May 2017 Issue

Chronic Kidney Disease Prevention — Part One in a Two-Part Series
By Judith C. Thalheimer, RD, LDN
Today's Dietitian
Vol. 19, No. 5, P. 40

The following look at diet's essential role in decreasing risk of CKD is the first in a two-part series bringing nutrition professionals the latest information needed to prevent and treat this growing health burden.

Nearly one in seven American adults has chronic kidney disease (CKD), and millions more are at risk.1,2 When the kidneys are failing, challenging dietary changes become essential, but data increasingly show that diet also may be the key to heading off kidney disease, which is the ninth leading cause of death in America.3 Without a dramatic change in preventive measures, it's now estimated that 54% of people aged 30 to 49 will develop CKD in their lifetime.1 Unfortunately, many Americans don't know they're at risk of CKD.4 "The incidence of CKD in the United States is definitely increasing," says Michael Conrad, MD, a senior member of the Center for Kidney Care in New Jersey, "and the current rates of the major risk factors diabetes, hypertension, and obesity suggest the CKD numbers are going to keep climbing. Dietary factors can help control CKD and can theoretically prevent it as well."

Kidney Function
The kidneys remove waste and extra fluid from the body, make an active form of vitamin D to support bone health, regulate the production of red blood cells, control pH levels, and release hormones that regulate blood pressure.5 CKD includes any condition that damages the kidneys and decreases their ability to perform these tasks.2 Blood entering the kidney to be filtered first passes through a network of capillaries called the glomerulus. Glomerular filtration rate (GFR), a calculation of the volume of fluid filtered through these capillaries over time, is considered the best measure of kidney function. As kidney function falls, GFR rises.6 Protein in the urine (albuminuria) is also an early sign of kidney disease, indicating that the filtration system is, essentially, leaking.7 CKD is measured in stages, from stage 1 (where the kidney is damaged, but still functioning normally) to stage 5 (kidney failure necessitating dialysis or kidney transplantation).6

While CKD can be caused by genetic conditions, illness, infections, or prolonged exposure to drugs or toxins, other risk factors are more common. Uncontrollable risk factors include age, genetics, and race (blacks, Asian Americans, and Native Americans are at increased risk). Modifiable risk factors include smoking, obesity, and the two main culprits in kidney disease: high blood pressure and diabetes.8

How Major Risk Factors Lead to CKD
Diabetes and high blood pressure are responsible for up to two-thirds of CKD cases, and obesity, which leads to these two conditions, also is considered a major risk factor.2 "Most of the people I see with kidney disease have a history of uncontrolled diabetes or hypertension," says Kristen F. Gradney, MHA, RDN, LDN, a spokesperson for the Academy of Nutrition and Dietetics who works with renal patients. "Getting those chronic diseases under control is an important step to avoiding kidney problems."

Diabetes
Diabetes is the leading cause of CKD and is responsible for 30% to 40% of all end-stage renal disease in the United States.9,10 About 30% of patients with type 1 diabetes and 10% to 40% of those with type 2 diabetes eventually will suffer from kidney failure.11 The good news is that dietary changes and proper medical treatment can help. "For those with diabetes, strict blood sugar control has been shown to help prevent progression of CKD," Conrad says. And there's good evidence to suggest that early treatment and aggressive management of type 2 diabetes can even delay or prevent the onset of diabetic nephropathy.10

There are several mechanisms thought to influence the development of diabetic nephropathy. The American Diabetes Association patient education material explains that high levels of blood glucose make the kidneys work harder, eventually wearing them out.12 This phenomenon, known as hyperfiltration, is clearly an important factor, but other mechanisms also are involved.10

It's known that the glomeruli change in people with diabetes. The cells between the glomerular capillaries (called the mesangial matrix) expand, eventually impinging on the capillaries, the basement membrane thickens, and the glomeruli harden (glomerular sclerosis).10,13 One of the factors in these histological changes is the effect hyperglycemia has on proteins.13 The excess glucose in the blood binds with plasma proteins through a process known as glycation to form advanced glycation end products (AGEs), which play an important role in the development of diabetes complications such as nephropathy.14 This fact is particularly interesting because it's known that phytochemicals in foods such as berries can counteract AGEs.15

In addition to the direct impact hyperglycemia has on the kidneys, many people with diabetes develop high blood pressure, which also can damage the kidneys.16

Hypertension
High blood pressure is the second leading cause of kidney failure.17 Hypertension and CKD have a cause and effect relationship: Blood pressure typically rises as kidney function declines, and uncontrolled hypertension speeds the progression of kidney disease.18 The dense network of blood vessels that feed the kidneys are narrowed, weakened, or hardened over time by uncontrolled high blood pressure. Once the arteries become damaged, essential oxygen and nutrients can't be delivered adequately, and the kidneys no longer can function properly. Since the kidneys are responsible for producing aldosterone, a hormone that helps regulate blood pressure, poor kidney function leads to poor blood pressure regulation, which in turn decreases kidney function, creating a downward spiral.17

High serum sodium, such as that caused by excessive dietary sodium intake, is another key factor in the relationship between kidney disease and hypertension. The kidneys use osmosis to draw excess fluid out of the body. Excess sodium in the blood throws the balance off, reducing the ability of the kidneys to remove water. The resulting excess fluid raises blood pressure.19

Obesity
Obesity can be considered the number one preventable risk factor for developing kidney disease because of its link to both diabetes and hypertension.20 "Obesity is the key, since it can lead to hypertension and diabetes," Gradney says. "If we could get people to modify their diets to lose weight, we'd make a huge difference in CKD." Interestingly, obesity is a risk factor for kidney disease even independent of high blood pressure or diabetes. Like diabetes, obesity, and central obesity in particular, can cause hyperfiltration. "Hyperfiltration from an obese state can aggravate, and even cause, kidney problems," Conrad says, "which is one reason why obesity increases risk of CKD." Moreover, albuminuria and glomerular sclerosis are recognized as specific complications of severe obesity.21

The good news is that obesity's effects on kidney function can be reversed through dietary modification. Weight loss reduces GFR and proteinuria.20 In fact, some clinical observations have seen significant weight loss through caloric restriction reduce proteinuria by more than 80% from baseline.21 But weight loss may not be necessary to achieve improvement in kidney function; caloric restriction itself seems to reduce proteinuria even before weight begins to drop significantly. It's possible that high caloric intake on its own may increase CKD risk.20

However, good nutrition can prevent weight gain and decrease risk of diabetes and high blood pressure, and dietary modification is central to control all three of these major CKD risk factors. While medications may be necessary to help control blood pressure and blood glucose levels, dietary modification is clearly an essential part of preventing CKD. "The main measures people can take to prevent kidney disease are to maintain blood sugar levels, blood pressure, and appropriate weight," Gradney says.

Dietary Patterns
Since the major CKD risk factors, such as obesity, diabetes, and high blood pressure, are all greatly influenced by dietary choices, researchers have begun to take a closer look at diet as a means of preventing kidney disease. "While in the past research was focused on how best to treat CKD, in recent years there has been greater interest in preventing CKD in the first place, and in the role that diet and dietary pattern can play," says Deidra C. Crews, MD, ScM, FASN, FACP, an associate professor of medicine in the division of nephrology at Johns Hopkins University School of Medicine. The way researchers are evaluating nutrition and CKD also has changed. "Historically, there has been a focus on individual nutrients in kidney disease," Crews says, "but there's a growing interest in dietary pattern, not just specific nutrients."

DASH
In 1997, the Dietary Approaches to Stop Hypertension (DASH) trial, a multicenter, randomized feeding study that tested the effects of dietary patterns on blood pressure, found that following the DASH eating pattern lowers blood pressure and LDL cholesterol compared with the typical American diet.22 The DASH diet limits sodium between 1,500 and 2,300 mg per day; emphasizes vegetables, fruits, and whole grains; includes fat-free or low-fat dairy products as well as fish, poultry, beans, nuts, and vegetable oils; and limits saturated fats, sugar-sweetened beverages, and sweets.23,24

"The DASH dietary pattern is well established to lower blood pressure, and chances of developing diabetes, high blood pressure, and cardiovascular disease are all lower if you eat a DASH-like diet," Crews says. In August 2016, Rebholz, Crews, and others published the results of a prospective cohort study that found an association between consuming a DASH-style diet and lower risk of kidney disease.23 "At least from an observational standpoint, it looks like people who follow a diet closely aligned to the DASH dietary pattern are less likely to develop kidney disease," Crews says.

Mediterranean
"People who follow a Mediterranean dietary pattern also seem to have favorable outcomes," Crews says. The Mediterranean dietary pattern emphasizes vegetables, fruits, whole grains, nuts, and seeds, along with seafood and extra virgin olive oil. Observational studies and randomized trials find adherence to a Mediterranean-style diet lowers cardiovascular disease risk, purportedly by lowering blood pressure, improving lipid profile and endothelial function, and decreasing inflammation—all of which would be good for kidney health.25

A 2014 observational study by Khatri and colleagues in the Clinical Journal of the American Society of Nephrology found that greater adherence to a Mediterranean-style diet in the multiethnic cohort was associated with decreased loss of kidney function.25 It should be noted that a 2015 analysis of a randomized trial found no difference between the Mediterranean diet and a low-fat control diet when it came to participants' rates of diabetic nephropathy.26

Dietary Acid Load and Protein Intake
Both the DASH and Mediterranean dietary patterns have a lower dietary acid load than the traditional Western diet, which may be one of the reasons they help promote kidney health. "Acid load is higher in people who eat more animal-based proteins like meats and cheeses and lower in those who consume a dietary pattern richer in fruits and vegetables," Crews says.

The kidneys are responsible for maintaining acid-base balance in the body. The metabolism of dietary protein creates nonvolatile acids, and organic anion salts found primarily in plant foods form bicarbonate (a base) in the gastrointestinal tract. The difference between the acids and the base yields the dietary acid load, which the kidneys need to even out.27 "We need to educate the public to follow a DASH-style diet that's lower in dietary acid load, higher in fruits and vegetables, and lower in red meats, processed foods, and foods that have high caloric density," says Deborah Brommage, MD, RD, CSR, CDN, senior scientific director for the National Kidney Foundation.

Moreover, excess protein intake has long been suspected to increase risk of kidney disease. This possible connection has been attributed to the fact that high protein intake leads to hyperfiltration, which is thought to damage the kidneys. Dietary protein restriction is a part of treatment for people with CKD, but its role in prevention is less clear. Recent research shows that the role of protein in the development of CKD is nuanced. In a prospective cohort study of nearly 12,000 healthy adults published in the Journal of Renal Nutrition in 2017, intake of red and processed meats was associated with an increased risk of developing CKD, but higher dietary intake of protein sources such as nuts, legumes, and low-fat dairy products was associated with lower CKD risk.28 By joining these findings with research associating dietary acid load with development of CKD, it's possible to surmise that part of the connection between protein intake and kidney damage could be related to the higher acid load of animal-protein-based diets.

Counseling to Preserve Kidney Health
For dietitians, focusing on dietary pattern instead of individual nutrients for CKD prevention can make nutrition counseling easier. "Most people think in terms of food groups and food types when they sit down to dinner," Crews says, so dietary pattern is more intuitive and easier to follow than counting grams, milligrams, or calories. Advising adherence to a low acid load pattern such as the DASH or Mediterranean diet (adjusted for any special medical needs) addresses all of the known risk factors and prevention strategies. "One of the things my colleagues and I have been trying to understand is how we can better promote healthful dietary patterns among people who have established risk factors," Crews says. "Perhaps knowing dietary changes might reduce risk of kidney disease could affect their willingness to change their diet."

Whether or not the specter of kidney disease is motivational, the experts interviewed advise a collaborative approach to behavior change. "We have to meet people where they are," Gradney says. "Not every person is going to be able to follow every recommendation."

Brommage advocates starting with small changes in areas that will have the most impact. "Start off with what the person is doing now, then look for areas for improvement," Brommage says. "Try to make gradual changes. Substitutions are a good place to start: if they are using regular dairy products, switch to low fat. If they consume a lot of processed foods, talk about using fresh foods. Work with them on calorie intake to maintain a healthy weight."

Both emphasize meeting people where they are. "Modify their diet, not just a diet," Gradney says. "Interview the patient to determine what their resources are. What's available to them? What foods are really important to them? Then help them modify their behavior to ensure long-term success."

Beyond Counseling
Besides working one-on-one with clients and patients, advocating for public policy changes may be another step nutrition professionals can take to help decrease the incidence of kidney disease in the United States. "Most people don't have access to registered dietitians to help them adopt a diet that could prevent CKD," Crews says, "and many don't even have access to professional nutrition help after diagnosis." Even with access to good nutrition advice, education may not be enough. "It's one thing to know what foods are good for you, and another to have access to those foods," Crews says. "Many segments of American society lack the resources to be able to follow a healthful dietary pattern. Stores near them may not carry fresh fruits and vegetables, or they may lack the financial means to eat a more expensive healthful diet." Poverty and living in a food desert create food insecurity. "Food insecurity increases the risk of having CKD, and is a risk factor for progression to end-stage renal disease," Crews says.

Crews is studying ways public policy may be able to impact CKD rates. "There are opportunities for public policies that might help with this issue," Crews says. "We are starting a clinical trial to see if we can lower early markers of CKD in people who qualify for SNAP (the Supplemental Nutrition Assistance Program) by offering $30 worth of fruits and vegetables and counseling by a health coach trained by an RD." Crews reports that other researchers are looking at the role food insecurity may play in hypertension and diabetes.

"Prevention needs to be focused on those at greatest risk of developing CKD," Crews says. "Given the link between food insecurity and kidney disease, perhaps we can leverage the fact that our public policy system is already touching this at-risk group."

The incidence of CKD is rising along with the growing population of Americans with obesity, diabetes, and hypertension. Emerging research is showing that a healthful dietary pattern (one that's higher in fruits and vegetables and lower in animal proteins than the typical American diet, such as the DASH or Mediterranean dietary patterns) could prevent the physiological changes that lead to kidney disease. By educating, counseling, and advocating, nutrition professionals can play an important role in preventing this chronic condition.

— Judith C. Thalheimer, RD, LDN, is a freelance nutrition writer, speaker, and community educator in Philadelphia.


References
1. Hoerger TJ, Simpson SA, Yarnoff BA, et al. The future burden of CKD in the United States. Am J Kidney Dis. 2015;65(3):403-411.

2. About chronic kidney disease. National Kidney Foundation website. https://www.kidney.org/atoz/content/about-chronic-kidney-disease. Updated February 15, 2017.

3. National Center for Health Statistics. Leading causes of death. Centers for Disease Control and Prevention website. https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Updated January 20, 2017.

4. The right diet may help to prevent kidney disease, new study finds. National Kidney Foundation website. https://www.kidney.org/news/newsroom/nr/Right-Diet-May-Help-Prevent-KD. Published April 17, 2013.

5. Top 5 jobs kidneys do. National Kidney Foundation website. https://www.kidney.org/kidneydisease/top-5-jobs-kidneys-do. Updated 2016.

6. Glomerular filtration rate (GFR). National Kidney Foundation website. https://www.kidney.org/atoz/content/gfr

7. Albuminuria. National Kidney Foundation website. https://www.kidney.org/atoz/content/albuminuria. Updated August 12, 2016.

8. Chronic kidney disease risk factors. Mayo Clinic website. http://www.mayoclinic.org/diseases-conditions/kidney-disease/basics/risk-factors/con-20026778

9. Afkarian M, Zelnick LR, Hall YN, et al. Clinical manifestation of kidney disease among US adults with diabetes. JAMA. 2016;316(6):602-610.

10. Batuman V. Diabetic nephropathy. Medscape website. http://emedicine.medscape.com/article/238946-overview. Updated September 30, 2016.

11. Diabetes. National Kidney Foundation website. https://www.kidney.org/atoz/content/diabetes

12. Kidney disease (nephropathy). American Diabetes Association website. http://www.diabetes.org/living-with-diabetes/complications/kidney-disease-nephropathy.html. Updated February 9, 2017.

13. Abrass CK. Diabetic nephropathy. Mechanisms of mesangial matrix expansion. West J Med. 1995;162(4):318-321.

14. Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol. 2014;18(1):1-14.

15. Thangthaeng N, Poulose SM, Miller MG, Shukitt-Hale B. Preserving brain function in aging: the anti-glycative potential of berry fruit. Neuromolecular Med. 2016;18(3):465-473.

16. Diabetic kidney disease. National Institute of Diabetes and Digestive and Kidney Diseases website. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/diabetic-kidney-disease. Updated February 2017.

17. How high blood pressure can lead to kidney damage or failure. American Heart Association website. http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/
LearnHowHBPHarmsYourHealth/How-High-Blood-Pressure-Can-Lead-to-Kidney-Damage-or-Failure_UCM_301825_Article.jsp#.WL7JvbGZNPM
. Updated January 18, 2017.

18. Judd E, Calhoun DA. Management of hypertension in CKD: beyond the guidelines. Adv Chronic Kidney Dis. 2015;22(2):116-122.

19. Salt's effects on your body. Blood Pressure UK website. http://www.bloodpressureuk.org/microsites/salt/Home/Whysaltisbad/Saltseffects

20. Wickman C, Kramer H. Obesity and kidney disease: potential mechanisms. Semin Nephrol. 2013;33(1):14-22.

21. Praga M, Morales E. Obesity-related renal damage: changing diet to avoid progression. Kidney Int. 2010;78(7):633-635.

22. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med. 1997;336(16):1117-1124.

23. Rebholz CM, Crews DC, Grams ME, et al. DASH (Dietary Approaches to Stop Hypertension) diet and risk of subsequent kidney disease. Am J Kidney Dis. 2016;68(6):853-861.

24. Description of the DASH eating plan. National Heart, Lung, and Blood Institute website. https://www.nhlbi.nih.gov/health/health-topics/topics/dash. Updated September 16, 2015.

25. Khatri M, Moon YP, Scarmeas N, et al. The association between a Mediterranean-style diet and kidney function in the Northern Manhattan Study cohort. Clin J Am Soc Nephrol. 2014;9(11):1868-1875.

26. Díaz-López A, Babio N, Martínez-González MA, et al. Mediterranean diet, retinopathy, nephropathy, and microvascular diabetes complications: a post hoc analysis of a randomized trial. Diabetes Care. 2015;38(11):2134-2141.

27. Scialla JJ, Anderson CAM. Dietary acid load: a novel nutritional target in chronic kidney disease? Adv Chronic Kidney Dis. 2013;20(2):141-149.

28. Haring B, Selvin E, Liang M, et al. Dietary protein sources and risk for incident chronic kidney disease: results from the Atherosclerosis Risk in Communities (ARIC) study [published online January 5, 2017]. J Ren Nutr. doi: 10.1053/j.jrn.2016.11.004.