Urine epidermal growth factor as a biomarker for kidney function recovery and prognosis in glomerulonephritis with severe kidney function impairment.

BACKGROUND: Prognostication in glomerulonephritis with severe kidney function impairment is critical for evaluating the benefit-to-risk ratio of immunosuppression. We hypothesized that the urine biomarker epidermal growth factor (EGF) could have good discrimination power to identify subjects who might ultimately recover kidney function. METHODS: We included 82 subjects with glomerulonephritis and severe kidney function impairment at admission (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73m2): 58 with lupus nephritis (LN) and 24 with ANCA-associated vasculitis (AAV). Thirty-five subjects required kidney replacement therapy (KRT) at presentation. Urine epidermal growth factor was measured and corrected by urine creatinine (uEGF/Cr) and the population was analyzed by uEGF/Cr tertiles. The primary outcome was time to recovery of eGFR ≥ 30 mL/min/1.73m2 and time to recovery of kidney function with dialysis independence in those with initial KRT. RESULTS: Forty-four (54%) participants met the primary outcome of recovery of eGFR ≥ 30 mL/min/1.73m2. The 6-month recovery rates were 93%, 57%, and 0% for participants in the highest, middle, and lowest uEGF/Cr tertile, respectively. Recovery of the kidney function was faster and led to a higher post-therapy eGFR in the highest uEGF/Cr tertile. In the ROC analysis, uEGF/Cr was a predictor of recovery with an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98), and a cutoff of 2.60 ng/mg had 100% sensitivity to detect patients who recovered kidney function. In the subgroup of participants with initial KRT, the cut-off of uEGF/Cr of 2.0 ng/mg had 100% sensitivity to detect participants who recovered kidney function with dialysis independence by 6 months. CONCLUSIONS: Urine EGF/Cr is a promising biomarker to aid in the prediction of recovery of kidney function in glomerulonephritis with severe kidney function impairment.

Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: a retrospective cohort study.

INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

Effect of antimalarials on clinical outcomes in lupus nephritis.

OBJECTIVES: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort. METHODS: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological, and treatment variables. Antimalarial use was approached as 1) users versus no users, 2) according to prevalent vs incident use regarding the LN flare, and 3) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression. RESULTS: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92), and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect on these outcomes was modified by the presentation eGFR, histological class, and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7%, and 8.8% by 3-, 5-, and 7 years of continued antimalarial use. CONCLUSION: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.

Predictors of treatment outcomes in lupus nephritis with severe acute kidney injury and requirement of dialytic support.

INTRODUCTION/OBJECTIVES: Acute kidney injury (AKI) with the requirement of kidney replacement therapy (KRT) portends a poor prognosis for kidney function in lupus nephritis (LN). This study evaluated the kidney function recovery rates, the rates of reinitiation of KRT, and factors associated with these outcomes in LN. METHOD: All consecutive patients hospitalized for LN with KRT requirement between 2000 and 2020 were included. Their clinical and histopathologic characteristics were retrospectively registered. The outcomes and associated factors were evaluated by multivariable Cox regression analysis. RESULTS: Among 140 patients, 75 (54%) recovered kidney function, with recovery rates of 50.9% and 54.2% by 6 and 12 months of therapy. The factors associated with a lower probability of recovery included a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6 months of therapy initiation. There was no difference in the kidney function recovery rates between mycophenolate and cyclophosphamide treatment schemes. Out of 75 patients who recovered kidney function, 37 (49%) reinitiated KRT, with KRT reinitiation rates of 27.2% and 46.5% by 3 and 5 years. Seventy-three (52%) patients had at least one hospitalization within 6 months of initial therapy, 52 (72%) of them secondary to infectious events. CONCLUSIONS: Approximately 50% of patients with LN and KRT requirement recover kidney function within 6 months. The risk-to-benefit ratio decisions may be aided by clinical and histological factors. These patients require close follow-up as ≈50% of those who recover kidney function will reinitiate dialysis in the long term. Key Points • Approximately 50% of patients with severe acute lupus nephritis with the need for kidney replacement therapy requirement recover their kidney function. • The factors associated with a lower probability of recovery of kidney function include a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6 months of therapy initiation. • Patients who recover kidney function will require close follow-up as around 50% of them will eventually reinitiate kidney replacement therapy.