1131
hyperlipidaemia in nephrotic syndrome
Effect of vegetarian soy diet
Nephrotic patients with persistent proteinuria also have various lipid abnormalities that may promote atherosclerosis and more rapid progression of renal disease. We aimed to find out whether dietary manipulation can correct the hyperlipidaemia found in these patients. After a baseline control period of 8 weeks on their
usual diets, 20 untreated
patients with chronic long-lasting severe 3·4] g/24 h) and
stable
glomerular diseases, proteinuria (5·9 [SD hyperlipidaemia (mean serum cholesterol 8·69 [3·34] mmol/l) ate a vegetarian soy diet for 8 weeks. The diet was low in fat (28% of total calories) and protein (0·71 [0·36] g/kg ideal body weight daily),
cholesterol free, and rich in monounsaturated and polyunsaturated fatty acids (polyunsaturated/ saturated ratio 2·5) and in fibre (40 g/day). After the diet period the patients resumed their usual diets for 8 weeks (washout period). During the soy-diet period there were significant falls in serum cholesterol (total, and low-density lipoprotein, high-density and and B, but serum apolipoproteins A lipoprotein) triglyceride concentrations did not change. Urinary fell The protein excretion significantly. concentrations of all lipid fractions and the amount of proteinuria tended to return towards baseline values during the washout period. We do not know whether the favourable effect of this dietary manipulation on proteinuria was due to the qualitative or quantitative modifications of dietary protein intake or was a direct consequence of the manipulation of dietary lipid intake. Introduction
important feature of nephrotic syndrome is hyperlipidaemia, characterised by increased plasma concentrations of very-low-density (VLDL), intermediatedensity, and low-density lipoproteins (LDL) and, as the disorder progresses, also by hypertriglyceridaemia and decreased concentrations of high-density lipoproteins (HDL).l.2 Such lipid abnormalities may promote development of atherosclerotic lesions, which increase the risk of coronary heart disease3 and may predispose to more rapid progression of renal disease; in animals these lesions promote mesangial damage and glomerular sclerosis and possibly also aggravate the permeability abnormalities of the glomerular capillary wall.4-6 Dietary intervention is the most physiological and harmless approach for correction of hyperlipidaemia in nephrotic patients. However, no study has systematically tested the efficacy of this approach. The introduction of An
on
powerful lipid-lowering drugs has favoured a pharmacological approach, despite the possible risks associated with long-term administration of drugs that can have toxic effects. We aimed to find out whether a strictly vegetarian soy diet, low in fat, moderately low in protein, and rich in polyunsaturated and monounsaturated fatty acids and fibre, could correct the hypercholesterolaemia in patients with persistent severe urinary loss of proteins due to chronic glomerular disease. Patients and methods All patients referred to our unit with biopsy-proven glomerular disease were eligible for the study. We selected 20 patients (7 with idiopathic membranous nephropathy, 5 with idiopathic focal glomerulosclerosis, 4 with IgA nephropathy, 1 with
membranoproliferative glomerulonephritis, and 3 with Alport’s syndrome) on the basis of: consistent proteinuria of more than 1-5 g/24 h for a mean of 25 [SD 24; range 3-95] months; serum creatinine concentration below 220 umol/1; hyperlipidaemia (fasting serum cholesterol >5’95 mmol/1); no treatment with steroids or cytotoxic, non-steroidal anti-inflammatory, or lipidlowering drugs during the previous 6 months; and acceptance of the protocol. The reasons for the dietary intervention were explained in detail by the dieticians and the patients were allowed to taste some cooked soy foods before they finally decided to take part. Treatment of hypertensive patients with p-blockers and angiotensinconverting-enzyme inhibitors was replaced with calcium-channel blockers in doses necessary to control blood pressure. The diet was exclusively of vegetable origin, low in fat, rich in fibre, and almost cholesterol free. Dietary calorie intakes were calculated according to the patient’s nutritional requirements to achieve or maintain ideal body weight; 11 % of energy was from protein (0-7-0-8 g/kg ideal body weight daily), 28% from fat, and 61% from carbohydrates (46% complex, 15% sugars). 14-day menu plans were provided, with special recipes to ensure accurate and consistent intakes of energy, protein, fat, carbohydrates, and unsaturated and saturated fatty acids. Animal-protein foods (meat, fish, milk, and cheese) were replaced by textured soybean proteins (average composition protein 52%, fat 1%, fibre 3%, total carbohydrates 30%, minerals 6%, water 8%). Fats from animal
(butter, lard, cream) were replaced by highly polyunsaturated vegetable oils (corn and safflower oil, 50%) and highly monounsaturated vegetable oils (olive oil, 50%). The polyunsaturated/saturated fat ratio was 25 (4-3% of total calories saturated fatty acids, 12-8% monounsaturated, 10-9% polyunsaturated, 8.2% linoleic acid). The cholesterol content was zero, sodium 930 mg/day, and fibre 40 g/day. At enrolment, a complete history was taken and a physical examination and dietary interview with 3-day diet recall were done. For the next 8 weeks (baseline free-diet period), the patients continued to eat their usual diets. Then, we carefully instructed patients to change to the vegetarian soy diet for 8 weeks (diet sources
ADDRESSES. Division of Nephrology (Prof G. D’Amico, MD, M. G. Gentile, MD, G. Manna, MD, G. Fellin, MD, R. Ciceri, MD, F Cofano, MD) and Laboratory of Clinical Pathology (C Petrini, MD, F. Lavarda, MD, S Perolini, MD), San Carlo Hospital; and Department of Food Science and Microbiology, University of Milan (M. Porrini, PhD), Milan, Italy. Correspondence to Prof Giuseppe D’Amico, San Carlo Hospital, Via Pio II 3, 20153, Milan, Italy
1132
I I----i III
Baseline
Soy
diet
Washout
Fig 2-Mean (SEM) urinary protein excretion.
Serum
concentrations of total cholesterol, LDLHDL-cholesterol, triglycerides, and apolipoproteins A and B remained stable during the 8 weeks of the baseline free-diet period (fig 1, table l). During the 8 weeks on the vegetarian soy diet, serum concentrations of these substances were significantly lower than during the baseline period. Serum triglycerides were also lower during the soy-diet than the baseline period (table l) but this difference was not significant because of the wide variability (in fact, serum triglycerides were higher at the end of the soy-diet period than at baseline in 3 patients). Serum lipid concentrations returned towards baseline values after discontinuation of the soy diet; the differences between the washout and soy-diet periods were significant for all lipids except triglycerides. Urinary protein excretion fell significantly from baseline during the 8-week soy-diet period (fig 2), but returned towards baseline values during the washout period. Serum total protein, albumin, and transferrin concentrations did not change significantly during the study (table 11). There was a small but significant fall in creatinine clearance during the soy-diet period without any change in serum creatinine (table n). After discontinuation of the soy diet, creatinine clearance did not return towards the baseline value. Blood pressure did not change significantly during the study. Body weight and body mass index decreased during the soy-diet period and increased again during the washout period. During the baseline period, daily intakes of protein and lipid on free diet were 1-22 (0-56) and 86-3 (31-9) g/kg ideal
cholesterol,
t--------1 II III
Soy
Baseline
Fig 1-Mean (SEM)
serum
diet
Washout
cholesterol concentrations.
period). Afterwards, patients returned to the usual diet for 8 weeks (washout free-diet period). At enrolment and every 4 weeks, blood samples were taken after the subject had fasted overnight for measurement of glucose, urea, creatinine, electrolytes, uric acid, total proteins with electrophoretic fractions, and lipids; urine was collected for 24 h to measure urea, creatinine, total protein, and electrolyte excretion; and 3-day diet recalls were done. Three measurements were done during the baseline period and two each in the diet and washout periods. Total cholesterol and triglycerides were measured with an autoanalyser, by standard enzymic methods. Apolipoproteins A and B were measured for 19 patients by immunonephelometry. HDL-cholesterol was determined directly in the supernatant after treatment of plasma with phosphotungstic acid and magnesium ions, and the LDL-cholesterol concentration was calculated by the Friedewald equation.’ The technicians who did the chemical analyses were unaware of the subjects’ diets. Daily protein intake was calculated from the urinary urea excretion by the formula of Maroni et al;8 daily intakes of phosphate and sodium were taken from urinary excretion. Intake of lipids and quality of ingested proteins were assessed from the dietary interviews. Data were analysed with the SAS package, version 5, on a VAX computer. Differences between diet periods were tested by Student’s two-tailedt test for paired samples. A two-tailed p value of less than 0-05 was taken as significant. the
Results The ages of the 13 men and 7 women ranged from 17 to 71 (mean 41 [SD 18]). The mean serum creatinine concentration at enrolment was 123 (44) J.U1l01/1; only 6 patients had values above 133 umol/1. Mean creatinine clearance was 79-5 (33-0) ml/min. Proteinuria ranged from 1-5 to 13-0 g/24 h and was above 3-5 g/24 h for 15 patients. All patients completed the 24 weeks of the study. years
TABLE i!—BODY WEIGHT, BLOOD PRESSURE, AND SERUM AND URINE VARIABLES
TABLE I-SERUM LIPID AND LIPOPROTEIN CONCENTRATIONS I
*Means of all measurements dunng a period for each patient were used to calculate overall period means tn=19. p
hyperlipidaemia in nephrotic syndrome
Effect of vegetarian soy diet
Nephrotic patients with persistent proteinuria also have various lipid abnormalities that may promote atherosclerosis and more rapid progression of renal disease. We aimed to find out whether dietary manipulation can correct the hyperlipidaemia found in these patients. After a baseline control period of 8 weeks on their
usual diets, 20 untreated
patients with chronic long-lasting severe 3·4] g/24 h) and
stable
glomerular diseases, proteinuria (5·9 [SD hyperlipidaemia (mean serum cholesterol 8·69 [3·34] mmol/l) ate a vegetarian soy diet for 8 weeks. The diet was low in fat (28% of total calories) and protein (0·71 [0·36] g/kg ideal body weight daily),
cholesterol free, and rich in monounsaturated and polyunsaturated fatty acids (polyunsaturated/ saturated ratio 2·5) and in fibre (40 g/day). After the diet period the patients resumed their usual diets for 8 weeks (washout period). During the soy-diet period there were significant falls in serum cholesterol (total, and low-density lipoprotein, high-density and and B, but serum apolipoproteins A lipoprotein) triglyceride concentrations did not change. Urinary fell The protein excretion significantly. concentrations of all lipid fractions and the amount of proteinuria tended to return towards baseline values during the washout period. We do not know whether the favourable effect of this dietary manipulation on proteinuria was due to the qualitative or quantitative modifications of dietary protein intake or was a direct consequence of the manipulation of dietary lipid intake. Introduction
important feature of nephrotic syndrome is hyperlipidaemia, characterised by increased plasma concentrations of very-low-density (VLDL), intermediatedensity, and low-density lipoproteins (LDL) and, as the disorder progresses, also by hypertriglyceridaemia and decreased concentrations of high-density lipoproteins (HDL).l.2 Such lipid abnormalities may promote development of atherosclerotic lesions, which increase the risk of coronary heart disease3 and may predispose to more rapid progression of renal disease; in animals these lesions promote mesangial damage and glomerular sclerosis and possibly also aggravate the permeability abnormalities of the glomerular capillary wall.4-6 Dietary intervention is the most physiological and harmless approach for correction of hyperlipidaemia in nephrotic patients. However, no study has systematically tested the efficacy of this approach. The introduction of An
on
powerful lipid-lowering drugs has favoured a pharmacological approach, despite the possible risks associated with long-term administration of drugs that can have toxic effects. We aimed to find out whether a strictly vegetarian soy diet, low in fat, moderately low in protein, and rich in polyunsaturated and monounsaturated fatty acids and fibre, could correct the hypercholesterolaemia in patients with persistent severe urinary loss of proteins due to chronic glomerular disease. Patients and methods All patients referred to our unit with biopsy-proven glomerular disease were eligible for the study. We selected 20 patients (7 with idiopathic membranous nephropathy, 5 with idiopathic focal glomerulosclerosis, 4 with IgA nephropathy, 1 with
membranoproliferative glomerulonephritis, and 3 with Alport’s syndrome) on the basis of: consistent proteinuria of more than 1-5 g/24 h for a mean of 25 [SD 24; range 3-95] months; serum creatinine concentration below 220 umol/1; hyperlipidaemia (fasting serum cholesterol >5’95 mmol/1); no treatment with steroids or cytotoxic, non-steroidal anti-inflammatory, or lipidlowering drugs during the previous 6 months; and acceptance of the protocol. The reasons for the dietary intervention were explained in detail by the dieticians and the patients were allowed to taste some cooked soy foods before they finally decided to take part. Treatment of hypertensive patients with p-blockers and angiotensinconverting-enzyme inhibitors was replaced with calcium-channel blockers in doses necessary to control blood pressure. The diet was exclusively of vegetable origin, low in fat, rich in fibre, and almost cholesterol free. Dietary calorie intakes were calculated according to the patient’s nutritional requirements to achieve or maintain ideal body weight; 11 % of energy was from protein (0-7-0-8 g/kg ideal body weight daily), 28% from fat, and 61% from carbohydrates (46% complex, 15% sugars). 14-day menu plans were provided, with special recipes to ensure accurate and consistent intakes of energy, protein, fat, carbohydrates, and unsaturated and saturated fatty acids. Animal-protein foods (meat, fish, milk, and cheese) were replaced by textured soybean proteins (average composition protein 52%, fat 1%, fibre 3%, total carbohydrates 30%, minerals 6%, water 8%). Fats from animal
(butter, lard, cream) were replaced by highly polyunsaturated vegetable oils (corn and safflower oil, 50%) and highly monounsaturated vegetable oils (olive oil, 50%). The polyunsaturated/saturated fat ratio was 25 (4-3% of total calories saturated fatty acids, 12-8% monounsaturated, 10-9% polyunsaturated, 8.2% linoleic acid). The cholesterol content was zero, sodium 930 mg/day, and fibre 40 g/day. At enrolment, a complete history was taken and a physical examination and dietary interview with 3-day diet recall were done. For the next 8 weeks (baseline free-diet period), the patients continued to eat their usual diets. Then, we carefully instructed patients to change to the vegetarian soy diet for 8 weeks (diet sources
ADDRESSES. Division of Nephrology (Prof G. D’Amico, MD, M. G. Gentile, MD, G. Manna, MD, G. Fellin, MD, R. Ciceri, MD, F Cofano, MD) and Laboratory of Clinical Pathology (C Petrini, MD, F. Lavarda, MD, S Perolini, MD), San Carlo Hospital; and Department of Food Science and Microbiology, University of Milan (M. Porrini, PhD), Milan, Italy. Correspondence to Prof Giuseppe D’Amico, San Carlo Hospital, Via Pio II 3, 20153, Milan, Italy
1132
I I----i III
Baseline
Soy
diet
Washout
Fig 2-Mean (SEM) urinary protein excretion.
Serum
concentrations of total cholesterol, LDLHDL-cholesterol, triglycerides, and apolipoproteins A and B remained stable during the 8 weeks of the baseline free-diet period (fig 1, table l). During the 8 weeks on the vegetarian soy diet, serum concentrations of these substances were significantly lower than during the baseline period. Serum triglycerides were also lower during the soy-diet than the baseline period (table l) but this difference was not significant because of the wide variability (in fact, serum triglycerides were higher at the end of the soy-diet period than at baseline in 3 patients). Serum lipid concentrations returned towards baseline values after discontinuation of the soy diet; the differences between the washout and soy-diet periods were significant for all lipids except triglycerides. Urinary protein excretion fell significantly from baseline during the 8-week soy-diet period (fig 2), but returned towards baseline values during the washout period. Serum total protein, albumin, and transferrin concentrations did not change significantly during the study (table 11). There was a small but significant fall in creatinine clearance during the soy-diet period without any change in serum creatinine (table n). After discontinuation of the soy diet, creatinine clearance did not return towards the baseline value. Blood pressure did not change significantly during the study. Body weight and body mass index decreased during the soy-diet period and increased again during the washout period. During the baseline period, daily intakes of protein and lipid on free diet were 1-22 (0-56) and 86-3 (31-9) g/kg ideal
cholesterol,
t--------1 II III
Soy
Baseline
Fig 1-Mean (SEM)
serum
diet
Washout
cholesterol concentrations.
period). Afterwards, patients returned to the usual diet for 8 weeks (washout free-diet period). At enrolment and every 4 weeks, blood samples were taken after the subject had fasted overnight for measurement of glucose, urea, creatinine, electrolytes, uric acid, total proteins with electrophoretic fractions, and lipids; urine was collected for 24 h to measure urea, creatinine, total protein, and electrolyte excretion; and 3-day diet recalls were done. Three measurements were done during the baseline period and two each in the diet and washout periods. Total cholesterol and triglycerides were measured with an autoanalyser, by standard enzymic methods. Apolipoproteins A and B were measured for 19 patients by immunonephelometry. HDL-cholesterol was determined directly in the supernatant after treatment of plasma with phosphotungstic acid and magnesium ions, and the LDL-cholesterol concentration was calculated by the Friedewald equation.’ The technicians who did the chemical analyses were unaware of the subjects’ diets. Daily protein intake was calculated from the urinary urea excretion by the formula of Maroni et al;8 daily intakes of phosphate and sodium were taken from urinary excretion. Intake of lipids and quality of ingested proteins were assessed from the dietary interviews. Data were analysed with the SAS package, version 5, on a VAX computer. Differences between diet periods were tested by Student’s two-tailedt test for paired samples. A two-tailed p value of less than 0-05 was taken as significant. the
Results The ages of the 13 men and 7 women ranged from 17 to 71 (mean 41 [SD 18]). The mean serum creatinine concentration at enrolment was 123 (44) J.U1l01/1; only 6 patients had values above 133 umol/1. Mean creatinine clearance was 79-5 (33-0) ml/min. Proteinuria ranged from 1-5 to 13-0 g/24 h and was above 3-5 g/24 h for 15 patients. All patients completed the 24 weeks of the study. years
TABLE i!—BODY WEIGHT, BLOOD PRESSURE, AND SERUM AND URINE VARIABLES
TABLE I-SERUM LIPID AND LIPOPROTEIN CONCENTRATIONS I
*Means of all measurements dunng a period for each patient were used to calculate overall period means tn=19. p
