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Lee A. Hebert - One of the best experts on this subject based on the ideXlab platform.
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Oral Cyclophosphamide for Lupus GlomeruloNephritis: An Underused Therapeutic Option
Clinical journal of the American Society of Nephrology : CJASN, 2009Co-Authors: Alison M. Mckinley, Lee A. Hebert, Edward Park, Dan N. Spetie, Kevin V. Hackshaw, Smitha Nagaraja, Brad H. RovinAbstract:Background and objectives: In our center, systemic Lupus Erythematosus Nephritis is routinely treated with an oral cyclophosphamide (POCY) regimen. POCY is easy to administer and less expensive than intravenous cyclophosphamide (IVCY) as it is currently used in the United States; however, the use of POCY has declined in favor of IVCY. Our experience with POCY suggests that it is well tolerated and consistently associated with good long-term outcomes. Here we report this experience to build a case for maintaining POCY as a therapeutic option in Lupus Nephritis. Design, setting, participants, & measurements: This is a single-center, retrospective analysis of the outcome of 46 patients who had systemic Lupus Erythematosus with Nephritis and were treated with POCY between 1995 and 2006. POCY was given for 2 to 4 mo at a dosage of 1.0 to 1.5 mg/kg ideal body weight. After completing POCY, the patients received either azathioprine or mycophenolate mofetil. Results: Median follow-up was 23.5 mo, and median duration of POCY was 4 mo (range 1 to 16 mo). Durable complete or partial remission of proteinuria was achieved in 32 (70%) patients, whereas 5 (11%) progressed to ESRD. Outcomes were comparable in black and white individuals. Adverse effects occurred in fewer than 10% of the cohort, and only four patients discontinued POCY. Conclusions: These results suggest that sequential therapy of POCY followed by azathioprine or mycophenolate mofetil is comparable to IVCY regimens but that efficacy may not be affected by race.
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Random spot urine protein/creatinine ratio is unreliable for estimating 24-hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients.
Nephron. Clinical practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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random spot urine protein creatinine ratio is unreliable for estimating 24 hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients
Nephron Clinical Practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis: Diagnostic and Therapeutic Implications
Clinical journal of the American Society of Nephrology : CJASN, 2008Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, Lee A. HebertAbstract:Background and objectives: Albuminuria is regarded a sensitive measure of progression of glomerular disease. This study was undertaken in patients who had systemic Lupus Erythematosus glomeruloNephritis (n = 57) and were followed in the Ohio SLE Study to determine whether measuring albuminuria offered clinical advantages over that of total proteinuria. Design, setting, participants, & measurements: Twenty-four-hour urine collections (n = 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine. Results: There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio − microalbumin-creatinine ratio). Conclusions: For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic Lupus Erythematosus glomeruloNephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in protein-creatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic Lupus Erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic Lupus Erythematosus flare.
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spot urine protein creatinine ratios are unreliable estimates of 24 h proteinuria in most systemic Lupus Erythematosus Nephritis flares
Kidney International, 2007Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, X. Zou, Lee A. HebertAbstract:The diagnosis of glomeruloNephritis flares in systemic Lupus Erythematosus (SLE) is usually based on whether the magnitude of proteinuria has changed. Our study tests two methods to assess proteinuric change: protein/creatinine (P/C) ratios of intended 24-h urine collections or that of spot urine samples. Sixty-four patients with glomeruloNephritis due to SLE followed in the Ohio SLE Study provided bimonthly paired spot and intended 24-h urine collections. Completeness of each collection was estimated as the ratio of the measured creatinine to the expected creatinine based upon Cockroft–Gault. Intended 24-h urine collections with measured/expected creatinine ratios between 0.5 and 0.9 (237 samples overall) showed ratios that were not significantly different from ratios of complete 24-h urine collections with ratios of 0.9–1.1 (159 samples). To compare spot and 24 h P/C ratios, we randomly selected pairs of samples with measured/expected ratios above 0.75. Consistent with previous studies, spot and 24-h urine P/C ratios showed good correlation over the range of values as well as reasonably strong concordance. Over the range of most SLE glomeruloNephritis flares, however, correlation was present but concordance was poor. Our work suggests that the use of spot urine P/C ratios will yield more false-positive and -negative diagnoses of glomeruloNephritis flares in patients with SLE than the ratio in 24-h urines.
Brad H. Rovin - One of the best experts on this subject based on the ideXlab platform.
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Oral Cyclophosphamide for Lupus GlomeruloNephritis: An Underused Therapeutic Option
Clinical journal of the American Society of Nephrology : CJASN, 2009Co-Authors: Alison M. Mckinley, Lee A. Hebert, Edward Park, Dan N. Spetie, Kevin V. Hackshaw, Smitha Nagaraja, Brad H. RovinAbstract:Background and objectives: In our center, systemic Lupus Erythematosus Nephritis is routinely treated with an oral cyclophosphamide (POCY) regimen. POCY is easy to administer and less expensive than intravenous cyclophosphamide (IVCY) as it is currently used in the United States; however, the use of POCY has declined in favor of IVCY. Our experience with POCY suggests that it is well tolerated and consistently associated with good long-term outcomes. Here we report this experience to build a case for maintaining POCY as a therapeutic option in Lupus Nephritis. Design, setting, participants, & measurements: This is a single-center, retrospective analysis of the outcome of 46 patients who had systemic Lupus Erythematosus with Nephritis and were treated with POCY between 1995 and 2006. POCY was given for 2 to 4 mo at a dosage of 1.0 to 1.5 mg/kg ideal body weight. After completing POCY, the patients received either azathioprine or mycophenolate mofetil. Results: Median follow-up was 23.5 mo, and median duration of POCY was 4 mo (range 1 to 16 mo). Durable complete or partial remission of proteinuria was achieved in 32 (70%) patients, whereas 5 (11%) progressed to ESRD. Outcomes were comparable in black and white individuals. Adverse effects occurred in fewer than 10% of the cohort, and only four patients discontinued POCY. Conclusions: These results suggest that sequential therapy of POCY followed by azathioprine or mycophenolate mofetil is comparable to IVCY regimens but that efficacy may not be affected by race.
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Random spot urine protein/creatinine ratio is unreliable for estimating 24-hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients.
Nephron. Clinical practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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random spot urine protein creatinine ratio is unreliable for estimating 24 hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients
Nephron Clinical Practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis: Diagnostic and Therapeutic Implications
Clinical journal of the American Society of Nephrology : CJASN, 2008Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, Lee A. HebertAbstract:Background and objectives: Albuminuria is regarded a sensitive measure of progression of glomerular disease. This study was undertaken in patients who had systemic Lupus Erythematosus glomeruloNephritis (n = 57) and were followed in the Ohio SLE Study to determine whether measuring albuminuria offered clinical advantages over that of total proteinuria. Design, setting, participants, & measurements: Twenty-four-hour urine collections (n = 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine. Results: There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio − microalbumin-creatinine ratio). Conclusions: For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic Lupus Erythematosus glomeruloNephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in protein-creatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic Lupus Erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic Lupus Erythematosus flare.
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spot urine protein creatinine ratios are unreliable estimates of 24 h proteinuria in most systemic Lupus Erythematosus Nephritis flares
Kidney International, 2007Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, X. Zou, Lee A. HebertAbstract:The diagnosis of glomeruloNephritis flares in systemic Lupus Erythematosus (SLE) is usually based on whether the magnitude of proteinuria has changed. Our study tests two methods to assess proteinuric change: protein/creatinine (P/C) ratios of intended 24-h urine collections or that of spot urine samples. Sixty-four patients with glomeruloNephritis due to SLE followed in the Ohio SLE Study provided bimonthly paired spot and intended 24-h urine collections. Completeness of each collection was estimated as the ratio of the measured creatinine to the expected creatinine based upon Cockroft–Gault. Intended 24-h urine collections with measured/expected creatinine ratios between 0.5 and 0.9 (237 samples overall) showed ratios that were not significantly different from ratios of complete 24-h urine collections with ratios of 0.9–1.1 (159 samples). To compare spot and 24 h P/C ratios, we randomly selected pairs of samples with measured/expected ratios above 0.75. Consistent with previous studies, spot and 24-h urine P/C ratios showed good correlation over the range of values as well as reasonably strong concordance. Over the range of most SLE glomeruloNephritis flares, however, correlation was present but concordance was poor. Our work suggests that the use of spot urine P/C ratios will yield more false-positive and -negative diagnoses of glomeruloNephritis flares in patients with SLE than the ratio in 24-h urines.
Anne Davidson - One of the best experts on this subject based on the ideXlab platform.
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ifn α confers resistance of systemic Lupus Erythematosus Nephritis to therapy in nzb w f1 mice
Journal of Immunology, 2011Co-Authors: Zheng Liu, Ramalingam Bethunaickan, Meera Ramanujam, Weiqing Huang, Michael P. Madaio, Anne DavidsonAbstract:The critical role of IFN-α in the pathogenesis of human systemic Lupus Erythematosus has been highlighted in recent years. Exposure of young Lupus-prone NZB/W F1 mice to IFN-α in vivo leads to an accelerated Lupus phenotype that is dependent on T cells and is associated with elevated serum levels of BAFF, IL-6, and TNF-α, increased splenic expression of IL-6 and IL-21, formation of large germinal centers, and the generation of large numbers of short-lived plasma cells that produce IgG2a and IgG3 autoantibodies. In this study, we show that both IgG2a and IgG3 autoantibodies are pathogenic in IFN-α–accelerated Lupus, and their production can be dissociated by using low-dose CTLA4-Ig. Only high-dose CTLA4-Ig attenuates both IgG2a and IgG3 autoantibody production and significantly delays death from Lupus Nephritis. In contrast, BAFF/APRIL blockade has no effect on germinal centers or the production of IgG anti-dsDNA Abs but, if given at the time of IFN-α challenge, delays the progression of Lupus by attenuating systemic and renal inflammation. Temporary remission of Nephritis induced by combination therapy with cyclophosphamide, anti-CD40L Ab, and CTLA4-Ig is associated with the abrogation of germinal centers and depletion of short-lived plasma cells, but relapse occurs more rapidly than in conventional NZB/W F1 mice. This study demonstrates that IFN-α renders NZB/W F1 relatively resistant to therapeutic intervention and suggests that the IFN signature should be considered when randomizing patients into groups and analyzing the results of human clinical trials in systemic Lupus Erythematosus.
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IFN-α Confers Resistance of Systemic Lupus Erythematosus Nephritis to Therapy in NZB/W F1 Mice
Journal of immunology (Baltimore Md. : 1950), 2011Co-Authors: Zheng Liu, Ramalingam Bethunaickan, Meera Ramanujam, Weiqing Huang, Michael P. Madaio, Anne DavidsonAbstract:The critical role of IFN-α in the pathogenesis of human systemic Lupus Erythematosus has been highlighted in recent years. Exposure of young Lupus-prone NZB/W F1 mice to IFN-α in vivo leads to an accelerated Lupus phenotype that is dependent on T cells and is associated with elevated serum levels of BAFF, IL-6, and TNF-α, increased splenic expression of IL-6 and IL-21, formation of large germinal centers, and the generation of large numbers of short-lived plasma cells that produce IgG2a and IgG3 autoantibodies. In this study, we show that both IgG2a and IgG3 autoantibodies are pathogenic in IFN-α–accelerated Lupus, and their production can be dissociated by using low-dose CTLA4-Ig. Only high-dose CTLA4-Ig attenuates both IgG2a and IgG3 autoantibody production and significantly delays death from Lupus Nephritis. In contrast, BAFF/APRIL blockade has no effect on germinal centers or the production of IgG anti-dsDNA Abs but, if given at the time of IFN-α challenge, delays the progression of Lupus by attenuating systemic and renal inflammation. Temporary remission of Nephritis induced by combination therapy with cyclophosphamide, anti-CD40L Ab, and CTLA4-Ig is associated with the abrogation of germinal centers and depletion of short-lived plasma cells, but relapse occurs more rapidly than in conventional NZB/W F1 mice. This study demonstrates that IFN-α renders NZB/W F1 relatively resistant to therapeutic intervention and suggests that the IFN signature should be considered when randomizing patients into groups and analyzing the results of human clinical trials in systemic Lupus Erythematosus.
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A Unique Hybrid Renal Mononuclear Phagocyte Activation Phenotype in Murine Systemic Lupus Erythematosus Nephritis
Journal of immunology (Baltimore Md. : 1950), 2011Co-Authors: Ramalingam Bethunaickan, Meera Ramanujam, Erwin P. Bottinger, Celine C. Berthier, Ranjit Sahu, Weijia Zhang, Yezou Sun, Lionel B. Ivashkiv, Matthias Kretzler, Anne DavidsonAbstract:Renal infiltration with mononuclear cells is associated with poor prognosis in systemic Lupus Erythematosus. A renal macrophage/dendritic cell signature is associated with the onset of Nephritis in NZB/W mice, and immune-modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. In nephritic NZB/W mice, renal F4/80hi/CD11cint macrophages are located throughout the interstitium, whereas F4/80lo/CD11chi dendritic cells accumulate in perivascular lymphoid aggregates. We show here that F4/80hi/CD11cint renal macrophages have a Gr1lo/Ly6Clo/VLA4lo/MHCIIhi/CD43lo/CD62Llo phenotype different from that described for inflammatory macrophages. At Nephritis onset, F4/80hi/CD11cint cells upregulate cell surface CD11b, acquire cathepsin and matrix metalloproteinase activity, and accumulate large numbers of autophagocytic vacuoles; these changes reverse after the induction of remission. Latex bead labeling of peripheral blood Gr1lo monocytes indicates that these are the source of F4/80hi/CD11cint macrophages. CD11chi/MHCIIlo dendritic cells are found in the kidneys only after proteinuria onset, turnover rapidly, and disappear rapidly after remission induction. Gene expression profiling of the F4/80hi/CD11cint population displays increased expression of proinflammatory, regulatory, and tissue repair/degradation-associated genes at Nephritis onset that reverses with remission induction. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in Lupus Nephritis by mediating both local inflammation and excessive tissue remodeling.
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Selective blockade of BAFF for the prevention and treatment of systemic Lupus Erythematosus Nephritis in NZM2410 mice
Arthritis and rheumatism, 2010Co-Authors: Meera Ramanujam, Ramalingam Bethunaickan, Weiqing Huang, Haiou Tao, Michael P. Madaio, Anne DavidsonAbstract:Systemic Lupus Erythematosus (SLE) is an autoimmune disorder in which loss of tolerance to nucleic acids is associated with the development of pathogenic autoantibodies that damage target organs. Lupus Nephritis develops in up to 60% of adult SLE patients and is even more common in children. Induction of remission of Lupus Nephritis requires the use of potent immunosuppressive treatment with significant adverse effects, and frequent relapses (1). B cells are therapeutic targets in SLE because they produce pathogenic autoantibodies and because they have multiple effector functions including antigen presentation to T cells, cytokine production and migration to sites of inflammation (2). One way to modulate B cell function is by inhibiting the B cell survival molecule BAFF (BLyS). Therapeutic antagonism of BAFF and its homolog APRIL (a proliferation ligand) is based on the discoveries that BAFF provides a crucial homeostatic signal for B cell survival and selection (3–6) and that soluble BAFF and APRIL are highly expressed in the serum of SLE patients (7) and in the target organs of SLE prone mice (8, 9). BAFF binds to three receptors, BAFF-R, TACI and BCMA that are differentially expressed during B cell ontogeny (10), whereas APRIL binds only to TACI and BCMA. Selective blockade of BAFF can be achieved with a soluble BAFF-R-Ig fusion protein or an antibody to BAFF whereas blockade of both BAFF and APRIL is achieved with soluble TACI-Ig. Initial phase 2 and 3 studies of a selective antibody to soluble BAFF (belimumab) were recently completed (11) and studies of TACI-Ig (atacicept) are currently in progress. Questions remain about the mechanism of action of these reagents and about whether blocking both BAFF and APRIL will be more efficacious than blocking BAFF alone. The NZM2410 mouse is an inbred strain derived from NZB/W. NZM2410 mice manifest antibodies to nucleosomes and dsDNA and they develop rapidly progressive glomerulosclerosis with little lymphocytic infiltrate in the kidneys. These mice express high levels of IL-4 and they secrete large amounts of IgG1 antibodies (12). NZM2410 mice have a defect in migration of plasma cells to the bone marrow and retain large numbers of plasma cells in their spleens (13). We therefore hypothesized that disease in these mice might be more responsive to TACI-Ig, that depletes splenic plasma cells (14), than to BAFF-R-Ig. Our study shows that BAFF-R-Ig and TACI-Ig are equally effective at preventing disease and that a short course of either agent induces sustained remission when used as a single therapeutic. This appears to be due to prolonged B cell depletion and a decrease in the inflammatory response to renal immune complex deposition.
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Activated renal macrophages are markers of disease onset and disease remission in Lupus Nephritis.
Journal of immunology (Baltimore Md. : 1950), 2008Co-Authors: Lena Schiffer, Ramalingam Bethunaickan, Meera Ramanujam, Weiqing Huang, Mario Schiffer, Haiou Tao, Michael M. Madaio, Erwin P. Bottinger, Anne DavidsonAbstract:Costimulatory blockade with CTLA4Ig and anti-CD40L along with a single dose of cyclophosphamide induces remission of systemic Lupus Erythematosus Nephritis in NZB/W F1 mice. To understand the mechanisms for remission and for impending relapse, we examined the expression profiles of 61 inflammatory molecules in the perfused kidneys of treated mice and untreated mice at different stages of disease. Further studies using flow cytometry and immunohistochemistry allowed us to determine the cellular origins of several key markers. We show that only a limited set of inflammatory mediators is expressed in the kidney following glomerular immune complex deposition but before the onset of proteinuria. Formation of a lymphoid aggregate in the renal pelvis precedes the invasion of the kidney by inflammatory cells. Regulatory molecules are expressed early in the disease process and during remission but do not prevent the inevitable progression of active inflammation. Onset of proliferative glomeruloNephritis and proteinuria is associated with activation of the renal endothelium, expression of chemokines that mediate glomerular cell infiltration, and infiltration by activated dendritic cells and macrophages that migrate to different topographical areas of the kidney but express a similar profile of inflammatory cytokines. Increasing interstitial infiltration by macrophages and progressive tubular damage, manifested by production of lipocalin-2, occur later in the disease process. Studies of treated mice identify a type II (M2b)-activated macrophage as a marker of remission induction and impending relapse and suggest that therapy for systemic Lupus Erythematosus Nephritis should include strategies that prevent both activation of monocytes and their migration to the kidney.
Daniel J. Birmingham - One of the best experts on this subject based on the ideXlab platform.
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Random spot urine protein/creatinine ratio is unreliable for estimating 24-hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients.
Nephron. Clinical practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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random spot urine protein creatinine ratio is unreliable for estimating 24 hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients
Nephron Clinical Practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis: Diagnostic and Therapeutic Implications
Clinical journal of the American Society of Nephrology : CJASN, 2008Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, Lee A. HebertAbstract:Background and objectives: Albuminuria is regarded a sensitive measure of progression of glomerular disease. This study was undertaken in patients who had systemic Lupus Erythematosus glomeruloNephritis (n = 57) and were followed in the Ohio SLE Study to determine whether measuring albuminuria offered clinical advantages over that of total proteinuria. Design, setting, participants, & measurements: Twenty-four-hour urine collections (n = 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine. Results: There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio − microalbumin-creatinine ratio). Conclusions: For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic Lupus Erythematosus glomeruloNephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in protein-creatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic Lupus Erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic Lupus Erythematosus flare.
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spot urine protein creatinine ratios are unreliable estimates of 24 h proteinuria in most systemic Lupus Erythematosus Nephritis flares
Kidney International, 2007Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, X. Zou, Lee A. HebertAbstract:The diagnosis of glomeruloNephritis flares in systemic Lupus Erythematosus (SLE) is usually based on whether the magnitude of proteinuria has changed. Our study tests two methods to assess proteinuric change: protein/creatinine (P/C) ratios of intended 24-h urine collections or that of spot urine samples. Sixty-four patients with glomeruloNephritis due to SLE followed in the Ohio SLE Study provided bimonthly paired spot and intended 24-h urine collections. Completeness of each collection was estimated as the ratio of the measured creatinine to the expected creatinine based upon Cockroft–Gault. Intended 24-h urine collections with measured/expected creatinine ratios between 0.5 and 0.9 (237 samples overall) showed ratios that were not significantly different from ratios of complete 24-h urine collections with ratios of 0.9–1.1 (159 samples). To compare spot and 24 h P/C ratios, we randomly selected pairs of samples with measured/expected ratios above 0.75. Consistent with previous studies, spot and 24-h urine P/C ratios showed good correlation over the range of values as well as reasonably strong concordance. Over the range of most SLE glomeruloNephritis flares, however, correlation was present but concordance was poor. Our work suggests that the use of spot urine P/C ratios will yield more false-positive and -negative diagnoses of glomeruloNephritis flares in patients with SLE than the ratio in 24-h urines.
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Spot urine protein/creatinine ratios are unreliable estimates of 24 h proteinuria in most systemic Lupus Erythematosus Nephritis flares
Kidney international, 2007Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, X. Zou, Lee A. HebertAbstract:The diagnosis of glomeruloNephritis flares in systemic Lupus Erythematosus (SLE) is usually based on whether the magnitude of proteinuria has changed. Our study tests two methods to assess proteinuric change: protein/creatinine (P/C) ratios of intended 24-h urine collections or that of spot urine samples. Sixty-four patients with glomeruloNephritis due to SLE followed in the Ohio SLE Study provided bimonthly paired spot and intended 24-h urine collections. Completeness of each collection was estimated as the ratio of the measured creatinine to the expected creatinine based upon Cockroft–Gault. Intended 24-h urine collections with measured/expected creatinine ratios between 0.5 and 0.9 (237 samples overall) showed ratios that were not significantly different from ratios of complete 24-h urine collections with ratios of 0.9–1.1 (159 samples). To compare spot and 24 h P/C ratios, we randomly selected pairs of samples with measured/expected ratios above 0.75. Consistent with previous studies, spot and 24-h urine P/C ratios showed good correlation over the range of values as well as reasonably strong concordance. Over the range of most SLE glomeruloNephritis flares, however, correlation was present but concordance was poor. Our work suggests that the use of spot urine P/C ratios will yield more false-positive and -negative diagnoses of glomeruloNephritis flares in patients with SLE than the ratio in 24-h urines.
Haikady N. Nagaraja - One of the best experts on this subject based on the ideXlab platform.
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Random spot urine protein/creatinine ratio is unreliable for estimating 24-hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients.
Nephron. Clinical practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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random spot urine protein creatinine ratio is unreliable for estimating 24 hour proteinuria in individual systemic Lupus Erythematosus Nephritis patients
Nephron Clinical Practice, 2009Co-Authors: Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham, Ganesh Shidham, Haikady N. NagarajaAbstract:Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic Lupus Erythematosus (SLE) glomerul
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Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis: Diagnostic and Therapeutic Implications
Clinical journal of the American Society of Nephrology : CJASN, 2008Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, Lee A. HebertAbstract:Background and objectives: Albuminuria is regarded a sensitive measure of progression of glomerular disease. This study was undertaken in patients who had systemic Lupus Erythematosus glomeruloNephritis (n = 57) and were followed in the Ohio SLE Study to determine whether measuring albuminuria offered clinical advantages over that of total proteinuria. Design, setting, participants, & measurements: Twenty-four-hour urine collections (n = 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine. Results: There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio − microalbumin-creatinine ratio). Conclusions: For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic Lupus Erythematosus glomeruloNephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in protein-creatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic Lupus Erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic Lupus Erythematosus flare.
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spot urine protein creatinine ratios are unreliable estimates of 24 h proteinuria in most systemic Lupus Erythematosus Nephritis flares
Kidney International, 2007Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, X. Zou, Lee A. HebertAbstract:The diagnosis of glomeruloNephritis flares in systemic Lupus Erythematosus (SLE) is usually based on whether the magnitude of proteinuria has changed. Our study tests two methods to assess proteinuric change: protein/creatinine (P/C) ratios of intended 24-h urine collections or that of spot urine samples. Sixty-four patients with glomeruloNephritis due to SLE followed in the Ohio SLE Study provided bimonthly paired spot and intended 24-h urine collections. Completeness of each collection was estimated as the ratio of the measured creatinine to the expected creatinine based upon Cockroft–Gault. Intended 24-h urine collections with measured/expected creatinine ratios between 0.5 and 0.9 (237 samples overall) showed ratios that were not significantly different from ratios of complete 24-h urine collections with ratios of 0.9–1.1 (159 samples). To compare spot and 24 h P/C ratios, we randomly selected pairs of samples with measured/expected ratios above 0.75. Consistent with previous studies, spot and 24-h urine P/C ratios showed good correlation over the range of values as well as reasonably strong concordance. Over the range of most SLE glomeruloNephritis flares, however, correlation was present but concordance was poor. Our work suggests that the use of spot urine P/C ratios will yield more false-positive and -negative diagnoses of glomeruloNephritis flares in patients with SLE than the ratio in 24-h urines.
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Spot urine protein/creatinine ratios are unreliable estimates of 24 h proteinuria in most systemic Lupus Erythematosus Nephritis flares
Kidney international, 2007Co-Authors: Daniel J. Birmingham, Brad H. Rovin, Ganesh Shidham, Michael G Bissell, Haikady N. Nagaraja, X. Zou, Lee A. HebertAbstract:The diagnosis of glomeruloNephritis flares in systemic Lupus Erythematosus (SLE) is usually based on whether the magnitude of proteinuria has changed. Our study tests two methods to assess proteinuric change: protein/creatinine (P/C) ratios of intended 24-h urine collections or that of spot urine samples. Sixty-four patients with glomeruloNephritis due to SLE followed in the Ohio SLE Study provided bimonthly paired spot and intended 24-h urine collections. Completeness of each collection was estimated as the ratio of the measured creatinine to the expected creatinine based upon Cockroft–Gault. Intended 24-h urine collections with measured/expected creatinine ratios between 0.5 and 0.9 (237 samples overall) showed ratios that were not significantly different from ratios of complete 24-h urine collections with ratios of 0.9–1.1 (159 samples). To compare spot and 24 h P/C ratios, we randomly selected pairs of samples with measured/expected ratios above 0.75. Consistent with previous studies, spot and 24-h urine P/C ratios showed good correlation over the range of values as well as reasonably strong concordance. Over the range of most SLE glomeruloNephritis flares, however, correlation was present but concordance was poor. Our work suggests that the use of spot urine P/C ratios will yield more false-positive and -negative diagnoses of glomeruloNephritis flares in patients with SLE than the ratio in 24-h urines.
