The Incidence of Primary vs Secondary Focal Segmental Glomerulosclerosis: A Clinicopathologic Study

Abstract

Objectives To describe the change in the incidence rates of primary and secondary FSGS from 1994 to 2013 in Olmsted County and to identify the clinical and biopsy characteristics that can help distinguish primary from secondary FSGS. Patients and Methods Olmsted County adult residents with native kidney biopsy between January 1, 1994 and December 31, 2013 and FSGS as the only glomerulopathy were identified. The clinical and pathological charachterstics of primary and secondary FSGS were described and compared. Incidence rates of primary and secondary FSGS over period of 1994–2013 were calculated. Results Among 370 adults biopsied during this period, 281 had glomerular diseases, of which 46 (16%) had FSGS. From 1994–2003 to 2004–2013, there was a significant increase in kidney biopsy rates (14.7; 95% CI, 12.1–17.3 vs. 22.9; 95% CI, 20.0–25.7 per 100,000 person-years, 17% increase per 5 years, P<.001) and total FSGS rates (1.4; 95% CI, 0.6–2.2 vs. 3.2; 95% CI, 2.1–4.3 per 100,000 person-years, 41% increase per 5 years, P=.02). Compared to patients with limited foot process effacement (<80%), patients with diffuse effacement (≥80%) without an identifiable cause had lower serum albumin (−0.7 g/dl, P<.001), higher proteinuria (+4.5 g/day, P<.001) and were more likely to have nephrotic syndrome (100% vs 4%, P<.001). Patients with diffuse effacement without an identifiable cause were classified as primary FSGS, which accounted for 3/12 (25%) of cases during 1994–2003 and 9/34 (26%) of cases during 2004–2013. Conclusion While the incidence of FSGS has increased, the proportions of primary and secondary FSGS have remained stable.

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

“…In a series of adult and predominantly white patients with primary FSGS, median FPE was 100%. 29 In two older series, the mean degrees of FPE in primary FSGS were 75% 28 and 65%, with the greatest degrees in the collapsing (82%) and cellular (87%) forms. 27 There was considerable overlap with the degree of FPE observed in secondary FSGS, possibly related to the inclusion of unrecognized genetic FSGS under the primary FSGS designation.…”

“…27 In a mixed cohort of patients with secondary FSGS (that also included some patients with genetic FSGS), the median degree of FPE was 30%. 29 In primary FSGS, however, a putative circulating factor capable of crossing the GBM barrier causes generalized podocyte dysfunction, ensuing in sudden and widespread FPE (Figure 1). In a series of adult and predominantly white patients with primary FSGS, median FPE was 100%.…”

“…However, when primary FSGS was defined as FSGS with absence of conditions typically associated with secondary FSGS and with presence of diffuse FPE, the prevalence of nephrotic syndrome was 100%. 29 More consistently, patients with welldefined forms of maladaptive FSGS (such as obesity, vesicoureteral reflux, and renal mass reduction) present with subnephrotic-range to nephrotic-range proteinuria and rarely, if ever, develop nephrotic syndrome, 28,29,[43][44][45] despite often marked proteinuria well above 3.5 g/24 h.…”

“…Not otherwise specified is the most common variant, and it is equally distributed among primary and secondary forms. 29,50 Perihilar lesions are more usual in maladaptive FSGS, although they can also occur in primary FSGS 29,50,51 and genetic FSGS. 38 Tip lesion, cellular, and collapsing variants usually share the presenting features of heavy proteinuria and the nephrotic syndrome, but they may also present with subnephrotic-range proteinuria.…”

Disease Progression and End-Stage Renal Disease in Diverse Glomerulopathies

“…5,6 FSGS is a histologic lesion that may reflect 1 of 3 main mechanisms: (1) primary FSGS that is caused by an immunologic/cytotoxic process that targets the podocyte and is commonly associated with the nephrotic syndrome and progressive loss of renal function; (2) secondary FSGS that is caused by assorted diseases (eg, obesity, druginduced, and reflux nephropathy) in which proteinuria is often subnephrotic and renal functional decline slower than in primary FSGS; and (3) FSGS that is secondary to genetic defects. 5,6 It would be of interest to determine what percentage of patients with FSGS were represented by each of these subtypes, in particular, by primary FSGS, in view of the higher risk of this subtype to progress to ESRD; notably, proteinuria in patients with FSGS studied by Sim et al 2 ranged from subnephrotic levels to massive proteinuria. As regards the issue of heterogeneity within a specific glomerulopathy, this is perhaps best illustrated by LN, 1 of the 5 glomerulopathies studied by Sim et al 2 ; there are 6 distinct classes of LN, 1 of which is MN, a glomerulopathy also numbering among the 5 analyzed in this study.…”