Hyperuricemia, Elevated Body Mass Index, Female Sex, and Albuminuria Increase the Probability of Elevated High-Sensitivity C-Reactive Protein: Results From the National Health and Nutrition Examination Survey 2015-2018.

Importance: High uric acid (UA) is hypothesized to worsen kidney and cardiovascular disease morbidity via activation of systemic inflammation. Clinical trials of UA modification report reduction of the inflammatory marker high sensitivity C-reactive protein (hs-CRP) as an outcome measure, but studies have not demonstrated that hyperuricemia independently increases hs-CRP when adjusted for important confounders such as body mass index (BMI), sex, and age. Objective: To identify clinical risk factors for elevated hs-CRP, including but not limited to hyperuricemia, through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2015-2018. Results: In the final multivariate logistic regression model, the exposure with the strongest effect on the odds of elevated hs-CRP was BMI in the fourth quartile, OR = 13.1 (95% CI 6.25-27.42), followed by female sex (OR = 4.9, 95% CI 2.92-8.34), hyperuricemia (OR = 2.2, 95% CI 1.36-3.45), urine albumin creatinine ratio (ACR; OR = 1.5, 95% CI 1.09-2.18), poor overall health (OR = 1.4, 95% CI 1.18-1.58), and interactions between hyperuricemia and sex (OR = 1.4, 95% CI 1.05-1.83), and between BMI and sex (OR = 1.2, 95% CI 1.03-1.47). Notably, chronic kidney disease (CKD) and CKD surrogates were not associated with hs-CRP despite urine ACR maintaining a significant independent effect. Conclusions: In this national population-based study, we demonstrated that hyperuricemia significantly increases the odds of elevated hs-CRP, independent from BMI, female sex, urine ACR, and overall health status. Further study is recommended to better understand the sex difference in this association and the role of albuminuria, but not CKD, in systemic inflammation.

Hyperuricemia is associated with a lower glomerular filtration rate in pediatric sickle cell disease patients.

BACKGROUND: Sickle cell nephropathy (SCN) is a progressive disease that contributes significant morbidity and mortality in sickle cell disease (SCD), yet it remains poorly understood. Hyperuricemia negatively impacts renal function in the non-sickle cell population but is understudied in SCD. METHODS: We performed a cross-sectional analysis of the first 78 pediatric SCD patients enrolled in a cohort study. The mechanism of development of hyperuricemia (defined, serum uric acid (UA) ≥ 5.5 mg/dL) was characterized as a result of either UA overproduction or inefficient renal excretion by the Simkin index and fractional clearance of urate (FCU) equations. Associations between hyperuricemia and albuminuria or estimated glomerular filtration rate (eGFR) were determined by linear regression. RESULTS: The prevalence of hyperuricemia in this young population (mean age 11.6 ± 3.77 years) was 34.2%. Only 1 hyperuricemic participant overproduced UA by Simkin index, while 62.5% were inefficient renal excretors of UA (FCU < 4%). Hyperuricemia was associated with a significant decrease in average eGFR, -27 ml/min/1.73m2 below normouricemia (mean eGFR 151.6 ± 40.32), p = 0.0122. Notably, the previously accepted association between decline of eGFR with age is significantly modified by hyperuricemia stratification, where hyperuricemia explains 44% of the variance in eGFR by age (R2 = 0.44, p = 0.0004) and is nonsignificant in normouricemia (R2 = 0.07, p = 0.0775). CONCLUSION: These findings indicate that hyperuricemia may be associated with early eGFR decline in SCN. This association must be further characterized in prospective cohort studies in SCN, and hyperuricemia must be investigated as a potential therapeutic target for SCN.

Pediatric Nephrology and Rheumatology Practice Patterns in Granulomatosis with Polyangiitis: A Midwest Pediatric Nephrology Consortium Study.

OBJECTIVE: To assess practice pattern similarities and differences amongst pediatric rheumatologists and nephrologists in the management of pediatric Granulomatosis with Polyangiitis (GPA). METHODS: A voluntary survey was distributed to the Midwest Pediatric Nephrology Consortium Group (MWPNC) and an international pediatric rheumatology email listserv in 2016-2017. Data were collected on general practice characteristics and preferences for induction management under three clinical scenarios (A-C): newly diagnosed GPA with glomerulonephritis, GPA with rapidly progressive glomerulonephritis, and GPA with pulmonary hemorrhage. In addition, individual preferences for GPA maintenance medications, disease monitoring, and management of GPA with end-stage renal disease were ascertained. RESULTS: There was a 68% response rate from the MWPNC membership and equal numbers of rheumatology respondents. Survey results revealed Rituximab plus Cyclophosphamide is a more common induction choice for rheumatologists than nephrologists in induction Scenarios A and B, whereas Cyclophosphamide is more commonly chosen by nephrologists in Scenario A. Plasmapheresis rates increased for Scenarios A, B, and C for both specialties, but were overall low. There was no clear consensus on the duration of maintenance therapy nor diagnostic work-up. Rheumatologists more frequently chose Rituximab for maintenance and induction compared to nephrologists. There was also a higher than expected proportion of Mycophenolate Mofetil use for both specialties. CONCLUSION: This survey has revealed important differences in the way that rheumatologists and nephrologists manage this disease. It highlights the need for well-designed clinical trials in pediatric GPA patients and reveals that both specialties must be represented during consensus-building and clinical trial design efforts.