Obesity and CKD: How big is this?

How important is obesity to the field of nephrology? Perhaps obesity is the single strongest risk factor for CKD in the US and most of the developed world. While genetics are certainly important, obesity drives the diabetes epidemic and contributes significantly to the hypertensive burden in our population. But if obesity is this important, how can we best help our patients? Should nephrologists emphasize obesity along with our traditional targets (e.g. HbA1c < 7%, SBP < 130 or 140 mmHg, statin use, etc.)? Unfortunately, there is not a lot of data to guide us.

Attempting to look at obesity as a risk factor for CKD independent of diabetes or hypertension is challenging. However, there are a few studies that suggest an independent effect on CKD and its progression (Hsu, Cao). Whether or not “metabolically healthy” obese patients are at higher risk of CKD remains unclear (Hashimoto).

There are likely other mechanisms in obesity beyond diabetes and hypertension that are injurious to our beans (Rao). For example – increased abdominal pressure can activate RAAS and visceral fat itself can generate not just angiotensinogen but also inflammatory cytokines (such as leptin) which may stimulate renal fibrosis. Physiologic changes in obesity create glomerular hypertension, hyperfiltration, and glomerulomegaly. In a subset of these patients, for unclear reasons, overt glomerulosclerosis develops.

The effect of obesity on renal function was clearly reported in 1974 in four non-diabetic patients with severe obesity and nephrosis (Weisinger). The nephrosis and proteinuria resolved with significant weight loss during prolonged hospitalizations. Subsequent studies have also shown the resolution of glomerular hyperfiltration with weight loss.

The clinical and pathologic characteristics of obesity related glomerular damage have been described (Kambham). Notably, when compared to patients with idiopathic FSGS, obesity-related glomerulopathy demonstrates lower rates of true nephrotic syndrome as well as less, but certainly not insignificant, progression to ESRD. Importantly, clinical characteristics do not seem to differentiate between obesity-related glomerulomegaly with hyperfiltration and the development of obesity-related FSGS.

If obesity worsens renal function then how should we combat it? Data focusing on individual patient treatments in CKD is limited, with the majority of studies being small with short term follow-up. Weight loss is associated with a reduction in proteinuria but no clear change in GFR (Naveneethan). Bariatric surgery offers a therapy that can reliably produce significant weight loss, reduce or eliminate proteinuria, and improve diabetic and hypertensive control. Its effects on GFR however are hard to predict, especially given that creatinine often decreases post-surgery given the loss of lean body mass that parallels declines in adiposity. Likewise, the true risk of hyperoxaluria and worsened renal function in modern malabsorptive procedures is not well understood. The literature on bariatric surgery and diabetic nephropathy was recently reviewed here (Friedman).

Questions still remain.

• How aggressive should we be regarding weight loss in our patients? 
• Is it enough to recommend diet and exercise or should we advocate for weight loss programs? 
• Should we prescribe medications such as orlistat or phentermine/topiramate? 
• Should we refer patients for consideration of bariatric surgery? 

 Hopefully the coming decades will clarify these questions.

Robert Rope, Nephrology Fellow, Stanford