August 2009 Issue

Diabetic Kidney Disease: What RDs Need to Know
By Joyce M. Vergili, EdD, RD, CDE
Today’s Dietitian
Vol. 11 No. 8 P. 48
 
Suggested CDR Learning Codes: 5000, 5190, 5340; Level 2

Diabetes affects nearly 24 million people in the United States, or 7.8% of the population.1 The prevalence of diabetes is expected to increase 165% between 2000 and 2050.2 Diabetes is the leading cause of end-stage renal disease (ESRD), accounting for 44% of new cases of kidney failure in the United States in 2005.1

Chronic kidney disease (CKD), defined as a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 for three months or longer, is also on the rise, currently affecting more than 26 million Americans, or 13% of the adult population.3,4 Its increase is partially due to the increased incidence of diabetes and the population of people with long-standing diabetes.2,4

The National Kidney Foundation categorizes CKD into the following five stages, based on GFR3:

• Stage 1: GFR greater than or equal to 90 mL/min/1.73 m2;

• Stage 2: GFR 60 to 89 mL/min/1.73 m2;

• Stage 3: GFR 30 to 59 mL/min/1.73 m2;

• Stage 4: GFR 15 to 29 mL/min/1.73 m2; and

• Stage 5: GFR less than 15 mL/min/1.73 m2 (or dialysis). Note: Stage 5 is commonly referred to as ESRD.

GFR can be estimated, rather than measured directly, by the Modification of Diet in Renal Disease Study equation, which uses serum creatinine, age, race, and gender, available at www.kidney.org/professionals/kdoqi/gfr_calculator.cfm.3 Because many factors affect creatinine production, serum creatinine alone is not a valid indicator of GFR.3

Diagnosis of DKD
The term “diabetic kidney disease” (DKD) was first introduced in 2007 in the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. The term simply refers to the type of CKD that is specific to diabetes. The foundation recommends that DKD replace the term “diabetic nephropathy.”

Screening for DKD is simple, inexpensive, and widely available. It should be performed upon the diagnosis of type 2 diabetes and five years after the diagnosis of type 1 diabetes. A “spot urine” test to quantify the amount of urinary albumin and creatinine is all that is needed (ie, a 24-hour urine collection is not required).

If the elevated albumin-creatinine ratio is between 30 and 300 mg/g (and confirmed on two occasions over the next three to six months), then microalbuminuria is present. If the ratio is greater than 300 mg/g, the diagnosis is macroalbuminuria. Although not all kidney diseases that occur in patients with diabetes are secondary to diabetes, CKD is considered attributable to diabetes if macroalbuminuria is present or microalbuminuria is present concurrently with diabetic retinopathy or in type 1 diabetes of 10 years or more.2

Medical Nutrition Therapy
By definition, all people with DKD have CKD and diabetes. What may not be appreciated, however, is that most people with DKD also have cardiovascular disease (CVD) and, in fact, are more likely to die from CVD than to progress to stage 5 CKD. The combination of diabetes and CKD is one of the most powerful predictors of major adverse cardiovascular events.2 Clients in the early stages of kidney disease may be overweight or obese, while those in a more advanced stage may be underweight and malnourished. Some clients may be manifesting disturbances in mineral and bone metabolism, while others could be heading toward hyperkalemia.

Thus, medical nutrition therapy (MNT) is indicated for clients with DKD not only to delay the loss of renal function and promote good glycemic control but also to manage associated disorders (ie, dyslipidemia, hypertension, malnutrition, and/or obesity) and the sequelae of the CKD (ie, renal osteodystrophy, vitamin D deficiency, and hyperkalemia).
The MNT goals for a client with DKD may include the following:

• delay the progression of CKD;

• achieve and maintain good glycemic control;

• manage cardiovascular risk factors (eg, hypertension, dyslipidemia);

• promote weight loss in overweight clients;

• prevent and treat renal osteodystrophy; and

• maintain optimal serum potassium levels.

The dietitian must ensure that goals are individualized, achievable, based on a thorough nutrition assessment, and negotiated with the client. The overarching goal for MNT is to either prevent malnutrition in a well-nourished client or achieve and maintain optimal nutritional status in one who is nutritionally compromised.

Diet and Nutrition Recommendations
The diet for DKD is complicated, with recommendations for one condition often competing with recommendations for another. For example, while a mild protein restriction is recommended to stave off the progression of CKD, the concomitant increase in carbohydrate intake may exacerbate hyperglycemia.2

• Delay the progression of CKD: Protein. While it is fairly well established that high-protein diets increase albuminuria and may accelerate loss of kidney function—especially in people with diabetes—it is less certain that lower protein diets actually slow the progression of kidney disease, delaying the need for dialysis. The decision to advise a client to restrict dietary protein or continue with the reduced protein intake that may have spontaneously occurred as a response to uremia must be carefully deliberated, as a substantial decrease in protein intake may compromise nutritional status.5

Recent guidelines, meta-analyses, and expert opinion lean toward dietary protein restriction, although the optimal amount of protein and preferred protein food sources are unknown.2,6-8 In a meta-analysis, Fouque et al concluded that decreasing protein intake in patients with CKD reduces the occurrence of “renal death” (defined as the number of deaths or the number of patients who started renal replacement therapy) by about 40% compared with higher protein diets.6 Some experts also advocate for protein restriction, claiming that even without hard evidence that protein restriction delays the loss of renal function, such diets reduce waste products (thus lessening the signs and symptoms of uremia), suppress proteinuria, increase serum bicarbonate levels, decrease serum phosphorus levels, and ameliorate glucose intolerance.7

According to the American Dietetic Association’s Evidence Analysis Library, nutritional status can, in fact, be maintained with a low-protein diet. However, there is only one published randomized, controlled trial that yielded a positive outcome from dietary protein restriction (0.89 g/kg/day), and this effect was limited to patients with type 1 diabetes. No published trials suggest that diets providing as little as 0.6 g/kg body weight favorably alter the progression of CKD in people with diabetes.8

The Kidney Disease Outcomes Quality Initiative diabetes guidelines recommend a protein intake equivalent to the Recommended Daily Allowance (RDA) level of 0.8 g/kg ideal body weight/day for people with diabetes and stages 1 to 4 CKD.2 Although the RDA level may not appear to represent a protein restriction, most Americans consume 1.02 g protein/kg body weight/day, so 0.8 g protein/kg body weight/day is actually a 22% reduction. The guidelines also recommend a more severe protein restriction to 0.6 g protein/kg body weight/day if GFR begins to decline.2

For clients unable or unwilling to decrease their protein intake to the recommended level, or if doing so may jeopardize nutritional status, the guidelines recommend a red meat restriction as a reasonable alternative based on findings from several small studies, as well as the Nurses’ Health Study, which suggest that protein from sources such as fish, poultry, soy, nuts, and dairy may be kidney sparing.

Because most Americans consume so much protein, reducing the intake of this macronutrient may leave a significant caloric gap that will need to be filled to prevent unintentional or rapid weight loss and/or prevent dietary protein from being used as a source of energy. In the advanced stages of CKD, calorie intake may already be diminished due to nausea, vomiting, taste alterations, diabetic gastroparesis, fatigue, and the anorexia typically associated with uremia. The dietitian should educate the client regarding calorically dense, low-protein foods.

Calorie intake recommendations range from 30 to 35 kcal/kg/day, although the optimal calorie intake is unknown.2 The best course of action may simply be the frequent monitoring of clients who have experienced or are at risk for unintentional or rapid weight loss. Low-protein, high-calorie supplements designed for CKD patients (eg, Suplena with Carb Steady by Abbott Nutrition) may be helpful.

• Achieve and maintain good glycemic control: Carbohydrate. Hyperglycemia is a fundamental cause of kidney disease. Intensive hyperglycemia treatment reduces the incidence of DKD and may slow the progression of established kidney disease.2 For every percentage point drop in hemoglobin A1c (HbA1c) (eg, from 9% to 8%), the risk of kidney damage is reduced by 40%.1 Glycemic goals include attaining and maintaining an HbA1c of less than 7%, preprandial capillary glucose of 90 to 130 mg/dL, and peak postprandial glucose (one to two hours after beginning a meal) of less than 180 mg/dL.2

It is well established that controlling dietary carbohydrate intake is essential for preventing hyperglycemia.2 For clients who require additional carbohydrate intake to compensate for the decrease in dietary protein, whole grain, high-fiber, and low–glycemic-index foods may help to mitigate glycemic excursions. However, as CKD progresses, clients are at increased risk for hypoglycemia due to decreased insulin clearance and impaired kidney gluconeogenesis.2 Therefore, increasing the dietary carbohydrate in the nutrition prescription may indeed be warranted.

Good glycemic control is generally not achieved through dietary intervention alone; medications play an important role. The diabetes medication regimen may need to be altered in DKD either to treat hyperglycemia due to a higher carbohydrate intake or to prevent hypoglycemia due to the progression of kidney disease. It is important that dietitians are aware of how DKD influences medication choice and dosing.

Oral medications that are contraindicated in DKD include the following:

• metformin (Glucophage) and medications that contain metformin, such as sitagliptin/metformin (Janumet); and

• alpha-glucose inhibitors such as acarbose (Precose) and miglitol (Glyset).

Preferred medications include the following:

• glipizide (Glucotrol);

• meglitinides such as repaglinide (Prandin) and nateglinide (Starlix) (The initial dose of nateglinide must be reduced to 80 mg.);

• thiazolidinediones such as piaglitazone (Actos) and rosiglitazone (Avandia) (This class of drugs is not recommended in patients with symptomatic heart failure. Also, rosiglitazone carries a black box warning that it may cause or exacerbate congestive heart failure and myocardial ischemia.);

• amylin analogs such as pramlintide (Symlin);

• DPP-4 inhibitors such as sitagliptin (Januvia) (The dose must be reduced to 50 mg or 25 mg, depending on the CKD stage.); and

• insulin.2

• Manage cardiovascular risk factors. Most people with DKD have CVD. The Kidney Disease Outcomes Quality Initiative diabetes guidelines recommend that total fat intake be limited to less than 30% of total calories, saturated fat to less than 10%, and cholesterol intake to less than 200 mg/day. The guidelines also state that “increased intake of omega-3 and monounsaturated fatty acids may be considered because of potentially favorable effects on progression of CKD.”2

The dyslipidemia typically seen in DKD (high triglycerides and low HDL cholesterol) generally require drug therapy. In fact, statins, the medication of choice, are probably more effective than diet for treating dyslipidemia. Other medication options include niacin and omega-3 fatty acids.2,9

It bears repeating that most people with CKD will die of cardiovascular causes well before the question of which type of dialysis is best arises. Therefore, a primary goal of nutrition intervention is to reduce cardiovascular risk. Progress toward that goal can be assessed by measuring LDL cholesterol, the target for which is less than 100 mg/dL.2

Most people with DKD have hypertension. Effective hypertension treatment reduces CVD risk and can reduce the decline in kidney function by up to 70%.1,2 The Kidney Disease Outcomes Quality Initiative guidelines recommend a target blood pressure of less than 130/80 mm Hg. The Dietary Approaches to Stop Hypertension (DASH) diet, a low-sodium (less than 2.3 g sodium/day), high-potassium diet, provides the basis for the nutrition intervention for hypertension.2 However, because the DASH diet provides 1.4 g protein/kg body weight/day, the guidelines recommend that it be modified to decrease its protein content and, depending on the client’s serum potassium and phosphorus levels, further adjusted to reduce one or both of these minerals. Elevated serum levels of potassium and phosphorus are more likely to be a challenge in stages 4 and 5 than in the earlier stages of CKD.

• Promote weight loss in overweight clients. Independent of its association with diabetes and hypertension, obesity may be a risk factor for CKD. Weight management strategies can be helpful in the earlier stages of DKD to promote optimal blood pressure, glycemic control, and a favorable lipid profile. The Kidney Disease Outcomes Quality Initiative recommendation for overweight patients is to attain and maintain a body mass index of 18.5 to 24.9 kg/m2 through reduced calorie intake and regular physical exercise. High-protein weight reduction diets are strongly contraindicated for DKD patients.2

• Prevent and treat renal osteodystrophy. As kidney function declines, abnormalities in bone and mineral metabolism arise. Such abnormalities manifest as elevated serum phosphorus levels (due to a diminished ability to excrete phosphorus), reduced serum calcium (due to the inability of the failing kidneys to activate vitamin D), and elevated intact parathyroid hormone (iPTH) levels (as the body attempts to rectify the hyperphosphatemia and hypocalcemia). Long-term consequences of altered bone mineral metabolism include calcification of soft tissue, bone pain, and an increased incidence of bone fractures.10

In stages 3 and 4 CKD, the goal range for serum phosphorus is 2.7 to 4.6 mg/dL; for calcium, the goal is simply the reference range of the laboratory (approximately 8.4 to 10.2 mg/dL). The target for iPTH depends on the CKD stage. In stage 3, the range is 35 to 70 pg/mL and in stage 4, 70 to 110 pg/mL.10

When either serum phosphorus or iPTH levels are elevated, dietary phosphorus should be limited to 800 to 1,000 mg/day. If necessary, a phosphate binder medication can also be prescribed to maintain phosphorus and iPTH levels within their respective target ranges. The Kidney Disease Outcomes Quality Initiative guidelines recommend using a calcium-based binder, such as calcium acetate (eg, Phoslo), as the initial therapy. To minimize the risk of soft tissue calcification, elemental calcium from calcium-containing binders, supplements, or antacids should be limited to 1,500 mg, and total calcium from all sources should be no more than 2,000 mg/day.10

The elevated iPTH levels seen in CKD are known as secondary hyperparathyroidism. Although phosphorus control through diet modification and binder therapy may help to lower iPTH levels, it is often necessary to treat secondary hyperparathyroidism with a vitamin D analog such as doxercalciferol (Hectorol) or paricalcitol (Zemplar). Once vitamin D therapy is initiated, iPTH should be closely monitored to ensure that levels remain within the target range, as neither overtreatment nor undertreatment of secondary hyperparathyroidism is desirable. Further, serum levels of both calcium and phosphorus should be monitored regularly, as vitamin D therapy may cause hypercalcemia and/or hyperphosphatemia.

The interaction between calcium, phosphorus, iPTH, and vitamin D analogs is complex. The reader is referred to the Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Bone Metabolism and Disease in CKD for more information.10

• Maintain optimal serum potassium levels. Serum potassium must remain within the target range of approximately 3.5 to 5.5 mEq/L to minimize the risk of cardiac arrest. As CKD progresses, clearance of excess potassium from the body may decline, leading to increasing serum levels. Constipation, hyperglycemia due to insulin deficiency, protein catabolism, hemorrhage, blood transfusions, metabolic acidosis, certain medications, and/or excess dietary potassium intake may tip the balance into frank hyperkalemia.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, antihypertension medications often used in this patient population, are quite effective for slowing the progression of CKD in patients with diabetes. Their kidney-sparing effects are evident even in patients without hypertension. Thus, they are often prescribed for normotensive patients as well.2 However, one of the side effects of ACE inhibitors and angiotensin receptor blockers is hyperkalemia. When serum potassium levels begin to increase, physicians may opt to discontinue these extremely beneficial medications. A better option would be for the physician to refer the patient to a dietitian for counseling on a potassium-restricted diet. A 2 to 4 g potassium diet may, in fact, permit the continuation of these renal-protective medications.

Hyperkalemia is not inevitable for DKD patients. In patients who are on potassium-losing diuretics such as furosemide (Lasix) and who continue to produce urine, serum potassium levels may remain within an acceptable range well into stage 5 CKD. Therefore, the dietitian and physician should use serum potassium levels to determine when, if, and to what degree dietary potassium should be restricted.

The chart summarizes the dietary recommendations for patients with DKD. It would not be surprising if a DKD client perceived the recommended diet, with its many restrictions, as unpalatable. To address this anticipated reaction, the Kidney Disease Outcomes Quality Initiative diabetes workgroup included a sample menu and recipes in its guidelines. Additional recipes are provided in the monthly E-Kidney Newsletter (www.kidney.org/news/newsletters.cfm).

The RD is an important member of the healthcare team. According to the diabetes guidelines, “Management of diabetes and CKD should include nutritional intervention.”2 MNT is a covered service for Medicare beneficiaries with CKD. (It is important to note that the beneficiary must have a GFR of 13 to 50 mL/min/1.73 m2 before he or she is eligible for MNT and that this GFR range does not correspond to the stages of CKD as set by the National Kidney Foundation.

The American Dietetic Association recommends an initial assessment upon a CKD diagnosis, followed by quarterly reassessments.2 Follow-ups may actually need to be more frequent for DKD, as these patients have both kidney disease and diabetes and typically have several other nutrition-related diagnoses (eg, CVD, hypertension, dyslipidemia). Frequent follow-ups are also warranted as dietary recommendations may need to be modified as DKD progresses and renal clearance of certain nutrients (eg, potassium, phosphorus) and/or insulin declines. Finally, close monitoring of clients who are restricting dietary protein is important to guard against overrestriction of protein intake, and subsequent malnutrition, in an effort to delay the need for dialysis.

— Joyce M. Vergili, EdD, RD, CDE, is the renal dietitian at Columbia-Greene Dialysis Center in Catskill, N.Y., and a visiting scholar at Teachers College, Columbia University in New York City. She is also a member of six American Dietetic Association practice groups, including Renal Dietitians and Diabetes Care and Education, and of the Council on Renal Nutrition of the National Kidney Foundation and the American Association of Diabetes Educators.

Chart 1: Dietary Recommendations for Diabetic Kidney Disease

 

Learning Objectives
After completing this continuing education exercise, the learner should be able to:

1. Define diabetic kidney disease (DKD).

2. List at least three goals for medical nutrition therapy (MNT) in DKD.

3. Discuss the risks and benefits of dietary protein restriction, citing at least one benefit and one risk.

4. Explain why hypoglycemia may become more frequent as DKD progresses.

5. Explain how the Dietary Approaches to Stop Hypertension diet needs to be modified for a client in the later stages of kidney disease.

6. List three possible reasons for unintentional and/or rapid weight loss in DKD.

7. Identify the two laboratory values that, when either of which is elevated, warrant a dietary phosphorus restriction.

8. Explain how MNT can be of tremendous value in mitigating the side effects of certain renal protective medications.

9. List the recommendations for dietary protein, sodium, potassium, and phosphorus in stages 3 and 4 chronic kidney disease.

 

Examination
1. Which of the following is a goal for medical nutrition therapy for diabetic kidney disease (DKD)?
a. To delay the progression of chronic kidney disease (CKD)
b. To achieve and maintain good glycemic control
c. To manage cardiovascular risk factors
d. All of the above

2. The Kidney Disease Outcomes Quality Initiative guidelines recommend which of the following dietary protein levels for stages 3 and 4 CKD?
a. 0.6 to 0.8 g protein/kg/ideal body weight
b. 0.8 to 1 g protein/kg/ideal body weight
c. 1 to 1.2 g protein/kg/ideal body weight
d. 1.2 to 1.4 g protein/kg/ideal body weight

3. Which of the following medications is contraindicated in DKD?
a. Repaglinide (Prandin)
b. Glipizide (Glucotrol)
c. Metformin (Glucophage)
d. Sitagliptin (Januvia)

4. Most people with CKD will die of ____________ before reaching end-stage renal disease.
a. nephrolithiasis
b. renal osteodystrophy
c. cardiovascular disease
d. secondary hyperparathyroidism

5. Which of the following describes how the Dietary Approaches to Stop Hypertension diet may need to be modified for someone in stage 4 CKD?
a. Protein content would need to be decreased.
b. Potassium content would need to be increased.
c. Phosphorus content would need to be increased.
d. Omega-3 fatty acid content would need to be decreased.

6. Which of the following represent the metabolic goals for a person with DKD?
a. Hemoglobin A1c (HbA1c) less than 7%, LDL cholesterol less than 130 mg/dL, blood pressure less than 140/90 mm Hg
b. Preprandial glucose of 90 to 130 mg/dL, LDL cholesterol less than 130 mg/dL, blood pressure less than 135/85 mm Hg
c. Peak postprandial capillary glucose less than 200 mg/dL, LDL cholesterol less than 100 mg/dL, blood pressure less than 130/80 mm Hg
d. Hemoglobin A1c less than 7%, LDL cholesterol less than 100 mg/dL, blood pressure less than 130/80 mm Hg

7. Which of the following factors may contribute to unintentional and/or rapid weight loss in patients with DKD?
a. Diabetic gastroparesis
b. Uremia-induced anorexia
c. Taste alterations
d. All of the above

8. In which of the following situations would a dietary potassium restriction be initiated?
a. When parathyroid hormone levels are elevated
b. When serum potassium levels are elevated
c. When the patient is taking a diuretic (eg, furosemide)
d. When the glomerular filtration rate is less than 60 mL/min/1.73 m2

9. Which of the following represents a potential adverse outcome for patients following a protein-restricted diet?
a. Insufficient calorie intake
b. Malnutrition
c. Overrestriction of dietary protein
d. All of the above

10. Which of the following represents a potential positive outcome for patients following a protein-restricted diet?
a. The progression of CKD is slowed.
b. Signs and symptoms of uremia are lessened.
c. Glucose intolerance is ameliorated.
d. All of the above

 

References
1. Centers for Disease Control and Prevention. National diabetes fact sheet: General information and national estimates on diabetes in the United States, 2007. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2008.

2. National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis. 2007;49(2 Suppl 2):S12-154.

3. National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1-266.

4. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298(17):2038-2047.

5. Kopple JD, Greene T, Chumba WC, et al. Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD study. Kidney Int. 2000;57(4):1688-1703.

6. Fouque D, Wang P, Laville M, Boisel JP. Low protein diets delay end-stage renal disease in non-diabetic adults with chronic renal failure. Nephrol Dial Transplant. 2000;15(12):1986-1992.

7. Mitch WE, Remuzzi G. Diets for patients with chronic kidney disease, still worth prescribing. J Am Soc Nephrol. 2004;15(1):234-237.

8. American Dietetic Association Evidence Analysis Library. What are macronutrient and micronutrient needs to minimize disease progression while to maintaining adequate nutrition status in adult non-dialyzed patients with diabetic nephropathy? June 2007. Available at: http://www.adaevidencelibrary.com/conclusion.cfm?conclusion_statement_id
=251094. Accessed May 16, 2009.

9. Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol. 2008;51(25):2375-2384.

10. National Kidney Foundation. KDOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1-201.