Kidney Disease Update
Today’s Dietitian
By Alison J. Rigby, PhD, MPH, RD
Vol. 6, No. 11, p. 44

Growing numbers of people with chronic kidney disease require that dietitians get up to speed on prevention and treatment.

Approximately 20 million people in the United States have chronic kidney disease (CKD). The term kidney has replaced the word renal in much of the terminology to create a better understanding for the patient population. More than 100,000 people in the United States develop CKD annually, and the number has doubled each decade since 1980 (United States Renal Data System). The leading cause of end-stage kidney disease (ESKD) is diabetic nephropathy, and this trend is expected to accelerate in the next two decades in the United States. Diabetes mellitus and hypertension account for roughly 75% of all cases of CKD, with African Americans, Native Americans, and older adults being at high risk. The average life expectancy on hemodialysis (HD) is still only five years. Cardiovascular death is the common outcome of CKD.

CKD is defined as either kidney damage or Glomerular filtration rate (GFR) < 60 milliliters per minute per 1.73 square meters for > three months. Early detection of CKD can help prevent the progression of kidney disease to kidney failure. GFR is the best estimate of kidney function, and the key is to know both serum creatinine and GFR. Persistent proteinuria is usually a marker of kidney damage, and three simple tests can detect CKD: blood pressure, urinary protein, and serum creatinine. Under most circumstances, “spot” (untimed) urine samples can be used to detect and monitor proteinuria in adults and children. If a standard protein dipstick test is positive, it should be confirmed by quantitative protein tests, such as the urine protein-to-creatinine or albumin-to-creatinine ratios. The other common markers of kidney damage are red blood cell or white blood cell casts in the urine, which can be detected by using a routine urine dipstick, followed by microscopic examination of the urine sediment.

Lowering blood pressure is the most important independent intervention for slowing the progression of kidney disease. The target blood pressure for patients with CKD is 130/80 millimeters of mercury or lower. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers play an important role in the delay of kidney disease. A low-density lipoprotein cholesterol level of less than 100 milligrams per deciliter is advised, the same target as that recommended by the Adult Treatment Panel III for high-risk patients.

The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI) is a set of clinical practice guidelines for working with renal or kidney patients. The overall objectives of the DOQI were to improve patient survival, reduce patient morbidity, improve the quality of life of dialysis patients, and increase efficiency of care. Launched in 1995, this has been an evolving plan, and guidelines are being developed on an ongoing basis and revised based on the evidence-based review of the literature and the opinion of work group experts.

Protein-Energy Malnutrition (PEM)
PEM is common among patients with advanced chronic kidney failure (CKF) and those who undergo maintenance dialysis (MD), including both HD and chronic peritoneal dialysis (CPD). The presence of PEM is a strong predictor of morbidity and mortality in these patients. There are many causes contributing to PEM, including inadequate food intake, the metabolic response to illness, the dialysis procedure itself, loss of blood, the endocrine disorders of uremia, and conditions associated with CKF that may induce a chronic inflammatory state. Metabolic acidosis is commonly seen in CKD patients and is shown to be associated with increased protein catabolism. Resistance to the anabolic hormones insulin, growth hormone, and insulinlike growth factor is also associated with worsening kidney function.

Historically, PEM has been the main nutritional concern in the ESKD population; however, the rapid rise in obesity—defined as an epidemic public health problem—may have an important impact on this patient group. Several studies have reported a “reverse epidemiology” in the dialysis setting—ie, with each unit increase in body mass index (BMI), there is a reduction in the relative risk of mortality. However, in kidney transplant candidates, a higher BMI may be associated with a significantly higher risk for death. Other studies have suggested that an obese patient (BMI > 30) may be at risk for wound infection, onset of diabetes mellitus, and delayed graft function. Sometimes a modest weight loss of 10% to 15% of body weight may assist with blood pressure, glucose tolerance, lipid panel results, and postoperative complications in these patients.

Some key nutritional assessment tools in the dialysis patient include a review of important biochemical markers, the use of protein catabolic rate (PCR) or protein equivalent of total nitrogen appearance (PNA), subjective global assessment (SGA), and the evaluation of protein and energy requirements in these patients.

Biochemical Markers
The interpretation of serum measures of nutritional status such as visceral protein pools, including serum albumin and prealbumin (transthyretin), is complicated by the influence of the inflammatory process on many of these values. Increased concentrations of the proinflammatory cytokines and acute phase reactants, such as C-reactive protein levels, have been shown in CKD patients. Nonetheless, serum albumin and body weight are still recommended for routine measurement and evaluation in MD patients. A stabilized albumin > 4.0 grams per deciliter is the outcome goal. The combination of several methods of assessment of visceral and somatic protein pools, body weight, and nutrient intake are recommended. Plasma electrolytes should continue to be monitored, with diet restrictions usually of 2 to 3 grams potassium, 2 grams sodium, and 1 gram phosphorus in CKD patients.

PCR or PNA are clinically useful measures of net protein degradation and protein intake and degradation in MD patients. The estimation of normalized PCR or PNA (nPCR or nPNA) (normalized to some function of body weight such as actual, adjusted, or standardized National Health and Nutrition Examination Survey body weight) from the measurement of urea nitrogen is readily performed from the routine kinetic modeling in HD patients. Kinetic modeling is an important tool in the measurement of dialysis delivery and therefore for the evaluation of dialysis adequacy.

SGA is also recommended as a nutritional assessment tool because it provides an overview of nutritional intake and body composition and it is correlated with mortality rates. The physical examination with SGA includes an evaluation of the patient’s subcutaneous tissue and muscle mass.

Protein and Energy Requirements
It is difficult for HD patients to maintain their intake of protein, since foods containing protein are also high sources of phosphorus and dietary fat. The recommended intake for almost all clinically stable HD patients ingesting 25 to 35 kilocalories per kilogram per day is 1.2 grams protein per kilogram body weight per day, with at least 50% of high biological value protein. The recommended protein intake for chronic peritoneal dialysis (CPD) patients is 1.2 to 1.3 grams per kilogram. Protein losses into the peritoneal dialysate are higher than protein losses into hemodialysate. Reduced intake and malnutrition in CPD patients may also be caused by the anorexia created from the glucose absorption from the dialysate. If the daily protein intake is inadequate, oral nutritional supplements should be prescribed. Nutritional counseling and careful glycemic control with a goal of A1c (Hemoglobin A1c) < 7% for those with diabetes mellitus is recommended.

For advanced CKF patients without dialysis (GFR < 25 milliliters per minute per 1.73 square meters), a lower-protein diet providing 0.6 to 0.75 grams protein per kilogram per day should be considered. There is also some evidence that lowering protein intake to 0.8 to 1.0 grams per kilograms per day in patients with microalbuminuria or overt nephropathy will assist in the slowing of kidney disease. The recommended daily energy intake for advanced CKF patients with or without MD is 35 kilocalories per kilogram body weight per day for those younger than the age of 60 and 30 to 35 kilocalories per kilogram body weight per day for individuals aged 60 or older (if more sedentary).

Some of the important implications of kidney failure include susceptibility to anemia, the use of new drug therapies, including recombinant erythropoietin or EPO, nondextran forms of intravenous iron, L-carnitine, and B vitamins. Another complication of kidney failure is the disruption in calcium and phosphorus metabolism, leading (if uncorrected) to bone disease and soft tissue calcification or calciphylaxis.

Red blood cell production and the correction of anemia is an important role of nutrition therapy. The replacement of EPO with a recombinant form plays a primary role in the treatment of anemia. Iron management is an important supportive treatment to improve the response to EPO therapy. The use of nondextran forms of intravenous iron has been an important advance in this area. The rate of anaphylactic reactions appears to have been reduced greatly with nondextran drugs, iron sucrose, and ferric gluconate. Patient survival outcome is better when the values of hemoglobin/hematocrit are 11 to 12 grams per deciliter, or 33% to 36%. However, there is a growing recognition that the target ranges may be too narrow because of the variation in hemoglobin levels.

As hemoglobin levels rise, blood viscosity also increases, and there may be unanticipated untoward events. Serum ferritin is a frequently used marker of iron status in dialysis patients. Iron administration is withheld when ferritin values are > 800 nanograms per milliliter in dialysis patients, according to the K/DOQI guidelines. Serum ferritin is also an acute phase reactant and can be increased in inflammation. Inflammation is closely linked with PEM in dialysis patients, and therefore ferritin levels may be increased independently of iron stores.

L-carnitine is known to be an essential cofactor in fatty acid and energy metabolism; hence, its supplementation is a treatment tool for various metabolic abnormalities in ESKD, including poor nutritional status, hyperlipidemia, and anemia. Its use in HD patients has also included the treatment of several complications of dialysis, such as hypotension, low cardiac output, general weakness or fatigue, and skeletal muscle cramps.

The daily intakes of water-soluble vitamins should achieve 100% of the Dietary Reference Intake or Recommended Daily Allowance. Clinical practice has been to provide a daily vitamin B complex supplement, including folic acid (taken after dialysis in the MD patient). Studies have shown that folic acid can reduce plasma homocysteine levels and improve morbidity and mortality levels, although this question is still being explored. Serum vitamin A and E levels may be elevated even without supplementation in CKD patients.

Role of Nutrition in Bone Homeostasis
In addition to anemia, complications of CKD include hyperparathyroidism, calcium, phosphorus metabolic abnormalities, and bone disease. It is estimated that more than 60% of HD patients have phosphorus levels of greater than 5.5 milligrams per deciliter, the upper limit of normal for dialysis patients. A high phosphorus level elevates the calcium-phosphorus product (Ca x P04) and stimulates the secretion of parathyroid hormone (PTH), promoting vascular calcification and increasing the risk of cardiovascular disease (CVD). The principle goal of treatment is to prevent hyperphosphatemia while avoiding excessive calcium and phosphate release from bone tissue. The molecular consequence of a positive phosphorus and calcium balance is a change in vascular smooth muscle cells to the osteoblast cell type capable of forming bone matrix in soft tissue locations. This change results in vascular calcification and accelerated atherosclerosis, with narrowing luminal walls, plaque rupture, and ischemic events.

Assays of PTH have evolved to provide 2-site immunometric assays that are highly specific for the intact 84 amino-acid peptide, PTH 1-84. It has been demonstrated that the prior generation of assays thought to detect an intact PTH also detected a PTH peptide that was truncated at the N-terminus. A new field of research has opened up in parathyroid physiology and its implication on the biological effects of PTH and bone disease in the kidney patient.

Dietitians play a vital role in the management of renal osteodystrophy by providing reinforcement for the use of phosphate binders (often now non–calcium-based) with all meals to control phosphorus levels, provide low phosphorus diet information (phosphorus goal: < 1,000 milligrams per day), and clinical educational recommendations for vitamin D analog and recent calcimimetic drug therapy. Vitamin D analogs act on vitamin D receptors on parathyroid cells to reduce PTH secretion but cause enhanced calcium absorption. Calcimimetics increase the sensitivity of the calcium-sensing receptor on parathyroid cells to serum calcium concentrations. Therefore, lower calcium concentrations are needed to stimulate the receptors, causing lowered PTH secretion.

Adherence problems significantly impact the kidney patient’s care. At least 50% of HD patients are believed to be noncompliant with some part of their medical regimen. Interactive education, positive reinforcement, and professional follow-up, for example, with phosphorus control are the keys to encouraging improved compliance. Interdialytic weight gain from overeating sodium-rich food, causing dialysis patients to drink more fluids between dialysis treatments, is often the cause of fluid overload and therefore perceived noncompliance with fluid intake. The well-counseled and controlled patient is going to have better overall mortality and morbidity outcomes.

We have come a long way since the late Dr. Belding Scribner’s first renal replacement treatments at the University of Washington, Seattle, in the 1960s, but we have continued his determined interest in exploring the adequacy of appropriate nutritional status in his patients. Ongoing nutrition counseling and support for patients with kidney disease and their families is vital. As patients over the age of 65 become the fastest-growing segment of the treated ESKD population, dietitians must also become well-versed in the many issues specific to this group.

Expanding the role of the general medicine clinical dietitian into the renal practice arena creates exciting opportunities. Dietitians with skills in the field of chronic disease such as CVD and diabetes mellitus, and also weight management and gerontology, including long-term care expertise, have the versatility to apply these skills to work with the increasing number of kidney patients. Moving into a nontraditional position is recommended to increase the number of practicing dietitians in the kidney outpatient field.

— Alison J. Rigby, PhD, MPH, RD, is a researcher at Stanford University and teaches nutrition/dietetics classes at San Francisco State University. She is a board-certified specialist in renal nutrition.

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