S 42 Indian Journal of Nephrology Introduction Protein-energy malnutrition (PEM) is very common among patients with advanced chronic kidney disease (CKD). In the Indian scenario, where malnutrition is widely prevalent in the general population, this problem becomes even more intense in patients with CKD. The main causes of malnutrition are: (a) Inadequate food intake secondary to: Anorexia caused by the uremic state altered taste sensation intercurrent illness emotional distress or illness impaired ability to procure, prepare, or mechanically ingest foods unpalatable prescribed diets (b) The catabolic response to superimposed illnesses (c) The dialysis procedure itself, which may promote wasting by removing such nutrients as amino acids, peptides, protein, glucose, water-soluble vitamins, and other bioactive compounds, and may promote protein catabolism, due to bioincompatibility (d) Conditions associated with chronic kidney disease that may induce a chronic inflammatory state and may promote hypercatabolism and anorexia (e) Loss of blood due to: Gastrointestinal bleeding frequent blood sampling blood sequestered in the hemodialyzer and tubing (f) Endocrine disorders of uremia (resistance to the actions of insulin and IGF-I, hyperglucagonemia, and hyperparathyroidism) (g) Possibly the accumulation of endogenously formed uremic toxins or the ingestion of exogenous toxins. Several studies have shown that nutritional status is an important factor determining the outcome of patients with CKD. Nutritional therapy therefore deserves as much emphasis, if not more, as medical therapy. Guidelines are now available for optimum management of nutritional status of patients with CKD. These guidelines, called Dialysis Outcome Quality Initiative (DOQI) have been prepared by the American National Kidney Foundation (NKF). Considering differences in the dietary habits of Indian subjects, the guidelines have been modified to suit the conditions prevailing in our country. GUIDELINE I Assessment of nutritional status: Nutritional status should be assessed with a combination of valid, complementary measures rather than any single measure alone. In our situation, the nutritional status could be assessed by: (a) dietary interviews and diaries (b) Urea nitrogen appearance (UNA) for assessment of protein intake. (c) subjective global assessment (SGA) (d) anthropometry (e) biochemical parameters like creatinine, bicarbonate, albumin and cholesterol Dietary interviews and/or diaries are valid and clinically useful for measuring dietary protein and energy intake in maintenance dialysis patients. The dietary recall (usually obtained for the previous 24 hours) is a simple, rapid method of obtaining crude assessment of dietary intake. Diet diaries are written reports of foods eaten during a specified length of time (3 to 7 days) Urea nitrogen appearance (UNA) is measured as the amount of urea nitrogen excreted in the urine plus the amount accumulated in the body water. In the steady state, UNA is equal to 24 hour urinary urea nitrogen. Non urea nitrogen (NUN) excretion (i.e. nitrogen in feces and in urinary creatinine, uric acid, amino acids, peptides ammonia) does not vary substantially with dietary protein and averages 0.031 g/kg/day. For a patient in nitrogen balance, nitrogen intake equals nitrogen loss (UNA + NUN). Multiplying this value by 6.25 (1 g of nitrogen corresponds to 6.25 g of protein) provides protein intake. SGA (appendix 1) is a valid and clinically useful measure of protein-energy nutritional status in maintenance dialysis patients. It is a simple method in which 4 parameters are used to assess the nutritional status: weight loss in 6 months, anorexia, visual assessment of subcutaneous tissue and muscle mass. The anthropometric measurements that are valid for assessing nutritional status include: (i) percent of usual body weight (% UBW) - calculated as [(actual weight / UBW) x 100] (ii) percent of standard body weight (% SBW)
determined from LIC of India table (appendix 2) calculated as [(actual weight / SBW) x 100] (iii) body mass index (BMI) calculated by dividing weight (in kg) by height squared (in meters) (iv)skin fold thickness measured at 3 sites: biceps, triceps, subscapula. These measurements are operator dependent. To be useful, they must be performed in a precise, standardized, and reproducible manner. They are also more time consuming and less precise than % UBW, % SBW and BMI. Therefore, they may not be used in routine practice. Biochemical parameters that are simple to analyze include: creatinine, bicarbonate, albumin and cholesterol. The predialysis serum creatinine reflects intake of foods rich in creatine and creatinine and endogenous creatinine production. Individuals with low predialysis serum creatinine (less than approximately 10mg/dL) should be evaluated for protein-energy malnutrition and wasting of skeletal muscle. The bicarbonate value provides idea about acid-base status. A low bicarbonate value, suggesting metabolic acidosis, may contribute to malnutrition. Acidosis has been associated with protein catabolism, negative nitrogen balance, reduced albumin synthesis, and loss of lean muscle mass. The predialysis serum albumin is a measure of visceral protein pool size. The serum albumin at the time of initiations of chronic dialysis therapy or during the course of maintenance dialysis is an indicator of future mortality risk. A predialysis serum albumin equal to or greater than the lower limit of the normal range (approximately 3.5 g/ dl for the bromcersol green method) is the outcome goal. The presence of acute or chronic inflammation limits the specificity of serum albumin as a nutritional marker. Serum cholesterol is a valid and clinically useful marker of protein energy nutritional status in maintenance dialysis patients. Low or declining serum cholesterol concentrations are predictive of increased mortality risk. Individuals with low, low-normal (less than approximately 150 to 180 mg/dl), or declining serum cholesterol levels should be investigated for possible nutritional deficits. How frequently should nutrition status be assessed? Nutrition status should be assessed 1 to 3 monthly by a skilled dietician dedicated to the kidney unit. It should be assessed more frequently if there is inadequate nutrient intake, frank protein-energy malnutrition, or the presence of an illness that may worsen nutritional status. GUIDELINE II Assessment of inflammatory status An inflammatory state indicated by increased CRP levels and IL-6 is associated with malnutrition, atherosclerosis S 43 and increased mortality in the general population. As well as in CKD and dialysis patients. Levels of IL-6, IL-8 and TNFa are elevated in End Stage Kidney Disease, HD and especially in CAPD patients. About 50% of haemodialysis patients show CRP levels above 5 mg/l. In patients on peritoneal dialysis, more than 30% have CRP concentrations above 8 mg/l, or persistent high CRP levels > 5 mg/l for more than 6 months. Even slightly increased C-reactive protein levels (2.6 to 5.2 mg/l) predict an increased risk of death in haemodialysis patients. The inflammatory state may be caused by: 1. Decreased renal function. This results in the accumulation of proinflammatory compounds such as nonenzymatic glycated or oxidated proteins and lipids which are otherwise eliminated by the kidney and in the reduction of plasma antioxidative activity. 2. Dialysis procedure related factors such as exposure of blood to bioincompatible dialysis membranes, use of non-treated dialysate fluid, unrecognised or clinically apparent infections of the vascular access, skin exit site or tunnel infection of the PD-catheter or peritonitis in PD patients. 3. Non dialysis-procedure related inflammatory conditions such as infections based on the immunocompromised state of uraemic patients or Diabetes mellitus complicated by infected leg and foot ulcers Guideline III Diet for predialysis CKD patients: 1. Energy and protein intake: Energy expenditure of nondialyzed individuals with CKD is similar to that of healthy individuals. Metabolic balance studies of such individuals indicate that a diet providing about 35kcal/kg/d engenders neutral nitrogen balance and maintains serum albumin and anthropometric indices. Note that energy intake is prescribed based on patient s ideal body weight (IBW). Because individuals more than 60 years of age tend to be more sedentary, a lower total energy intake of 30 to 35kcal/kg/d is acceptable. When properly implemented and monitored, low-protein (0.6 g/ kg/day), high-energy diets maintain nutritional status while limiting the generation of potentially toxic nitrogenous metabolities, the development of uremic symptoms and the occurrence of other metabolic complications. Low protein diets may retard the progression of renal failure or delay the need for dialysis therapy. At least 50% of the dietary protein should be of high biologic value. In practice however these diets are difficult to follow. Protein restricted diets involve a major change in lifestyle. In a
S 44 Indian Journal of Nephrology study carried out at our center, out of 25 patients with CKD advised dietary protein restriction (DPR), (0.6 g/kg/ d with 50% being of high biologic value), 22 followed up regularly. Only 4 out of 22 patients felt that they could follow the diet plan on a long-term basis. Nine patients felt that they could manage with the advised diet with great difficulty; 4 patients felt that they could manage with the diet plan only for a short period while 5 felt that it was impossible to follow the prescribed diet. Another important limitation of DPR in our country is that Indians, particularly vegetarians, consume a diet low in proteins. This spontaneously reduces further in patients with CKD. Beheray and Shah estimated dietary protein intake in 20 stable patients with CKD who were on an unrestricted vegetarian diet. The mean protein intake was 0.64+0.15 g/kg/day. Based on the observations in our subjects, it is recommended that in vegetarian subjects, prescribe DPR if protein intake (PI) exceeds 0.8 g/kg/day and in nonvegetarian subjects if PI exceeds 0.6 g/kg/day. If the protein intake is lower than the minimum recommended value, patient should be counseled to improve the protein intake. There are many commercial products available to improve the protein intake (appendix 3). Diabetic patients: Energy intake should be the same (30-35 kcal/kg of IBW/day) as for non-diabetic subjects. About 60% of calories should be from carbohydrates, 30% from fats (< 10% from saturated fats, < 10% from polyunsaturated fats and about 15% from monosaturated fats. Patients with nephrotic range proteinuria: It is a common misconception to provide high protein diet to patients with nephrotic range proteinuria. In fact, doing so increases proteinuria and worsens hypercholesterolemia. A diet providing 0.8 g/kg/day protein (plus 1 g protein/g of proteinuria) and 30-35 kcal/kg of IBW/day maintains nitrogen balance. Role of essential amino acid (EAA) and ketoacid (KA) supplemented diet regimens: The basis of prescribing DPR is to minimize adaptive changes that play some role in progression of CKD, and to diminish the production of nitrogenous wastes. Attempts have been made to prescribe very low protein diet (VLPD) containing about 0.3 g /kg/d of unrestricted quality protein plus a supplement of EAAs or KAs. In general, such regimens promptly correct uremic symptoms. Ketoacids (the nitrogen-free analogues of EAA) supplemented diet regimens given to patients with CKD stage V, decrease urea nitrogen appearance sharply, maintain body weight, nitrogen balance, serum albumin, and transferrin in the normal range for periods from 4 to 19 months. A direct comparison of a VLPD diet providing 0.28 protein kg/day plus either an isomolar mixture of EAA or KA revealed that both diets yielded a neutral nitrogen balance, but because the KA-based regimen contained less nitrogen, there was a greater decrease in UNA. The KA regimen has been associated with a lower serum phosphorus level and an improvement in secondary hyperparathyroidism, alkaline phosphatase, and parathyroid hormone, along with higher levels of serum calcium and 1, 25-dihydroxycholecalciferol levels. These improvements are likely related to the lower intake of phosphates (with calcium salts of KAs, there also could be less gastrointestinal phosphate absorption). All low-protein dietary regiments also reduce the intake of fixed acid, and because KAs can be metabolized to bicarbonate, acidosis is infrequent. This factor undoubtedly contributed to the beneficial effect of proteinrestricted diets. Finally, a KA-based regimen can improve glucose intolerance in uremia by increasing tissue sensitivity to insulin: fasting hyperglycemia and insulin resistance improve in children treated with this regimen. It must be noted that the EAAs and KA supplements do not yield nutritional benefits in CKD patients eating more than the minimal amount of protein because they represent an excess of amino acids and hence are oxidized. In our experience, KA (1 tab/5 kg weight) supplemented diets do not offer significant advantage as regards rate of progression of CKD. However, because the production of nitrogenous wastes is reduced, they can delay the need for dalysis. 2. Fluid and electrolytes Fluid: In addition to dietary intake of fluids from liquids and solid food, water is produced from oxidative metabolism (about 200-300 ml/day). Water is lost from body by urine, stool and evaporation (skin and respiratory tract). In non-edematous patients with CKD (usually due to tubulointerstitial disease), fluid retention is usually not a problem and no recommendation may be necessary for fluid intake. In patients with tendency to become edematous (usually those with proteinuric CKD), fluid and salt intake should be restricted to the maximum extent tolerated by the patient, ensuring that it does not compromise their calorie and protein intake. Diuretics will also have to be used to maintain patient edema free. Potassium intake to be advised according to serum potassium levels. 3. Maintaining acid-base balance: Serum bicarbonate should be measured in advanced CKD once monthly. Serum bicarnonate levels should be maintained at or above 22 mmol/ L. This can be achieved by oral supplement with bicarbonate (sodamint tablets. Each tablet provides approximately 4 Meq of bicarbonate). Correction of acidosis has been associated with
increased serum albumin and decreased protein degradation rates. GUIDELINE IV Indications for renal replacement therapy: In patients with advanced CKD (eg. GFR < 10 ml/min) if protein-energy malnutrition develops or persists despite vigorous attempts to optimize protein and energy intake and there is no apparent cause for malnutrition other than low nutrient intake, initiation of maintenance dialysis or a renal transplant is recommended. GUIDELINE V Diet for MHD & CAPD patients: 1. Energy and protein intake: The energy expenditure of patients undergoing maintenance HD or CAPD is similar to that of normal healthy individuals. Metabolic balance studies of people undergoing maintenance HD indicate that a diet providing about 35kcal/kg/d engenders neutral nitrogen balance and maintains serum albumin and anthropometric indices. Because individuals more than 60 years of age tend to be more sedentary, a lower total energy intake of 30 to 35kcal/kg/d is acceptable. The recommended DPI for clinically stable MHD patients is 1.2g/kg body weight / d. At least 50% of the dietary protein should be of high biological value. The recommended DPI for clinically stable CAPD patients in 1.2 to 1.3 g/kg body weight / d. Dietary protein intake should be no less than 1.2g/kg/d. At least 50% of the dietary protein should be of high biological value 2. Fluid and electrolytes: In patients on maintenance hemodialysis, fluid and salt intake should be such that interdialytic weight gain does not exceed 1 to 1.5 kg. For patients with good urine output, no restriction may be necessary while anuric patients may need stringent restriction. Potassium intake to be advised according to predialysis potassium levels. For patients with a tendency to high predialysis potassium level, we use potassium free dialysate. This practice brings down postdialysis potassium level more and thereby minimizes potassium restriction. Again, it is important to ensure that dietary restriction does not compromise energy and protein intake. In patients on CAPD, fluid and salt restriction will have to be adjusted according to negative balance achieved. These patients usually need less restriction on fluid, salt and potassium compared to hemodialysis patients. 3. Maintaining acid-base balance: S 45 Serum bicarbonate should be measured once monthly. Serum bicarnonate levels should be maintained at or above 22 mmol/ L. This can be achieved by oral supplement with bicarbonate (sodamint tablets.each tablet provides approximately 4 Meq of bicarbonate). In hemodialysis patients a higher dialysate bicarbonate concentration (> 38 mmol/l) has been shown to safely increase predialysis bicarbonate concentration. Correction of acidosis has been associated with increased serum albumin and decreased protein degradation rates. GUIDELINE VI Indications for nutritional support: Individuals undergoing maintenance dialysis who are unable to meet their protein and energy requirement with food intake for an extended period of time should receive nutrition support. Before considering nutrition support, the patient should receive a complete nutritional assessment. Any potentially reversible or treatable condition or medication that might interfere with appetite or cause malnutrition should be eliminated or treated. For nutrition support, the oral diet may be fortified with energy and protein supplements. If oral nutrition (including nutrition supplement) is inadequate, tube feeding should be offered. If tube feeding is not possible, intradialytic parenteral nutrition (IDPN) for hemodialysis patients and intraperitoneal amino acids (IPAA) for peritoneal dialysis patients whould be considered. If the combination of oral intake and IDPN or IPAA does not meet protein and energy requirements, daily total or partial parenteral nutrition should be considered. GUIDELINE VII Indications for use of L-Carnitine in maintenance dialysis patients: There are insufficient data to support the routine use of L-carnitine for maintenance dialysis patients. Although the administration of L-carnitine may improve subjective symptoms such as malaise, muscle weakness, intradialytic cramps and hypotension, and quality of life in selected maintenance dialysis patients, the totality of evidence is insufficient to recommend its routine provision for any proposed clinical disorder without prior evaluation and attempts at standard therapy. The most promising of proposed applications is treatment of erythropoietinresistant anemia.
S 46 Indian Journal of Nephrology APPENDICES Appendix 1: SGA: SUBJECTIVE GLOBAL ASSESSMENT The SGA was developed for use in assessing the nutrition of general surgery patients. It is recommended also for patients on dialysis, because it is a valid clinical assessment of nutritional status and is strongly associated with patient survival.