High Protein Diets and Renal Disease
Dietary protein restriction has been the standard recommendation for those with end stage renal failure for many years. This is based on evidence from trials dating as far back as the 1970s and summarised in several Cochrane Reviews, most recently in 2009. A Cochrane review in 2007 specifically considering diabetes concluded that reducing protein intake slowed progression of renal failure slightly but not statistically significantly. Diabetic nephropathy is characterised by early glomerular hyperfiltration and later by evolving proteinuria and progressive decline in glomerular filtration. Therefore the potential for dietary protein to influence the pathogenesis and/or the progression of diabetic nephropathy is clear. Despite this, few studies have tested the effect of a low-protein diet on diabetic nephropathy solely in those with type 2 diabetes. Furthermore it is difficult to compare studies with different measures of nephropathy, small sample sizes, and varying protein intakes in the low-protein diets used.
Pijls et al. randomised 121 people with type 2 diabetes and microalbuminuria or high normal albuminuria to either a low-protein diet (protein restriction of 0.8 g/kg/day) or control group for one year. After six months, the low-protein group had a 28% reduction in microalbuminuria compared with the control group, despite achieving only 1.12 g/kg/day, but this had reduced to 18% by 12 months. The same authors repeated this study with a follow-up of 28 months. No significant differences were found in GFR or microalbuminuria but the difference in protein intake was not sustained past six months.
In a small study by Sugimoto et al., 14 hospital in-patients with type 2 diabetes and overt nephropathy (proteinuria >1 g/day) were placed either on a conventional diet or a low-protein diet for four weeks (<0.8 g/kg/day). The 24-hour urinary protein excretion rate decreased significantly in the low-protein group but there was no change in serum creatinine or creatinine clearance rate.
Meloni et al. conducted two studies with good compliance in subjects with either type 1 or type 2 diabetes, with results not separated for type of diabetes. The earlier study (n=69) randomised people with type 1 or 2 diabetes and diabetic nephropathy to either a low-protein diet (0.6 g/kg/day) or an ad libitum diet. There was no significant difference between the two groups for GFR after 12 months. The later study compared a group of 80 patients with diabetic nephropathy (type 1 and 2 diabetes) with a group of 89 patients with CRF not due to diabetes. Half of each group were assigned to protein restriction (0.8 g/kg/day) and the other half to an ad libitum diet. There were no changes in measures of renal function in the group with diabetes, but in the CRF-only group there was a significant reduction in the rate of decline of renal function on the protein- restricted diet, suggesting that a low-protein diet may be more appropriate for treatment of CRF due to other causes.
In a Mexican trial, 60 patients with type 2 diabetes and either normo-, micro- or macro-albuminuria were randomised to either a low-protein diet (0.6–0.8 g/kg/day) or normal diet for four months. After four months, only the patients with macroalbuminuria on the low-protein diet experienced a significant decrease in urinary AER and increase in GFR. Also in a mixed diabetic population, Dussol et al. followed 63 patients (37 with type 2 diabetes) randomised to either a low-protein or usual protein diet for 2 years. In patients with type 2 diabetes, the rate of decline in GFR was no different between groups over two years. While both groups consumed 20% of TE as protein at baseline, the usual-protein group maintained this intake, while the low-protein group achieved and maintained a reduction to 16% of TE.
Therefore, from the limited literature in patients with type 2 diabetes, whilst protein restriction may result in a decrease in urinary AER in the short term (≤6 months) in patients with some renal impairment, in the longer term it appears to make no difference to renal function. Current available evidence suggests that long-term protein restriction is difficult to maintain. Moreover, when dietary protein is restricted, patient satisfaction decreases, which in turn affects compliance. Concern has also been raised over the nutritional adequacy of low-protein diets, particularly when combined with other restrictions, such as of potassium and phosphorus, as well as their effect on the state of wellbeing of the patient.
Protein Restriction to Treat Nephropathy in Type 2 Diabetes
Dietary protein restriction has been the standard recommendation for those with end stage renal failure for many years. This is based on evidence from trials dating as far back as the 1970s and summarised in several Cochrane Reviews, most recently in 2009. A Cochrane review in 2007 specifically considering diabetes concluded that reducing protein intake slowed progression of renal failure slightly but not statistically significantly. Diabetic nephropathy is characterised by early glomerular hyperfiltration and later by evolving proteinuria and progressive decline in glomerular filtration. Therefore the potential for dietary protein to influence the pathogenesis and/or the progression of diabetic nephropathy is clear. Despite this, few studies have tested the effect of a low-protein diet on diabetic nephropathy solely in those with type 2 diabetes. Furthermore it is difficult to compare studies with different measures of nephropathy, small sample sizes, and varying protein intakes in the low-protein diets used.
Microalbuminuria
Pijls et al. randomised 121 people with type 2 diabetes and microalbuminuria or high normal albuminuria to either a low-protein diet (protein restriction of 0.8 g/kg/day) or control group for one year. After six months, the low-protein group had a 28% reduction in microalbuminuria compared with the control group, despite achieving only 1.12 g/kg/day, but this had reduced to 18% by 12 months. The same authors repeated this study with a follow-up of 28 months. No significant differences were found in GFR or microalbuminuria but the difference in protein intake was not sustained past six months.
Macroalbuminuria
In a small study by Sugimoto et al., 14 hospital in-patients with type 2 diabetes and overt nephropathy (proteinuria >1 g/day) were placed either on a conventional diet or a low-protein diet for four weeks (<0.8 g/kg/day). The 24-hour urinary protein excretion rate decreased significantly in the low-protein group but there was no change in serum creatinine or creatinine clearance rate.
Meloni et al. conducted two studies with good compliance in subjects with either type 1 or type 2 diabetes, with results not separated for type of diabetes. The earlier study (n=69) randomised people with type 1 or 2 diabetes and diabetic nephropathy to either a low-protein diet (0.6 g/kg/day) or an ad libitum diet. There was no significant difference between the two groups for GFR after 12 months. The later study compared a group of 80 patients with diabetic nephropathy (type 1 and 2 diabetes) with a group of 89 patients with CRF not due to diabetes. Half of each group were assigned to protein restriction (0.8 g/kg/day) and the other half to an ad libitum diet. There were no changes in measures of renal function in the group with diabetes, but in the CRF-only group there was a significant reduction in the rate of decline of renal function on the protein- restricted diet, suggesting that a low-protein diet may be more appropriate for treatment of CRF due to other causes.
Mixed Renal Function
In a Mexican trial, 60 patients with type 2 diabetes and either normo-, micro- or macro-albuminuria were randomised to either a low-protein diet (0.6–0.8 g/kg/day) or normal diet for four months. After four months, only the patients with macroalbuminuria on the low-protein diet experienced a significant decrease in urinary AER and increase in GFR. Also in a mixed diabetic population, Dussol et al. followed 63 patients (37 with type 2 diabetes) randomised to either a low-protein or usual protein diet for 2 years. In patients with type 2 diabetes, the rate of decline in GFR was no different between groups over two years. While both groups consumed 20% of TE as protein at baseline, the usual-protein group maintained this intake, while the low-protein group achieved and maintained a reduction to 16% of TE.
Therefore, from the limited literature in patients with type 2 diabetes, whilst protein restriction may result in a decrease in urinary AER in the short term (≤6 months) in patients with some renal impairment, in the longer term it appears to make no difference to renal function. Current available evidence suggests that long-term protein restriction is difficult to maintain. Moreover, when dietary protein is restricted, patient satisfaction decreases, which in turn affects compliance. Concern has also been raised over the nutritional adequacy of low-protein diets, particularly when combined with other restrictions, such as of potassium and phosphorus, as well as their effect on the state of wellbeing of the patient.
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