Dietary protein restriction in diabetic nephropathy
Original article:
Effect of dietary protein restriction on prognosis in patients with diabetic
nephropathy. Hansen HP, Tauber-Lassen E, Jensen BR, Parving H-H. Kidney
Int 2002; 62: 220–8.
Summary
Eighty-two type 1 diabetic patients with progressive diabetic nephropathy
took part in a 4-year study to explore the effects of a low-protein diet on
the rate of decline in glomerular filtration rate (GFR). Prior to entry into
the study, patients were declining at a mean rate of 7.1 ml/min per year
(95% CI 5.8–8.5).
The original intention was for patients to continue with their usual protein
intake (around 1 g/kg per day) or follow a low-protein diet (0.6 g/kg per
day). In the event the patients assigned to lower protein intake only
managed a reduction to 0.89 g/kg per day (95% CI 0.83–0.95). This was,
however, significantly lower than the protein intake of the control group
(1.02 g/kg per day, 95% CI 0.95–1.10).
There was no change in the rate of decline of GFR in either dietary group.
Interestingly, the rate of decline was almost identical at 3.9 ml/min per
year, which was significantly reduced from the pre-study period.
The combined endpoint of endstage renal disease (ESRD), defined as
requirement for dialysis or transplantation, or death was significantly
lower in the low-protein group (10% vs. 27%, p = 0.042) (Fig. 1).
Fig. 1: Cumulative incidence of ESRD or death in
type 1 diabetic patients with progressive diabetic nephropathy following
usual- or low-protein diets. Log-rank test, p = 0.042. Numbers at the bottom
of the figure denote numbers of patients in each group at risk for the event
at baseline and at each 6-month period.
The relative risk for this combined endpoint was 0.23 (95% CI 0.07– 0.72)
for patients on the low-protein diet.
The authors conclude that a modest reduction in dietary protein intake
improves clinical prognosis in type 1 diabetic patients with progressive
diabetic nephropathy.
Comment
This study adds to others which suggest that restricting dietary protein
intake can benefit type 1 diabetic patients with established nephropathy.
However, there was no significant impact on the rate of decline of GFR in
patients following a low-protein diet. Why should this be so?
One of the reasons may be that the rate of decline was almost halved in the
control patients. Thus, clinical intervention, better compliance, or other
factors, contributed to an improvement in nephropathy independent of dietary
protein intake. At first sight, therefore, it seems curious that there was a
significant difference in the number of patients achieving the combined
endpoint of ESRD or death on the two diets. However, the results section
makes clear that the number requiring dialysis or transplantation was four
on the usual-protein diet and two on the low-protein diet. The main
difference was in the mortality rate: seven on the usual-protein diet and
two on the low-protein diet. All of these deaths were cardiac-related. There
is therefore a potential bias of the impact of cardiovascular disease at
baseline, particularly as the numbers of patients in each group were
relatively small. In order to overcome this, all patients had a 12-lead ECG
coded using the Minnesota Rating Scale, and a detailed history of any
previous myocardial infarction was sought. Nonetheless there remains the
possibility that those assigned to the usual-protein diet may have had more
subclinical ischemic heart disease than those on protein restriction.
There does not appear to be any difference in achieved blood pressure or
plasma lipid levels between the two groups. However, slightly more of the
patients following the usual-protein diet were taking low-dose aspirin both
at baseline and at follow-up, which would support the idea that this group
was slightly more at risk of ischemic heart disease.
An interesting finding was the reduction in the rate of decline of GFR by
almost 50% despite no obvious difference in blood pressure before or during
the study. There also did not seem to be a major increase in the number of
patients taking ACE inhibitors or other anti-hypertensive agents.
Interestingly, the number of lipid-lowering agents (statins) did increase
significantly. A recent meta-analysis of the impact of lipid-lowering agents
on progressive nephropathies suggested that they may confer benefit [1].
Moreover, in microalbuminuric type 2 diabetic patients, a multifaceted
approach to the management of cardiorenal risk factors showed a significant
reduction in numbers progressing to clinical nephropathy [2]. It is possible
that a similar more intensive management in the type 1 diabetic patients
reported in this paper may have resulted in the observed improved prognosis.
Another important message from this paper is the difficulty in sustaining
significant reductions in dietary protein intake even when participating in
a clinical trial in a tertiary specialist diabetes unit. This must call into
question the feasibility of using significant protein restriction in
ordinary clinical practice.
The most important conclusion from this study is that aggressive management
of established nephropathy can result in significant improvements in
cardiovascular outcome and a dramatic slowing of the rate of decline of GFR.
Once again the challenge is not so much to discover new treatments but to
learn ways of better using those that we already know to be effective.
References
1. Fried LF, Orchard TJ, Kasiske BL. Effect of lipid
reduction on the progression of renal disease: a meta-analysis. Kidney Int
2001; 59: 260–9.
2. Gaede P, Vedel P, Larsen N et al. Multi-factorial intervention and
cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;
348: 383–93.
Summary and Comment:
Rudy Bilous, Middlesbrough, UK
