Walker, James David; (1994) Dietary protein and the progression of diabetic nephropathy. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Nineteen insulin-dependent diabetic patients with diabetic nephropathy were studied prospectively for up to five years. Patients served as their own controls and were treated with a diet reduced in protein (low protein diet (LPD)) for a mean (range) of 33 (12-49) months following a run-in period of 29 (12-39) months on a normal protein diet (NPD). The prescribed diet achieved a mean (SE) reduction of 41% in protein intake from 1.11 (0.06) on NPD to 0.66 (0.03) g/Kg/day on LPD (p<0.0001). On LPD carbohydrate intake rose by 15% and fat intake fell by 27% (p<0.05 and p<0.006 respectively). Dietary phosphate was lower (1484 (92) vs 1009 (33) mg/day, p<0.0001) and although total energy intake and body weight fell in the first six months of LPD they thereafter plateaued (1935 (116) to 1729 (106) kcal/day and 73 (3) to 70 (3) Kg respectively, p<0.02 for both). Plasma albumin increased (38 (0.8) to 40 (0.9) g/1, p<0.002) and mid-arm muscle circumference remained stable at 25 (1) cm. Glycosylated haemoglobin level remained similar during the two diet periods (NPD 8.9 (0.3) vs LPD 9.0 (0.5) %, NS) while mean supine blood pressure fell by 4 mmHg (p=0.001) during the LPD period due to commencement or modification of antihypertensive therapy in nine patients. During the period of NPD the mean glomerular filtration rate (GFR) fell at a rate of 0.61 (0.14) ml/min/mo. which was considerably higher than the rate of fall of 0.14 (0.08) ml/min/mo. on LPD (p=0.001). The effect of LPD on the rate of change of GFR remained highly significant (p=0.002) after adjustments were made for the potentially confounding variables of blood pressure and glycosylated haemoglobin. The effect of LPD on the rate of decline of GFR was heterogeneous with 10 of the 19 patients showing a significant (p<0.05) slowing in the rate of decline by linear regression or a significant 'break' in the decline of GFR using a 'breakpoint' analysis. No factors could be identified to differentiate those who responded from those who failed to respond. The rise in the fractional clearance of albumin seen during NPD was halted on LPD. A low protein diet effecting reductions in dietary protein and other dietary components such as phosphate and fat appears to retard the rate of decline of GFR in diabetic nephropathy, though in a heterogenous manner, and may be a useful therapy for certain patients. During the two diet periods 164 simultaneous comparisons of the plasma clearance of 51CrEDTA and creatinine clearance as markers of GFR were analysed in 19 patients. A high degree of correlation was seen between the two methods on both diets (r=0.77, p<0.001 and r=0.85, p<0.0001, for NPD and LPD respectively). However, during NPD creatinine clearance over-estimated the clearance of 51CrEDTA by a mean of 5.8 ml/min/1.73 m2 with wide scatter of differences (±2SD 28.2 to -39.8). During LPD the creatinine clearance again over-estimated the clearance of 51CrEDTA on average by 5.3 ml/min/1.73 m2 with a narrower scatter of differences (±2SD 19.0 to -29.6). Thus, on both the normal and low protein diets the creatinine clearance on average overestimated GFR (i.e. shows bias) and there were wide limits of agreements (standard deviations) between the two methods. The limits of agreement were 40% lower on LPD compared to NPD. Creatinine clearance is not a reliable marker for the estimation of GFR compared to the clearance of 51CrEDTA although it is more accurate on a low compared to a normal protein diet.

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