Brad H Rovin

The Ohio State University, Columbus, Ohio, United States

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Publications (192)1185.79 Total impact

  • S. V. Parikh · A. Malvar · H. Song · V. Alberton · B. Lococo · J. Vance · J. Zhang · L. Yu · B. H. Rovin ·

    11/2015; 2(1):e000112-e000112. DOI:10.1136/lupus-2015-000112
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    ABSTRACT: Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.
    Journal of the American Society of Nephrology 11/2015; DOI:10.1681/ASN.2015060612 · 9.34 Impact Factor
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    ABSTRACT: Background: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histological LN activity. Methods: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n=47) at the time of kidney biopsy. Histological LN activity was measured by the NIH Activity Index (NIH-AI) and the Tubulointerstitial Activity Index (TIAI). High LN-activity status (vs. moderate/low) was defined as NIH-AI scores > 10 (vs. ≤ 10) or TIAI scores >5 (vs. ≤ 5). RAIL algorithms that predicted LN-activityNIH-AI and LN-activityTIAI status were derived by stepwise multivariate logistical regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. Results: The differential excretion of six UBMs (NGAL, MCP-1, ceruloplasmin, adiponectin, hemopexin, KIM-1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activityNIH-AI status with >92% accuracy and LN-activityTIAI status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71 and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. Conclusion: The RAIL is a robust and highly accurate noninvasive measure of LN-activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation. This article is protected by copyright. All rights reserved.
    10/2015; DOI:10.1002/acr.22762
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    ABSTRACT: Lupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy. This review discusses the underlying reasons for these unmet medical needs and options of how to overcome them in the future.
    CKJ: Clinical Kidney Journal 10/2015; 8(5). DOI:10.1093/ckj/sfv072
  • Samir V. Parikh · Anthony Alvarado · Ana Malvar · Brad H. Rovin ·

    Seminars in Nephrology 09/2015; 35(5):465-477. DOI:10.1016/j.semnephrol.2015.08.008 · 3.48 Impact Factor
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    ABSTRACT: Treatment response in lupus nephritis (LN) is defined clinically, without consideration of renal histology. Few studies have systematically examined histologic responses to induction therapy. In LN patients who underwent protocol kidney biopsies after induction immunosuppression, we describe the renal histology of the second biopsy and correlate histologic activity and damage with short- and long-term kidney outcomes. Patients with suspected LN were biopsied for diagnosis (Biopsy 1), and those with proliferative LN were rebiopsied after induction (Biopsy 2). Histologic activity and damage at each biopsy were calculated as the National Institutes of Health activity and chronicity indices. Complete and partial renal responses after induction and after long-term follow-up were determined clinically. One-third of patients who achieved a complete clinical response after induction had persistently high histologic activity, and 62% of patients who had complete histologic remission on rebiopsy were still clinically active. Chronic renal damage increased after induction even in complete clinical responders. Chronicity at Biopsy 2 associated with long-term kidney function and development of chronic kidney disease. Early clinical and histologic outcomes are discordant in proliferative LN, and neither correlates with long-term renal outcome. The kidney accrues chronic damage rapidly and despite clinical response in LN. Preservation of kidney function may require therapeutic targeting of both chronic damage and inflammation during LN induction treatment. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
    Nephrology Dialysis Transplantation 08/2015; DOI:10.1093/ndt/gfv296 · 3.58 Impact Factor
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    ABSTRACT: To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score: ≤ 10 vs. > 10; Tubulointerstitial Activity Index (TIAI) score: ≤ 5 vs. > 5) or the absence vs. presence of LN chronicity [NIH Chronicity Index (NIH-CI) score: 0 vs. ≥ 1]. There were 10, 50 and 23 patients with class I/II, III/IV and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with LN-activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between LN-activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture LN chronicity was 23.5% and 91.7%, respectively. Despite designed to measure LN-activity, SLICC-RAS and SLEDAI-R scores significantly differed with LN chronicity status. Current clinical indices of LN fail to discriminate ISN/RPS Class in children. Despite its shortcomings, the SLEDAI-R appears to best for measuring LN activity in a clinical setting. The SDI-R is a poor correlate of LN chronicity. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    07/2015; DOI:10.1002/acr.22651
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    ABSTRACT: Brodifacoum (BDF) is a superwarfarin that is used primarily as a rodenticide. There have been increasing numbers of reports of human cases of accidental or intentional BDF ingestion with high mortality rate. Its broad availability and high lethality suggest that BDF should be considered a potential chemical threat. Currently, there is no biomarker for early detection of BDF ingestion in humans; patients typically present with severe coagulopathy. Since we demonstrated earlier that warfarin can induce acute kidney injury with hematuria, we tested whether BDF would also lead to change in urinary biomarkers. BDF was administered to Sprague Dawley rats via oral gavage. N-acetylcysteine (NAC) was given per os in drinking water 24 h prior to BDF. Urinalysis was performed at different times after BDF administration. Anticoagulation and serum creatinine levels were analyzed in the blood. We observed that within a few hours the animals developed BDF-dose-dependent transient hemoglobinuria, which ceased within 24 h. This was accompanied by a transient decrease in hematocrit, gross hemolysis and an increase in free hemoglobin in the serum. At later times, animals developed true hematuria with red blood cells in the urine, which was associated with BDF anticoagulation. NAC prevented early hemoglobinuria, but not late hematuria associated with BDF. We propose that transient early hemoglobinuria (associated with oxidative stress) with consecutive late hematuria (associated with anticoagulation) are novel biomarkers of BDF poisoning, and they can be used in clinical setting or in mass casualty with BDF to identify poisoned patients. © 2015 S. Karger AG, Basel.
    American Journal of Nephrology 06/2015; 41(4-5):392-399. DOI:10.1159/000433568 · 2.67 Impact Factor
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    ABSTRACT: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with IV rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy. © 2015 S. Karger AG, Basel.
    06/2015; 130(3). DOI:10.1159/000430849

  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):172.1-172. DOI:10.1136/annrheumdis-2015-eular.3278 · 10.38 Impact Factor
  • Brad H Rovin · Jon B Klein ·
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    ABSTRACT: Proteomics has long been considered an ideal platform, and urine an ideal source for biomarker discovery in human autoimmune kidney diseases. A number of studies have examined the urine proteome to identify biomarkers of disease activity, kidney pathology, and response to therapy. Increasingly, proteomic studies of kidney disease have expanded to include blood, circulating cells and kidney tissue. Recently the clinical potential of renal proteomics has been realized through a handful of investigations whose results appear to be applicable to patient care. In this review, approaches to the proteomic evaluation of autoimmune kidney diseases will be considered in the context of developing clinically useful disease biomarkers. Copyright © 2015. Published by Elsevier Inc.
    Clinical Immunology 05/2015; DOI:10.1016/j.clim.2015.04.021 · 3.67 Impact Factor
  • Brad H Rovin · Isabelle Ayoub ·

    Nature Reviews Nephrology 04/2015; 11(7). DOI:10.1038/nrneph.2015.65 · 8.54 Impact Factor
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    ABSTRACT: A spate of recent publications describes a newly recognized form of glomerulonephritis associated with active staphylococcal infection. The key kidney biopsy findings, glomerular immunoglobulin A (IgA) deposits dominant or codominant with IgG deposits, resemble those of IgA nephritis. Many authors describe this condition as "postinfectious" and have termed it "poststaphylococcal glomerulonephritis." However, viewed through the prism of poststreptococcal glomerulonephritis, the prefix "post" in poststaphylococcal glomerulonephritis is historically incorrect, illogical, and misleading with regard to choosing therapy. There are numerous reports describing the use of high-dose steroids to treat poststaphylococcal glomerulonephritis. The decision to use steroid therapy suggests that the treating physician believed that the dominant problem was a postinfectious glomerulonephritis, not the infection itself. Unfortunately, steroid therapy in staphylococcus-related glomerulonephritis can precipitate severe staphylococcal sepsis and even death and provides no observable benefits. Poststreptococcal glomerulonephritis is an authentic postinfectious glomerulonephritis; poststaphylococcal glomerulonephritis is not. Making this distinction is important from the perspective of history, pathogenesis, and clinical management. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 04/2015; 65(6). DOI:10.1053/j.ajkd.2015.01.023 · 5.90 Impact Factor
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    ABSTRACT: Significant advances are needed to improve the diagnosis, prognosis, and management of persons with CKD. Discovery of new biomarkers and improvements in currently available biomarkers for CKD hold great promise to achieve these necessary advances. Interest in identification and evaluation of biomarkers for CKD has increased substantially over the past decade. In 2009, the National Institute of Diabetes and Digestive and Kidney Diseases established the CKD Biomarkers Consortium (, a multidisciplinary, collaborative study group located at over a dozen academic medical centers. The main objective of the consortium was to evaluate new biomarkers for purposes related to CKD in established prospective cohorts, including those enriched for CKD. During the first 5 years of the consortium, many insights into collaborative biomarker research were gained that may be useful to other investigators involved in biomarkers research. These lessons learned are outlined in this Special Feature and include a wide range of issues related to biospecimen collection, storage, and retrieval, and the internal and external quality assessment of laboratories that performed the assays. The authors propose that investigations involving biomarker discovery and validation are greatly enhanced by establishing and following explicit quality control metrics, including the use of blind replicate and proficiency samples, by carefully considering the conditions under which specimens are collected, handled, and stored, and by conducting pilot and feasibility studies when there are concerns about the condition of the specimens or the accuracy or reproducibility of the assays. Copyright © 2015 by the American Society of Nephrology.
    Clinical Journal of the American Society of Nephrology 03/2015; 10(5). DOI:10.2215/CJN.11541114 · 4.61 Impact Factor
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    ABSTRACT: Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36-50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    PROTEOMICS - CLINICAL APPLICATIONS 03/2015; DOI:10.1002/prca.201400175 · 2.96 Impact Factor
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    ABSTRACT: Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/√2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 µg/min and mean iohexol GFR 129 mL/min/1.73 m(2). No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = -0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN. Published by Oxford University Press on behalf of ERA-EDTA 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
    Nephrology Dialysis Transplantation 02/2015; 30(4). DOI:10.1093/ndt/gfv012 · 3.58 Impact Factor
  • Lee A Hebert · Anthony Alvarado · Brad Rovin ·

    New England Journal of Medicine 01/2015; 372(4):385. DOI:10.1056/NEJMc1414728#SA1 · 55.87 Impact Factor
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    ABSTRACT: Objective: There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We utilized data from the Euro-Lupus Nephritis Trial (ELNT) to evaluate the performance of proteinuria, serum creatinine (SCr), and urine red blood cells (RBCs) as predictors of good long-term renal outcome. Methods: ELNT subjects with measures of proteinuria, SCr, and urine RBCs at 3, 6 or 12 months and a minimum 7 year follow-up were included (n=76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as SCr ≤ 1.0mg/dL) at 7 years. Receiver operating characteristic (ROC) curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters; sensitivity and specificity were calculated for the parameters alone and in combination. Results: Proteinuria of <0.8g/day 12 months after randomization was the single best predictor of good long-term renal function (sensitivity=81%, specificity=78%). The addition of SCr to proteinuria did not improve performance; addition of urine RBCs significantly decreased sensitivity to 47%. Conclusions: This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome. Inclusion of urine RBCs as part of a composite outcome measure actually undermines the predictive value of the trial data. We therefore suggest that urine RBCs should not be included as a component of clinical trial response criteria in lupus nephritis. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    Arthritis and Rheumatology 01/2015; 67(5). DOI:10.1002/art.39026
  • Samir V Parikh · Isabelle Ayoub · Brad H Rovin ·

    Nephrology Dialysis Transplantation 11/2014; 30(1). DOI:10.1093/ndt/gfu348 · 3.58 Impact Factor
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    ABSTRACT: Objective. To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce "clinical tolerance," defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy. Methods. Patients with active lupus nephritis (n = 134) were enrolled in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus Nephritis Trial regimen of low-dose cyclophosphamide (CYC) followed by azathioprine (AZA). The primary efficacy outcome was the frequency of complete response at week 24. Thereafter, patients who met either complete or partial response criteria continued blinded treatment through week 52. During this phase of the study, subjects in the abatacept treatment group in whom a complete response was achieved at week 24 discontinued immunosuppressive therapy other than prednisone (10 mg/day). Results. There were no statistically significant differences between groups with respect to the primary outcome or any of the secondary outcomes, including measures of safety. A complete response was achieved in 33% of the subjects in the treatment group and in 31% of the subjects in the control group at week 24. Fifty percent of the subjects in the treatment group who met complete response criteria and therefore discontinued immunosuppressive therapy at week 24 maintained their complete response status through week 52. Conclusion. The addition of abatacept to a regimen of CYC followed by AZA did not improve the outcome of lupus nephritis at either 24 or 52 weeks. No worrisome safety signals were encountered.
    11/2014; 66(11):3096-3104. DOI:10.1002/art.38790

Publication Stats

7k Citations
1,185.79 Total Impact Points


  • 1992-2015
    • The Ohio State University
      • • Center for Integrative Medicine
      • • Pathology
      • • Department of Internal Medicine
      • • Division of Nephrology
      • • Division of Hospital Medicine
      Columbus, Ohio, United States
  • 2009
    • University of Louisville
      Louisville, Kentucky, United States
  • 1990-1991
    • Washington University in St. Louis
      • Department of Medicine
      San Luis, Missouri, United States