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Progression of Polycystic Kidney Disease: A Personal Experience
Case Study
Progression of Polycystic Kidney Disease: A Personal Experience Carol Victor, MS, RO*
This autobiographical case study presents a unique self-imposed dietary and life-style regimen in autosomal dominant polycystic kidney disease, the most common hereditary disease in the United States. The enhanced quality of life and decreased dialysis treatment time described has not been scientifically studied, nor can it be recommended for routine care. However, it confirms the essential role of monitoring the adequacy of dialysis and maintaining optimal nutritional status as a means to attain such goals. The potential implications of this cost-effective treatment scenario and time-effective life-style are discussed from the viewpoint of a registered dietitian who is also a hemodialysis patient. The case study is followed by a commentary perspective from the attending nephrologist. © 1994 by the National Kidney Foundation, Inc.
APPROXIMATELY 500,000 people are affected by autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary disease in the United States. 1 It is a true systemic disease despite initial classification as a solely renal disorder. Gastrointestinal and cardiovascular abnormalities, particularly mitral valve prolapse, have been reported. Renal complications, including nephrolithiasis, nephromegaly, renal cysts and adeomas, urinary tract infections, hypertension, and renal failure,2 are common in adults. The median age of patients with ADPKD progressing to end-stage renal disease is 54 years, representing nearly 4.0% of the dialysis population. 3 Patients often remain asymptomatic for many years before diagnosis. The scenario of autosomal dominant gene transmission results in only individuals with ADPKD passing the gene on to offspring, which have a 50% chance of having ADPKD them-
1"'\
*Consultant Dietitian, Private Practice, Westfield, NJ. Address reprint requests to Carol Victor, MS, RD, 35 Plymouth Rd, Westfield NJ, 07090. © 1994 by the National Kidney Foundation, Inc. 1051-2276/94/0402-0004$03.00/0
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selves. Less than 10% of patients without a family history may have developed the disease through spontaneous mutation and then pass the gene on to their offspring in the same manner. Research in 1985 isolated a gene linkage that accounted for the majority of ADPKD incidence, and subsequent research discovered that at least one other genetic defect is involved. 2 I first became aware of my own renal failure when my brother began hemodialysis and asked me to donate a kidney for him. Testing by a nephrologist revealed that I, too, had ADPKD at age 46. My brother and I had both inherited the disease from our father. Although I had no outward symptoms except hypertension, my kidneys were already enlarged and extended below my navel because the cysts. Because I considered myself too old to become a nephrologist, I did what I considered to be the next best thing. I went back to school to take 30 credits in science and subsequently completed a master's degree in biochemical animal nutrition from Rutgers University. I spent countless hours in the medical library from 1979 to 1982, looking up all the literature about renal
Journal of Renal Nutrition, Vol 4, No 2 (April), 1994: pp 88-93
PROGRESSION OF ADPKD: A PERSONAL EXPERIENCE
failure and ADPKD. I passed the American Dietetic Association registration examination in 1982 and joined the Council on Renal Nutrition the same year. From what I discovered, I decided to put myself on a low-protein diet of 50 to 60 g/d and approximately 2 g sodium. Because I had read nothing about phosphorus, I included the four food groups at each meal. I exercised every day approximately 20 minutes on my stationary bicycle and rested when I felt like it. My chemistries remained normal until the spring of 1984, when my creatinine first increased above 132 j.Lmol/L (1.5 mg/dL); my creatinine clearance rate was 0.58 mL/s (34.8 mL/min) for a urine volume of 1.2 L. At that point, I contacted Dr William E. Mitch who was at Brigham and Women's Hospital in Boston. I had read about his work with low-protein diets and kidney disease. He was kind enough to see me and share his nutritional recommendations. I spoke with Dr Mitch's renal dietitians on the phone every Saturday morning for 30 minutes for approximately 6 weeks until I had worked out most of the "kinks" and was on my way. I faithfully followed a protein intake of 0.5 g/kg body weight (BW) and used one dairy product per day and substituted Oscal (Marion Laboratories, Kansas City, MO) for the other portion. I included the remaining three food groups in each meal to provide balanced metabolic meals with 20 to 23 kcal/kg BW. I also included-low protein pasta in my meal plan per Dr Mitch's recommendation. I maintained myself on this diet for 3Y2 years until the spring of 1988, when my creatinine had increased to 751 j.Lmol/L (8.5 mg/dL) and my creatinine clearance rate had decreased to 0.12 m L/ s (7.1 mL/min) for a urine volume of 1.5 L. At that point, I began a very low-protein diet of 20 g protein with two to three essential amino acid tablets and phosphate binders. I continued riding 10 miles/don my exercise bicycle. This diet seemed very restrictive, and I was not really satisfied while I was on it because of the extreme limitation of food choices. My uremia also increased, and I was becoming very tired. Six months later, I
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began hemodialysis 2 times/wk for 3 Y2 hour treatments. When I began hemodialysis, I realized I could again eat more than 20 g/d protein and was delighted. My nephrologist, Dr Carl Goldstein, and the unit dietitian urged me to take 50 to 70 g protein/d, but I insisted that my digestion was more comfortable when I was on Dr Mitch's diet of 40 g/protein/d (0.5 g/kg BW). They agreed I could continue until such time as my monthly chemistries showed evidence of protein malnutrition, at which time I would go up to the suggested higher level of protein. That was more than five years ago. My chemistries have remained consistently good at that protein intake level, with albumin ranges of 37 to 40 gil (3.7 to 4.0 g/dL) while consuming calorie ranges of 22 to 24 kcal/kg BW depending on exercise level to maintain my present weight of 67 kg (149 pounds) at 5 ft, 5Y2 in tall. The major advantage to eating this level of protein is that I only need to dialyze 2 d/wk. From the patient's point of view, this is all the incentive I need to stay on the diet. My current creatinine clearance of 0.004 mL/s (0.26 mL/min) shows neglible residual renal function in less than 200 mL urine output/d. On May 21, 1993, Kenneth J. Storch, MD, PhD, estimated 30.3% body fat based on mid-arm muscle circumference of 23.9 mm on my nonfistula arm. He was amazed at my nutritional status within the context of my dialysis history. A typical meal pattern is found in Table 1. I include 3 oz cooked weight of 20% fat red meat at dinner to maintain my hematocrit at 0.33 I (33%) and hemoglobin at a minimum of 101 gil (10.1 g/dL). I seldom vary the content of these meals except when dining out when, for example, I have a salad, 40z roast beef, and a small baked potato with butter and sour cream. I drink bottled water at home and maintain a fluid restriction of approximately 1 L/d. Exercise is a vital part of my regimen (Fig 1). For 12 years, I faithfully rode my exercise bicycle. Now I walk 2 miles/d and find it an even better form of exercise, because the weight-bearing nature of walking makes me feel better and stronger. I include rest in my
TABLE 1. Typical Daily Food Intake Nondialysis day 10:00 AM 3 oz Ocean Spray sweetened cranberry juice cocktail* 11 :30 AM Y2 small pink grapefruit Y2 cup regular cream of wheat (iron fortified) made with Y2 cup water 1 tbsp raisins 2 tbsp brown sugar 4 oz vanilla Dovet ice cream bar with chocolate coating 5 :00 PM 4 oz canned white corn Pasta Alfredo % c cooked low-protein pasta 2 tbsp grated Parmesan cheese 1 tbsp cream cheese Stuffed Pepper 4 oz 20% fat ground beef (3 oz cooked) 1 small green pepper 2 tbsp tomato chili sauce 1 tbsp Minute rice:j: 8:00 PM Baked Apple Crisp 1 medium Granny Smith apple , peeled & sliced y., tsp cinnamon 1 Y2 tsp flour 3 tsp sugar 1 tsp sweet butter Nutrient analysis: 1,585 kcal , 38 .4 g protein (10%) , 49 9 fat (28%) , 247 g carbohydrate (62%) , 525 mg phosphorus, 1,667 mg potassium, less than 1,250 mg sodium Additional for dialysis day 8:10 AM 6 oz English caffeinated breakfast tea, brewed 2 tsp sugar 1 medium Dunkin ' Donuts§ blueberry muffin Nutrient analysis: 237 kcal, 4.5 9 protein , 5.6 9 fat, 42 9 carbohydrate, 80 mg phosphorus, 70 mg potassium, less than 350 mg sodium Medications: Twice per week at dialysis treatment: 1,000 U Epogenll .125 /-Lcg Calcijex'll Daily oral medications 3 tablets Surbex'll 1 mg folic acid 100 mg vitamin B6 320 mg ferrous glutamate 25 mg zinc 4 9 Oscal** *Ocean Spray, Lakeville-Middleboro, MA. tMars, Inc, Burr Ridge, IL. :j:Kraft General Foods, White Plains, NY. §Dunkin Donuts, New Brunswick, NJ . IIAmgen. Thousand Oaks CA. 'IlAbbott Laboratories, North Chicago, IL. * *Marion Laboratories , Kansas City, MO .
daily pattern, sitting sometimes for up to an hour after meals to help settle the food in my stomach. I get at least ten hours of resting activities such as watching televi-
FIGURE 1. Carol walking with one of her Great Danes during her daily exercise session. sion, reading, writing, talking on the telephone, or sleep each night. My blood urea nitrogen (BUN) levels over time are shown in Fig 2. I usually run a predialysis BUN of 28.5 mmol/L (80 mg/ dL) or higher. I have my hemodialysis in the morning, and I find it helpful to have 3 oz of cranberry juice cocktail and a B complex vitamin (Surbex, Abbott Laboratories, North Chicago, IL) before I drive to the hospital. Immediately predialysis, I have a commercially made blueberry muffin and a cup of Start Hemodialysis
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FIGURE 2. Annual typical serum BUN over time with a Kt/V range of 1 .10 to 1.42 since the start of hemodialysis.
PROGRESSION OF ADPKD: A PERSONAL EXPERIENCE
strongly brewed English tea with 2 tsp sugar. This additional "reward" meal works for me and may offset the protein losses of the hemodialysis treatment itself. From the patient's point of view, I am grateful that my life is as good as I can make it. My husband and I have taken four "dialysis cruises" and they are wonderful. We often travel to visit our grandchildren in Florida from Friday afternoon to Monday evening; nice long weekend outings are possible, because only 2 d/wk are reserved for dialysis treatments. I also have traveled to many professional programs, including the National Kidney Foundation Spring Clinical Meetings, and do not have to make arrangements for any dialysis at the meeting location. I realize that many nephrologists would be concerned that I am underdialyzed. In fact, my Kt/V consistently ranges from 1.42 to 1.10 (Fig 1) using a 1211 dialyzer with a predialysis blood pressure of 150/80 and an initial postdialysis blood pressure of 110/70 without antihypertensive medication. If they forced me to eat more protein, I would probably have to dialyze three times per week. My health has been excellent, and I have been hospitalized less than 5 days in 5 years! It is true that my predialysis creatinine levels hover around 1,237 to 1,326 I-lmol/L (14 to 15 mg/dL), which is much higher than the "usual" 8 mg/dL for most female, sedentary hemodialysis patients. But I am an exerciser. In the summer, I swim and walk 2 miles/d. I also eat approximately 1 Ib red meat/wk to offset anemia and provide a excellent source of heme iron. I am not suggesting that every hemodialysis patient could do what I am doing. Probably only 1% of the entire renal population would even want to try. Anyone who might attempt what I've been doing should spend at least 2 years predialysis working out the "kinks" in his or her own diet under the guidance of a dietitian analogous to the Modification of Diet in Renal Disease (MDRD) clinical trial. For me, this philosophy has resulted in a quality, timeeffective life-style while providing a costeffective, efficient treatment scenario for the medical team. By eliminating the need for
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the third dialysis treatment, I am saving Medicare $15,000 per year and providing myself tremendous benefits. I have spent many hours becoming an informed dialysis consumer and have formed a mnemonic for anyone who wants to try what I am doing: R = rest, E = exercise, A = attitude (positive), 0 = diet. READ means participating, learning everything you can about your condition and your hemodialysis treatment, and modifying your life-style to promote the best quality of life that you can have. My brother? He has always eaten generous amounts dietary protein and continues to eat more than 70 grams of protein/d. He is 6 ft, 21;2 in tall, dialyzes at home 3 times/wk for 5 h/session, and is starting his 15th year on dialysis. During that time, he served as the President of the American Association of Kidney Patients for 4 years.
ACKNOWLEDGEMENT I would like to acknowledge William E. Mitch, MD, Carl Goldstein, MD, FACP, Luanne Prestifilippo, MS, RD, Kenneth J. Storch, MS, PhD, Judith Beto, PhD, RD, and the entire hemodialysis nursing staff of Overlook Hospital, Summit, NJ, for their help and encouragement.
REFERENCES 1. Grabow PA: Autosomal dominant polycystic kidney disease. Am J Kidney Dis 22:511-512, 1993 2. Grabow PA: Autosomal dominant polycystic kidney disease-More than a renal disease. Am J Kidney Dis 16:403-413, 1990 3. US Renal Data System: USRDS 1993 Annual Data Report. Bethesda, MD, The National Institutes of Diabetes and Digestive and Kidney Diseases, 1993.
COMMENTARY In this issue of the Journal of Renal Nutrition, Carol Victor describes her personal experience with progressive renal failure resulting from autosomal dominant polycystic kidney disease (ADPKD). Through her scholarship as a certified renal dietitian, Mrs Victor outlines her very low-protein and low-calorie diet, on which she has enjoyed tremendous physical and psychological well being.
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Protein restriction may have different effects in the patient approaching end-stage renal disease (ESRD) compared with the patient undergoing maintenance dialysis treatments. Mrs Victor's dietary program is properly considered first as a strategy to retard the progression of renal failure in the predialysis phase of her disease, then as a means of nutritional support for patients undergoing regular hemodialysis treatments . Why should a low-protein diet retard the progression of azotemia in ADPKD? The specific etiology of progressive renal failure in ADPKD is poorly understood. There is no histological evidence that cyst enlargement compresses and thereby damages adjacent renal parenchyma; however, larger kidneys are associated with a younger age of onset of dialysis-dependent ESRD in ADPKD.1 This advances the notion that cyst enlargement may influence renal deterioration. Cultures of human polycystic kidney epithelial cells have an amplified proliferative response to epidermal growth factor,2 sug gesting that cytokines may play a role in promoting cyst growth. Low-protein diets have been shown to decrease cyst growth in experimental animals. 3 One can speculate that low-protein diets may have an indirect effect on slowing cyst growth by decreasing cytokine production, thus leading to preservation of kidney function. A substantial amount of literature establishes the salutary effects of low-protein diets on progressive glomerulosclerosis resulting from glomerular hypertension and glomerular hyperfiltration in a variety of experimental and human renal diseases. Curiously, ADPKD should not be one of them . Zeier et al 4 show that in advanced ADPKD, the predominant lesions are vascular sclerosis and interstitial fibrosis with minimal glomerular injury. Therefore , the effect of low-protein diets , ie, to attenuate glomerular hemodynamic consequences of reduced renal mass does not necessarily apply to ADPKD patients. The renin-angiotensin system has been shown to be stimulated in ADPKD and has been proposed as a cause of hypertension
CARL S. GOLDSTEIN
in this diseaseS Could a low-protein diet modulate this humoral system to preserve renal function? Low-protein diets have been shown to reduce renin secretion and plasma angiotensin " levels and produce intense renal vasoconstriction that results in decreased renal blood flow in rats . Highprotein diets increase plasma renin activity and plasma angiotensin /I levels and produce renal vasodilatation with increased renal blood flow. Low-protein diets decrease blood pressure, whereas highprotein diets increase blood pressure. Conflicting results in animal experiments measuring the effect of varied dietary protein content on renin mRNA production , renal renin content , and other transcriptional and translational processes do not clearly support this hypothesis. 6 Are risks associated with very lowprotein diets? Could extreme protein restriction before the institution of dialysis therapy lead to a state of advanced protein calorie malnutrition in ESRD patients? Surprisingly, data exist that suggest that very lowprotein diets do not lead to hypoalbuminemia at the start of dialysis. ? Walser? suggests that perhaps some constituent of protein-rich foods contributes to anorexia and induces adverse metabolic effects that may lead to protein malnutrition in patients treated with more liberal dietary protein content, providing an advocacy position on behalf of Mrs Victor's regimen. There is a growing consensus that a premium exists on nutritional adequacy once regular dialysis treatments have begun. The mortal value of hypoalbuminemia has been demonstrated by Lowrie and Lew,s whose data show an inverse relationship between serum albumin concentration and risk of death among hemodialysis patients . These observations have amplified interest in more generous protein and highercalorie diets with larger doses of delivered dialysis . The pathophysiology of malnutrition among patients undergoing maintenance dialysis treatments is complex, but protein requirements are probably increased because of the effects of chronic metabolic acidosis , loss of protein-metabolizing renal
COMMENTARY
tissue, catabolic effects of infections, reduced protein ,synthesis, and dialysisrelated loss of amino acids, Low energy intake reduces the utilization of dietary protein, and bioincompatible dialysis membranes may stimulate the production of inflammatory mediators, which exacerbate the general catabolic environment of the dialysis patient. 9 How can we determine that a patient with renal disease is adequately nourished? The means by which we can measure nutritional adequacy are often incomplete or inaccurate 10 ,11 and frequently are limited by parsimonious reimbursement policies for ESRD,12 Although severe protein malnutrition can be easily recognized, our ability to certify that the patient is receiving enough calories and protein may not be as precise, In spite of these difficulties, current recommendations favor higher-protein diets that contain 0,75 to 1,25 g/kg/d with at least 35 kcal/kg/d 9 ,12 Given these observations, what does Mrs Victor's experience represent? If Mrs Victor is malnourished by currently accepted standards, why is she a stunning clinical success? Her subjective sense of well-being is outstanding and she has suffered no significant intercurrent complication of chronic dialysis therapy, Progression to ESRD and clinical outcome on dialysis are complex variables, This report showcases a well patient who is thriving on her selected modality of renal replacement therapy, Mrs Victor's accomplishments, including the strict discipline required to follow the diet she describes, deserve notice and praise, However, the etiological link between her diet and well being is not unambiguously defined, and her career on dialysis is far from complete, Embraced within Mrs Victor's personal triumph may be issues that merit formal scientific inquiry into the potential benefits of very low-protein diets in ADPKD, If careful experiments can demonstrate that dietary protein restriction slows the progression of ADPKD without nutritional penalties, then large numbers of ADPKD patients will be justified in following Mrs Victor's example, Until these studies are performed and validated, it remains speculative as to
93 which patients will derive a genuine benefit from this approach, Once uremia therapy has begun, the potential hazards of proteincalorie malnutrition must be seriously considered before restricting dietary protein, Careful and regular assessment of nutritional adequacy must accompany lowprotein diets for hemodialysis patients to identify deficiencies early and to promote prompt correction. Carl S. Goldstein, MD Assistant Clinical Professor of Medicine College of Physicians and Surgeons, Columbia University, New York, NY Director, Dialysis Services Division Chief, Nephrology Section Overlook Hospital, Summit, NJ 1, Gabow PA, Johnson AM, Kaehny WD, et al: Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int 41: 1311-1319, 1992 2, Gabow PA: Autosomal dominant polycystic kidney disease. New Engl J Med 329:332-342, 1993 3, Aukema HM, Ogborn MR, Tomobe K, et al: Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease, Kidney Int 42:837-842, 1992 4, Zeier M, Fehrenbach P, Geberth S, et al: Renal histology in polycystic kidney disease with incipient and advanced renal failure, Kidney Int 42:1259-1265, 1992 5. Chapman AB, Johnson A, Gabow PA, et al: The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. New Engl J Med 323: 1091-1 096, 1990 6. Benabe JE, Martinez-Maldonado M: Dietary modification of the renin angiotensin system. Semin NephroI13:567-572,1993 7, Walser M: Does prolonged protein restriction preceding dialysis lead to protein malnutrition at the onset of dialysis? Kidney Int 44: 1139-1144, 1993 8. Lowrie EG, Lew NL: Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458482, 1990 9. Bergstrom J: Nutrition and adequacy of dialysis in hemodialysis patients. Kidney Int 43:S261-S267, 1993 (suppl 41) 10. Rayner He, Stroud DB, Salamon KM, et al: Anthropometry underestimates body protein depletion in hemodialysis patients. Nephron 59:33-40, 1991 11, Hakim RM, Levin N: Malnutrition in hemodialysis patients, Am J Kidney Dis 21 : 125-137, 1993 12. Lazarus JM: Nutrition in hemodialysis patients, Am J Kidney Dis 21 :99-105, 1993
Progression of Polycystic Kidney Disease: A Personal Experience Carol Victor, MS, RO*
This autobiographical case study presents a unique self-imposed dietary and life-style regimen in autosomal dominant polycystic kidney disease, the most common hereditary disease in the United States. The enhanced quality of life and decreased dialysis treatment time described has not been scientifically studied, nor can it be recommended for routine care. However, it confirms the essential role of monitoring the adequacy of dialysis and maintaining optimal nutritional status as a means to attain such goals. The potential implications of this cost-effective treatment scenario and time-effective life-style are discussed from the viewpoint of a registered dietitian who is also a hemodialysis patient. The case study is followed by a commentary perspective from the attending nephrologist. © 1994 by the National Kidney Foundation, Inc.
APPROXIMATELY 500,000 people are affected by autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary disease in the United States. 1 It is a true systemic disease despite initial classification as a solely renal disorder. Gastrointestinal and cardiovascular abnormalities, particularly mitral valve prolapse, have been reported. Renal complications, including nephrolithiasis, nephromegaly, renal cysts and adeomas, urinary tract infections, hypertension, and renal failure,2 are common in adults. The median age of patients with ADPKD progressing to end-stage renal disease is 54 years, representing nearly 4.0% of the dialysis population. 3 Patients often remain asymptomatic for many years before diagnosis. The scenario of autosomal dominant gene transmission results in only individuals with ADPKD passing the gene on to offspring, which have a 50% chance of having ADPKD them-
1"'\
*Consultant Dietitian, Private Practice, Westfield, NJ. Address reprint requests to Carol Victor, MS, RD, 35 Plymouth Rd, Westfield NJ, 07090. © 1994 by the National Kidney Foundation, Inc. 1051-2276/94/0402-0004$03.00/0
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selves. Less than 10% of patients without a family history may have developed the disease through spontaneous mutation and then pass the gene on to their offspring in the same manner. Research in 1985 isolated a gene linkage that accounted for the majority of ADPKD incidence, and subsequent research discovered that at least one other genetic defect is involved. 2 I first became aware of my own renal failure when my brother began hemodialysis and asked me to donate a kidney for him. Testing by a nephrologist revealed that I, too, had ADPKD at age 46. My brother and I had both inherited the disease from our father. Although I had no outward symptoms except hypertension, my kidneys were already enlarged and extended below my navel because the cysts. Because I considered myself too old to become a nephrologist, I did what I considered to be the next best thing. I went back to school to take 30 credits in science and subsequently completed a master's degree in biochemical animal nutrition from Rutgers University. I spent countless hours in the medical library from 1979 to 1982, looking up all the literature about renal
Journal of Renal Nutrition, Vol 4, No 2 (April), 1994: pp 88-93
PROGRESSION OF ADPKD: A PERSONAL EXPERIENCE
failure and ADPKD. I passed the American Dietetic Association registration examination in 1982 and joined the Council on Renal Nutrition the same year. From what I discovered, I decided to put myself on a low-protein diet of 50 to 60 g/d and approximately 2 g sodium. Because I had read nothing about phosphorus, I included the four food groups at each meal. I exercised every day approximately 20 minutes on my stationary bicycle and rested when I felt like it. My chemistries remained normal until the spring of 1984, when my creatinine first increased above 132 j.Lmol/L (1.5 mg/dL); my creatinine clearance rate was 0.58 mL/s (34.8 mL/min) for a urine volume of 1.2 L. At that point, I contacted Dr William E. Mitch who was at Brigham and Women's Hospital in Boston. I had read about his work with low-protein diets and kidney disease. He was kind enough to see me and share his nutritional recommendations. I spoke with Dr Mitch's renal dietitians on the phone every Saturday morning for 30 minutes for approximately 6 weeks until I had worked out most of the "kinks" and was on my way. I faithfully followed a protein intake of 0.5 g/kg body weight (BW) and used one dairy product per day and substituted Oscal (Marion Laboratories, Kansas City, MO) for the other portion. I included the remaining three food groups in each meal to provide balanced metabolic meals with 20 to 23 kcal/kg BW. I also included-low protein pasta in my meal plan per Dr Mitch's recommendation. I maintained myself on this diet for 3Y2 years until the spring of 1988, when my creatinine had increased to 751 j.Lmol/L (8.5 mg/dL) and my creatinine clearance rate had decreased to 0.12 m L/ s (7.1 mL/min) for a urine volume of 1.5 L. At that point, I began a very low-protein diet of 20 g protein with two to three essential amino acid tablets and phosphate binders. I continued riding 10 miles/don my exercise bicycle. This diet seemed very restrictive, and I was not really satisfied while I was on it because of the extreme limitation of food choices. My uremia also increased, and I was becoming very tired. Six months later, I
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began hemodialysis 2 times/wk for 3 Y2 hour treatments. When I began hemodialysis, I realized I could again eat more than 20 g/d protein and was delighted. My nephrologist, Dr Carl Goldstein, and the unit dietitian urged me to take 50 to 70 g protein/d, but I insisted that my digestion was more comfortable when I was on Dr Mitch's diet of 40 g/protein/d (0.5 g/kg BW). They agreed I could continue until such time as my monthly chemistries showed evidence of protein malnutrition, at which time I would go up to the suggested higher level of protein. That was more than five years ago. My chemistries have remained consistently good at that protein intake level, with albumin ranges of 37 to 40 gil (3.7 to 4.0 g/dL) while consuming calorie ranges of 22 to 24 kcal/kg BW depending on exercise level to maintain my present weight of 67 kg (149 pounds) at 5 ft, 5Y2 in tall. The major advantage to eating this level of protein is that I only need to dialyze 2 d/wk. From the patient's point of view, this is all the incentive I need to stay on the diet. My current creatinine clearance of 0.004 mL/s (0.26 mL/min) shows neglible residual renal function in less than 200 mL urine output/d. On May 21, 1993, Kenneth J. Storch, MD, PhD, estimated 30.3% body fat based on mid-arm muscle circumference of 23.9 mm on my nonfistula arm. He was amazed at my nutritional status within the context of my dialysis history. A typical meal pattern is found in Table 1. I include 3 oz cooked weight of 20% fat red meat at dinner to maintain my hematocrit at 0.33 I (33%) and hemoglobin at a minimum of 101 gil (10.1 g/dL). I seldom vary the content of these meals except when dining out when, for example, I have a salad, 40z roast beef, and a small baked potato with butter and sour cream. I drink bottled water at home and maintain a fluid restriction of approximately 1 L/d. Exercise is a vital part of my regimen (Fig 1). For 12 years, I faithfully rode my exercise bicycle. Now I walk 2 miles/d and find it an even better form of exercise, because the weight-bearing nature of walking makes me feel better and stronger. I include rest in my
TABLE 1. Typical Daily Food Intake Nondialysis day 10:00 AM 3 oz Ocean Spray sweetened cranberry juice cocktail* 11 :30 AM Y2 small pink grapefruit Y2 cup regular cream of wheat (iron fortified) made with Y2 cup water 1 tbsp raisins 2 tbsp brown sugar 4 oz vanilla Dovet ice cream bar with chocolate coating 5 :00 PM 4 oz canned white corn Pasta Alfredo % c cooked low-protein pasta 2 tbsp grated Parmesan cheese 1 tbsp cream cheese Stuffed Pepper 4 oz 20% fat ground beef (3 oz cooked) 1 small green pepper 2 tbsp tomato chili sauce 1 tbsp Minute rice:j: 8:00 PM Baked Apple Crisp 1 medium Granny Smith apple , peeled & sliced y., tsp cinnamon 1 Y2 tsp flour 3 tsp sugar 1 tsp sweet butter Nutrient analysis: 1,585 kcal , 38 .4 g protein (10%) , 49 9 fat (28%) , 247 g carbohydrate (62%) , 525 mg phosphorus, 1,667 mg potassium, less than 1,250 mg sodium Additional for dialysis day 8:10 AM 6 oz English caffeinated breakfast tea, brewed 2 tsp sugar 1 medium Dunkin ' Donuts§ blueberry muffin Nutrient analysis: 237 kcal, 4.5 9 protein , 5.6 9 fat, 42 9 carbohydrate, 80 mg phosphorus, 70 mg potassium, less than 350 mg sodium Medications: Twice per week at dialysis treatment: 1,000 U Epogenll .125 /-Lcg Calcijex'll Daily oral medications 3 tablets Surbex'll 1 mg folic acid 100 mg vitamin B6 320 mg ferrous glutamate 25 mg zinc 4 9 Oscal** *Ocean Spray, Lakeville-Middleboro, MA. tMars, Inc, Burr Ridge, IL. :j:Kraft General Foods, White Plains, NY. §Dunkin Donuts, New Brunswick, NJ . IIAmgen. Thousand Oaks CA. 'IlAbbott Laboratories, North Chicago, IL. * *Marion Laboratories , Kansas City, MO .
daily pattern, sitting sometimes for up to an hour after meals to help settle the food in my stomach. I get at least ten hours of resting activities such as watching televi-
FIGURE 1. Carol walking with one of her Great Danes during her daily exercise session. sion, reading, writing, talking on the telephone, or sleep each night. My blood urea nitrogen (BUN) levels over time are shown in Fig 2. I usually run a predialysis BUN of 28.5 mmol/L (80 mg/ dL) or higher. I have my hemodialysis in the morning, and I find it helpful to have 3 oz of cranberry juice cocktail and a B complex vitamin (Surbex, Abbott Laboratories, North Chicago, IL) before I drive to the hospital. Immediately predialysis, I have a commercially made blueberry muffin and a cup of Start Hemodialysis
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FIGURE 2. Annual typical serum BUN over time with a Kt/V range of 1 .10 to 1.42 since the start of hemodialysis.
PROGRESSION OF ADPKD: A PERSONAL EXPERIENCE
strongly brewed English tea with 2 tsp sugar. This additional "reward" meal works for me and may offset the protein losses of the hemodialysis treatment itself. From the patient's point of view, I am grateful that my life is as good as I can make it. My husband and I have taken four "dialysis cruises" and they are wonderful. We often travel to visit our grandchildren in Florida from Friday afternoon to Monday evening; nice long weekend outings are possible, because only 2 d/wk are reserved for dialysis treatments. I also have traveled to many professional programs, including the National Kidney Foundation Spring Clinical Meetings, and do not have to make arrangements for any dialysis at the meeting location. I realize that many nephrologists would be concerned that I am underdialyzed. In fact, my Kt/V consistently ranges from 1.42 to 1.10 (Fig 1) using a 1211 dialyzer with a predialysis blood pressure of 150/80 and an initial postdialysis blood pressure of 110/70 without antihypertensive medication. If they forced me to eat more protein, I would probably have to dialyze three times per week. My health has been excellent, and I have been hospitalized less than 5 days in 5 years! It is true that my predialysis creatinine levels hover around 1,237 to 1,326 I-lmol/L (14 to 15 mg/dL), which is much higher than the "usual" 8 mg/dL for most female, sedentary hemodialysis patients. But I am an exerciser. In the summer, I swim and walk 2 miles/d. I also eat approximately 1 Ib red meat/wk to offset anemia and provide a excellent source of heme iron. I am not suggesting that every hemodialysis patient could do what I am doing. Probably only 1% of the entire renal population would even want to try. Anyone who might attempt what I've been doing should spend at least 2 years predialysis working out the "kinks" in his or her own diet under the guidance of a dietitian analogous to the Modification of Diet in Renal Disease (MDRD) clinical trial. For me, this philosophy has resulted in a quality, timeeffective life-style while providing a costeffective, efficient treatment scenario for the medical team. By eliminating the need for
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the third dialysis treatment, I am saving Medicare $15,000 per year and providing myself tremendous benefits. I have spent many hours becoming an informed dialysis consumer and have formed a mnemonic for anyone who wants to try what I am doing: R = rest, E = exercise, A = attitude (positive), 0 = diet. READ means participating, learning everything you can about your condition and your hemodialysis treatment, and modifying your life-style to promote the best quality of life that you can have. My brother? He has always eaten generous amounts dietary protein and continues to eat more than 70 grams of protein/d. He is 6 ft, 21;2 in tall, dialyzes at home 3 times/wk for 5 h/session, and is starting his 15th year on dialysis. During that time, he served as the President of the American Association of Kidney Patients for 4 years.
ACKNOWLEDGEMENT I would like to acknowledge William E. Mitch, MD, Carl Goldstein, MD, FACP, Luanne Prestifilippo, MS, RD, Kenneth J. Storch, MS, PhD, Judith Beto, PhD, RD, and the entire hemodialysis nursing staff of Overlook Hospital, Summit, NJ, for their help and encouragement.
REFERENCES 1. Grabow PA: Autosomal dominant polycystic kidney disease. Am J Kidney Dis 22:511-512, 1993 2. Grabow PA: Autosomal dominant polycystic kidney disease-More than a renal disease. Am J Kidney Dis 16:403-413, 1990 3. US Renal Data System: USRDS 1993 Annual Data Report. Bethesda, MD, The National Institutes of Diabetes and Digestive and Kidney Diseases, 1993.
COMMENTARY In this issue of the Journal of Renal Nutrition, Carol Victor describes her personal experience with progressive renal failure resulting from autosomal dominant polycystic kidney disease (ADPKD). Through her scholarship as a certified renal dietitian, Mrs Victor outlines her very low-protein and low-calorie diet, on which she has enjoyed tremendous physical and psychological well being.
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Protein restriction may have different effects in the patient approaching end-stage renal disease (ESRD) compared with the patient undergoing maintenance dialysis treatments. Mrs Victor's dietary program is properly considered first as a strategy to retard the progression of renal failure in the predialysis phase of her disease, then as a means of nutritional support for patients undergoing regular hemodialysis treatments . Why should a low-protein diet retard the progression of azotemia in ADPKD? The specific etiology of progressive renal failure in ADPKD is poorly understood. There is no histological evidence that cyst enlargement compresses and thereby damages adjacent renal parenchyma; however, larger kidneys are associated with a younger age of onset of dialysis-dependent ESRD in ADPKD.1 This advances the notion that cyst enlargement may influence renal deterioration. Cultures of human polycystic kidney epithelial cells have an amplified proliferative response to epidermal growth factor,2 sug gesting that cytokines may play a role in promoting cyst growth. Low-protein diets have been shown to decrease cyst growth in experimental animals. 3 One can speculate that low-protein diets may have an indirect effect on slowing cyst growth by decreasing cytokine production, thus leading to preservation of kidney function. A substantial amount of literature establishes the salutary effects of low-protein diets on progressive glomerulosclerosis resulting from glomerular hypertension and glomerular hyperfiltration in a variety of experimental and human renal diseases. Curiously, ADPKD should not be one of them . Zeier et al 4 show that in advanced ADPKD, the predominant lesions are vascular sclerosis and interstitial fibrosis with minimal glomerular injury. Therefore , the effect of low-protein diets , ie, to attenuate glomerular hemodynamic consequences of reduced renal mass does not necessarily apply to ADPKD patients. The renin-angiotensin system has been shown to be stimulated in ADPKD and has been proposed as a cause of hypertension
CARL S. GOLDSTEIN
in this diseaseS Could a low-protein diet modulate this humoral system to preserve renal function? Low-protein diets have been shown to reduce renin secretion and plasma angiotensin " levels and produce intense renal vasoconstriction that results in decreased renal blood flow in rats . Highprotein diets increase plasma renin activity and plasma angiotensin /I levels and produce renal vasodilatation with increased renal blood flow. Low-protein diets decrease blood pressure, whereas highprotein diets increase blood pressure. Conflicting results in animal experiments measuring the effect of varied dietary protein content on renin mRNA production , renal renin content , and other transcriptional and translational processes do not clearly support this hypothesis. 6 Are risks associated with very lowprotein diets? Could extreme protein restriction before the institution of dialysis therapy lead to a state of advanced protein calorie malnutrition in ESRD patients? Surprisingly, data exist that suggest that very lowprotein diets do not lead to hypoalbuminemia at the start of dialysis. ? Walser? suggests that perhaps some constituent of protein-rich foods contributes to anorexia and induces adverse metabolic effects that may lead to protein malnutrition in patients treated with more liberal dietary protein content, providing an advocacy position on behalf of Mrs Victor's regimen. There is a growing consensus that a premium exists on nutritional adequacy once regular dialysis treatments have begun. The mortal value of hypoalbuminemia has been demonstrated by Lowrie and Lew,s whose data show an inverse relationship between serum albumin concentration and risk of death among hemodialysis patients . These observations have amplified interest in more generous protein and highercalorie diets with larger doses of delivered dialysis . The pathophysiology of malnutrition among patients undergoing maintenance dialysis treatments is complex, but protein requirements are probably increased because of the effects of chronic metabolic acidosis , loss of protein-metabolizing renal
COMMENTARY
tissue, catabolic effects of infections, reduced protein ,synthesis, and dialysisrelated loss of amino acids, Low energy intake reduces the utilization of dietary protein, and bioincompatible dialysis membranes may stimulate the production of inflammatory mediators, which exacerbate the general catabolic environment of the dialysis patient. 9 How can we determine that a patient with renal disease is adequately nourished? The means by which we can measure nutritional adequacy are often incomplete or inaccurate 10 ,11 and frequently are limited by parsimonious reimbursement policies for ESRD,12 Although severe protein malnutrition can be easily recognized, our ability to certify that the patient is receiving enough calories and protein may not be as precise, In spite of these difficulties, current recommendations favor higher-protein diets that contain 0,75 to 1,25 g/kg/d with at least 35 kcal/kg/d 9 ,12 Given these observations, what does Mrs Victor's experience represent? If Mrs Victor is malnourished by currently accepted standards, why is she a stunning clinical success? Her subjective sense of well-being is outstanding and she has suffered no significant intercurrent complication of chronic dialysis therapy, Progression to ESRD and clinical outcome on dialysis are complex variables, This report showcases a well patient who is thriving on her selected modality of renal replacement therapy, Mrs Victor's accomplishments, including the strict discipline required to follow the diet she describes, deserve notice and praise, However, the etiological link between her diet and well being is not unambiguously defined, and her career on dialysis is far from complete, Embraced within Mrs Victor's personal triumph may be issues that merit formal scientific inquiry into the potential benefits of very low-protein diets in ADPKD, If careful experiments can demonstrate that dietary protein restriction slows the progression of ADPKD without nutritional penalties, then large numbers of ADPKD patients will be justified in following Mrs Victor's example, Until these studies are performed and validated, it remains speculative as to
93 which patients will derive a genuine benefit from this approach, Once uremia therapy has begun, the potential hazards of proteincalorie malnutrition must be seriously considered before restricting dietary protein, Careful and regular assessment of nutritional adequacy must accompany lowprotein diets for hemodialysis patients to identify deficiencies early and to promote prompt correction. Carl S. Goldstein, MD Assistant Clinical Professor of Medicine College of Physicians and Surgeons, Columbia University, New York, NY Director, Dialysis Services Division Chief, Nephrology Section Overlook Hospital, Summit, NJ 1, Gabow PA, Johnson AM, Kaehny WD, et al: Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int 41: 1311-1319, 1992 2, Gabow PA: Autosomal dominant polycystic kidney disease. New Engl J Med 329:332-342, 1993 3, Aukema HM, Ogborn MR, Tomobe K, et al: Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease, Kidney Int 42:837-842, 1992 4, Zeier M, Fehrenbach P, Geberth S, et al: Renal histology in polycystic kidney disease with incipient and advanced renal failure, Kidney Int 42:1259-1265, 1992 5. Chapman AB, Johnson A, Gabow PA, et al: The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. New Engl J Med 323: 1091-1 096, 1990 6. Benabe JE, Martinez-Maldonado M: Dietary modification of the renin angiotensin system. Semin NephroI13:567-572,1993 7, Walser M: Does prolonged protein restriction preceding dialysis lead to protein malnutrition at the onset of dialysis? Kidney Int 44: 1139-1144, 1993 8. Lowrie EG, Lew NL: Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458482, 1990 9. Bergstrom J: Nutrition and adequacy of dialysis in hemodialysis patients. Kidney Int 43:S261-S267, 1993 (suppl 41) 10. Rayner He, Stroud DB, Salamon KM, et al: Anthropometry underestimates body protein depletion in hemodialysis patients. Nephron 59:33-40, 1991 11, Hakim RM, Levin N: Malnutrition in hemodialysis patients, Am J Kidney Dis 21 : 125-137, 1993 12. Lazarus JM: Nutrition in hemodialysis patients, Am J Kidney Dis 21 :99-105, 1993