#3269 EPIDEMIOLOGY OF PRIMARY FSGS INCLUDING CLUSTER ANALYSIS OVER A 20-YEAR PERIOD
Authors: Mcdonnell Thomas , Storrar Josh , Hughes Sabena , Chinnadurai Rajkumar , Heal Calvin , Kalra Philip A , Sinha Smeeta 
Published: June 2023

Abstract

Background and Aims
Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome (NS) in adults. This epidemiological study describes a renal centre's 20 year ‘real world' experience of patients with primary FSGS including cluster analysis.

Method
This retrospective analysis was conducted on patients diagnosed with primary FSGS at a tertiary renal centre with a catchment population of 1.55 million, over 2 decades. Data collection included baseline demographics, laboratory results, immunosuppression (IS) and outcomes: Complete & partial remission, relapse, progression to renal replacement therapy (RRT) and mortality. A two-step cluster analysis was used to reveal groupings to aid prognostication and treatment decisions. Pre-specified cluster variables were: Serum albumin (sAlb), urine protein: creatinine ratio (uPCR) & estimated glomerular filtration rate (eGFR).

Results
87 patients were identified with primary FSGS after exclusion of secondary causes. Mean age was 49.3 years, 60.9% male, 86.2% white with median eGFR 46 ml/min, uPCR 573 mg/mmol, sAlb 33g/l (Table 1). Rates of partial and complete remission were 23% & 49.4% respectively. Progression to RRT occurred in 27.4%, death in 27.4%. Comparing those receiving IS vs not: sAlb was lower 23 g/L vs 40 g/L (p&lt;0.001), uPCR was higher 795 mg/mmol vs 318 mg/mmol (p &lt;0.001). The IS group was more likely to achieve complete remission (62% vs 40%, p = 0.041), but relapsed more 48.6% vs 22% (p&lt;0.027). There were no statistically significant differences between mortality or RRT. The 2-step cluster analysis separated the cohort into 3 clusters, see Fig. 1: Cluster 1 (n = 26) with ‘nephrotic range proteinuria’ mean sAlb 30 g/L, uPCR 778 mg/mmol and eGFR 72 ml/min; Cluster 2 (n = 43) with ‘non-nephrotic range proteinuria’, mean sAlb 39 g/L, uPCR 284 mg/mmol and eGFR 46 ml/min; Cluster 3 (n = 18) ‘NS’ sAlb 20 g/L, uPCR 1117 mg/mmol and eGFR 25 ml/min. IS use was comparable in the NS (cluster 3) and nephrotic range proteinuria (cluster 1) cohorts, but lower in cluster 2 (non-nephrotic range proteinuria) 77.8% & 69.2% vs 11.6% p &lt;0.001. Rates of complete remission were greatest in clusters 1 & 3 vs cluster 2: 57.7% &66.7% vs 37.2% though this did not achieve statistical significance (p 0.067).

Conclusion
Although there have been several recent US & Asian reviews of primary FSGS, this study provides a review of the epidemiology of FSGS over a 20-year period in a predominantly white cohort in the UK. In general, the patients who received IS had lower sAlb and achieved remission more frequently. Although the aetiology of primary FSGS is unknown, it is hypothesised that it is due to an undiscovered circulating permeability factor. After the exclusion of secondary causes, KDIGO suggests only making the diagnosis in the presence of NS. Despite this the average sAlb in most epidemiological studies of primary FSGS have been above 30g/l. This is likely because of the inclusion of undiagnosed genetic or adaptive FSGS, but it may also be true that NS phenotype alone is too insensitive to diagnose primary ‘antibody driven’ FSGS. Our cluster analysis highlighted 3 potential FSGS phenotypes: A nephrotic cluster that clearly require IS; a cohort with preserved sAlb and non-nephrotic range proteinuria who will benefit from supportive care; lastly a cluster with heavy proteinuria but a sAlb &gt; 30g/l. This group may still have antibody driven disease and thus benefit from immunosuppression and potentially genetic testing. The study received grant support from CSL Vifor