Weight-loss guidelines aim to curb chronic renal failure

Obesity is a complex and ever-increasing problem in the United States. It has been linked to a growing number of metabolic and medical conditions, such as diabetes, hyperlipidemia and hypertension, and is increasingly linked to chronic renal failure.

Although the primary effect of obesity on renal function appears to be related to other obesity-related comorbidities such as diabetes and hypertension, there appears to be an increase in the risk directly and independently related to obesity itself.

Dara P. Schuster

In the Framingham cohort study, BMI was positively correlated to the odds of having a glomerular filtration rate in the fifth percentile or less during long-term follow-up. Similarly, follow-up among participants in U.S. health screening programs demonstrated a significant positive relationship between BMI and risk for end-stage renal disease. Age at onset of overweight or obesity of age 20 years or younger has also been shown to play a role in future development of declining renal function — with and without the presence of diabetes and hypertension. Furthermore, obesity is known to worsen pre-existing renal disease such as IgA nephropathy, urate nephropathy and other types of kidney disease.

Pathophysiology

Although the increase in chronic renal failure parallels the increase in rates of obesity, the mechanisms that lead to renal damage in obesity are not completely understood. Increased renal blood flow, increased glomerular filtration rate and microalbuminuria have been demonstrated in obesity. Activation of the renin-angiotensin-aldosterone system has been observed in the overweight population, and high levels of aldosterone can be seen in the obese patients.

It is postulated that intrarenal pressure increases can be attributed to tubular sodium reabsorption, possibly triggered by renal vasodilatation and accumulation of visceral adipose tissue with compression of Henle’s loop.

In addition, there are numerous potential hormonal pathways that play a role in the obesity-related inflammatory process, including leptin, resistin and various cytokines produced by the adipose tissue. Ultimately, these changes lead to increased glomerular wall stress, extracellular matrix formation and fibrosis.

Furthermore, renal biopsies performed on morbidly obese patients who did not have renal disease demonstrated significant glomerular and structural lesions, including enlarged glomeruli, mesangial hypercellularity or focal segmental glomerulosclerosis. This form of focal segmental glomerulosclerosis appears to be unique to obesity and, when compared with idiopathic focal segmental glomerulosclerosis, is more indolent, has lower incidence of nephrotic syndrome, presence of glomerulomegaly and milder foot process fusion.

Weight loss, renal function

Weight loss has been shown to improve renal function with decreased proteinuria, glomerular hyperfiltration and inflammation, and improved blood pressure and blood glucose control for individuals with and without overt renal disease.

Given the potential benefits of weight reduction in the setting of chronic renal disease, the National Kidney Foundation has published clinical practice guidelines. In patients with chronic kidney disease stages I to IV, the foundation recommended a healthy lifestyle that included a healthy diet and regular exercise. With regard to weight loss, the clinical practice guidelines recommend weight loss for patients with CKD stages I to IV if diabetes is present, BMI is ≥30 or waist circumference is increased. Weight loss is recommended for stage V CKD if obesity precludes transplantation. In the transplant population, graft survival is negatively affected by the presence of morbid obesity.

The benefits of weight loss on stabilization have been observed with nonsurgical and surgical intervention. However, weight loss is a challenge in this population, given the nutritional limitations and deficiencies seen. Conventional weight-loss diets consisting of a high-fiber, low-energy diet and physical activity are often not suited for the patient with CKD. As seen in the general population, nonsurgical weight loss has a high rate of failure to attain and maintain substantial weight loss.

There are limited studies to indicate that bariatric surgery may be a safe and effective means of weight loss for the patient with chronic renal insufficiency. In studies examining renal function after bariatric surgery, glomerular hyperfiltration improved with reduction in glomerular filtration rate, microalbuminuria was reduced and renal function was stabilized.

Bariatric surgery for weight loss

In our retrospective, long-term study of renal function in patients after bariatric surgery, we examined change in creatinine from baseline in 872 patients. The patients were divided into two groups: creatinine <1.5 mg/dL (n=836) or creatinine >1.5 mg/dL (n=30) at baseline. All patients were followed for at least one year and for as long as nine years. Thirty-six patients had creatinine >1.5 mg/dL. Thirty of those patients experienced a reduction in their creatinine to <1.5 mg/dL, with 18 remaining in the normal range for the long term. For the 836 patients who started with a creatinine <1.5 mg/dL, only 80 developed a creatinine >1.5 mg/dL during follow-up (average number of days postop=104), and 77 of those returned to normal.

Therefore, it appeared that bariatric surgery did not have a negative effect on renal function in those individuals with normal renal function — despite probably underlying glomerular lesions — and in those with renal impairment, 50% demonstrated long-term improvement.

Despite studies that demonstrated improved renal function with bariatric surgery in the morbidly obese population, there are no large, long-term prospective trials examining this issue; however, data are currently being collected. It is important to keep in mind the risks of bariatric surgery in patients with CKD who may be at increased risk for infection and comorbid conditions. Special attention must be paid to risks of dehydration, rhabdomyolysis and hyperoxaluria postoperatively. Nevertheless, including renal disease and dysfunction in the discussion of risk and benefits of bariatric surgery is a must.

Given that the rate of overweight and obesity is 66.3%, according to CDC 2003 to 2004 data, and 16% of the adult population has CKD, based on NHANES 1999 to 2004 data, and that the risk for ESRD increases with increasing BMI, weight loss will be an appropriate treatment modality for a large percentage of these patients. Further long-term, prospective studies that examine primary and secondary prevention of obesity-related renal disease in the morbidly obese population are needed.

Dara P. Schuster, MD, is an Associate Professor of Internal Medicine and Pediatrics at The Ohio State University.