Obesity, a risk factor for de novo chronic kidney disease (CKD), confers survival advantages in advanced CKD. This so-called obesity paradox is the archetype of the reverse epidemiology of cardiovascular risks, in addition to the lipid, blood pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical phenomena are in sharp contradistinction to the known epidemiology of cardiovascular risks in the general population. In addition to advanced CKD, the obesity paradox has also been observed in heart failure, chronic obstructive lung disease, liver cirrhosis, and metastatic cancer, as well as in the elderly. These are populations in whom protein-energy wasting and inflammation are strong predictors of early death. Both larger muscle mass and higher body fat provide longevity in these patients, whereas thinner body habitus and weight loss are associated with higher mortality. Muscle mass appears to be superior to body fat in conferring an even greater survival. The obesity paradox may be the result of a time discrepancy between competing risk factors, i.e., overnutrition as the long-term killer versus undernutrition as the short-term killer. Hemodynamic stability of obesity, lipoprotein defense against circulating endotoxins, protective cytokine profiles, toxin sequestration of fat mass, and antioxidation of muscle may play important roles. Despite claims that obesity paradox is a statistical fallacy and a result of residual confounding, the consistency of data and other causality clues suggest a high biologic plausibility. Examining the causes and consequences of the obesity paradox may help discover important pathophysiologic mechanisms leading to improved outcomes in patients with CKD.

Background

Chronic pain is a common condition in the general population. However, large epidemiologic studies examining the role of pain in the deterioration of kidney function, development of chronic kidney disease, and risk for death are lacking.

Study design

Retrospective cohort study.

Setting & participants

A nationally representative cohort of 2,360,056 US veterans with baseline estimated glomerular filtration rates (eGFRs) ≥ 60mL/min/1.73m(2), followed up from October 2004 to September 2006.

Predictor

4 pain categories were compared: none (score, 0), mild (1-4), moderate (5-6), or severe (≥7).

Outcomes

eGFR decline (determined by eGFR slope) and combined incident eGFR<60mL/min/1.73m(2) or all-cause death.

Measurements

We examined the pain management pattern and association of reported pain with (1) rapid eGFR decline and (2) a composite outcome of incident eGFR<60mL/min/1.73m(2) or all-cause death using logistic regression and Cox models adjusted for baseline eGFR, demographics, comorbid conditions, cardiovascular risk factors, and depression.

Results

∼60% of veterans reported pain of any severity during the baseline period. The most commonly prescribed analgesics were opioids. In a dose-response relationship, veterans reporting moderate or severe pain had a higher risk for faster eGFR decline compared with those reporting none (ORs of 1.11 [95% CI, 1.09-1.14] and 1.17 [95% CI, 1.13-1.21] for moderate and severe pain, respectively). In combined analyses, veterans reporting moderate or severe pain both had 30% higher risk of the combined outcome (incident eGFR, 60 mL/min/1.73 m(2) or death) compared with those reporting none (HRs of 1.30 [95% CI, 1.28-1.31] and 1.30 [95% CI, 1.28-1.32] for moderate and severe pain, respectively).

Limitations

Lack of granular data regarding type and location of pain.

Conclusions

We observed a high prevalence of pain and analgesic prescription in the US veteran population with normal eGFRs. Pain was associated with a higher incidence of eGFRs<60mL/min/1.73m(2), faster kidney function decline, and higher mortality.