RESUMO
RATIONALE & OBJECTIVE: Pain is a frequent complication of autosomal dominant polycystic kidney disease (ADPKD) and includes back and abdominal pain. We hypothesized that in adults with early- and late-stage ADPKD, overweight and obesity are independently associated with greater self-reported back, abdominal, and radicular pain at baseline and that weight loss would be associated with decreased pain over a follow-up period. STUDY DESIGN: Post hoc analysis of pooled data from 2 randomized trials. SETTING & PARTICIPANTS: Participants in the HALT-PKD study A or B. 867 individuals were included in a cross-sectional analysis. 4,248 observations from 871 participants were included in a longitudinal analysis. PREDICTOR: Overweight and obesity (cross-sectional); annual change in weight as a time-varying predictor (longitudinal). OUTCOME: Pain (Likert-scale responses; cross-sectional); annual change in pain (binary outcome of worsening pain or not worsening; longitudinal). ANALYTICAL APPROACH: Multivariable ordinal logistic regression (cross-sectional); generalized estimating equation analysis (longitudinal). RESULTS: Participants were aged 42±10 years and baseline estimated glomerular filtration rate was 71±26 mL/min/1.73 m2. Back, abdominal, and radicular pain were reported more frequently in individuals with increasing body mass index category (all P < 0.05 for trend). After multivariable adjustment, obesity was associated with increased odds of greater back and radicular pain, but not abdominal pain. Associations remained similar after further adjustment for baseline height-adjusted kidney and liver volume (study A only, n = 457); back pain: OR, 1.88 (95% CI, 1.15-3.08); and radicular pain: OR, 2.92 (95% CI, 1.45-5.91). Longitudinally (median follow-up, 5 years), weight loss (annual decrease in weight ≥ 4%) was associated with decreased adjusted odds of worsening back pain (OR, 0.87 [95% CI, 0.76-0.99]) compared with the reference group (stable weight). LIMITATIONS: Post hoc, associative analysis. CONCLUSIONS: In early- and late-stage ADPKD, obesity was associated with greater back and radicular pain independent of total kidney/liver volume. Mild weight loss was associated with favorable effects on back pain.
RESUMO
Inflammatory activity is evident in patients with chronic kidney disease with limited data available in autosomal dominant polycystic kidney disease (ADPKD). We hypothesized that inflammation is an upstream event in the pathogenesis of ADPKD and may be a contributing factor in the disease severity and progression. Serum samples from 61 HALT study A group patients were compared with samples from 49 patients from HALT study B group with moderately advanced disease. Targeted MS analysis of bioactive lipid mediators as markers of inflammation was performed and correlated with eGFR and total kidney volume (TKV) normalized to the body surface area (BSAR) to assess if these markers are predictive of ADPKD severity. ADPKD patients with eGFR >60 ml/min/1.73 m(2) showed higher levels of 5- and 12/15-lipoxygenase (LOX) and cyclooxygenase, and generated higher levels of hydroxy-octadecadienoic acids 9-HODE and 13-HODE and HETEs 8-HETE, 11-HETE, 12-HETE, and 15-HETE as compared with healthy subjects. Linear regression of 9-HODE and 13-HODE revealed a significant relationship with eGFR and TKV, while 15-HETE significantly correlated with TKV/BSAR. Production of 20-HETE, a P450-produced metabolite of arachidonic acid, was higher in ADPKD patients as compared with healthy subjects and significantly correlated with eGFR and TKV/BSAR. Perturbation in fatty acid metabolism is evident early in ADPKD patients, even in those with preserved kidney function. The identified LOX pathways may be potential therapeutic targets for slowing down ADPKD progression.