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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: 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).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.

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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Related in: MedlinePlus

Evaluation of LDH, platelet and 4-variable panel in extra cohorts.(A) All levels of platelet, LDH and the 4-variable panel were evaluated in 157 suspected patients diagnosed with SLE and could discriminate patients with TMA, with an AUC of 0.823, 0.76 and 0.872, respectively. (B) To further validate in another independent group of 113 patients and ROC curve analysis showed that the levels of LDH and the 4-variable panel yielded an AUC of 0.843 and 0.825, showing an good discrimination of TMA (both P<0.001).
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pone-0111992-g004: Evaluation of LDH, platelet and 4-variable panel in extra cohorts.(A) All levels of platelet, LDH and the 4-variable panel were evaluated in 157 suspected patients diagnosed with SLE and could discriminate patients with TMA, with an AUC of 0.823, 0.76 and 0.872, respectively. (B) To further validate in another independent group of 113 patients and ROC curve analysis showed that the levels of LDH and the 4-variable panel yielded an AUC of 0.843 and 0.825, showing an good discrimination of TMA (both P<0.001).

Mentions: Since renal TMA lesions occur in a number of kidney diseases, we focused on a specific condition and 157 renal patients diagnosed with SLE were selected in extra validation (Table S3 in File S1). All levels of platelets, LDH and the 4-variable panel could discriminate patients with TMA in SLE. The ability of discrimination in the 4-variable panel was higher than the levels of platelets and LDH, with an AUC of 0.872 (Figure 4A). With the use of the cutoff point of 0.248, the diagnostic panel has 74.1% sensitivity and 83.6% specificity.


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)

Evaluation of LDH, platelet and 4-variable panel in extra cohorts.(A) All levels of platelet, LDH and the 4-variable panel were evaluated in 157 suspected patients diagnosed with SLE and could discriminate patients with TMA, with an AUC of 0.823, 0.76 and 0.872, respectively. (B) To further validate in another independent group of 113 patients and ROC curve analysis showed that the levels of LDH and the 4-variable panel yielded an AUC of 0.843 and 0.825, showing an good discrimination of TMA (both P<0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111992-g004: Evaluation of LDH, platelet and 4-variable panel in extra cohorts.(A) All levels of platelet, LDH and the 4-variable panel were evaluated in 157 suspected patients diagnosed with SLE and could discriminate patients with TMA, with an AUC of 0.823, 0.76 and 0.872, respectively. (B) To further validate in another independent group of 113 patients and ROC curve analysis showed that the levels of LDH and the 4-variable panel yielded an AUC of 0.843 and 0.825, showing an good discrimination of TMA (both P<0.001).
Mentions: Since renal TMA lesions occur in a number of kidney diseases, we focused on a specific condition and 157 renal patients diagnosed with SLE were selected in extra validation (Table S3 in File S1). All levels of platelets, LDH and the 4-variable panel could discriminate patients with TMA in SLE. The ability of discrimination in the 4-variable panel was higher than the levels of platelets and LDH, with an AUC of 0.872 (Figure 4A). With the use of the cutoff point of 0.248, the diagnostic panel has 74.1% sensitivity and 83.6% specificity.

Bottom Line: 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).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.

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