Should proteinuria reduction be the criterion for antihypertensive drug selection for patients with kidney disease?
OBJECTIVE
Proteinuria, that is, more than 200 mg/day of urinary albumin, is associated with the presence of kidney disease. Its increase over time is strongly correlated with progression of nephropathy. Retrospective analyses of nephropathy outcome trials show that proteinuria reduction of 30% or more after initiation of blood pressure (BP)-lowering therapy is associated with slower nephropathy progression than lowering BP without its reduction.


RESULTS
Retrospective analyses of five large nephropathy outcome trials demonstrate that nephropathy progression slowed by an additional 28-39% over the control or placebo group when proteinuria was reduced in concert with BP. Two separate trials demonstrate that nephropathy progression was slowed to a lesser degree when BP was reduced to a similar degree, but proteinuria reduced less than 30%. These associations do not hold for those with microalbuminuria, in which BP reduction is the key element to slowing nephropathy progression. Recent cardiovascular outcome trials fail to show a relationship between reductions in proteinuria and nephropathy outcomes. This large cardiovascular endpoint trial, however, was not only powered for nephropathy outcomes but also failed to show a benefit between proteinuria reduction and cardiovascular events, a previously established observation.


CONCLUSIONS
All patients with a history of hypertension and either kidney disease or diabetes should have an annual check for albuminuria. If albumin is present in amounts of more than 200 mg/day, strategies for BP-lowering therapy should also focus on a reduction of more than 30% of urinary protein.
Kalaitzidis
Rigas G
RG
Department of Medicine, Hypertensive Diseases Unit, University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, USA.
Bakris
George L
GL
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000652:urine*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000517:prevention & control / Q000652:urine*; D011507:Proteinuria / Q000188:drug therapy*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers