Abstract
IntroductionGuidelines advise initial therapy with corticosteroids (CSs) in patients with presumed primary focal segmental glomerular sclerosis (pFSGS). Many patients do not achieve complete remission (CR) after 8 or 16 weeks. Although these patients are considered steroid resistant, clinical outcomes are ill defined.MethodsA retrospective cohort study of patients with pFSGS who were referred between January 1995 and December 2014. Data of clinical presentation until last follow-up were collected from patient records.ResultsA total of 51 patients (median age 47 years, 20 female/31 male) were included (median follow-up 7.1 years). There were 10 patients who achieved partial response (PR) at 8 weeks. High-dose CS monotherapy was continued for a median of 17 weeks (interquartile range [IQR] 11–21 weeks) (total duration 56 weeks [IQR 28–83 weeks]). With CSs, the cumulative incidence of CR + PR was 18% and 35%, respectively. Of 24 patients with persistent nephrotic-range proteinuria, 22 received additional immunosuppressive (IS) therapy, resulting in CR in 3 (14%) and PR in 11 patients (50%). A decrease of >20% of proteinuria at 8 weeks predicted response. In addition, 8 patients (36%) were considered primary nonresponders. A genetic cause was found in 2 patients. Proteinuria at end of follow-up was 1.2 g (IQR 0.4–3.0 g/24 hours or g/10 mmol creatinine). Renal survival at 3, 5, and 10 years was 92%, 87%, and 64%, respectively.ConclusionPatients with presumed pFSGS often respond late to IS therapy. A decrease in proteinuria of >20% after 8 weeks of therapy is a predictor of responsiveness. Regardless of CR in some patients, improved biomarkers are needed to predict response/outcomes in patients with pFSGS.
Highlights
Guidelines advise initial therapy with corticosteroids (CS) in patients with presumed primary focal segmental glomerulosclerosis
3.1 Patients From the Focal segmental glomerulosclerosis (FSGS) cohort (n=190) we identified 70 patients who presented with nephrotic syndrome (NS) and were initially treated with high dose corticosteroids as monotherapy
Primary FSGS is defined as a clinicalpathological entity, characterized by nephrotic syndrome, complete foot process effacement, Journal Pre-proof variable responsiveness to immunosuppressive therapy, and recurrence after kidney transplantation
Summary
Guidelines advise initial therapy with corticosteroids (CS) in patients with presumed primary focal segmental glomerulosclerosis (pFSGS). Primary FSGS (pFSGS) remains a clinical (“presumed”) diagnosis, Journal Pre-proof and is defined by the presence of nephrotic syndrome with low serum albumin, complete foot process effacement, in the absence of underlying secondary causes (such as small kidney size, refluxnephropathy, a positive family history or obesity). 21-40% of the treated patients attain a complete remission.[4,5,6,7] Patients who are steroid-unresponsive are considered steroid resistant, but there is no consensus in literature regarding the duration of prednisone therapy that defines steroid-resistance.[8] In children steroid resistance is defined as no response within four to eight weeks of treatment with high dose corticosteroids.[9] In adults, some authors define steroid resistance as persistent nephrotic syndrome after eight weeks treatment with high dose corticosteroids.[10] Others describe remissions in patients after prolonged treatment with high dose corticosteroids and argue that steroid resistance should be defined after a treatment duration with high dose corticosteroids of up to four months.[8, 11,12,13,14] The variation in definitions used to define steroid resistance hampers the interpretation of clinical course and outcome. Several studies included patients without overt nephrotic syndrome (i.e. without hypo-albuminemia).[4, 5, 15] These patients do not fulfill the definition of presumed primary FSGS, and the recently published KDIGO guideline includes the category FSGS of undetermined cause (FSGS-UC).[2, 16] It is generally accepted that patients with secondary forms of FSGS are unresponsive to corticosteroids
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