Risk factors for the progression of diabetic nephropathy: role of hyperlipidaemia and its correction

Hypertension, proteinuria and hyperlipidaemia are major factors implicated in the progression of chronic renal failure towards uraemia. All of these factors are frequently more pronounced in diabetic nephropathy. We evaluated the rate of progression of renal insufficiency in 12 patients with diabetic nephropathy (DN group) and 18 patients with non-diabetic chronic nephropathy (CN group) during a 2-year period. All patients had high blood pressure on angiotensin-converting enzyme (ACE) inhibitor therapy, hypercholesterolaemia and proteinuria in the non-nephrotic range. Basal glomerular filtration rate (GFR) had an overlapping range in the two groups. The rate of GFR decline during the 2-year period was similar for the DN and CN groups (0.23 vs 0.21 ml/min per month) and correlated with the mean values of low-density lipoprotein (LDL)-cholesterol for both groups (DNr=0.569, CNr=0.511,P<0.05). After 1 year of ACE inhibitor therapy we randomly allocated a subset of patients in each group (6 DN and 9 CN) to receive HMG-CoA-reductase inhibitor (simvastatin or pravastatin 10 mg/day). We observed a decrease in total (–21%) and LDL-cholesterol (–32%) and triglycerides (–11%) and an increase in high-density lipoprotein (HDL)-cholesterol (+8%). The rate of GFR decline was lower in the statin-treated group compared with the previous period (DN–0.21 vs –0.25 ml/min per month; CN –0.18 vs –0.22 ml/min per month). Our data support the hypothesis that associated risk factors rather than diabetes per se are responsible for the rate of progression of renal failure in DN and that the correction of lipid abnormalities may play a key role in slowing the rate of renal function decline.