Publications by authors named "Youssef Rizk"

9 Publications

  • Page 1 of 1

Mechanisms and management of drug-induced hyperkalemia in kidney transplant patients.

Rev Endocr Metab Disord 2021 Jul 22. Epub 2021 Jul 22.

Department of Medicine, Division of Nephrology, Hypertension and Kidney Transplantation, School of Medicine, University of California, CA, Irvine, Orange, USA.

Hyperkalemia is a common and potentially life-threatening complication following kidney transplantation that can be caused by a composite of factors such as medications, delayed graft function, and possibly potassium intake. Managing hyperkalemia after kidney transplantation is associated with increased morbidity and healthcare costs, and can be a cause of multiple hospital admissions and barriers to patient discharge. Medications used routinely after kidney transplantation are considered the most frequent culprit for post-transplant hyperkalemia in recipients with a well-functioning graft. These include calcineurin inhibitors (CNIs), pneumocystis pneumonia (PCP) prophylactic agents, and antihypertensives (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers). CNIs can cause hyperkalemic renal tubular acidosis. When hyperkalemia develops following transplantation, the potential offending medication may be discontinued, switched to another agent, or dose-reduced. Belatacept and mTOR inhibitors offer an alternative to calcineurin inhibitors in the event of hyperkalemia, however should be prescribed in the appropriate patient. While trimethoprim/sulfamethoxazole (TMP/SMX) remains the gold standard for prevention of PCP, alternative agents (e.g. dapsone, atovaquone) have been studied and can be recommend in place of TMP/SMX. Antihypertensives that act on the Renin-Angiotensin-Aldosterone System are generally avoided early after transplant but may be indicated later in the transplant course for patients with comorbidities. In cases of mild to moderate hyperkalemia, medical management can be used to normalize serum potassium levels and allow the transplant team additional time to evaluate the function of the graft. In the immediate post-operative setting following kidney transplantation, a rapidly rising potassium refractory to medical therapy can be an indication for dialysis. Patiromer and sodium zirconium cyclosilicate (ZS-9) may play an important role in the management of chronic hyperkalemia in kidney transplant patients, although additional long-term studies are necessary to confirm these effects.
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http://dx.doi.org/10.1007/s11154-021-09677-7DOI Listing
July 2021

Expanded Access Programs, compassionate drug use, and Emergency Use Authorizations during the COVID-19 pandemic.

Drug Discov Today 2021 02 27;26(2):593-603. Epub 2020 Nov 27.

National Coalition on Health Care, Washington, DC, USA.

The US Food and Drug Administration (FDA) Expanded Access (EA) Program, which allows for compassionate uses of unapproved therapeutics and diagnostics outside of clinical trials, has gained significant traction during the Coronavirus 2019 (COVID-19) pandemic. While development of vaccines has been the major focus, uncertainties around new vaccine safety and effectiveness have spawned interest in other pharmacological options. Experimental drugs can also be approved under the FDA Emergency Use Authorization (EUA) program, designed to combat infectious disease and other threats. Here, we review the US experience in 2020 with pharmacological EA and EUA approvals during the pandemic. We also provide a description of, and clinical rationale for, each of the EA- or EUA-approved drugs (e.g. remdesivir, convalescent plasma, propofol 2%, hydroxychloroquine, ruxolitinib, bamlanivimab, baricitinib, casirivimab plus imdevimab) during the pandemic and concluding reflections on the EA program and its potential future uses.
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http://dx.doi.org/10.1016/j.drudis.2020.11.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694556PMC
February 2021

Novel approaches to management of hyperkalaemia in kidney transplantation.

Curr Opin Nephrol Hypertens 2021 01;30(1):27-37

Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine School of Medicine, Orange.

Purpose Of Review: Medications used frequently after kidney transplantation, including calcineurin inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers and antimicrobials, are considered the leading culprit for posttransplant hyperkalaemia in recipients with a well functioning allograft. Other risk factors include comorbidities such as diabetes, hypertension and heart failure; and consumption of a potassium-enriched diet. We review the mechanisms for hyperkalaemia following kidney transplantation that are addressed using nonpharmacological and pharmacological interventions. We also discuss emerging therapeutic approaches for the management of recurrent hyperkalaemia in solid organ transplantation, including newer potassium binding therapies.

Recent Findings: Patiromer and sodium zirconium cyclosilicate are emerging potassium binders approved for the treatment of hyperkalaemia. Patiromer is a polymer that exchanges potassium for calcium ions. In contrast, sodium zirconium cyclosilicate is a nonpolymer compound that exchanges potassium for sodium and hydrogen ions. Both agents are efficacious in the treatment of chronic or recurrent hyperkalaemia and may result in fewer gastrointestinal side effects than older potassium binders such as sodium polystyrene sulfonate and calcium polystyrene sulfonate. Large-scale clinical studies have not been performed in kidney transplant patients. Patiromer may increase serum concentrations of tacrolimus, but not cyclosporine. Sodium zirconium cyclosilicate does not appear to compromise tacrolimus pharmacokinetics, although it may have a higher sodium burden.

Summary: Patiromer and sodium zirconium cyclosilicate may be well tolerated options to treat asymptomatic hyperkalaemia and have the potential to ease potassium dietary restrictions in kidney transplant patients by maintaining a plant-dominant, heart-healthy diet. Their efficacy, better tolerability and comparable cost with respect to previously available potassium binders make them an attractive therapeutic option in chronic hyperkalaemia following kidney transplantation.
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http://dx.doi.org/10.1097/MNH.0000000000000657DOI Listing
January 2021

Authors' Reply to Vrachatis et al. "Pharmaco-Immunomodulatory Therapy I COVID-19".

Drugs 2020 09;80(14):1501-1503

Division of Infectious Diseases, Department of Medicine, University of California, Irvine, School of Medicine, Irvine, CA, USA.

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http://dx.doi.org/10.1007/s40265-020-01396-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471515PMC
September 2020

Pharmaco-Immunomodulatory Therapy in COVID-19.

Drugs 2020 Sep;80(13):1267-1292

Division of Infectious Diseases, Department of Medicine, University of California, Irvine, School of Medicine, Irvine, CA, USA.

The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms.
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http://dx.doi.org/10.1007/s40265-020-01367-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372203PMC
September 2020

Rupture of Abdominal Aortic Aneurysm in Patients with and without Antecedent Endovascular Repair.

Ann Vasc Surg 2017 Feb 12;39:99-104. Epub 2016 Aug 12.

Henry Ford-Macomb Hospital, Clinton Township, MI; St. John Macomb Hospital, Warren, MI. Electronic address:

Background: Reported results of ruptured abdominal aortic aneurysm (rAAA) in patients with antecedent endovascular aneurysm repair (EVAR) to those presenting with de novo rupture show a similar or slightly improved outcome. The aim of this study was to compare differences in the presentation and outcomes of rAAA with and without prior EVAR.

Methods: A retrospective review of 121 patients with rAAA, ruptured identified 2 groups. Group A included 17 patients (rAAA n = 17) with antecedent EVAR and group B consisted of 104 patients (rAAA n = 104) with de novo ruptures, from January 2001 to March 2015 in 3 teaching hospitals. Patient characteristics and perioperative variables were compared; Fisher's exact test was used for categorical variables. For continuous variables, Student's t-test and Mann-Whitney U test were used.

Results: Both groups were similar in age, gender, the incidence of hypertension, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, and nicotine abuse. Mean time of presentation from EVAR to rupture in group A was 42 ± 22 months. Mean preoperative transverse or anteroposterior diameter of AAA was 6.6 cm in group A and 7.1 cm in group B. Three patients of 17 (17.6%) in group A were hemodynamically unstable as compared to 47 of 104 patients (45.1%) in group B (P = 0.03). Mean red blood cells, fresh frozen plasma, and platelet transfusion were similar in both groups. Thirty-day mortality was 8 of 17 (44.7%) in group A and 44 of 104 (42.3%) in group B (P = 1.0). Postoperative complications were also similar in both groups except the incidence of postoperative respiratory failure was higher in group B (38%) as compared with 11.1% in group A (P = 0.001).

Conclusions: Patients presenting with rAAA with antecedent EVAR are hemodynamically more stable as compared with patients with de novo rupture of AAA. Postoperative respiratory failure is more common in patients with de novo rupture. rAAA carry high mortality with and without prior EVAR.
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http://dx.doi.org/10.1016/j.avsg.2016.05.104DOI Listing
February 2017

Results of iliac stenting and aortofemoral grafting for iliac artery occlusions.

J Vasc Surg 2013 Apr 22;57(4):1030-7. Epub 2012 Nov 22.

St. John Providence Health System, Detroit, MI, USA.

Objective: To compare long-term results of percutaneous iliac artery stenting (PCIS) with aortobifemoral (ABF) grafting for patients with symptomatic iliac artery occlusions.

Methods: A retrospective review of 229 patients (January 2000 to December 2011) with symptomatic iliac artery occlusions was performed. In 100 patients, 103 PCIS procedures were performed, and 101 patients underwent ABF grafting. Outcome data including periprocedural complications, improvement in ankle-brachial index, morbidity, and mortality were collected in a vascular registry. Kaplan-Meier estimates for patency and survival were analyzed. Univariate (Fisher exact test) and multivariate analyses of variables associated with the loss of primary patency were performed.

Results: Patients in the ABF grafting group were younger (60 ± 0.9 years old vs 65 ± 1.2 years old; P = .002) and more commonly had a history of nicotine abuse (97% vs 86%; P = .002), chronic obstructive pulmonary disease (85% vs 70%; P = .02), and a greater incidence of superficial femoral artery disease (45% vs 24%; P = .001). The most common presenting symptoms in both groups consisted of intermittent claudication (66% ABF vs 71% PCIS), rest pain (20% ABF vs 17% PCIS), and ulceration or gangrene of toes (14% ABF vs 15% PCIS). At 72 months, the primary patency for ABF bypass was greater than for PCIS (91% vs 73%; P = .010). Secondary patency rates were equivalent in both groups (98% ABF vs 85% PCIS). Survival in the ABF bypass group was significantly greater than in the PCIS group (76% vs 68%; P = .013). Hyperlipidemia (hazard ratio, 2.55; P = .049) and concurrent superficial femoral artery lesion (hazard ratio, 2.61; P = .026) were factors associated with the loss of primary patency for the entire cohort. The average hospital stay was 7 ± 2 days in the ABF group and 1 ± 0.3 days in the PCIS group (P = .0001). There were no periprocedural deaths in the PCIS group; there were four deaths in the ABF group (P = .058). In the PCIS group, ankle-brachial index increased from 0.66 to 0.89, and in the ABF group, ankle-brachial index increased from 0.54 to 0.98 (both groups, P < .001).

Conclusions: This study demonstrates that PCIS remains a suitable, less invasive first-line therapy for iliac artery occlusions. PCIS has lower morbidity, shorter hospital length of stay, and equivalent secondary patency but inferior primary patency compared with ABF.
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http://dx.doi.org/10.1016/j.jvs.2012.09.038DOI Listing
April 2013

Technical strategies to expand stent-graft applicability in the aortic arch and proximal descending thoracic aorta.

J Endovasc Ther 2002 Jun;9 Suppl 2:II32-8

Center for Vascular Intervention, Union Memorial Hospital/MedStar Health, Baltimore, Maryland, USA.

The endovascular repair of thoracic aortic pathology is on an evolutionary threshold, as advancing technologies and techniques combine to offer the interventionist expanded treatment opportunities. A variety of maneuvers are recommended to address the landing zone limitations to thoracic endografting imposed by the arch vessels: transostial bare stent placement, intentional occlusion of the arch vessel origin, vessel transposition, and bypass grafting. These adjunctive techniques can help us extend the option of a minimally invasive treatment to a greater number of patients with severe thoracic aortic lesions and comorbidities that place them at high risk for standard surgical intervention.
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June 2002
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