The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease

Restricting protein intake and controlling hypertension delay the progression of renal disease, we tested these interventions in 840 patients with various chronic renal diseases. In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients.

The mean follow-up was 2.2 years. In study 1, the projected mean decline in the glomerular filtration rate at three years did not differ significantly between the diet groups or between the blood-pressure groups. As compared with the usual-protein group and the usual-blood-pressure group, the low-protein group and the low-blood-pressure group had a more rapid decline in the glomerular filtration rate during the first four months after randomization and a slower decline thereafter. In study 2, the very-low-protein group had a marginally slower decline in the glomerular filtration rate than did the low-protein group (P = 0.07). There was no delay in the time to the occurrence of end-stage renal disease or death. In both studies, patients in the low-blood-pressure group who had more pronounced proteinuria at base line had a significantly slower rate of decline in the glomerular filtration rate.

Among patients with moderate renal insufficiency, the slower decline in renal function that started four months after the introduction of a low-protein diet suggests a small benefit of this dietary intervention. Among patients with more severe renal insufficiency, a very-low-protein diet, as compared with a low-protein diet, did not significantly slow the progression of renal disease.

Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. N Engl J Med 1994;330:877-884.

Kusek JW, Coyne T, de Velasco A, et al. Recruitment experience in the full-scale phase of the Modification of Diet in Renal Disease Study. Control Clin Trials 1993;14:538-557.

Greene T, Bourgoignie JJ, Habwe V, et al. Baseline characteristics in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol 1993;3:1819-1834.

Response: Diet
By: D2- Gil Legarda and Joanalyn Balino

Title: Dietary protein intake does not affect IgG synthesis in patients with
nephrotic syndrome

Mauro Giordano, Paola Lucidi, Pierpaolo De Feo, Emanuela dePascale, Tiziana Ciarambino
and Pietro Castellino


Giordano, M., Lucidi, P. et al. made a study to observe the impact of dietary protein restriction on IgG synthesis and to assess the absolute synthesis rate (ASR) and fractional synthesis rate (FSR) of IgG in hypogammaglobulinaemic nephrotic patients. A total of fourteen people participated in this study. Under the control group, there were 7 healthy normal volunteers. And the remaining 7 participated in the study were patients with nephrotic syndrome. Inclusion criteria for the nephritic patients were: ( 1) with age 20–50 years; (2)urinary protein excretion of >3.5 g/24 h; (3) plasma IgG levels <900 mg/dl; and (4) no indication of endocrine or other major organ system disease. Exclusion criteria were: (1) Patients with diseases known to increase; and with evidence of IgG synthesis endocrine or other major organ system disease. The subjects in the control group were not taking any medication other than vitamins for the entire duration of the study and instructed to consume diet of 35–38 kcal/kg per day and should have 250–300 g of carbohydrate and protein of 1.1 g /kg per day for at least 7 days prior to their participation in the study. Those Patients with established nephrosis participated in two separate experimental protocols. The first dietary regimen was patients were instructed to consume a diet 35–38 kcal/kg per day and protein of 1.1 g /kg per day and this dietary regimen is called normal protein diet (NPD). The second dietary regimen was patients were instructed to consume a similar caloric intake but the dietary protein was reduced to 0.6 g/kg per day and >65% of the ingested proteins were of a high biological value.This dietary regimen is under Low protein diet (LPD). All patients return to the clinical unit weekly with their dietary diary and 24 urinary collection specimens were obtained to determine urinary protein and nitrogen excretion in order to verify their compliance with the diet, during each 4 week dietary regimen. Metabolic evaluations were performed in the post-absorptive state after a 12 h overnight fasting. For those patients with established nephrosis, the study was performed after each 4 week period of dietary regimen, which were started in random order and completed in all patients. Two consecutive 24 h urinary collections were also obtained to determine urinary protein excretion that was performed at the end of the dietary periods. On the day of the study, the investigators inserted a 19 gauge catheter into an antecubital vein for the infusion of all test substances a. A second catheter was placed retrogradely into a wrist vein for blood sampling, and the hand was kept in a heated box at 60ºC to ensure arterialization of the venous blood.

Plasma IgG levels in control group were 1.20±0.08 g/dl.The plasma IgG concentration in nephrotic patients was 0.76±0.13 g/dl while consuming the normal protein diet ( NPD). and did not change significantly during the Low Protein diet (LPD) period (0.75±0.07 g/dl). The difference between the two (control and treatment group) was P<0.01 . The plasma IgG circulating pool in control subjects was 32.7±2 g/1.73m2 Plasma IgG pool in nephritic patients during the NPD period was reduced (24.4±4 g/1.73m2 and their comparison ( P<0.01). The plasma IgG pool didn’t change significantly after the LPD period the value is 25.2±3 g/1.73m2. The fractional synthesis rate (FSR) of IgG was 6.2± 0.2% per day in control subjects. The FSR of IgG in nephrotic patients consuming Normal Protein diet, was markedly increased to 23.1±4%/day and after the low protein diet (LPD) period it didn’t change significantly 24.2±4%/day. The comparison with control group was P<0.03. The absolute synthesis rate ASR of IgG averaged 2.0±0.1 g/ 1.73m2/day in control subjects and it was markedly increased in nephrotic patients during the normal protein diet regimen 5.2±0.7 g/1.73m2/day. P<0.03 if compared with control group. There was no difference was observed in IgG synthesis rate (6.1±1.3 g/ 1.73m2/day) in response to the LPD regimen.Those patients with established nephrosis had a significant inverse correlation between the IgG FSR and the intravascular IgG pool during both the Normal Protein Diet (r¼_0.828; P<0.05) and Low Protein Diet (r¼_0.861; P<0.05) regimens.

There was no relationship was found between the degree of proteinuria or albuminuria and plasma IgG concentration, IgG pool, IgG absolute synthesis rate ASR or IgG fractional synthesis rate FSR. During normal protein intake, the nephrotic subjects with a decrease of the IgG intravascular pool have an increase in IgG FSR and ASR, which are not reduced by a low-protein diets LPD regimen. Low protein diet has no adverse effect on IgG metabolism (Low IgG concentrations stimulate IgG synthesis). The stimulation of IgG synthesis might represent an important mechanism that prevents further falls in circulating immunoglobulin G (IgG) levels.

Giordano, M., Lucidi, P., Feo, P., de Pascale, E., Ciarambino, T., and Catellino, P. (2004). Nephrology Dialysis Transplantation 19(10):2494-2498. Retrieved June 29, 2009 from http://ndt.oxfordjournals.org/cgi/reprint/19/10/2494?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&minscore=20&resourcetype=HWCIT

Nutrition
In patients with nephrotic syndrome, the tubular function of the kidneys to conserve sodium is not affected, thus, total body sodium is uniformly increased. Patients are often treated with glucocorticoids, which further curtails renal sodium excretion. Patients with nephrotic syndrome will usually be prescribed a sodium-restricted diet. Alterations in protein are not indicated, and fluid restriction is unnecessary unless the a patient’s thirst is excessive that fluid intake is extreme.

References:

Agraharkar, M. (2004), Nephrotic Syndrome. Retrieved June 29, 2009, from http://www.emedicine.com.

Travis, L. (2005). Nephrotic Syndrome. Retrieved June 29, 2009, from http://www.emedicine.com.