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. 2020 Dec 1;2(1):105-113.
doi: 10.34067/KID.0006172020. eCollection 2021 Jan 28.

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

Benjamin M Forster  1 , Robert Nee  1 , Dustin J Little  2 , Peter J Greasley  3 , James B Hughes  1 , Sarah M Gordon  4 , Stephen W Olson  1
Affiliations

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

Benjamin M Forster et al. Kidney360. .

Abstract

Background: FSGS is a heterogeneic glomerular disease. Risk factors for kidney disease ESKD and the effect of immunosuppression treatment (IST) has varied in previously published cohorts. These cohorts were limited by relatively small case numbers, short follow-up, lack of racial/ethnic diversity, a mix of adult and pediatric patients, lack of renin-angiotensin-aldosterone system (RAAS) inhibition, or lack of subgroup analysis of IST.

Methods: We compared demographics, clinical characteristics, histopathology, and IST to long-term renal survival in a large, ethnically diverse, adult cohort of 338 patients with biopsy-proven FSGS with long-term follow-up in the era of RAAS inhibition using data from the US Department of Defense health care network.

Results: Multivariate analysis showed that nephrotic-range proteinuria (NRP), eGFR <60 ml/min per 1.73 m2, hypoalbuminemia, interstitial fibrosis and tubular atrophy, and interstitial inflammation at diagnosis and the absence of remission were all associated with worse long-term renal survival. IgM, C3, and a combination of IgM/C3 immunofluorescence staining were not associated with reduced renal survival. IST was not associated with improved renal survival in the whole cohort, or in a subgroup with NRP. However, IST was associated with better renal survival in a subgroup of patients with FSGS with both NRP and hypoalbuminemia and hypoalbuminemia alone.

Conclusions: Our study suggests that IST should be reserved for patients with FSGS and nephrotic syndrome. It also introduces interstitial inflammation as a potential risk factor for ESKD and does not support the proposed pathogenicity of IgM and complement activation.

Keywords: end stage kidney disease; estimated glomerular filtration rate; focal segmental glomerulosclerosis; glomerular and tubulointerstitial diseases; immunosuppression; proteinuria; renal survival; risk factors.

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Conflict of interest statement

D. Little and P. Greasley both work for AstraZeneca. They have no significant financial arrangements to produce or sell products that are the subject of the studies reported in this manuscript. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
FSGS Kaplan-Meier curves for renal survival on the basis of disease acuity variables. These include (A) nephrotic range proteinuria versus non-nephrotic range proteinuria; (B) serum albumin ≤2.5 g/dl versus >2.5 g/dl; (C) serum albumin ≤3.0 mg/dl versus >3.0 mg/dl; and (D) interstitial inflammation ≥15% versus <15%. Dx, diagnosis.
Figure 2.
Figure 2.
FSGS Kaplan-Meier curves for renal survival on the basis of disease chronicity variables. These include (A) eGFR ≥60 ml/min/1.732 versus <60 ml/min/1.732 at diagnosis; and (B) interstitial fibrosis and tubular atrophy (IFTA) ≥15% versus <15%.
Figure 3.
Figure 3.
FSGS Kaplan-Meier curves for renal survival curves. These are for (A) immunosuppression treatment (IST) versus no IST; (B) IST versus no IST stratified by nephrotic-range proteinuria; (C) IST versus no IST stratified by albumin ≤3.0 mg/dl; and (D) IST versus no IST stratified by both nephrotic-range proteinuria (NRP) and albumin ≤3.0 mg/dl.
Figure 4.
Figure 4.
FSGS Kaplan-Meier curves for renal survival curve for complete remission (blue), partial remission (red), and no remission (green).
See this image and copyright information in PMC

References

    1. Korbet SM: Treatment of primary FSGS in adults. J Am Soc Nephrol 23: 1769–1776, 2012. 10.1681/ASN.2012040389 - DOI - PubMed
    1. De Vriese AS, Sethi S, Nath KA, Glassock RJ, Fervenza FC: Differentiating primary, genetic, and secondary FSGS in adults: A clinicopathologic approach. J Am Soc Nephrol 29: 759–774, 2018. 10.1681/ASN.2017090958 - DOI - PMC - PubMed
    1. Korbet SM, Schwartz MM, Lewis EJ: Primary focal segmental glomerulosclerosis: clinical course and response to therapy. Am J Kidney Dis 23: 773–783, 1994. 10.1016/S0272-6386(12)80128-4 - DOI - PubMed
    1. Laurin LP, Gasim AM, Poulton CJ, Hogan SL, Jennette JC, Falk RJ, Foster BJ, Nachman PH: Treatment with glucocorticoids or calcineurin inhibitors in primary FSGS. Clin J Am Soc Nephrol 11: 386–394, 2016. 10.2215/CJN.07110615 - DOI - PMC - PubMed
    1. Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC; Toronto Glomerulonephritis Registry Group: Focal and segmental glomerulosclerosis: Definition and relevance of a partial remission. J Am Soc Nephrol 16: 1061–1068, 2005 - PubMed