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      Safe Use of Opioids in Chronic Kidney Disease and Hemodialysis Patients: Tips and Tricks for Non-Pain Specialists

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          Abstract

          In patients suffering from moderate-to-severe chronic kidney disease (CKD) or end-stage renal disease (ESRD), subjected to hemodialysis (HD), pain is very common, but often underestimated. Opioids are still the mainstay of severe chronic pain management; however, their prescription in CKD and HD patients is still significantly low and pain is often under-treated. Altered pharmacokinetics and the lack of clinical trials on the use of opioids in patients with renal impairment increase physicians’ concerns in this specific population. This narrative review focused on the correct and safe use of opioids in patients with CKD and HD. Morphine and codeine are not recommended, because the accumulation of their metabolites may cause neurotoxic symptoms. Oxycodone and hydromorphone can be safely used, but adequate dosage adjustments are required in CKD. In dialyzed patients, these opioids should be considered as second-line agents and patients should be carefully monitored. According to different studies, buprenorphine and fentanyl could be considered first-line opioids in the management of pain in CKD; however, fentanyl is not appropriate in patients undergoing HD. Tapentadol does not need dosage adjustment in mild-to-moderate renal impairment conditions; however, no data are available on its use in ESRD. Opioid-related side effects may be exacerbated by common comorbidities in CKD patients. Opioid-induced constipation can be managed with peripherally-acting-μ-opioid-receptor-antagonists (PAMORA). Unlike the other PAMORA, naldemedine does not require any dose adjustment in CKD and HD patients. Accurate pain diagnosis, opioid titration and tailoring are mandatory to minimize the risks and to improve the outcome of the analgesic therapy.

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          Most cited references 106

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          The prevalence of symptoms in end-stage renal disease: a systematic review.

          Symptoms in end-stage renal disease (ESRD) are underrecognized. Prevalence studies have focused on single symptoms rather than on the whole range of symptoms experienced. This systematic review aimed to describe prevalence of all symptoms, to better understand total symptom burden. Extensive database, "gray literature," and hand searches were undertaken, by predefined protocol, for studies reporting symptom prevalence in ESRD populations on dialysis, discontinuing dialysis, or without dialysis. Prevalence data were extracted, study quality assessed by use of established criteria, and studies contrasted/combined to show weighted mean prevalence and range. Fifty-nine studies in dialysis patients, one in patients discontinuing dialysis, and none in patients without dialysis met the inclusion criteria. For the following symptoms, weighted mean prevalence (and range) were fatigue/tiredness 71% (12% to 97%), pruritus 55% (10% to 77%), constipation 53% (8% to 57%), anorexia 49% (25% to 61%), pain 47% (8% to 82%), sleep disturbance 44% (20% to 83%), anxiety 38% (12% to 52%), dyspnea 35% (11% to 55%), nausea 33% (15% to 48%), restless legs 30% (8%to 52%), and depression 27% (5%to 58%). Prevalence variations related to differences in symptom definition, period of prevalence, and level of severity reported. ESRD patients on dialysis experience multiple symptoms, with pain, fatigue, pruritus, and constipation in more than 1 in 2 patients. In patients discontinuing dialysis, evidence is more limited, but it suggests they too have significant symptom burden. No evidence is available on symptom prevalence in ESRD patients managed conservatively (without dialysis). The need for greater recognition of and research into symptom prevalence and causes, and interventions to alleviate them, is urgent.
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            KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.

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              Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.

              Over 11 million Americans have both diabetes and hypertension-comorbid diseases that strongly predispose people to both renal as well as cardiovascular (CV) injury. Hypertension substantially contributes to CV morbidity and mortality in people with diabetes. Diabetes is the most common cause of end-stage renal disease in the United States. Furthermore, hypertension and diabetes are particularly prevalent in certain populations, such as African-Americans and Native Americans. Since the 1994 Working Group Report on Hypertension and Diabetes, a large body of clinical trial data has affirmed the original blood pressure goal of less than 130/85 mmHg recommended to preserve renal function and reduce CV events in people with hypertension and diabetes. Data that are more recent have emerged, however, to support an even lower diastolic blood pressure goal, ie, 80 mmHg, in order to optimally preserve renal function and reduce CV events in people with diabetic nephropathy. A review of clinical trials indicates that more than 65% of people with diabetes and hypertension will require two or more different antihypertensive medications to achieve the new suggested target blood pressure of 130/80 mmHg. The purpose of this report is to update the previous recommendations with a focus on level of blood pressure control, proteinuria reduction, and therapeutic approaches to achieve these goals. We provide an evidence-based approach, integrating data from the major clinical trials that were designed as randomized prospective, long-term studies that had as a primary endpoint either progression of diabetic nephropathy or reduction in CV events. This report also addresses socioeconomic and cultural barriers that hinder achievement of blood pressure goals. Lastly, the report discusses approaches to resolve cultural barriers, both physician- and patient-derived, that interfere with achievement of lower blood pressure goals.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                tcrm
                tcriskman
                Therapeutics and Clinical Risk Management
                Dove
                1176-6336
                1178-203X
                09 September 2020
                2020
                : 16
                : 821-837
                Affiliations
                [1 ]Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome , Polo Pontino, Latina, Italy
                [2 ]Unit of Anesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital , Rome, Italy
                [3 ]Department of Pharmacy and Biotechnology, Alma Mater Studiorum University , Bologna, Italy
                [4 ]Division of Neurosurgery, Ca’Foncello Hospital, ASL Marca Trevigiana, University of Padova , Treviso, Italy
                [5 ]Unit of Urology, Sapienza c/o I.C.O.T , Polo Pontino, Latina, Italy
                [6 ]Department of Clinical and Surgical Translational Medicine, Sapienza University of Rome , Rome, Italy
                Author notes
                Correspondence: Flaminia Coluzzi Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome , Corso della Repubblica 79, Polo Pontino04100, Latina, ItalyTel +39 06 33775673 Email flaminia.coluzzi@uniroma1.it
                Article
                262843
                10.2147/TCRM.S262843
                7490082
                © 2020 Coluzzi et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 1, Tables: 8, References: 116, Pages: 17
                Categories
                Review

                Medicine

                pamora, opioids, neuropathic pain, hemodialysis, pain, chronic kidney disease

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