Increased urinary excretion of alpha1-microglobulin at 6 months after transplantation is associated with urinary excretion of transforming growth factor-beta1 and indicates poor long-term renal outcome.
BACKGROUND
Albumin and alpha1-microglobulin (alpha1M) are absorbed by two specific receptors in tubular epithelial cells. Any cell injury will disturb the reabsorption of these proteins, The increased urinary excretions of albumin or alpha1M could thus serve as a marker of subclinical graft lesions and as an early indicator of chronic allograft dysfunction.


METHODS
We measured 24-hour urinary excretions of albumin, alpha1M, and transforming growth factor (TGF)-beta1 at 6 months after transplantation in 79 renal-graft recipients and recorded the changes in 24-hour creatinine clearance an average 51 (range 14-72) posttransplant follow-up months.


RESULTS
At 6 months from transplantation, 46 of 79 (58%) patients were normoalbuminuric, 25 (32%) microalbuminuric, and 8 (10%) macroalbuminuric. In normoalbuminuric patients, urinary alpha1M/creatinine ratio was 10 times, and TGF-beta1/creatinine ratio approximately 5 times, higher than in the healthy subjects but lower than in albuminuric patients. In all patients, urinary alpha1M correlated with urinary TGF-beta1 (r=0.508, P<0.001), with albumin (r=0.220, P<0.05), and with the annual changes in 24-hour creatinine clearance (r=-0.273, P<0.05). During follow-up, renal function deteriorated in 20 of 33 (60%) patients with alpha1M/creatinine ratio greater than 5 mg/mmol, but only in 1 of 46 (2%) patients whose ratio was less than 5 mg/mmol (P<0.01), giving the ratio 5 mg/mmol or greater a 95% sensitivity to detect patients with poor long-term outcome.


CONCLUSIONS
We show proximal tubular injury, measured by increased urinary alpha1M, to be present even in normoalbuminuric patients and to be associated with increased excretion of TGF-beta1 and with the annual deterioration of glomerular filtration rate. These findings show increased alpha1M/creatinine ratio to be an early and sensitive indicator of poor long-term outcome in renal-transplant patients.
Teppo
Anna-Maija
AM
Department of Medicine, Division of Nephrology, Helsinki University Hospital, Helsinki, Finland.
Honkanen
Eero
E
Finne
Patrik
P
Törnroth
Tom
T
Grönhagen-Riska
Carola
C
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000473:pathology; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000652:urine*; D053773:Transforming Growth Factor beta1; D017211:Treatment Failure; D016896:Treatment Outcome; D000511:alpha-Macroglobulins / Q000652:urine*
D015415:Biomarkers; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000511:alpha-Macroglobulins; D003404:Creatinine