Obesity and Kidney Disease: addressing hyperfiltration, diet, and caloric restriction

Obesity

In 1908 life expectancy within the United States reached an all-time average high of 50 years.  The year 1908 is also marked by the election of William Howard Taft.  At almost 6 feet tall and over 300 lbs, President Taft was morbidly obese with a body mass index (BMI) of approximately 42 kg/m2 and the first and only morbidly obese president to ever reside in the white house.  In 1908, morbid obesity was extremely rare but the paucity of obesity no longer exists.  Currently 1 in 20 U.S. adults are now morbidly obese (BMI ≥40 kg/m2)1, 2  and overweight and obesity affect approximately 60% of the U.S. adult population.  Only one in three US adults currently has an ideal BMI (18.5-24.9 kg/m2). 

Obesity

In 1908 life expectancy within the United States reached an all-time average high of 50 years.  The year 1908 is also marked by the election of William Howard Taft.  At almost 6 feet tall and over 300 lbs, President Taft was morbidly obese with a body mass index (BMI) of approximately 42 kg/m2 and the first and only morbidly obese president to ever reside in the white house.  In 1908, morbid obesity was extremely rare but the paucity of obesity no longer exists.  Currently 1 in 20 U.S. adults are now morbidly obese (BMI ≥40 kg/m2)1, 2  and overweight and obesity affect approximately 60% of the U.S. adult population.  Only one in three US adults currently has an ideal BMI (18.5-24.9 kg/m2). 

Obesity has been strongly linked with risk of end-stage renal disease (ESRD) when obesity is present during adolescence or young adulthood.3, 4  In contrast, obesity among older adults is very weakly associated with ESRD risk 5-8and ESRD risk associated with obesity among older adults appears to be limited to those with metabolic syndrome and/or elevated blood pressure.6  Thus, public health strategies for reducing ESRD incidence should address the obesity epidemic among young individuals.  

Obesity which starts at a young age translates to decades of metabolic abnormalities such as elevated blood pressure, insulin resistance and inflammation, and all these factors heighten CKD risk and progression.  Unfortunately, public health efforts to address the obesity epidemic have been extremely slow to respond, and it is likely that ESRD incidence will increase in future decades when individuals born during the height of the obesity epidemic reach late adulthood.  Weight loss for older obese adults (> age 60 years) may also have health benefits but the overall public health benefits of obesity treatment and prevention is just so much larger for young individuals who have several decades of life ahead of them. 

Obesity and Hyperfiltration

As a person gains weight, the metabolic rate increases.  The kidney responds via increases in glomerular filtration rate (GFR), and renal plasma flow and these changes are accommodated by increases in glomerular diameter.9  The heightened GFR that sometimes occurs in obese individuals, especially morbid obesity, has been termed hyperfiltration, defined as GFR increasing to a level two standard deviations above the normal of healthy individuals.10  However, the higher GFR noted with obesity is not necessarily a pathophysiologic state and may simply reflect kidney symmorphosis, or the matching of kidney function with the metabolic demands of the individual.  Hyperfiltration may be achieved without increases in glomerular intracapillary pressure via augmentation of glomerular filtration surface area and proportionate increases in afferent and efferent arteriolar vasodilation to increase RPF.  Glomerular hypertrophy and increases in RPF are consistent findings in morbidly obese individuals and glomerular diameter is highly correlated with body surface area.

Obesity itself is likely not sufficient itself for development of CKD and additional factors are required. Such factors include reduced nephron mass, diabetes, hypertension and primary glomerular diseases.   Total GFR is the sum of single nephron GFR and total nephron number varies within populations.16  Individuals with low nephron number at birth, history of nephrectomy or those with CKD from any cause are at highest risk for obesity associated kidney disease.  Given the propensity for glomerular hypertension in obese individuals with CKD, renin-angiotensin system (RAS) blockade has been suggested as an intervention to slow kidney disease progression.  RAS blockade provides renal protective effects for obese and non-obese adults with established proteinuria.  However, superior benefits from angiotensin converting enzyme inhibitors or angiotensin receptor blockers vs. diuretics or calcium channel blockers have not been demonstrated in large scale clinical trials.  Focusing solely on use of RAS blockade for blood pressure control in obese individuals ignores the volume expanded state in obesity due to high salt intake which attenuates the blood pressure lowering effects of RAS blockade.17  The ALLHAT Study included over 33,000 older adults with a mean BMI of 29.7 kg/m2 18  and showed no difference in cardiovascular outcomes or ESRD risk by allocation status to chlorthalidone, lisinopril or amlodipine regardless of baseline GFR.19  During all years of the trial, mean systolic blood pressure was lowest in ALLHAT participants treated with chlorthalidone and stroke and heart failure risk were significantly higher with lisinopril use compared to chlorthalidone.18  While no differences in ESRD risk were noted for the amlodipine arm vs. chlorthalidone arm, clinicians should consider avoiding use of dihydropyridine calcium channel blockers without concomitant use of RAS blockade.  Dihydropyridine calcium channel blockers vasodilate the afferent arteriole and can further impair renal autoregulation. 20, 21  Regardless of medication choice, tight blood pressure control is imperative in obese individuals with CKD due to impaired renal autoregulation and the inherent susceptibility to barotrauma.

Diet

Obese individuals will in general have a higher salt and animal protein intake compared to lean individuals.22, 23  High salt intake leads to volume expansion and hypertension.  High salt intake may also impact kidney disease by magnifying oxidative stress through stimulation of renal cortical nicotinamide adenine dinucleotide (NADH)- and nicotinamide adenine dinucleotide phosphate (NADPH) superoxide anion generation.24, 25  Glomerular scarring with barotrauma may also be accelerated with high salt intake because salt induces fibrogenic pathways via upregulation of transforming growth factor-β. 26, 27  Moderating animal protein intake may also help slow kidney disease progression associated with obesity.  Most obese individuals consume 80% more protein than what is currently recommended for healthy adults. 28  This high intake animal protein intake compounds an already heightened risk of barotruma because the amino acid load from animal protein triggers the release of local mediators that vasodilate the afferent arteriole.  This afferent vasodilatation impairs renal autoregulation,  enhances transmission of systemic pressures to the glomerular capillary, and can lead to glomerular hypertension.29-32  Other dietary factors such as low intake of fruits and vegetables and low fiber intake may also contribute to the overall kidney disease risk in the obese state. 

Caloric Restriction

The impact of obesity on CKD and mortality differs by age, presence of obesity related co-morbidities and expected years of survival. In an older patient with limited years of remaining life, the benefits of weight loss will likely not outweigh the risks.  However, in young individuals, caloric restriction and weight loss may reduce ESRD risk in obese adults with non-dialysis dependent CKD.  While ESRD risk is highest in adults with morbid obesity, dietary interventions fail and fail consistently in this group.  Both clinicians and patients may be hesitant to pursue bariatric surgery due to the associated risks, especially among individuals with CKD.  Overall mortality is quite low -around 1% or lower -at most bariatric surgery centers, but acute kidney injury may occur in 8% or more of patients.  Hospital stay and post-operative complications along with kidney stones may also be higher in patients with CKD after bariatric surgery compared to patients without CKD.33-35  However, bariatric surgery, especially the Roux-en-Y procedure, does lead to sustained (over 10 years) and substantial weight loss in most individuals and remission of diabetes may be as high as 50% after ten years.36  Bariatric surgery with the Roux-en-Y procedure appears to reduce risk of kidney function decline and the composite outcome of doubling of serum creatinine or ESRD.37  However, bariatric surgery remains reserved largely for younger individuals with limited co-morbidities who can demonstrate compliance with dietary restrictions.  Despite this requirement of dietary compliance, weight loss is not maintained in many individuals who undergo bariatric surgery, especially with gastric banding or sleeve gastrectomy procedures.  The weight regain after gastric banding or sleeve gastrectomy procedures is similar to weight regain after severe caloric restriction.  Weight regain remains a major issue for persons who lose over 20% of their body weight and is attributed to metabolic adaptation.  Resting metabolic rate may drop by 500 kcal/day or more after drastic weight loss. 38  Unless these individuals with substantial weight loss exercise vigorously every day to maintain high caloric expenditure, caloric intake must be kept very low to maintain the weight loss. 38  Metabolic adaptation appears to be mitigated with gastric bypass procedures such as the Roux-en-Y procedures but more research is needed.38

Conclusion

Obesity remains an important modifiable risk factor for CKD due to its impact on multiple aspects of glomerular hemodynamics, structure, and response to injury.   Public policy efforts to address the obesity epidemic must include the nephrology community because obesity among young adults substantially heightens lifetime risk of ESRD.  Strong attention to blood pressure control and dietary factors may help mitigate CKD risk and its progression. 

Disclosures: none

 

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