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A non-invasive laboratory panel as a diagnostic and prognostic biomarker for thrombotic microangiopathy: development and application in a Chinese cohort study.

Zhang T, Chen H, Liang S, Chen D, Zheng C, Zeng C, Zhang H, Liu Z - PLoS ONE (2014)

Bottom Line: The discrimination effects of these three markers were confirmed in patients with SLE.Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed.The noninvasive laboratory diagnostic panel is better for the early detection and prognosis of TMA compared with a single parameter, and may provide a promising biomarker for clinical application.

View Article: PubMed Central - PubMed

Affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P. R. China.

ABSTRACT

Background: Thrombotic microangiopathy (TMA) in the kidney is a histopathologic lesion that occurs in a number of clinical settings and is often associated with poor renal prognosis. The standard test for the diagnosis of TMA is the renal biopsy; noninvasive parameters such as potential biomarkers have not been developed.

Methods: We analyzed routine parameters in a cohort of 220 patients with suspected TMA and developed a diagnostic laboratory panel by logistic regression. The levels of candidate markers were validated using an independent cohort (n = 46), a cohort of systemic lupus erythematosus (SLE) (n = 157) and an expanded cohort (n = 113), as well as 9 patients with repeat biopsies.

Results: Of the 220 patients in the derivation cohort, 51 patients with biopsy-proven TMA presented with a worse renal prognosis than those with no TMA (P = 0.002). Platelet and L-lactate dehydrogenase (LDH) levels showed an acceptable diagnostic value of TMA (AUC = 0.739 and 0.756, respectively). A panel of 4 variables - creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate patients with TMA (AUC = 0.800). In the validation cohort, the platelet and LDH levels and the 4-variable panel signature robustly distinguished patients with TMA. The discrimination effects of these three markers were confirmed in patients with SLE. Moreover, LDH levels and the 4-variable panel signature also showed discrimination values in an expanded set. Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed. Importantly, only the 4-variable panel was an independent prognostic marker for renal outcome (hazard ratio = 3.549; P<0.001).

Conclusions: The noninvasive laboratory diagnostic panel is better for the early detection and prognosis of TMA compared with a single parameter, and may provide a promising biomarker for clinical application.

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Receiver operating characteristic curves of laboratory parameters.(A) The fraction of true positive results (sensitivity) and the fraction of false positive results (1-specificity) for LDH, HGB, SCr, PLT, THBD and ADAMTS13 activity were developed in 220 patients (all P≤0.001), and the levels of platelet and LDH showed acceptable discrimination, with AUC 0.739 and 0.756, respectively. (B) The levels of platelet and LDH could discriminate patients with TMA from those with no TMA in the validation cohort (n = 46), with AUC 0.747 and 0.741, respectively.
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pone-0111992-g002: Receiver operating characteristic curves of laboratory parameters.(A) The fraction of true positive results (sensitivity) and the fraction of false positive results (1-specificity) for LDH, HGB, SCr, PLT, THBD and ADAMTS13 activity were developed in 220 patients (all P≤0.001), and the levels of platelet and LDH showed acceptable discrimination, with AUC 0.739 and 0.756, respectively. (B) The levels of platelet and LDH could discriminate patients with TMA from those with no TMA in the validation cohort (n = 46), with AUC 0.747 and 0.741, respectively.

Mentions: The levels of serum creatinine, LDH and thrombomodulin (THBD) were significantly higher in patients with TMA than those without TMA, while levels of hemoglobin, platelets and ADAMTS13 activity were remarkably lower (all P<0.05; Table 1). With a cutoff of 0.05 (P value, in Table 1), 6 laboratory parameters were included in the next binary logistic regression analysis. The ROC curve showed that these 6 parameters individually can distinguish patients with TMA in the derivation set (all P<0.05; Figure 2A). Only the platelet and LDH levels showed acceptable discrimination values (0.7≤AUC<0.8), while levels of hemoglobin, serum creatinine, ADAMSTS13 activity and THBD had low discrimination accuracy (0.5≤AUC<0.7). With the use of the cutoff point of 97.5×109/L, platelets had 82.4% sensitivity and 60.9% specificity, and with the cutoff point of 289 u/L, LDH had 67.3% sensitivity and 74.1% specificity (Table S1 in File S1).


A non-invasive laboratory panel as a diagnostic and prognostic biomarker for thrombotic microangiopathy: development and application in a Chinese cohort study.

Zhang T, Chen H, Liang S, Chen D, Zheng C, Zeng C, Zhang H, Liu Z - PLoS ONE (2014)

Receiver operating characteristic curves of laboratory parameters.(A) The fraction of true positive results (sensitivity) and the fraction of false positive results (1-specificity) for LDH, HGB, SCr, PLT, THBD and ADAMTS13 activity were developed in 220 patients (all P≤0.001), and the levels of platelet and LDH showed acceptable discrimination, with AUC 0.739 and 0.756, respectively. (B) The levels of platelet and LDH could discriminate patients with TMA from those with no TMA in the validation cohort (n = 46), with AUC 0.747 and 0.741, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221199&req=5

pone-0111992-g002: Receiver operating characteristic curves of laboratory parameters.(A) The fraction of true positive results (sensitivity) and the fraction of false positive results (1-specificity) for LDH, HGB, SCr, PLT, THBD and ADAMTS13 activity were developed in 220 patients (all P≤0.001), and the levels of platelet and LDH showed acceptable discrimination, with AUC 0.739 and 0.756, respectively. (B) The levels of platelet and LDH could discriminate patients with TMA from those with no TMA in the validation cohort (n = 46), with AUC 0.747 and 0.741, respectively.
Mentions: The levels of serum creatinine, LDH and thrombomodulin (THBD) were significantly higher in patients with TMA than those without TMA, while levels of hemoglobin, platelets and ADAMTS13 activity were remarkably lower (all P<0.05; Table 1). With a cutoff of 0.05 (P value, in Table 1), 6 laboratory parameters were included in the next binary logistic regression analysis. The ROC curve showed that these 6 parameters individually can distinguish patients with TMA in the derivation set (all P<0.05; Figure 2A). Only the platelet and LDH levels showed acceptable discrimination values (0.7≤AUC<0.8), while levels of hemoglobin, serum creatinine, ADAMSTS13 activity and THBD had low discrimination accuracy (0.5≤AUC<0.7). With the use of the cutoff point of 97.5×109/L, platelets had 82.4% sensitivity and 60.9% specificity, and with the cutoff point of 289 u/L, LDH had 67.3% sensitivity and 74.1% specificity (Table S1 in File S1).

Bottom Line: The discrimination effects of these three markers were confirmed in patients with SLE.Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed.The noninvasive laboratory diagnostic panel is better for the early detection and prognosis of TMA compared with a single parameter, and may provide a promising biomarker for clinical application.

View Article: PubMed Central - PubMed

Affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P. R. China.

ABSTRACT

Background: Thrombotic microangiopathy (TMA) in the kidney is a histopathologic lesion that occurs in a number of clinical settings and is often associated with poor renal prognosis. The standard test for the diagnosis of TMA is the renal biopsy; noninvasive parameters such as potential biomarkers have not been developed.

Methods: We analyzed routine parameters in a cohort of 220 patients with suspected TMA and developed a diagnostic laboratory panel by logistic regression. The levels of candidate markers were validated using an independent cohort (n = 46), a cohort of systemic lupus erythematosus (SLE) (n = 157) and an expanded cohort (n = 113), as well as 9 patients with repeat biopsies.

Results: Of the 220 patients in the derivation cohort, 51 patients with biopsy-proven TMA presented with a worse renal prognosis than those with no TMA (P = 0.002). Platelet and L-lactate dehydrogenase (LDH) levels showed an acceptable diagnostic value of TMA (AUC = 0.739 and 0.756, respectively). A panel of 4 variables - creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate patients with TMA (AUC = 0.800). In the validation cohort, the platelet and LDH levels and the 4-variable panel signature robustly distinguished patients with TMA. The discrimination effects of these three markers were confirmed in patients with SLE. Moreover, LDH levels and the 4-variable panel signature also showed discrimination values in an expanded set. Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed. Importantly, only the 4-variable panel was an independent prognostic marker for renal outcome (hazard ratio = 3.549; P<0.001).

Conclusions: The noninvasive laboratory diagnostic panel is better for the early detection and prognosis of TMA compared with a single parameter, and may provide a promising biomarker for clinical application.

Show MeSH
Related in: MedlinePlus