Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Division of Nephrology, Department of Medicine, Sunnybrook Health Science Center, University of Toronto, Toronto, Ontario, Canada.
Nephrol Dial Transplant. 2023 Mar 31;38(4):950-960. doi: 10.1093/ndt/gfac238.
Although the clinical benefit of obtaining a remission in proteinuria in nephrotic patients with focal segmental glomerulosclerosis (FSGS) is recognized, the long-term value of maintaining it and the impact of relapses on outcome are not well described.
We examined the impact of remissions and relapses on either a 50% decline in kidney function or end-stage kidney disease (combined event) using time-dependent and landmark analyses in a retrospective study of all patients from the Toronto Glomerulonephritis Registry with biopsy-proven FSGS, established nephrotic-range proteinuria and at least one remission.
In the 203 FSGS individuals with a remission, 89 never relapsed and 114 experienced at least one relapse. The first recurrence was often followed by a repeating pattern of remission and relapse. The 10-year survival from a combined event was 15% higher in those with no relapse versus those with any relapse. This smaller than anticipated difference was related to the favourable outcome in individuals whose relapses quickly remitted. Relapsers who ultimately ended in remission (n = 46) versus in relapse (n = 68) experienced a 91% and 32% 7-year event survival (P < .001), respectively. Using time-varying survival analyses that considered all periods of remission and relapse in every patient and adjusting for each period's initial estimated glomerular filtration rate, the state of relapse was associated with a 2.17 (95% confidence interval 1.32-3.58; P = .002) greater risk of experiencing a combined event even in this FSGS remission cohort.
In FSGS, unless remissions are maintained and relapses avoided, long-term renal survival remains poor. Treatment strategies addressing remission duration remain poorly defined and should be an essential question in future trials.
尽管在局灶节段性肾小球硬化症(FSGS)肾病患者中获得蛋白尿缓解具有临床益处,但维持缓解的长期价值以及复发对结局的影响尚不清楚。
我们通过对多伦多肾小球肾炎登记处所有 FSGS 活检证实、肾病范围内蛋白尿和至少一次缓解的患者进行回顾性研究,使用时间依赖性和标志分析来检查缓解和复发对肾功能下降 50%或终末期肾病(复合事件)的影响。
在 203 例有缓解的 FSGS 个体中,89 例从未复发,114 例至少复发一次。第一次复发后常出现缓解和复发的重复模式。无复发者与有复发者相比,10 年复合事件的生存率高 15%。这种预期差异较小与复发迅速缓解的个体预后良好有关。最终缓解(n=46)与持续复发(n=68)的复发者 7 年事件生存率分别为 91%和 32%(P<0.001)。使用考虑每个患者所有缓解和复发期的时变生存分析,并根据每个期的初始估计肾小球滤过率进行调整,复发状态与经历复合事件的风险增加 2.17 倍(95%置信区间 1.32-3.58;P=0.002),即使在这个 FSGS 缓解队列中也是如此。
在 FSGS 中,除非维持缓解并避免复发,否则长期肾脏存活率仍然较差。解决缓解持续时间的治疗策略仍未得到充分定义,应成为未来试验的一个重要问题。