scholarly journals Renal Safety Profile of EGFR Targeted Therapies: A Study from VigiBase® the WHO Global Database of Individual Case Safety Reports

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5907
Author(s):  
Alexandre Crosnier ◽  
Chadi Abbara ◽  
Morgane Cellier ◽  
Laurence Lagarce ◽  
Marina Babin ◽  
...  
Keyword(s):  
Renal Failure ◽  
Safety Profile ◽  
Kidney Injury ◽  
Individual Case ◽  
Reporting Odds Ratio ◽  
Glomerular Diseases ◽  
Global Database ◽  
Egfr Expression ◽  
Uremic Syndrome ◽  
Renal Safety

Kidney EGFR expression together with reported cases of glomerular diseases in the context of anti-EGFR drug administration raise concerns about the renal safety profile of these drugs. This issue is addressed in a case/non-case study carried out on VigiBase®, the WHO global database of individual case safety reports (ICRS). Disproportionality analysis of renal adverse effects related to the selected anti-EGFR drugs, erlotinib, gefitinib, afatinib, osimertinib, cetuximab and panitumumab, was assessed using the reporting odds ratio (ROR). Nine hundred and eighty-nine ICRSs were included. A signal of disproportionate reporting (SDR) was found for afatinib (ROR = 2.70; 95% CI [2.22–3.29]) and erlotinib (ROR = 1.73; 95% CI [1.46–2.04]) with acute kidney injury, and for afatinib (ROR = 2.41; 95% CI [1.78–3.27]), cetuximab (ROR = 1.42; 95% CI [1.14–1.78]) and erlotinib (ROR = 2.23; 95% CI [1.80–2.77]) with renal failure. The preferred term “diarrhoea” was frequently reported in the included cases. An SDR was found for erlotinib with haemolytic and uremic syndrome (ROR = 4.01; 95% CI [1.80–8.94]) and thrombotic microangiopathy (ROR = 4.94; 95% CI [2.80–8.72]). No SDR was seen for glomerular or tubule-interstitial diseases. This study showed that the anti-EGFR drug renal toxicity is mainly related to renal failure in the context of digestive toxicity.

Therapeutic Apheresis and Immunosuppression in Renal Diseases

2021 ◽  
Vol 7 (3) ◽  
pp. 01-15
Author(s):  
Rolf Bambauer
Keyword(s):  
Acute Kidney Injury ◽  
Renal Failure ◽  
Transplant Rejection ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Blood Purification ◽  
Renal Diseases ◽  
Uremic Syndrome ◽  
American Society ◽  
Apheresis Therapy

Therapeutic plasma exchange (TPE) with hollow fiber modules is used in different severe diseases since more than 40 years. The authors try to give an overview of therapeutic apheresis (TA) in renal diseases. The updated information on immunology and molecular biology of different renal diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different renal diseases can be treated by various apheresis methods such as TPE with substitution solution, or with online plasma or blood purification using adsorption columns, which contain biological or non-biological agents. The following diseases are discussed: rapidly progressive glomerulonephritis (RPGN) including anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM RPGN), RPGN with or without glomerular deposition (ANCA-ab), pauci-immune RPGN, immune complex nephritis (ICN), and various glomerulonephritis with nephrotic syndrome (NS), acute kidney injury (AKI), myoglobulinemic renal failure, hemolytic-uremic syndrome (HUS), and kidney transplant rejection. For the renal diseases, which can be treated with TA, the guidelines of the Apheresis Applications Committee (AAC) of the American Society for Apheresis (ASFA) are shown.

scholarly journals Mitomycin-C-Induced TTP/HUS Treated Successfully with Rituximab: Case Report and Review of the Literature

2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Gunjan Shah ◽  
Hanah Yamin ◽  
Hedy Smith
Keyword(s):  
Rectal Cancer ◽  
Acute Kidney Injury ◽  
Renal Failure ◽  
Mitomycin C ◽  
Kidney Injury ◽  
Review Of The Literature ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
Uremic Syndrome

Microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, renal failure, and neurologic symptoms comprise the cardinal features of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Etiologies can include medications, infections, cancers, or transplantation. We present a patient with a history of rectal cancer treated with mitomycin-C who developed MAHA, acute kidney injury, and thrombocytopenia 6 months after completing therapy and to did not respond the plasmapheresis or steroids. She was treated with four weekly doses of rituximab with full recovery.

scholarly journals Evaluation of Renal Safety Between Imipenem/Relebactam and Colistin Plus Imipenem in Patients With Imipenem-Nonsusceptible Bacterial Infections in the Randomized, Phase 3 RESTORE-IMI 1 Study

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Michelle L Brown ◽  
Johann Motsch ◽  
Keith S Kaye ◽  
Thomas M File ◽  
Helen W Boucher ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Adverse Events ◽  
Safety Profile ◽  
Bacterial Infections ◽  
Kidney Injury ◽  
Gram Negative ◽  
End Stage ◽  
Time To Onset ◽  
Renal Safety

Abstract Background In the randomized controlled RESTORE-IMI 1 clinical trial (NCT02452047), imipenem/cilastatin (IMI) with relebactam (IMI/REL) was as effective as colistin plus IMI for the treatment of imipenem-nonsusceptible gram-negative infections. Differences in nephrotoxicity were observed between treatment arms. As there is no standard definition of nephrotoxicity used in clinical trials, we conducted analyses to further understand the renal safety profile of both treatments. Methods Nephrotoxicity was retrospectively evaluated using 2 acute kidney injury assessment criteria (Kidney Disease Improving Global Outcomes [KDIGO] and Risk, Injury, Failure, Loss, and End-stage Kidney Disease [RIFLE]). Additional outcomes included time to onset of protocol-defined nephrotoxicity and incidence of renal adverse events. Results Of 47 participants receiving treatment, 45 had sufficient data to assess nephrotoxicity (IMI/REL, n = 29; colistin plus IMI, n = 16). By KDIGO criteria, no participants in the IMI/REL but 31.3% in the colistin plus IMI group experienced stage 3 acute kidney injury. No IMI/REL-treated participants experienced renal failure by RIFLE criteria, vs 25.0% for colistin plus IMI. Overall, the time to onset of nephrotoxicity varied considerably (2–22 days). Fewer renal adverse events (12.9% vs 37.5%), including discontinuations due to drug-related renal adverse events (0% vs 12.5%), were observed in the IMI/REL group compared with the colistin plus IMI group, respectively. Conclusions Our analyses confirm the findings of a preplanned end point and provide further evidence that IMI/REL had a more favorable renal safety profile than colistin-based therapy in patients with serious, imipenem-nonsusceptible gram-negative bacterial infections. ClinicalTrials.gov Identifier NCT02452047.

scholarly journals Familial atypical hemolytic uremic syndrome with positive p.S1191L (c.3572C>T) mutation on the CFH gene: A single-center experience

2021 ◽  
Vol 24 (1) ◽  
pp. 81-88
Author(s):  
F Ersoy Dursun ◽  
G Yesil ◽  
G Sasak ◽  
H Dursin
Keyword(s):  
Acute Kidney Injury ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Family History ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Gene Mutations ◽  
Kidney Injury ◽  
The Other ◽  
History Of ◽  
Uremic Syndrome

Abstract The atypical hemolytic uremic syndrome (aHUS) is characterized by thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI), which can exhibit a poor prognosis. Complement factor H (CFH) gene mutations play a key role in this disease, which may be sporadic or familial. We studied 13 people from the same family, investigated for gene mutations of the familial aHUS after a family member presented to our emergency clinic with the aHUS and reported a family history of chronic renal failure. The p.S1191L mutation on the CFH gene was heterozygous in six people from the patient’s family with the aHUS. One of these family members is our patient with acute kidney injury, and the other two are followed at the Nephrology Clinic, Medeniyat University, Goztepe Training and Research Hospital, Istanbul, Turkey, due to chronic renal failure. The other three family members showed no evidence of renal failure. The index case had a history of six sibling deaths; three died of chronic renal failure. Plasmapheresis and fresh frozen plasma treatment were administered to our patient. When the patient showed no response to this treatment, eculizumab (ECZ) therapy was started. The study demonstrated that thorough family history should be taken in patients with the aHUS. These patients may have the familial type of the disease, and they should be screened genetically. Eculizumab should be the first choice in the treatment with plasmapheresis. It should be kept in mind that the use of ECZ as prophylaxis in posttransplant therapy is extremely important for preventing rejection.

scholarly journals Acute kidney injury associated with febuxostat and allopurinol: a post-marketing study

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Amayelle Rey ◽  
Benjamin Batteux ◽  
Solène M. Laville ◽  
Justine Marienne ◽  
Kamel Masmoudi ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Kidney Injury ◽  
Renal Stones ◽  
World Health ◽  
Sensitivity Analyses ◽  
Reporting Odds Ratio ◽  
Pharmacovigilance Database ◽  
Post Marketing ◽  
Medical Dictionary

Abstract Background For patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, urate-lowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. Due to the widespread use of these ULTs (especially in patients with impaired renal function), assessment of the associated renal risk is essential. Accordingly, we performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat. Methods We carried out a case/non-case study of the World Health Organization’s VigiBase® pharmacovigilance database between January 1, 2008, and December 31, 2018. The frequency of reports of ARF as a standardized Medical Dictionary for Regulatory Activities query for allopurinol and febuxostat was compared with that of all other reports for the two drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. The results’ stability was assessed in a series of sensitivity analyses (notably after the exclusion of putative competing drugs). Results Among 3509 “suspected drug” notifications for febuxostat and 18,730 for allopurinol, we identified respectively 317 and 1008 cases of ARF. Acute renal failure was reported significantly more frequently for febuxostat and allopurinol than for other drugs (ROR [95%CI] 5.67 [5.05–6.36] and 3.25 [3.05–3.47], respectively). For both drugs, the ROR was higher in women than in men, respectively 11.60 [9.74–13.82] vs. 3.14 [2.69–3.67] for febuxostat and 4.45 [4.04–4.91] vs. 2.29 [2.11–2.50] for allopurinol. The sensitivity analyses confirmed the disproportionality for these two ULTs. Conclusions Acute renal failure was reported respectively 5.7 and 3.3 times more frequently for febuxostat and for allopurinol than for other drugs. Due to the potential consequences of ARF, physicians should take account of this disproportionality signal when prescribing the ULTs febuxostat and allopurinol.

ACUTE KIDNEY INJURY IN ELDERLY PATIENTS

2019 ◽  
Vol 72 (8) ◽  
pp. 1466-1472
Author(s):  
Grażyna Kobus ◽  
Jolanta Małyszko ◽  
Hanna Bachórzewska-Gajewska
Keyword(s):  
Acute Kidney Injury ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Elderly Patients ◽  
Older Patients ◽  
Age Groups ◽  
Kidney Injury ◽  
The Elderly ◽  
Younger Patients ◽  
Common Cause

Introduction: In the elderly, impairment of kidney function occurs. Renal diseases overlap with anatomic and functional changes related to age-related involutionary processes. Mortality among patients with acute renal injury is approximately 50%, despite advances in treatment and diagnosis of AKI. The aim: To assess the incidence of acute kidney injury in elderly patients and to analyze the causes of acute renal failure depending on age. Materials and methods: A retrospective analysis included medical documentation of patients hospitalized in the Nephrology Clinic during the 6-month period. During this period 452 patients were hospitalized in the clinic. A group of 77 patients with acute renal failure as a reason for hospitalization was included in the study. Results: The prerenal form was the most common cause of AKI in both age groups. In both age groups, the most common cause was dehydration; in the group of patients up to 65 years of age, dehydration was 29.17%; in the group of people over 65 years - 43.39%. Renal replacement therapy in patients with AKI was used in 14.29% of patients. In the group of patients up to 65 years of age hemodialysis was 16.67% and above 65 years of age. -13.21% of patients. The average creatinine level in the group of younger patients at admission was 5.16 ± 3.71 mg / dl, in the group of older patients 3.14 ± 1.63 mg / dl. The size of glomerular filtration GFR in the group of younger patients at admission was 21.14 ± 19.54 ml / min, in the group of older patients 23.34 ± 13.33 ml / min. Conclusions: The main cause of acute kidney injury regardless of the age group was dehydration. Due to the high percentage of AKI in the elderly, this group requires more preventive action, not only in the hospital but also at home.

scholarly journals Lupus cystitis: unusual cause of renal failure in systemic lupus erythematosus

2019 ◽  
Vol 12 (12) ◽  
pp. e233446
Author(s):  
Kevin John ◽  
Krupa Varughese ◽  
Ranil Johann Boaz ◽  
Tarun George
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Acute Kidney Injury ◽  
Renal Failure ◽  
Renal Function ◽  
Lupus Erythematosus ◽  
Kidney Injury ◽  
Systemic Lupus ◽  
Uncommon Presentation ◽  
Acute Dyspnoea ◽  
Chronic Fever

A 42-year-old woman presented with chronic fever, abdominal pain, intermittent loose stools and dysuria for 3 months. She had recently developed acute dyspnoea with acute kidney injury. She was found to have a contracted, thick-walled bladder with bilateral hydroureteronephrosis. She underwent bilateral percutaneous nephrostomies, following which her renal function recovered. She satisfied the clinical and immunological features of the Systemic Lupus International Collaborating Clinics criteria for systemic lupus erythematosus (SLE). She was initiated on immunosuppression. Lupus cystitis with a contracted bladder is an uncommon presentation of SLE.

Tissue-resident macrophages mediate neutrophil recruitment and kidney injury in shiga toxin-induced hemolytic uremic syndrome.

2021 ◽  
Author(s):  
Julia K. Lill ◽  
Stephanie Thiebes ◽  
Judith-Mira Pohl ◽  
Jenny Bottek ◽  
Nirojah Subramaniam ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Kidney Injury ◽  
Neutrophil Recruitment ◽  
Uremic Syndrome

scholarly journals Renal Complications Related to Checkpoint Inhibitors: Diagnostic and Therapeutic Strategies

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1187
Author(s):  
Julie Belliere ◽  
Julien Mazieres ◽  
Nicolas Meyer ◽  
Leila Chebane ◽  
Fabien Despas
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Immunosuppressive Drugs ◽  
Peripheral Tolerance ◽  
Electrolyte Disorders ◽  
Glomerular Diseases ◽  
Renal Complications ◽  
Lower Baseline ◽  
Low Incidence

Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have unprecedentedly improved global prognosis in several types of cancers. However, they are associated with the occurrence of immune-related adverse events. Despite their low incidence, renal complications can interfere with the oncologic strategy. The breaking of peripheral tolerance and the emergence of auto- or drug-reactive T-cells are the main pathophysiological hypotheses to explain renal complications after ICI exposure. ICIs can induce a large spectrum of renal symptoms with variable severity (from isolated electrolyte disorders to dialysis-dependent acute kidney injury (AKI)) and presentation (acute tubule-interstitial nephritis in >90% of cases and a minority of glomerular diseases). In this review, the current trends in diagnosis and treatment strategies are summarized. The diagnosis of ICI-related renal complications requires special steps to avoid confounding factors, identify known risk factors (lower baseline estimated glomerular filtration rate, proton pump inhibitor use, and combination ICI therapy), and prove ICI causality, even after long-term exposure (weeks to months). A kidney biopsy should be performed as soon as possible. The treatment strategies rely on ICI discontinuation as well as co-medications, corticosteroids for 2 months, and tailored immunosuppressive drugs when renal response is not achieved.

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