Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome

Abstract

Cyclophosphamide (CP) has been used for over 40 years in patients with steroid-sensitive nephrotic syndrome (SSNS) presenting frequent relapses or steroid dependence (SD). We evaluated retrospectively and tried to identify parameters possibly associated with a prolonged and sustained remission (PSR+) ≥5 years in 108 children with steroid-dependent nephrotic syndrome (SDNS) treated with oral CP. Patients had a follow-up time ≥5 years and were divided into two groups according to achievement of PSR (+ and -). Gender, histological injury, cumulative doses of CP, age of onset of illness, and start of treatment and prednisone dose on the occasion of relapse were analyzed. The overall cumulative sustained remission for 5 and 10 years was 25 and 21.6%, respectively. The only factor that influenced a PSR was the degree of SD: the group PSR+ relapsed at prednisone dose of 0.96 ± 0.51 mg/kg vs. 1.29 ± 0.59 mg/kg in group PSR- (p = 0.01). Also, patients who relapsed in the presence of prednisone doses ≤1.4 mg/kg showed a cumulative sustained remission of 43, 35, and 32.7% at 2, 5, and 10 years, respectively, versus 22.5, 12.5, and 5% in those with prednisone >1.4 mg/kg (p = 0.001). Our findings suggest that patients with SDNS who relapse on prednisone dose >1.4 mg/kg are especially prone to an unfavorable response to CP use.

Efficacy of leflunomide combined with prednisone in the treatment of refractory nephrotic syndrome

“…[5][6][7][8] CTX is a classical drug that has been used to treat RNS in clinical settings since the 1970s. [9][10][11][12] The therapeutic effects of CTX in the treatment of refractory NS have been unanimously accepted. 13 However, recent U.S. guidelines, published in 2009, no longer strongly recommend using CTX for refractory nephritic syndrome because of its relatively low efficacy, gonadal toxicity, myelosuppression, and carcinogenicity.…”

“…13,14 Currently, CTX is defined as the third-line drug for steroid-dependent nephritic syndrome in U.S. guidelines. [9][10][11][12][13] Among the newly therapeutic targeted agents, rituximab can effectively anti-inflammatory and protect kidney function from decline and can decrease protein excretion retard relapse. However, most patients cannot afford targeted therapeutic agents because of their high cost.…”

“…Steroid-dependence is defined as the occurrence of relapse during treatment with alternate-day steroids or no more than 14 days after gradually cessation of the use steroids. Steroid-resistant refers to persistent proteinuria after an [8][9][10][11][12] week course of oral prednisolone 1 mg/kg/d. Frequently relapsing nephrotic syndrome refers to at least two relapses during treatment within six months or more than three relapses within 12 months of the initial presentation.…”

Clinical Course of Steroid Sensitive Nephrotic Syndrome in Children: Outcome and Outlook

“…Nevertheless, CYC I.V. is usually recommended as an optional treatment to maintain remission in SSNS [7,11,[13][14][15][16][17][18][19][20][21][22]. In different studies, the percentage of relapse-free patients varies between 5 and 67% during 24 months, and between 17 and 65% during 60 months, respectively [5,18,[19][20][21][22][23][24].…”

“…It is well known that the number of AEs and their degree limited the duration of both PRED and alkylating agents' courses [4,10,13,14,19,22]; the general tendency is to reducing their cumulative dosage. However, though that our protocols provided relatively high drug cumulative dosages we did not observe the deterioration of AEs spectrum.…”