IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.

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Background: Two-stage exchange arthroplasty with a high-dose antibiotic-loaded bone cement (ALBC) spacer and intravenous or oral antibiotics is the most common method of managing a periprosthetic joint infection (PJI) after a total knee arthroplasty (TKA). However, little is known about the contemporary incidence, the risk factors, and the outcomes of acute kidney injuries (AKIs) in this cohort. Methods:We identified 424 patients who had been treated with 455 ALBC spacers after resection of a PJI following a primary TKA from 2000 to 2017. The mean age at resection was 67 years, the mean body mass index (BMI) was 33 kg/m 2 , 47% of the patients were women, and 15% had preexisting chronic kidney disease (CKD). The spacers (87% nonarticulating) contained a mean of 8 g of vancomycin and 9 g of an aminoglycoside per construct (in situ for a mean of 11 weeks). Eighty-six spacers also had amphotericin B (mean, 412 mg). All of the patients were concomitantly treated with systemic antibiotics for a mean of 6 weeks. An AKI was defined as a creatinine level of ‡1.5 times the baseline or an increase of ‡0.3 mg/dL within any 48-hour period. The mean follow-up was 6 years (range, 2 to 17 years).Results: Fifty-four AKIs occurred in 52 (14%) of the 359 patients without preexisting CKD versus 32 AKIs in 29 (45%) of the 65 patients with CKD (odds ratio [OR], 5; p = 0.0001); none required acute dialysis. Overall, when the vancomycin concentration or aminoglycoside concentration was >3.6 g/batch of cement, the risk of AKI increased (OR, 1.9 and 1.8, respectively; p = 0.02 for both). Hypertension (b = 0.17; p = 0.002), perioperative hypovolemia (b = 0.28; p = 0.0001), and acute atrial fibrillation (b = 0.13; p = 0.009) were independent predictors for AKI in patients without preexisting CKD. At the last follow-up, 8 patients who had sustained an AKI had progressed to CKD, 4 of whom received dialysis.Conclusions: In our study, the largest series to date that we are aware of regarding this issue, AKI occurred in 14% of patients with normal renal function at baseline, and 2% developed CKD after undergoing a 2-stage exchange arthroplasty for a PJI after TKA. However, the risk of AKI was fivefold greater in those with preexisting CKD. The causes of acute renal blood flow impairment were independent predictors for AKI.Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. P eriprosthetic joint infection (PJI) continues to be one of the most common failure mechanisms after primary total knee arthroplasty (TKA), resulting in high mor-bidity 1-4 and mortality 5 . In North America, the management of chronic PJIs after TKA most commonly consists of a 2-stage exchange arthroplasty with a high-dose antibiotic-loaded bone Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked "yes" to ind...

Background: The purpose of this study was to investigate the rate and risk factors associated with the development of acute kidney injury after total hip arthroplasty, including the perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs). Methods: We retrospectively collected the demographic and comorbidity data of all patients who underwent total hip arthroplasty between 2004 and 2014 at our institution (n = 8,949). We conducted analyses of the entire cohort and a nested case-control subset. Subjects who developed acute kidney injury were matched by age, sex, and year of surgical procedure to subjects without acute kidney injury. Variables associated with acute kidney injury were determined using univariate and multivariate logistic regressions. Results: The mean patient age (and standard deviation) was 64.6 ± 13.8 years, 48.6% of patients were male, and 114 cases (1.1%) developed acute kidney injury, mostly stage 1 (79%). Variables associated with acute kidney injury included older age (odds ratio [OR], 1.4 per decade; p < 0.001), male sex (OR, 1.78; p = 0.005), chronic kidney disease (OR, 4.6; p < 0.001), heart failure (OR, 4.5; p < 0.001), diabetes (OR, 2.1; p < 0.001), and hypertension (OR, 2.1; p = 0.007). The results were consistent in the case-control analysis. NSAIDs were not associated with acute kidney injury (OR, 1.26; p = 0.36), but were avoided in subjects at risk, making any interpretation difficult because of confounding. A risk model for acute kidney injury after total hip arthroplasty was developed for clinical use and had good discrimination (area under the curve, 0.82; p < 0.001). Conclusions: The rate of acute kidney injury after total hip arthroplasty is low, but increases significantly, from <1% to >20%, in those with several independent risk factors present preoperatively. Increasing awareness of these risk factors may help to decrease the risk of acute kidney injury after total hip arthroplasty. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.