INTRODUCTION AND AIMS: Immunosuppressive strategies combining glucocorticoids with an alkylating agent have become central for the treatment of most glomerulonephritis (GN), particularly in patients with nephrotic syndrome or with progressive GFR loss. These regimens were associated with short and long-term benefits, but also with severe side effects. In this context, the aim of this study was to assess the efficiency of using a monthly pulse intravenous (iv) corticosteroids (CS) plus cyclophosphamide (CYC) instead of continuous oral CS plus CYC in adult patients with GN.
METHODS: This was a retrospective cohort study conducted at a single nephrology center. Primary membranous GN and membranoproliferative GN were the major histological groups included. During a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g/day at the end of these six months, received a combination of CS and CYC.The patients were divided in two groups: 1) Group 1 (23 patients) - obese patients, with prediabetes or diabetes, severe cardiovascular disease, erosive gastritis received monthly Methylprednisolone 1g/day, 3 days and iv CYC (dose adjusted according to the age of the patient and eGFR) for six months and 2) Group 2 (86 patients) received oral CS (as per KDIGO recommended dose) and iv CYC.The primary outcome - time to a combined end point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission (proteinuria < 0.3 g/day (uPCR < 300 mg/g [<30 mg/mmol]); partial remission (proteinuria >0.3 but <3.5 g/day or a decrease in proteinuria by at least 50% from the initial value) and adverse events.
RESULTS: Our cohort included 109 Caucasian patients: 61.5% were men, mean eGFR - 37.3 ml/min per 1.73 m², mean proteinuria - 3.9 g/d.At 6 months, the primary composite end-point occurred in 8.7% patients with combined iv therapy and in 20.9% patients with oral CS and iv CYC (P = 0.06) - see table 1. Similar data were recorded also at 12 mo. Moreover, two patients from group 1 and seventeen patients from group 2 required dialysis, P= NS.At 6 months, complete remission was noted in 30.4% patients with combined iv therapy and in 18.6% patients from the second group (P = NS). Also, at 12 months, there was no statistically significant difference between the two arms.At 6 months, partial remission was noted in 34.8% patients with combined iv therapy and in 23.3% patients the second group (P = NS). Also, at 12 months, there was no statistically significant difference between the two arms.Adverse Events: 43.3% subjects from the iv group and 67% subjects from the second group reported at least one adverse event (P = NS). More patients receiving oral CS experienced infections, but without statistically significance. Eight patients from this second group had increases in serum glucose that led to a change in the steroid regimen. Table 1. The primary and secondary outcomes after 6 and 12 months of treatment
CONCLUSIONS: The results suggest that low dose CS (monthly pulses + iv CYC) is non-inferior to conventional treatment (with oral CS and CYC) for adult with primary GN.
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