Differential effects of calcium channel blockers on size selectivity of proteinuria in diabetic glomerulopathy.
BACKGROUND
Calcium channel blockers (CCBs) are known to have differential effects on both changes in proteinuria as well as progression of diabetic nephropathy. No clinical study, however, has evaluated whether the differential antiproteinuric effects of CCBs may be explained by their effect on glomerular membrane permeability. We, therefore, tested the hypothesis that certain subclasses of CCBs reduce proteinuria by changing size selectivity of the glomerular membrane, hence changing its permeability.


METHODS
Twenty-one patients with type 2 diabetes and the presence of nephropathy with hypertension were randomized to receive either diltiazem CD or nifedipine GITS after baseline data for mean systolic and diastolic pressure, urinary protein excretion, glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearances were obtained. Glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearance were measured every three months, arterial pressure and heart rate every month. Patients were followed for 21 months.


RESULTS
At 21 months, both patient groups had similar levels of blood pressure control, however, only the diltiazem group had a change in proteinuria (4+/-10%delta, nifedipine vs. -57+/-18%delta, diltiazem; P < 0.001) with improvement in glomerular size selectivity and change in IgG clearance.


CONCLUSIONS
These data support the hypothesis that CCBs that provide sustained reductions in proteinuria do so, in part, by improving glomerular size permselectivity.
Smith
A C
AC
Rush University Hypertension Center, Department of Preventive Medicine, Chicago, Illinois 60612, USA.
Toto
R
R
Bakris
G L
GL
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004110:Diltiazem / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy* / Q000473:pathology
D002121:Calcium Channel Blockers; D004110:Diltiazem; D009543:Nifedipine