Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy.
BACKGROUND
Little is known of the effects of blood pressure reduction by specific classes of antihypertensive drugs on the association between proteinuria reduction and progression of kidney insufficiency and development of end-stage kidney disease in patients with overt diabetic nephropathy in type 2 diabetes mellitus.


METHODS
Associations between baseline proteinuria and proteinuria reduction by either irbesartan, amlodipine, or control for similar decrements in blood pressure and the cumulative incidence of renal end points were examined using the Kaplan-Meier method in patients enrolled in the Irbesartan Diabetic Nephropathy Trial.


RESULTS
Risk for kidney failure doubled for each doubling of baseline proteinuria level (hazard ratio, 2.04; 95% confidence interval, 1.87 to 2.22; P < 0.001). For each halving of proteinuria level between baseline and 12 months with treatment, risk for kidney failure was reduced by more than half (hazard ratio, 0.44; 95% confidence interval, 0.40 to 0.49; P < 0.001). For the same proportional change in proteinuria, the reduction in risk for kidney failure was significantly greater for irbesartan compared with amlodipine ( P = 0.048), but not control ( P = 0.245). Proteinuria reduction in the first 12 months of therapy with irbesartan is associated with 36% of the total renoprotective effect observed.


CONCLUSIONS
Baseline proteinuria is an important risk factor for kidney failure and provides a means to identify patients at greatest risk. Halving proteinuria halves the kidney risk. Proteinuria reduction using an angiotensin receptor-blocking agent, such as irbesartan, should be regarded as an important therapeutic goal in renoprotective strategies.
Atkins
Robert C
RC
Department of Nephrology, Monash Medical Centre, Victoria, Australia. bob.atkins@med.monash.edu.au <bob.atkins@med.monash.edu.au>
Briganti
Esther M
EM
Lewis
Julia B
JB
Hunsicker
Lawrence G
LG
Braden
Gregory
G
Champion de Crespigny
Paul J
PJ
DeFerrari
Giacomo
G
Drury
Paul
P
Locatelli
Francesco
F
Wiegmann
Thomas B
TB
Lewis
Edmund J
EJ
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000652:urine*; D003928:Diabetic Nephropathies / Q000209:etiology*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051437:Renal Insufficiency / Q000209:etiology* / Q000517:prevention & control; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
D001713:Biphenyl Compounds; D013777:Tetrazoles; D017311:Amlodipine; D000077405:Irbesartan