There are no randomized trials that have evaluated the treatment of C1q nephropathy. Current therapy involves treatment of the underlying light microscopic lesion. Glucocorticoids remain the mainstay of treatment. Most of the studies have indicated poor response to glucocorticoids (
1, 3). Methylprednisolone pulse therapy has shown to be effective in steroid resistant cases. Sequential therapy with cyclophosphamide, azathioprine, mycophenolatemofetil, tacrolimus and rituximab used separately or in combination with steroids has shown good clinical response in different studies. Since its initial description there have been numerous published case series and several case reports of patients with this condition.
Tanja Kersnik Levart et al. followed up 12 children with C1q nephropathy (
20). Eight out of 12 patients presented with nephrotic syndrome. Only one of these, a patient with MCD, responded excellently to corticosteroid therapy and experienced no relapse during the 1-year follow-up period. Four patients, three with MCD and one with FSGS associated with DMP, became corticosteroid dependent, but responded very well to cyclophosphamide. Three patients with MCD experienced complete remission, while in one patient with FSGS associated with DMP, partial remission was achieved. The remaining three patients with nephrotic syndrome and FSGS, two of them with associated DMP, were corticosteroid resistant and unfortunately also showed very poor response to other immunosuppressive therapy (cyclophosphamide, cyclosporine A, chlorambucil and mycophenolatemofetil). One of them progressed to end-stage renal failure, one had transitory acute renal failure, while in the last patient the follow-up was too short (6 months) to predict the final outcome. In addition, end-stage renal failure was observed in one patient with FSGS, who presented with nephrotic proteinuria and renal insufficiency.
Alenka Vizjak et al. followed up 53 patients with C1q nephropathy, for 4 months to 21 years (mean 5.4 ± 5.1) (
13). A kidney donor with no light microscopy lesions retained normal kidney function after 15 years. Among five patients with asymptomatic hematuria and/or proteinuria and no light microscopy lesions, one had complete remission, one had partial remission, and three had stable renal disease after 6 months to 7.5 years without treatment. All 13 patients with nephrotic syndrome and minimal change like lesion and eight of nine with nephrotic syndrome and FSGS received corticosteroids (10 received sequential therapy with cyclophosphamide including one who also received cyclosporine, one cyclosporine and mycophenolatemofetil, and one azathioprine, tacrolimus, and mycophenolatemofetil; one received sequential therapy with mycophenolatemofetil; and one with cyclosporine). The majority (76.9%) of the minimal change like group but only one third (33.3%) of the FSGS group were in complete remission after 4 months to 21 years, and four patients had partial remission after 4 months to 3 years. One patient with FSGS had resistant nephrotic syndrome despite 3 years of combined immunosuppressive therapy, and three (33.3%) had end-stage renal disease (ESRD) 2.5, 4.0, and 9.0 years after biopsy. Among 14 patients with proliferative glomerulonephritis, only four received immunosuppressive therapy. Two were treated with cyclophosphamide and had complete remission after 1.5 and 4.0 years. One patient received corticosteroids and had stable renal disease after 3.0 years. One patient, treated with corticosteroids and azathioprine, had stable renal disease after 2.0 years. Among 10 untreated patients, six had stable renal disease after 0.5 to 6.5 years, two had progressive renal disease after 12.0 years, and two had ESRD after 5.5 and 7.0 years.
Satoshi Hisano et al. followed up 61 patients with C1q nephropathy. According to presentation at onset, patients were divided into two groups: asymptomatic urinary abnormalities (asymptomatic) (n = 36) and nephrotic syndrome (NS) (n = 25) (
21). Nine of 10 patients in the asymptomatic group and all patients in the NS group were treated with prednisolone and/or cyclosporine. Normal urinalysis was found in 10 patients in asymptomatic group and 8 in NS group during the follow-up. Thirteen patients in the NS group were frequent relapsers at the latest follow-up. Three patients with FSGS developed chronic renal failure 8 to 15 years after the diagnosis. C1q deposits disappeared in 3 of 8 patients receiving repeat biopsy, and 2 of these 3 showed FSGS. They concluded that in long-term follow up, the prognosis of C1q nephropathy is good.
Rituximab, an anti-CD20 antibody has been tried in two patients who had failed to respond to immunosuppressive therapy. One of them achieved normalization of renal function; and hemodialysis was eliminated in the other patient (
On the contrary, relevance of C1q-dominant deposition in allograft is addressed by Said et al. in 2010 in a series of 24 patients. None of them were diagnosed as C1q nephropathy in the native renal biopsy or had any features of systemic lupus erythematosus. Mesangial deposits of C1q were detected in up to 82 % of the cases, and it was usually detected after the first year of transplantation. They concluded that C1q-dominant mesangial deposition in the renal allograft is a morphological pattern with no apparent clinical significance in majority of the patients (
In summary, a trial of glucocorticoids similar to that described for treatment of FSGS may be tried. A better response to this therapy would be expected in those with the minimal change lesion than those with an underlying lesion of FSGS.