Juan M. Mejía-Vilet

Renal Thrombotic Microangiopathy in Proliferative Lupus Nephritis: Risk Factors and Clinical Outcomes: A Case-Control Study.

BackgroundRenal thrombotic microangiopathy (TMA) may be associated with lupus nephritis. Its relationship to other disease factors and its specific effect on prognosis are not precisely known. Evidence regarding these aspects is controversial, and information focusing on kidney-limited TMA in systemic lupus erythematosus (SLE) patients is scarce. ObjectivesThe aims of this study were to identify risk factors for renal TMA in patients with lupus nephritis and to determine its impact on clinical outcomes. MethodsA case-control study was performed. We studied 245 renal biopsies from SLE patients. We included patients with renal TMA, as well as control subjects adjusted for glomerulonephritis class, estimated glomerular filtration rate, activity and chronicity indices, and follow-up time. Serological and clinical features were measured at the time of the biopsy and during follow-up. ResultsTwenty-three patients with renal TMA and 21 control subjects were included. There were no differences in Systemic Lupus Erythematosus Disease Activity Index score, end-stage renal disease, or mortality between groups during follow-up. After multivariate analysis, lymphopenia (odds ratio, 10.69; 95% CI, 1.35–84.74) and anti-Ro antibody positivity (odds ratio, 8.96; 95% CI, 1.49–53.57) remained significantly associated with renal TMA. ConclusionsLymphopenia and anti-Ro positivity are independent risk factors for renal TMA in SLE patients. This increased risk could be a consequence of the potential role of these factors in endothelial dysfunction and damage. Outcomes were similar for patients with the same estimated glomerular filtration rate and biopsy characteristics, regardless of the presence of TMA.

Comparison of Lupus Nephritis Induction Treatments in a Hispanic Population: A Single-center Cohort Analysis

Objective. To evaluate response rates in an adult lupus nephritis (LN) cohort in Mexico City, Mexico. Methods. We analyzed 165 patients with biopsy-proven LN histological International Society of Nephrology/Renal Pathology Society classes III, IV, or V, distributed by treatment drug in 3 groups: mycophenolate mofetil (MMF; dosage > 2 g/day per 6 mos, n = 63), intravenous cyclophosphamide (IVC; 0.7 g/m2 body surface area monthly per 6 pulses, n = 66), or azathioprine (AZA; dosage > 1.5 mg/kg/day per 6 mos, n = 36). Median followup was 31 ± 18 months. The primary endpoint was the proportion of patients achieving complete renal response (CR). Secondary endpoints included the proportion of patients achieving renal response (complete or partial), renal flare–free survival, doubling of serum creatinine, and progression to endstage renal disease (ESRD). Results. MMF induction was superior to IVC (HR 2.00, 95% CI 1.23–3.25, p = 0.005) and AZA (HR 2.12, 95% CI 1.23–3.66, p = 0.007) in the primary endpoint. Censored CR rates at 6, 12, 24, and 36 months were 32.6%, 56.1%, 76.6%, and 94.1% for MMF; 24.2%, 34.4%, 57.9%, and 62.1% for IVC; and 8.4%, 39.8%, 49.7%, and 49.7% for AZA. MMF was also superior in renal response to treatment and renal flare–free survival outcomes. There were no differences between groups in doubling of serum creatinine or progression to ESRD. The induction treatment with MMF (HR 2.04, 95% CI 1.25–3.33, p = 0.005) and absence of vascular lesions on renal biopsy (HR 2.05, 95% CI 1.25–3.37, p = 0.004) were associated with CR, whereas proteinuria at the time of presentation was negatively associated with CR (HR 0.91, 95% CI 0.84–0.98, p = 0.013). Conclusion. MMF induction therapy is superior to IVC and AZA in patients with LN of Mexican-mestizo race.

Simple risk score for prediction of haemorrhagic complications after a percutaneous renal biopsy: A risk score for complications after PRB

To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys.

Facing the Metabolic Syndrome Epidemic in Living Kidney Donor Programs

BACKGROUND Due to the shortage of organs for transplantation, there has been increased interest in developing living-donor kidney transplantation (LDKT) programs. MATERIAL AND METHODS A total of 668 potential living kidney donors (PLKD) for 496 intended recipients were evaluated in a LDKT program between 2010 and 2014. Causes for PLKD exclusion were recorded, as well as patient survival. RESULTS After evaluation, 250 (37.4%) PLKD were considered suitable for kidney donation, 331 (49.6%) were excluded for medical reasons, and 87 (13.0%) withdrew their consent. The main cause of exclusion was metabolic syndrome and its components: 131 (39.6%) obesity, 37 (11.2%) new diagnosis of diabetes mellitus, and 25 (7.6%) new diagnosis of hypertension. Sixty-three (19.0%) were excluded for previously undetected renal diseases. Forty-six (13.9%) PLKD were excluded for immunological incompatibility. A total of 158 patients (31.9%) were transplanted from living donors and 31 (6.3%) from deceased donors (after the donor was considered non-suitable). Three-year patient survival was 99.4% for transplanted patients and 41.4% for patients who remained on dialysis. CONCLUSIONS Metabolic diseases constitute the main cause of donor exclusion in some LDKT programs. The high mortality rate of patients whose donor is excluded renews the debate over expanding donor criteria against the long-term risks they may pose to the living kidney donor.

Immune gene expression in kidney biopsies of lupus nephritis patients at diagnosis and at renal flare

Background Up to 50% of lupus nephritis (LN) patients experience renal flares after their initial episode of LN. These flares contribute to poor renal outcomes. We postulated that intrarenal immune gene expression is different in flares compared with de novo LN, and conducted these studies to test this hypothesis. Methods Glomerular and tubulointerstitial immune gene expression was evaluated in 14 patients who had a kidney biopsy to diagnose LN and another biopsy at their first LN flare. Ten healthy living kidney donors were included as controls. RNA was extracted from laser microdissected formalin-fixed paraffin-embedded kidney biopsies. Gene expression was analyzed using the Nanostring nCounter® platform and validated by quantitative real-time polymerase chain reaction. Differentially expressed genes were analyzed by the Ingenuity Pathway Analysis and Panther Gene Ontology tools. Results Over 110 genes were differentially expressed between LN and healthy control kidney biopsies. Although there was considerable molecular heterogeneity between LN biopsies at diagnosis and flare, for about half the LN patients gene expression from the first LN biopsy clustered with the repeated LN biopsy. However, in all patients, a set of eight interferon alpha-controlled genes had a significantly higher expression in the diagnostic biopsy compared with the flare biopsy. In contrast, nine tumor necrosis factor alpha-controlled genes had higher expression in flare biopsies. Conclusions There is significant heterogeneity in immune-gene expression of kidney tissue from LN patients. There are limited but important differences in gene expression between LN flares, which may influence treatment decisions.

Calcineurin Inhibitors With Reduced-Dose Steroids as First-Line Therapy for Focal Segmental Glomerulosclerosis

Introduction High-dose corticosteroids remain the first-line therapy for focal and segmental glomerulosclerosis (FSGS), whereas calcineurin inhibitors (CNIs) are reserved for those patients resistant to corticosteroid therapy. Methods This is a retrospective cohort analysis in patients with primary FSGS diagnosed between 2007 and 2014. According to the administered treatment, patients were segregated into 3 groups: high-dose prednisone, first-line CNIs plus low-dose prednisone, and rescue CNIs. Cumulative corticosteroid doses were compared as well as response to therapy and long-term renal survival by Cox regression analysis. Results A total of 66 patients were included (39 treated with high-dose prednisone, 11 treated with first-line CNI, 16 treated with high-dose prednisone followed by rescue CNI). Cumulative doses of prednisone in the high-dose group were 9.3 g (interquartile range [IQR] = 7.5−12.5 g), compared to 2.5 g (IQR = 1.82−3.12 g) in the first-line CNI plus low-dose corticosteroid group and 13.8 g (IQR = 9.2−15.8 g) rescue CNI groups, respectively (P < 0.001). Time under corticosteroid management was also higher in the high-dose prednisone group compared to the first-line CNI group. There was a response to treatment in 76.9%, 72.7%, and 87.5% of high-dose prednisone, first-line CNI and rescue CNI groups, with complete remission in 48.7%, 36.4%, and 31.3% respectively. There was no difference in relapse incidence after treatment (48.4%, 44.4%, and 46.7%) or in 5-year renal survival (87.2%, 81.8%, and 87.5%). Baseline proteinuria, biopsy chronicity score, and response to therapy were independent predictors of renal survival. Conclusion An initial CNI plus low-dose corticosteroid approach in primary FSGS reduces corticosteroid exposure with a response-to-therapy rate similar to that of the currently recommended high-dose corticosteroid regimen. These findings justify a randomized trial to formally test this hypothesis.

Establishing Surrogate Kidney Endpoints for Lupus Nephritis Clinical Trials: Development and Validation of a Novel Approach to Predict Future Kidney Outcomes

End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long‐term kidney survival. This study was undertaken to identify short‐term end points that predict long‐term kidney outcomes for use in clinical trials.