Gout, an inflammatory arthritis, affects over nine million people in the US with increasing prevalence. Some medical societies do not recommend treating gout unless it is recurrent. While soft tissue urate deposits (tophi), resultant bone erosions, and joint inflammation are frequently recognized in gout, urate crystal deposits in other sites have been thought to be rare. Recent diagnostic testing, such as dual energy computed tomography (DECT), has led to the recognition that urate deposits are not uncommon in other tissues including the vasculature. To understand the potential risks for untreated gout, we reviewed the literature on extra-articular urate deposition documented by autopsy, histopathology, surgery, and radiology, including the heart, blood vessels, kidney, spine, eye, skin, and gastrointestinal system. These studies extend the significance of gout beyond the rheumatologist and emphasize the need for physicians to follow the American College of Rheumatology guidelines to treat subjects with gout to a goal of achieving serum urate <6 mg/dl. Given the growing body of literature on extraarticular urate deposition, further studies and clinical trials are needed to determine the clinical consequences of systemic urate deposition, including if reducing cardiac and vascular urate deposits may provide a survival benefit for this at-risk population.

Gout patients have higher mortality, heavier comorbidity burden, and lower quality of life than non-gout patients, but information is sparse on how gout affects advanced CKD patients. This study examined the prevalence and potential health impacts in stage 3–5 CKD patients. Gout was defined as being listed as a comorbidity, ULT use, and/or reported gout symptoms (tophi, >1 flare). Uncontrolled gout was defined as hyperuricemia (serum urate >6 mg/dL) with tophi, ≥2 gout flares/year, or ≥1 swollen/tender joint. This study included 746 patients (55% men, age: 56.2 ± 18.3 years, CKD-duration: 4.0 ± 4.8 years, eGFR: 32.2 ± 15.5 mL/min/1.73 m²), of which 23% met the gout criteria. Prevalence was highest in patients with stage 3b and 4 CKD. Gout patients had a significantly higher prevalence of cardiovascular comorbidities, CKD-mineral bone disorder, and back pain than non-gout patients. Uncontrolled gout patients had more hypertension, joint issues, chronic pain, febuxostat use, and colchicine use than controlled patients. Compared to those without gout, gout patients had higher rates of cardiovascular and bone diseases, with uncontrolled patients having an even higher burden. In conclusion, these data suggest that identifying and monitoring gout in CKD patients provides health benefits. However, more than one-third of gout patients did not have a formal gout diagnosis in their medical record.

Key Points: Gout is a common inflammatory arthropathy, and it can be as frequent in patients with ESKD as in the general adult population. Patient outcomes and providers' practice patterns for ESKD patients with gout are unknown. We sought to address these gaps in this study. We found that gout is not associated with worse clinical or patient-reported outcomes, despite being frequent and possibly under-reported. Introduction: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. Methods: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012–2020) and 5117 PD patients (PDOPPS, 2014–2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). Results: The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%–3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%–12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%–6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs. Conclusion: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs.

Key Points: Population-based retrospective cohort study to evaluate clinical correlates of gout and its impact on patients undergoing chronic dialysis. 13.5% of US dialysis-dependent patients had gout and were older and male, with a higher prevalence of hypertension and cardiovascular disease. Gout diagnosis was associated with a higher incidence of cardiovascular conditions, levels of anemia, hospitalization, and mortality. Background: An association between gout and nondialysis chronic renal disease has long been recognized, yet limited research exists regarding prevalence, treatment, anemia management, and outcomes in patients with ESKD undergoing dialysis. Methods: Using data from United States Renal Data System, we conducted a population-based retrospective cohort study in adult patients covered by Medicare and on dialysis in 2017. Multivariate logistic regression models were used to estimate potential factors and odds of gout diagnosis. Antigout medications and impact on anemia management were assessed and compared between gout and nongout dialysis patients using descriptive and regression analyses. Associations for all-cause mortality and cardiovascular-related hospitalizations during 1 year of study follow-up were compared between gout and nongout patients using multivariate Cox regression models. Results: Of 231,841 ESKD Medicare patients in 2017 undergoing continuous dialysis, 31,300 (13.5%) had one or more gout diagnostic code(s). Increased odds of having a gout diagnosis were independently associated with older age, male sex, Asian race, obesity, hypertension, and cardiovascular disease. Gout diagnosis was associated with higher prevalence for anemia as indicated by increased erythropoietin-stimulating agent requirements (odds ratio=1.18 for high versus low erythropoietin-stimulating agent dose, 95% confidence interval [95% CI], 1.14 to 1.22) and likelihood of blood transfusions (odds ratio=1.34, 95% CI, 1.30 to 1.38). During the 1-year study follow-up, mortality among gout versus nongout patients was higher by 3% (95% CI, 0 to 6) and a composite association of mortality and cardiovascular disease hospitalization was higher by 6% (95% CI, 3 to 9) after adjusting for comorbid conditions. Conclusions: A gout diagnosis was found in 13.5% of US dialysis-dependent patients and was associated with a higher burden of comorbid cardiovascular conditions as well as an elevated incidence of hospitalization and mortality. These observations improve our current understanding of gout among the dialysis population and highlight the importance of new and better treatments to improve outcomes.

Introduction: Gout is 12-times more prevalent in kidney transplant (KT) recipients than in non-transplanted population. We report quality-of-life (QOL) and clinical assessment findings from the PROTECT trial examining pegloticase efficacy and safety in KT recipients with uncontrolled gout.Methods: Patients with serum urate (SU) ≥7 mg/dL, oral urate-lowering therapy refractory/intolerant, and with one of the following were enrolled: ≥2 flares/year, unresolving tophi, or chronic gouty arthritis. Patients were ≥1 year post-transplant, with a graft eGFR ≥15 ml/min/1.73m² and received stable immunosuppression. Pegloticase was administered for 24 weeks. QOL endpoints included the Health Assessment Questionnaire (HAQ; Disability Index [DI], Health, Pain) and Physician Global Assessment (PhGA) of Gout. Key clinical assessments included proportion of patients with resolution of ≥1 tophus and change from baseline in blood pressure (BP) at Week 24.Results: Twenty KT recipients (85.0% male, age: 53.9±10.9 years, BMI: 30.6±7.2 kg/m², eGFR: 45.8±11.9 ml/min/1.73 m², time since kidney transplant: 14.6±6.9 years) were included. The primary endpoint was achieved with 89% of patients reaching and maintaining a SU of <6 mg/dL during Month 6. Meaningful improvements occurred over 24 weeks of treatment in all QOL measures (mean [95% CI] change from baseline: HAQ-DI: -0.3 [-0.6, 0.1], HAQ-Pain: -35.5 [-54.5, -16.5], HAQ-Health: -22.4 [-39.5, -5.2], PhGA: -2.4 [-3.7, -1.1]) and clinical assessments (≥1 tophus resolved: 3 of 7 with tophi at baseline [42.9%]; change from baseline in mean arterial BP: -6.8 [-12.5, -1.0] mmHg).Conclusions: Given the high prevalence of uncontrolled gout in KT recipients, proper SU management is of particular importance. Additionally, intensive urate-lowering with pegloticase may have clinical and QOL benefits.