The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa

Background The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. Methods All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. Results Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0–24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). Conclusions In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. Trial registration ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018

Complement C3 Plays an Essential Role in the Control of Opportunistic Fungal Infections▿

The innate recognition of fungal pathogens is a crucial first step in the induction of protective antifungal immunity. Complement is thought to be one key component in this process, facilitating fungal recognition and inducing early inflammation. However, the roles of the individual complement components have not been examined extensively. Here we have used mice lacking C3 to examine its role in immunity to opportunistic fungal pathogens and show that this complement component is essential for resistance to infections with Candida albicans and Candida glabrata. We demonstrate that the absence of C3 impairs fungal clearance but does not affect inflammatory responses. We also show that the presence of C3 contributes to mortality in mice challenged with very high doses of Saccharomyces cerevisiae, although these effects were found to be mouse strain dependent

The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa

Background The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. Methods All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. Results Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0–24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). Conclusions In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. Trial registration ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018