weill Cornell Medicine/New York Presbyterian, New York, USA
| | - Haikoo Shah
- Northeast Ohio Medical University, Rootstown, OH USA
| | - Abhijit Das
- Northeast Ohio Medical University, Rootstown, OH USA
| | - Natthavat Tanphaichitr
- Department of Internal Medicine and Nephrology, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307 USA
| | - Robert Novak
- Department of Pathology, Akron Children’s Hospital, Akron, OH USA
| | - Rupesh Raina
- Department of Internal Medicine and Nephrology, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307 USA
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Weitz IC. Thrombotic microangiopathy in cancer. Thromb Res 2018; 164 Suppl 1:S103-S105. [PMID: 29703465 DOI: 10.1016/j.thromres.2018.01.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 01/08/2018] [Indexed: 12/28/2022]
Abstract
Thrombotic microangiopathy (TMA) is clinical syndrome based on the presence of thrombocytopenia (platelet count <150 K or a reduction of the platelet count by >30% from baseline) accompanied by fragmentation hemolysis (MAHA) and evidence of organ damage. It can be seen in a variety of disorders including thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (aHUS), shigatoxin related hemolytic uremic syndrome (STEC-HUS). Cancer itself has long been associated with both macro and microvascular thrombosis. In addition, treatment with chemotherapy as well as hematopoetic stem cell transplantation (HCST) has been associated with atypical hemolytic uremic (aHUS) like syndrome. In this review, I will discuss the pathophysiology of TMA in cancer, chemotherapy associated HUS, and HSCT, well as new therapeutic interventions.
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Affiliation(s)
- Ilene Ceil Weitz
- Jane Anne Nohl Division of Hematology, Department of Medicine, University of Southern California-Keck School of Medicine, Los Angeles, CA, USA.
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Assayag M, Rouvier P, Gauthier M, Costel G, Cluzel P, Mercadal L, Deray G, Isnard Bagnis C. Renal failure during chemotherapy: renal biopsy for assessing subacute nephrotoxicity of pemetrexed. BMC Cancer 2017; 17:770. [PMID: 29145816 PMCID: PMC5689204 DOI: 10.1186/s12885-017-3705-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 10/26/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Pemetrexed, a multitargeted antifolate cytotoxic agent, is currently used primarily in combination with cisplatin for metastatic non-small cell lung cancer and for malignant mesothelioma. Acute renal toxicity of pemetrexed has been recently described with polychemotherapy, in which the individual responsibility of each drug is difficult to establish. Only one recent report documents renal involvement in long-term exposed patients. CASE PRESENTATION We report on a case of rapidly progressive nephropathy leading to the cessation of platinum salts and the secondary interruption of pemetrexed and bevacizumab. Acute tubular necrosis shown on the renal biopsy could potentially be due to pemetrexed. Persistent severe renal failure after the resumption of all drugs led to new treatment lines with gemcitabine (while the glomerular filtration rate was below 30 ml/min/1.73m2), then followed by Taxol. CONCLUSIONS The optimal strategy with regard to renal complications in cancer patients is not clear. Acute or chronic loss in renal function generally leads to a new treatment line, possibly impairing the overall success of the treatment. The use of chemotherapy in patients with a glomerular filtration rate below 30 ml/min/1.73m2 is usually associated with an increased risk of side effects when not contraindicated by renal elimination of the drug.
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Gosain R, Gill A, Fuqua J, Volz LH, Kessans Knable MR, Bycroft R, Seger S, Gosain R, Rios JA, Chao JH. Gemcitabine and carfilzomib induced thrombotic microangiopathy: eculizumab as a life-saving treatment. Clin Case Rep 2017; 5:1926-1930. [PMID: 29225827 PMCID: PMC5715608 DOI: 10.1002/ccr3.1214] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 08/21/2017] [Accepted: 09/05/2017] [Indexed: 12/31/2022] Open
Abstract
Drug‐induced aHUS is rare; however, early diagnosis is vital to reduce morbidity and mortality. With confirmation of the diagnosis, eculizumab appears to be a viable treatment option to suppress the pro‐inflammatory surge. Furthermore, adverse side effects of medications such as carfilzomib and gemcitabine should be considered in the appropriate settings.
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Affiliation(s)
- Rahul Gosain
- Division of Hematology and Medical Oncology James Graham Brown Cancer Center University of Louisville School of Medicine Louisville Kentucky
| | - Amitoj Gill
- Division of Hematology and Medical Oncology James Graham Brown Cancer Center University of Louisville School of Medicine Louisville Kentucky
| | - Jacob Fuqua
- Department of Medicine University of Louisville School of Medicine Louisville Kentucky
| | - Lesley H Volz
- Department of Pharmacy James Graham Brown Cancer Center University of Louisville Louisville Kentucky
| | - Mika R Kessans Knable
- Department of Pharmacy James Graham Brown Cancer Center University of Louisville Louisville Kentucky
| | - Ryan Bycroft
- Department of Pharmacy James Graham Brown Cancer Center University of Louisville Louisville Kentucky
| | - Sarah Seger
- Department of Pharmacy James Graham Brown Cancer Center University of Louisville Louisville Kentucky
| | - Rohit Gosain
- Division of Hematology and Medical Oncology Roswell Park Cancer Institute Buffalo New York
| | - Jorge A Rios
- Division of Hematology and Medical Oncology The Mark H. Zangmeister Cancer Center Columbus Ohio
| | - Ju-Hsien Chao
- Division of Hematology and Medical Oncology Texas Transplant Physician Group - Methodist Physicians San Antonio Texas
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47
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Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost 2017; 15:1889-1900. [PMID: 28662310 PMCID: PMC5630501 DOI: 10.1111/jth.13764] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Indexed: 01/07/2023]
Abstract
Thrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS-13. In general, severe deficiency of plasma ADAMTS-13 activity (< 10 IU dL-1 ) with or without detectable inhibitory autoantibodies against ADAMTS-13 supports the diagnosis of TTP. A patient usually presents with thrombocytopenia and microangiopathic hemolytic anemia (i.e. schistocytes, elevated serum lactate dehydrogenase, decreased hemoglobin and haptoglobin) without other known etiologies that cause thrombotic microangiopathy (TMA). Normal to moderately reduced plasma ADAMTS-13 activity (> 10 IU dL-1 ) in a similar clinical context supports an alternative diagnosis such as atypical hemolytic uremic syndrome (aHUS) or other types of TMA. Prompt differentiation of TTP from other causes of TMA is crucial for the initiation of an appropriate therapy to reduce morbidity and mortality. Although plasma infusion is often sufficient for prophylaxis or treatment of hereditary TTP due to ADAMTS-13 mutations, daily therapeutic plasma exchange remains the initial treatment of choice for acquired TTP with demonstrable autoantibodies. Immunomodulatory therapies, including corticosteroids, rituximab, vincristine, cyclosporine, cyclophosphamide and splenectomy, etc., should be considered to eliminate autoantibodies for a sustained remission. Other emerging therapeutic modalities, including recombinant ADAMTS-13, adeno-associated virus (AAV) 8-mediated gene therapy, platelet-delivered ADAMTS-13, and antagonists targeting the interaction between platelet glycoprotein 1b and VWF are under investigation. This review highlights the recent progress in our understanding of the pathogenesis and diagnosis of, and current and potential novel therapies for, hereditary and acquired TTP.
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Affiliation(s)
- Manish Saha
- Division of Nephrology, Departments of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35249
| | - Jenny K. McDaniel
- Division of Hematology/Oncology, Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35249
| | - X. Long Zheng
- Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35249
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Bittar PG, Nickolich MS, Onwuemene OA. ASFA Category IV becomes Category I: Idiopathic thrombotic thrombocytopenic purpura in a patient with presumed gemcitabine-induced thrombotic microangiopathy. J Clin Apher 2017; 33:423-426. [PMID: 28940604 DOI: 10.1002/jca.21590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 08/28/2017] [Accepted: 09/12/2017] [Indexed: 11/11/2022]
Abstract
In the implementation of American Society for Apheresis national guidelines, the decision for therapeutic plasma exchange may be confounded by a clinical presentation that fits both a Category I and IV designation. We report the case of a 45-year-old female who presented with concern for a Category IV disorder, gemcitabine-induced thrombotic microangiopathy, and was ultimately diagnosed with a Category I disorder, idiopathic thrombotic thrombocytopenic purpura. This case highlights the importance of ruling out idiopathic TTP by a thorough evaluation for ADAMTS13 activity and inhibitor, even when an alternate thrombotic microangiopathy diagnosis may be likely.
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Affiliation(s)
- Peter G Bittar
- Duke University School of Medicine, Durham, North Carolina
| | - Myles S Nickolich
- Department of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Oluwatoyosi A Onwuemene
- Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
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Kheder El-Fekih R, Deltombe C, Izzedine H. [Thrombotic microangiopathy and cancer]. Nephrol Ther 2017; 13:439-447. [PMID: 28774729 DOI: 10.1016/j.nephro.2017.01.023] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Revised: 01/03/2017] [Accepted: 01/05/2017] [Indexed: 01/28/2023]
Abstract
Thrombotic microangiopathy (TMA) is a group of disorders characterized by mechanical hemolytic anemia with thrombocytopenia and an ischemic organic lesion of variable and potentially fatal importance affecting mostly the kidneys and the brain with histologically a disseminated and occlusive microvasculopathy. The incidence of TMA represents 15% of acute kidney failure in oncological setting, largely due to the introduction of anti-angiogenic agents over the past decade. It may be more rarely related to cancer itself. The iatrogenic TMA can be classified into 2 types: The type I, secondary to chemotherapy (mitomycinC, gemcitabine), exposes to a chronic dose-dependent renal injury as well as an increase in morbidity and mortality; iatrogenic type II, secondary to anti-angiogenic agents', results in a dose-independent renal involvement and renal functional recovery is usual when the drug is discontinued. There is no randomized controlled trial to establish EBM-type management in TMA support. However, complement activation pathways and regulatory factors analyses allowed us to understand the mechanisms of endothelial lesions. As a result, the current trend includes the use of immunosuppressive agents in recurrent or plasmapheresis-refractory MAT.
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Affiliation(s)
| | - Clément Deltombe
- Service de néphrologie, immunologie clinique, transplantation, CHU Hôtel-Dieu, Place Alexis-Ricordeau, 44000 Nantes, France
| | - Hassan Izzedine
- Clinique internationale du Parc Monceau, 21, rue de Chazelles, 75017 Paris, France.
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50
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Charmetant X, Jolivot A, Fournier T, Puthet JC, Cassier P, Lemoine S, Juillard L. [Gemcitabine-induced thrombotic microangiopathy: Can we improve screening and treatment?]. Nephrol Ther 2017; 13:251-254. [PMID: 28499586 DOI: 10.1016/j.nephro.2016.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 12/08/2016] [Accepted: 12/08/2016] [Indexed: 11/26/2022]
Abstract
Thrombotic microangiopathy is a rare but severe complication of treatment with gemcitabine. Its prevalence increases because gemcitabine's indications are growing. We report four cases, which presented with common clinical and biological manifestations, i.e. high blood pressure, proteinuria and increasing plasmatic creatinine level. However, severity was not similar, hemodialysis was inconstant. There is no consensus on treatment for this condition. Stopping gemcitabine is essential. Treatment was dispensed considering the severity of the presentation: plasma exchange therapy of variable outcome, and eculizumab, which was efficient when used. It's important to note that this syndrome includes common and frequent signs in patients receiving chemotherapies. But they must encourage the research of most specific signs, such as hypertension, mechanic hemolysis signs, proteinuria or hematuria, in order to recognize thrombotic microangiopathy as early as possible to treat it precociously, and to prevent additional gemcitabine injections.
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Affiliation(s)
- Xavier Charmetant
- Service de néphrologie, hôpital Édouard-Herriot, hospices civils de Lyon, 3, place d'Arsonval, 69347 Lyon cedex, France.
| | - Anne Jolivot
- Service de néphrologie, hôpital Édouard-Herriot, hospices civils de Lyon, 3, place d'Arsonval, 69347 Lyon cedex, France
| | - Thomas Fournier
- Service de néphrologie, hôpital Édouard-Herriot, hospices civils de Lyon, 3, place d'Arsonval, 69347 Lyon cedex, France
| | - Jean-Charles Puthet
- Service de néphrologie, hôpital Édouard-Herriot, hospices civils de Lyon, 3, place d'Arsonval, 69347 Lyon cedex, France
| | - Philippe Cassier
- Service de cancérologie médicale, centre Léon-Bérard, 28, rue Laënnec, 69008 Lyon, France
| | - Sandrine Lemoine
- Service d'exploration fonctionnelle rénale, hôpital Édouard-Herriot, hospices civils de Lyon, 3, place d'Arsonval, 69347 Lyon cedex, France
| | - Laurent Juillard
- Service de néphrologie, hôpital Édouard-Herriot, hospices civils de Lyon, 3, place d'Arsonval, 69347 Lyon cedex, France
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