Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy.
BACKGROUND
Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review.


METHODS
In this novel randomized controlled trial, 47 patients with chronic allograft nephropathy, severe renal impairment, and more than or equal to 1 g/24 hr proteinuria were randomized to lisinopril (group A) or other hypotensives (group B) for 1 year. Sodium bicarbonate was given to all patients to treat metabolic acidosis prophylactically (acidosis increases significantly with lisinopril). The annual rate of decline of graft function was measured isotopically (primary outcome) and 24 hr proteinuria, genotyping, radiolabeled polypeptide aprotinin proximal tubular catabolic studies (in group A only) as secondary outcome measurements were undertaken.


RESULTS
At baseline, groups were comparable except for greater proteinuria in group A. After 1 year, the rate of decline of graft function and graft survival were comparable in both groups. Proteinuria decreased significantly in group A patients only. Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism, plasma aldosterone, and ammonia excretion. Plasma potassium, bicarbonate, and mean arterial pressures were comparable in both groups. Patients with more than or equal to 30% reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene.


CONCLUSIONS
The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year. Lisinopril significantly reduced proteinuria, renal proximal tubular polypeptide catabolism, plasma aldosterone, and ammonia excretion suggesting relative preservation of graft function. Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors.
Amara
Alieu B
AB
Pathophysiology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom.
Sharma
Asheesh
A
Alexander
John L
JL
Alfirevic
Ana
A
Mohiuddin
Atif
A
Pirmohamed
Munir
M
Close
Graeme L
GL
Grime
Steve
S
Maltby
Paul
P
Shawki
Howida
H
Heyworth
Sally
S
Shenkin
Alan
A
Smith
Linda
L
Sharma
Ajay K
AK
Hammad
Abdel
A
Rustom
Rana
R
D000641:Ammonia / Q000652:urine*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002102:Cadaver; D003404:Creatinine / Q000097:blood; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D017706:Lisinopril / Q000627:therapeutic use*; D019520:Living Donors; D020641:Polymorphism, Single Nucleotide; D011507:Proteinuria / Q000235:genetics / Q000517:prevention & control*; D016019:Survival Analysis; D017741:Survivors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000473:pathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000641:Ammonia; D003404:Creatinine; D017706:Lisinopril