Background: Chronic pain is a common and distressing symptom reported by patients with chronic kidney disease (CKD). Clinical practice and research in this area do not appear to be advancing sufficiently to address the issue of chronic pain management in patients with CKD. Objectives: To determine the prevalence and severity of chronic pain 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 glomerular filtration rate (GFR) category 3 to 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 pain, and severity of pain. Methods: Databases searched included MEDLINE, CINAHL, EMBASE, and Cochrane Library, last searched on February 3, 2020. Two reviewers independently screened all titles and abstracts, assessed potentially relevant articles, and extracted data. We estimated pooled prevalence of overall chronic pain, musculoskeletal pain, bone/joint pain, muscle pain/soreness, and neuropathic pain 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 was used in the model calculations to account for potential overweighting of studies reporting either very high or very low prevalence measurements. Pain severity scores were calibrated to a score out of 10, to compare across studies. Weighted mean severity scores and 95% confidence intervals were reported. Results: Sixty-eight studies representing 16 558 patients from 26 countries were included. The mean prevalence of chronic pain in hemodialysis patients was 60.5%, and the mean prevalence of moderate or severe pain was 43.6%. Although limited, pain prevalence data for peritoneal dialysis patients (35.9%), those managed conservatively without dialysis (59.8%), those following withdrawal of dialysis (39.2%), and patients with earlier GFR category of CKD (61.2%) suggest similarly high prevalence rates. Limitations: Studies lacked a consistent approach to defining the chronicity and nature of pain. There was also variability in the measures used to determine pain severity, limiting the ability to compare findings across populations. Furthermore, most studies reported mean severity scores for the entire cohort, rather than reporting the prevalence (numerator and denominator) for each of the pain severity categories (mild, moderate, and severe). Mean severity scores for a population do not allow for “responder analyses” nor allow for an understanding of clinically relevant pain. Conclusions: Chronic pain is common and often severe across diverse CKD populations providing a strong imperative to establish chronic pain management as a clinical and research priority. Future research needs to move toward a better understanding of the determinants of chronic pain and to evaluating the effectiveness of pain management strategies with particular attention to the patient outcomes such as overall symptom burden, physical function, and quality of life. The current variability in the outcome measures used to assess pain limits the ability to pool data or make comparisons among studies, which will hinder future evaluations of the efficacy and effectiveness of treatments. Recommendations for measuring and reporting pain in future CKD studies are provided. Trial registration: PROSPERO Registration number CRD42020166965

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.

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Historians and philosophers of science rarely comment upon nephrological contributions to the development of general concepts of disease. In the present study, I examine this topic by starting from the premises that an idea of disease pervades most human societies, that received explanations of disease vary between people, societies and eras, and that an understanding of renal disease has often reflected general explanatory trends. Traditionally, most students of disease have belonged to one of four schools: descriptive, causal, mechanistic, or statistical. Descriptivists have tended to focus on manifestations, be these of a symptomatic, a structural, or a functional type. Causationists have focussed upon identification of the origins of diseases. Mechanists have emphasised pathogenetic processes. Statisticians have calculated mathematical differences of parameters from the mean (‘the normal’), without explaining the reasons for these. Mechanists currently appear to hold the ascendancy in nephrology through their focus upon the links that connect causes with manifestations. As, however, all schools of thought have historically waxed and waned, I question the wisdom of granting any of them hegemony. Rather, I promote an event idea of disease that encompasses the causal, mechanistic and descriptive schools. Such considerations should assist nephrologists both to treat disease and to identify those of their predecessors who most advanced knowledge.