Simvastatin maintains steady patterns of GFR and improves AER and expression of slit diaphragm proteins in type II diabetes

The factors determining the course of glomerular fitration
rate (GFR) and albumin excretion rate (AER) and the
expression of mRNA of slit diaphragm (SD) and podocyte
proteins in microalbuminuric, hypertensive type II diabetic
patients are not fully understood. GFR, AER, and SD protein
mRNA were studied in 86 microalbuminuric, hypertensive,
type II diabetics at baseline and after 4-year random
double-blind treatment either with 40mg simvastatin
(Group 1) or with 30g cholestyramine (Group 2) per day.
Both groups had at baseline a GFR decay per year in the
previous 2–4 years of 3ml/min/1.73m2. Both Groups 1 and
2 showed a significant decrease of low-density lipoprotein
cholesterol levels after simvastatin and cholestyramine
treatment (Po0.01). No change from base line values was
observed as for hs-C-reactive protein and interleukin-6. A
significant decrease of 8-hydroxydeoxyguanosine urinary
excretion was observed after simvastatin treatment. GFR
did not change from baseline with simvstatin, whereas a
decrease was observed with cholestyramine treatment
(simvastatin vs cholestyramine: 0.21 vs –2.75ml/min/
1.73m2, Po0.01). AER decreased in Group 1 (Po0.01), but
not in Group 2 patients. Real-time polymerase chain reaction
measurement of mRNA SD proteins (CD2AP, FAT, Actn 4,
NPHS1, and NPHS2) significantly increased in kidney biopsy
specimens after simvastatin, but not cholestyramine
treatment. Simvastatin, but not cholestyramine, 4-year
treatment maintains steady patterns of GFR, and improves
AER and expression of SD proteins in type II diabetes,
despite similar hypocholesterolemic effects in circulation.