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.
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Dara P.
Schuster
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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.
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 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.
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.