Gellermann Jutta, Schaefer Franz, Querfeld Uwe
Department of Pediatric Nephrology, Charité Universitätsmedizin Berlin, Charité Children's Hospital, Augustenburger Platz 1, 13353, Berlin, Germany.
Pediatr Nephrol. 2014 Dec;29(12):2411-4. doi: 10.1007/s00467-014-2913-5. Epub 2014 Aug 17.
Soluble urokinase-type plasminogen activator receptor (suPAR) could be a causative factor in idiopathic focal segmental glomerulosclerosis (FSGS). It is currently unknown to what extent suPAR levels could be affected by treatment with immunosuppressive drugs such as cyclosporin A (CsA) and mycophenolate mofetil (MMF). Treatment with CsA, but not MMF, is accompanied by nephrotoxicity, and since suPAR levels correlate with glomerular filtration rate (GFR), treatment with these drugs could indirectly modulate suPAR levels by their effect on renal function.
We measured suPAR levels in a recent prospective multicenter crossover trial comparing the efficacy of MMF and CsA in pediatric patients with minimal change disease (MCD) and frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). All patients had biopsy-proven MCD and normal renal function; they were treated with each drug for 1 year in a crossover study design. Serum suPAR levels were measured before and after 1 year of therapy with MMF (n = 40) and CsA (n = 35).
The suPAR levels decreased after 1 year of treatment with MMF (p < 0.05). Conversely, suPAR levels increased after 1 year of treatment with CsA in the same patients (p = 0.01). These changes in suPAR levels were not correlated to the estimated glomerular filtration rate (eGFR) or changes in the GFR.
Data from this prospective randomized trial suggest that treatment with MMF and CsA is associated with different effects on suPAR levels in children with MCD and that these are independent of their effects on GFR.
可溶性尿激酶型纤溶酶原激活物受体(suPAR)可能是特发性局灶节段性肾小球硬化(FSGS)的致病因素。目前尚不清楚免疫抑制药物如环孢素A(CsA)和霉酚酸酯(MMF)的治疗会在多大程度上影响suPAR水平。CsA治疗会伴有肾毒性,而MMF则不会,并且由于suPAR水平与肾小球滤过率(GFR)相关,这些药物的治疗可能通过其对肾功能的影响间接调节suPAR水平。
在一项近期的前瞻性多中心交叉试验中,我们比较了MMF和CsA对患有微小病变病(MCD)和频繁复发的激素敏感型肾病综合征(FR-SSNS)的儿科患者的疗效,并测量了suPAR水平。所有患者均经活检证实为MCD且肾功能正常;在交叉研究设计中,他们分别接受每种药物治疗1年。在接受MMF(n = 40)和CsA(n = 35)治疗1年之前和之后测量血清suPAR水平。
MMF治疗1年后suPAR水平下降(p < 0.05)。相反,同一批患者接受CsA治疗1年后suPAR水平升高(p = 0.01)。suPAR水平的这些变化与估计的肾小球滤过率(eGFR)或GFR的变化无关。
这项前瞻性随机试验的数据表明,MMF和CsA治疗对患有MCD的儿童的suPAR水平有不同影响,且这些影响独立于它们对GFR的影响。