Analgesic Use in Patients With Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Pain is common in patients with chronic kidney disease (CKD). Analgesics may be appropriate for some CKD patients. Objectives: To determine the prevalence of overall analgesic use and the use of different types of analgesics including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), adjuvants, and opioids in patients with CKD. Design: Systematic review and meta-analysis. Setting: Interventional and observational studies presenting data from 2000 or later. Exclusion criteria included acute kidney injury or studies that limited the study population to a specific cause, symptom, and/or comorbidity. Patients: Adults with stage 3-5 CKD including dialysis patients and those managed conservatively without dialysis. Measurements: Data extracted included title, first author, design, country, year of data collection, publication year, mean age, stage of CKD, prevalence of analgesic use, and the types of analgesics prescribed. Methods: Databases searched included MEDLINE, CINAHL, EMBASE, and Cochrane Library. Two reviewers independently screened all titles and abstracts, assessed potentially relevant articles, and extracted data. We estimated pooled prevalence of analgesic use and the I2 statistic was computed to measure heterogeneity. Random-effects models were used to account for variations in study design and sample populations, and a double arcsine transformation of the prevalence variables was used to accommodate potential overweighting of studies with very large or very small prevalence measurements. Sensitivity analyses were performed to determine the magnitude of publication bias and assess possible sources of heterogeneity. Results: Forty studies were included in the analysis. The prevalence of overall analgesic use in the random-effects model was 50.8%. The prevalence of acetaminophen, NSAIDs, and adjuvant use was 27.5%, 17.2%, and 23.4%, respectively, while the prevalence of opioid use was 23.8%. Due to the possibility of publication bias, the actual prevalence of acetaminophen use in patients with advanced CKD may be substantially lower than this meta-analysis indicates. A trim-and-fill analysis decreased the pooled prevalence estimate of acetaminophen use to 5.4%. The prevalence rate for opioid use was highly influenced by 2 large US studies. When these were removed, the estimated prevalence decreased to 17.3%. Limitations: There was a lack of detailed information regarding the analgesic regimen (such as specific analgesics used within each class and inconsistent accounting for patients on multiple drugs and the use of over-the-counter analgesics such as acetaminophen and NSAIDs), patient characteristics, type of pain being treated, and the outcomes of treatment. Data on adjuvant use were very limited. These results, therefore, must be interpreted with caution. Conclusions: There was tremendous variability in the prescribing patterns of both nonopioid and opioid analgesics within and between countries suggesting widespread uncertainty about the optimal pharmacological approach to treating pain. Further research that incorporates robust reporting of analgesic regimens and links prescribing patterns to clinical outcomes is needed to guide optimal clinical practice.

NSAID prescriptions in kidney transplant recipients

“…Despite guideline recommendations to avoid NSAIDs in kidney transplant recipients whenever possible, and to limit to specific acute pain syndromes such as gout, we found that 11% of recipients were prescribed an NSAID. This is less than the pooled prevalence of 17% in a recent systematic review of patients with chronic kidney disease categories G3-5, 33 but double the frequency of NSAID prescriptions (5%) in kidney transplant recipients reported by Chiasson et al 6 As our study could not capture over-the-counter NSAIDs, it is surprising that the frequency of NSAID prescriptions was higher in our study compared to that of Chiasson et al which captured over-the-counter NSAIDs through a comprehensive Veterans Affairs medical record system. In addition, NSAID prescriptions among kidney transplant recipients in our study was substantially higher than that observed in a U.S. study of living kidney donors, another population in whom risk of kidney-related complications is of concern due to solitary functioning kidney.…”

Population-Based Analysis of Nonsteroidal Anti-inflammatory Drug Prescription in Subjects With Chronic Kidney Disease

“…Our findings, while not directly comparable, are population-based and may reflect differences in health systems and access to care. A recent systematic review and meta-analysis 11 of patients with GFR category CKD G3-5 CKD reported a point prevalence of 17% for NSAID use. This review also reported an increase in NSAID use in more recent studies and speculated that this may reflect the desire of care providers to avoid opioids for pain management.…”

“…10 At present, reports on NSAID use in CKD are heterogeneous, often relying on self-report data and from older studies. 11 Furthermore, previous studies have largely been limited to the elderly population and to those with kidney failure and/or on dialysis. 9 , 11 , 12 …”

“… 11 Furthermore, previous studies have largely been limited to the elderly population and to those with kidney failure and/or on dialysis. 9 , 11 , 12 …”

Assessment of glycemia in chronic kidney disease

“…Severe hypoglycemic encephalopathy in a patient with CKD, masked by hyperuricemia, has been described [ 62 ]. Pain is common in patients with neuropathy and osteoarthritis and is preferentially treated with acetaminophen in patients with CKD [ 63 ]. Glucose dehydrogenase monitors are not affected by uric acid and acetaminophen but provide falsely high glucose readings in patients treated with icodextrin containing peritoneal dialysis solutions [ 64 ].…”