Serum concentrations of laminin-P1 in thrombotic microangiopathy: Usefulness as an index of activity and prognostic value

Laminin is the main noncollagenous constituent of the basement membrane, an d its serum levels could reflect the metabolic changes that occur in the ba sement membrane. Severe endothelial injury with thickening of basement memb rane is a characteristic feature of thrombotic microangiopathy (TMA). With this background, the aim of the study was to investigate in a prospective w ay (1) the relationship among serum Lam-P1, the extent of renal histopathol ogic lesions, and the biochemical parameters commonly used as markers of TM A activity, and (2) the usefulness of serum Lam-P1 concentrations as a rena l outcome prognostic index. To this end, 18 consecutive patients with activ e biopsy-proven TMA with renal involvement were studied. One hundred and tw enty-one healthy control subjects, 20 patients with systemic scleroderma wi thout renal involvement, and 35 patients with systemic lupus erythematosus (20 without nephropathy and 15 with diffuse proliferative type 4 lupus neph ritis) were used as control groups. In addition, to analyze the influence o f either renal failure or hemodialysis therapy on serum Lam-P1 levels, 91 p atients on regular hemodialysis therapy and 81 patients with predialysis ch ronic renal failure of different etiologies were included in the study. Ser um Lam-P1 was determined by RTA at admission, on days 10 and 30 of follow-u p in all patients, and after 6 and 12 mo of follow-up in all surviving pati ents. Serum lactate dehydrogenase, haptoglobin, platelet count, hemoglobin, and serum creatinine were determined as markers of endothelial dysfunction and hemolysis. At admission, serum levels of Lam-P1 were significantly hig her in patients with TMA than in healthy control subjects (3.39 +/- 0.56 U/ ml versus 1.40 +/- 0.18 U/ml; P < 0.0001). In addition, patients with TMA h ad significantly higher serum Lam-P1 levels than the other groups included in the study. At the first control, Lam-P1 correlated with lactate dehydrog enase (P = 0.006) and hemoglobin (P = 0.002). During follow-up, platelet co unt and hemolysis indicators normalized in all patients, while serum Lam-P1 decreased only in patients with renal function recovery. In multivariate a nalysis, serum creatinine and Lam-P1 at day 10 were the only independent pr edictors of renal outcome (r(2) = 0.94; P < 0.0001) and also correlated wit h indices of histopathologic damage (P < 0.001). Serum Lam-P1 normalized in all patients with chronic renal failure in the samples obtained at 6 and 1 2 mo of regular hemodialysis after solving active TMA, thus suggesting that histopathologic lesions, but not renal function itself, would be mainly re sponsible for the high Lam-P1 serum concentrations detected in TMA. In conc lusion, serum Lam-P1 concentrations are increased in patients with active T MA. Furthermore, patients with poor renal outcome show a prolonged increase of serum Lam-P1 that is related to the extent of renal histologic lesions. Unlike the biochemical markers of hemolysis commonly used to assess TMA ac tivity, the sequential determination of serum Lam-P1 provides valuable info rmation about long-term renal prognosis in patients with TMA.