Defining the Complement Biomarker Profile of C3 Glomerulopathy

Zhang, Yuzhou; Nester, Carla; Martin, Bertha; Skjoedt, Mikkel‐Ole; Meyer, Nicole C.; Shao, Dingwu; Borsa, Nicolò; Palarasah, Yaseelan; Smith, Richard J.H.

doi:10.2215/cjn.01820214

Cited by 71 publications

(80 citation statements)

References 20 publications

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“…7 Elevated soluble C5b-9 has recently been described as a new biomarker of C5 convertase activity, mainly associated with C3GN pattern. 31 In MIg-C3G, 40% of patients had low C3 level. Interestingly, hematological response was associated with a significant increase in C3 level, suggesting C3 level may serve as biomarker of treatment efficacy.…”

mentioning

confidence: 95%

Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Chauvet

Frémeaux‐Bacchi

Petitprez

et al. 2017

Blood

127

115

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Key Points• Monoclonal gammopathy is associated with C3 glomerulopathy.• Specific treatment of the underlying B-cell clone improves renal survival.The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of monoclonal immunoglobulin (MIg) in the occurrence of renal disease and raises the issue of the therapeutic management. The aim of the study was to evaluate the effect of chemotherapy in a large cohort of patients with MIgassociated C3G. Fifty adult patients with MIg and biopsy-proven C3G were extracted from the French national database of C3G. We retrospectively compared renal outcomes in patients who either received or did not receive chemotherapy targeting the underlying B-cell clone. At diagnosis, renal disease was severe, with nephrotic-range proteinuria in 20/46 (43%) patients and chronic kidney disease stage 3 or above in 42/49 (86%) patients. Monoclonal gammopathy was of IgG type in 47 (94%) patients. Hematological diagnosis was monoclonal gammopathy of renal significance in 30 (60%), multiple myeloma in 17 (34%), and chronic lymphocytic leukemia in 3 (6%) patients. Complement studies showed low C3 level in 22/50 (43%) and elevated soluble C5b-9 level in 27/34 (79%) patients. Twenty-nine patients received chemotherapy (including bortezomib in 22), whereas 8 and 13 patients received various immunosuppressive drugs or symptomatic measures alone, respectively. Patients who achieved hematological response after chemotherapy had higher renal response rates (P 5 .0001) and median renal survival (hazard ratio, 0.22; 95% confidence interval, 0.05-0.92; P 5 .009) than those receiving conservative/immunosuppressive therapy. In conclusion, our results suggest that chemotherapy adapted to the B-cell clone may constitute an efficient strategy for C3G in the setting of MIg, as rapid achievement of hematological response appears to result in improved renal

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confidence: 95%

Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Chauvet

Frémeaux‐Bacchi

Petitprez

et al. 2017

Blood

127

115

View full text Add to dashboard Cite

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“…115 In contrast, elevated soluble membrane attack complex was found to be a marker of response 68 in accordance with the mechanism of action of eculizumab on terminal pathway activation. However, in a series of 32 patients with biopsy-proven DDD, sMAC was elevated in only 3 (9%) patients.…”

Section: Inhibit Complement Activationmentioning

confidence: 70%

Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway

Vriese

Sethi²,

Praet

et al. 2015

Journal of the American Society of Nephrology

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Kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway (AP) are traditionally classified on the basis of clinical presentation (atypical hemolytic uremic syndrome as thrombotic microangiopathy), biopsy appearance (dense deposit disease and C3 GN), or clinical course (atypical postinfectious GN). Each is characterized by an inappropriate activation of the AP, eventuating in renal damage. The clinical diversity of these disorders highlights important differences in the triggers, the sites and intensity of involvement, and the outcome of the AP dysregulation. Nevertheless, we contend that these diseases should be grouped as disorders of the AP and classified on an etiologic basis. In this review, we define different pathophysiologic categories of AP dysfunction. The precise identification of the underlying abnormality is the key to predict the response to immune suppression, plasma infusion, and complement-inhibitory drugs and the outcome after transplantation. In a patient with presumed dysregulation of the AP, the collaboration of the clinician, the renal pathologist, and the biochemical and genetic laboratory is very much encouraged, because this enables the elucidation of both the underlying pathogenesis and the optimal therapeutic approach.

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“…We noted that the cancer concept was also closely related to that of genetics. We found here that the use of the keyword "pathway" highlighted all articles pertaining to cell signalling or gene pathways [20][21][22][23][24][25][26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Patient healthcare trajectory. An essential monitoring tool: a systematic review

Pinaire

Azé

Bringay

et al. 2017

Health Inf Sci Syst

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Background: Patient healthcare trajectory is a recent emergent topic in the literature, encompassing broad concepts. However, the rationale for studying patients' trajectories, and how this trajectory concept is defined remains a public health challenge. Our research was focused on patients' trajectories based on disease management and care, while also considering medico-economic aspects of the associated management. We illustrated this concept with an example: a myocardial infarction (MI) occurring in a patient's hospital trajectory of care. The patient follow-up was traced via the prospective payment system. We applied a semi-automatic text mining process to conduct a comprehensive review of patient healthcare trajectory studies. This review investigated how the concept of trajectory is defined, studied and what it achieves.Methods: We performed a PubMed search to identify reports that had been published in peer-reviewed journals between January 1, 2000 and October 31, 2015. Fourteen search questions were formulated to guide our review. A semi-automatic text mining process based on a semantic approach was performed to conduct a comprehensive review of patient healthcare trajectory studies. Text mining techniques were used to explore the corpus in a semantic perspective in order to answer non-a priori questions. Complementary review methods on a selected subset were used to answer a priori questions.Results: Among the 33,514 publications initially selected for analysis, only 70 relevant articles were semi-automatically extracted and thoroughly analysed. Oncology is particularly prevalent due to its already well-established processes of care. For the trajectory thema, 80% of articles were distributed in 11 clusters. These clusters contain distinct semantic information, for example health outcomes (29%), care process (26%) and administrative and financial aspects (16%). Conclusion:This literature review highlights the recent interest in the trajectory concept. The approach is also gradually being used to monitor trajectories of care for chronic diseases such as diabetes, organ failure or coronary artery and MI trajectory of care, to improve care and reduce costs. Patient trajectory is undoubtedly an essential approach to be further explored in order to improve healthcare monitoring.

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Defining the Complement Biomarker Profile of C3 Glomerulopathy

Cited by 71 publications

References 20 publications

Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway

Patient healthcare trajectory. An essential monitoring tool: a systematic review

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