Pedrini and colleagues [1] recently did a meta-analysis of the effect of dietary protein restriction on the progression of diabetic and nondiabetic renal disease. They concluded that "dietary protein restriction effectively slows the progression of both diabetic and nondiabetic renal diseases." The authors accepted different designs (randomized, controlled studies for nondiabetic renal disease and nonrandomized crossover studies for two of five analyses of diabetic renal disease) and trial end points (renal failure or death for nondiabetic renal disease, and urinary albumin level or a decline in glomerular filtration rate or creatinine clearance for diabetic renal disease).

The conclusion of Pedrini and colleagues in relation to nondiabetic renal disease seems to be valid, but what would have happened if they had used renal failure or death as end points in the study of diabetic patients with renal disease? More important, the conclusion in relation to diabetic renal disease should be interpreted with caution because I believe their analysis clearly revealed several methodologic problems.

Creatinine is unreliable in the assessment of renal function; the use of serum creatinine is particularly fraught with difficulties when a low-protein diet, which interferes with creatinine metabolism and pool, is administered [2, 3]. This concern is not trivial because the Modification of Diet in Renal Disease (MDRD) study would have shown a clear benefit with a low-protein diet if the creatinine data (the reciprocal of the plasma creatinine concentration) had been applied [3]. Two of the five studies of diabetic renal disease applied creatinine clearance, and the same studies used low-protein diets for only 4.5 and 17 months [1].

Levey and colleagues [2] clearly documented the importance of a longer duration of follow-up (>2 years) and the use of valid methods for determining glomerular filtration rate in assessment of the effect of low-protein diet on the progression of renal disease. Furthermore, the meta-analysis included a study of 30 microalbuminuric patients with insulin-dependent diabetes mellitus, despite the well-known fact that glomerular filtration rate remains stable in the microalbuminuria stage. The limitations of the two remaining studies of diabetic renal disease have been examined elsewhere [4, 5].