Focal Segmental Glomerulosclerosis: Assessing the Risk of Relapse

Abstract

Introduction: Kidney outcomes are improved in primary focal segmental glomerulosclerosis (FSGS) by maintaining a remission in proteinuria. However, characteristics associated with relapses are uncertain. We sought to identify these by analyzing each remission.

Methods: We performed a retrospective study in patients with biopsy-proven lesions of FSGS, absent identifiable secondary cause, who had at least 1 remission from nephrotic-range proteinuria. In each patient, we identified every remission, every relapse, and their durations. Using a multilevel logistic regression to account for the clustering of multiple remissions within a patient, we tested which clinical characteristics were independently associated with relapses.

Results: In 203 individuals, 312 remissions occurred, 177 with and 135 without relapse. A minority of remissions were atypical, defined by either absent hypoalbuminemia and/or no immunosuppression (IS), in contrast to the classic nephrotic syndrome that remits with IS. Atypical remission variants were just as likely to relapse as the classical presentation. Only 24% of remission events were on maintenance therapy at relapse. Independent characteristics associated with relapses were higher maximal proteinuria while nephrotic; and in remission, higher nadir proteinuria, lower serum albumin, and higher blood pressure. Using these variables, we created a tool estimating the 1-year risk of relapse ranging from 9% to 80%, well-calibrated to the observed data.

Conclusion: In FSGS, relapses are frequent but predictable using independent clinical characteristics. We also provide evidence that atypical presentations remit and relapse following the same pattern as classic FSGS presentations. Treatment strategies to prolong remission duration should be addressed in future trials.

Keywords: FSGS; albuminemia; event-analysis; immunosuppression; proteinuria; relapse.

Graphical abstract

Figure 1

Remission event variables of interest. Individuals who relapse can experience subsequent remission events. FU, follow-up; Tx, treatment.

Figure 2

Patient recruitment and flow-chart. FSGS, focal segmental glomerulosclerosis.

Figure 3

Time to relapse (a) in events with and without immunosuppression and (b) in events with and without hypoalbuminemia. IS, immunosuppression.

Figure 4

Univariate factors associated with a relapse by 1-year following a remission when maintenance immunosuppression is tapered, stopped, or not given. The maximal proteinuria during the nephrotic period was categorized into 3 categories: <6, 6–10, and >10 g/d, approximating the tertile cut-offs of 6.2 and 10.4 g per day. The mean arterial pressures of 97 and 107 mmHg approximate blood pressures of 130/80 and 140/90 mm Hg.

Figure 5

Independent factors (a) associated with a relapse at 1 year following the remission, model calibration (b) and applicability to events with and without atypical features (c). Atypical events are defined by remissions that followed nephrotic range proteinuria without hypoalbuminemia or remissions that occurred without the use of immunosuppression. The predicted risk was the predicted probabilities obtained from the multilevel logistic regression. MAP, mean arterial pressure.