Abstract
BackgroundTherapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. suPAR has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease. This study was targeted to evaluate the application of monitoring suPAR in TPE treated rFSGS.MethodsA retrospective (n = 19) and a prospective (n = 15) cohort of post transplant FSGS patients treated with TPE and rituximab were enrolled. We measured serum suPAR levels before and after the combined therapies, and assessed the role of suPAR changes on proteinuria reduction and podocyte β3- integrin activity.ResultsTreatment with TPE and rituximab resulted in significant decrease in proteinuria and suPAR levels. Among the variables including baseline suPAR, serum creatinine, proteinuria, eGFR, age at diagnosis, age at transplantation, transplantation numbers, time to recurrence, and TPE course numbers, only the reduction in suPAR levels and baseline proteinuria significantly correlated with the changes in proteinuria after treatment, with the former performed better in predicting proteinuria alteration. Additionally, the mean podocyte β3 integrin activity significantly decreased after TPE and rituximab treatment (1.10 ± 0.08) as compared to before treatment (1.34 ± 0.08), p < 0.05. Only the reduction in suPAR predicted the response to therapies with an odds ratio of 1.43, 95% CI (1.02, 2.00), p < 0.05.ConclusionsSerum suPAR levels reduced significantly after TPE and rituximab treatment in post transplant FSGS patients. The reduction in suPAR levels may be utilized to assess the changes in proteinuria and monitor the response to the therapies. Larger, multi-centered prospective studies monitoring serum suPAR levels in TPE managed post transplant FSGS are warranted.
Highlights
Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis post kidney transplant. Soluble urokinase receptor (suPAR) has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease
Single course of TPE on suPAR removal To look at the immediate effect of TPE on serum suPAR levels, we compared serum suPAR right before and after a single course of TPE
We found that single course of TPE could remove on average 37% of serum suPAR (Fig. 1a)
Summary
Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. suPAR has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease. Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. This study was targeted to evaluate the application of monitoring suPAR in TPE treated rFSGS. Several longitudinal studies in a variety of patient cohorts (cardiac risk, healthy middle-aged, pre-diabetic, dialysis patients) have found that baseline circulating suPAR levels predict chronic kidney disease (CKD) incidence and progression [11,12,13], strongly suggesting the application of circulating suPAR as a biomarker for monitoring CKD. As TPE has been found to remove suPAR from blood circulation in several studies [9, 14,15,16], we sought to evaluate the application of serum suPAR as a biomarker monitoring TPE treated rFSGS patients in this study
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