Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: Long‐term followup of a cohort of 145 patients participating in randomized controlled studies

Illei, Gabor G.; Takada, Kazuki; Parkin, Donald Maxwell; Austin, Howard A.; Crane, Marianna; Yarboro, Cheryl; Vaughan, Ellen M.; Kuroiwa, Takashi; Danning, Carol L.; Pando, Jackelina; Steinberg, Alfred D.; Gourley, Mark F.; Klippel, John H.; Balow, James E.; Boumpas, Dimitrios T.

doi:10.1002/art.10142

Cited by 290 publications

(234 citation statements)

References 31 publications

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“…It is not clear which disease-related or kidney-associated parameter correlates best with long-term outcome, particularly the development of ESRD. In previous studies, factors that have been associated with worse renal outcomes over the long term have included elevated titers of anti-double-stranded DNA (anti-dsDNA) antibodies (7)(8)(9)(10)(11), low levels of C3 complement (11)(12)(13)(14)(15), 422 RENAL DISEASE SUBCOMMITTEE OF THE ACR AD HOC COMMITTEE ON SLE RESPONSE CRITERIA increased levels of serum creatinine (3,8,9,12,13,, decreased rates of creatinine clearance (11,23,31,36,37), the presence of extrarenal manifestations (38,39), the number of lupus flares (9,28,35), the presence of hypertension (12,13,18,21,30,31,35,36,(40)(41)(42)(43), the presence of nephrotic syndrome (31,(44)(45)(46), an increased activity index on histologic assessment of renal biopsy tissues (9,12,…”

Section: Resultsmentioning

confidence: 99%

“…The committee defined improved as a 50% reduction in the urinary protein: urinary creatinine ratio. The literature is replete with definitions of improvement based on the 24-hour urine protein excretion level (5,9,15,16,18,24,32,34,35,38,47,52,66,72,74,75,80,81,(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98). In addition, the committee thought that a reduction in proteinuria from the nephrotic range (Ն3.5 gm/day) to the non-nephrotic range was an important and distinctive end point.…”

Section: Resultsmentioning

confidence: 99%

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The American college of rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials

Liang

Schur

Fortin

et al. 2006

Arthritis & Rheumatism

231

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The American college of rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials

Liang

Schur

Fortin

et al. 2006

Arthritis & Rheumatism

231

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“…In contrast, proteinuric flares, in which SCr does not increase but proteinuria increases above predesignated target levels, have been considered to confer less long-term risk to the kidneys. This conclusion is based on limited evidence (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Renal Flare as a Predictor of Incident and Progressive CKD in Patients with Lupus Nephritis

Parikh

Nagaraja

Hebert

et al. 2014

Clinical Journal of the American Society of Nephrology

102

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SummaryBackground and objectives Renal flares are common in lupus nephritis. The impact of flares on the development of CKD in lupus nephritis was examined.Design, setting, participants, & measurements A retrospective analysis of prospectively collected data from the Ohio Systemic Lupus Erythematosus (SLE) Study was conducted to determine if renal flares predispose to new CKD or progression of preexisting CKD. Patients in the Ohio SLE Study were followed from 2001 to 2009, with a median follow-up of 6 years. For this analysis, patients with biopsy-proven lupus nephritis and at least 3 years of follow-up were included (n=56). Frequency and duration of renal flares were compared between patients who never developed CKD (n=29) and patients who developed new CKD (n=12) and between patients with preexisting but stable CKD (n=7) and patients who progressed (n=8). Groups were also combined into good (no CKD and stable CKD) or poor (new CKD and progressive CKD) for analysis.Results The new CKD group had more renal flares per year compared with the no CKD group (median=0.56 flares/yr [range=0-2] versus median=0 flares/yr [range=0-1.4]; P,0.001). Additionally, the poor outcome group had more renal flares per year compared with the good outcome group (median=0.50 flares/yr [range=0-2] versus median=0 flares/yr [range=0-1.4]; P,0.001). New or progressive CKD was not preferentially associated with nephritic compared with proteinuric renal flares. Logistic regression showed that spending more than 30% of time in renal flare (odds ratio, 20; 95% confidence interval, 4.6 to 91.3; P,0.001) and age.35 years (odds ratio, 69; 95% confidence interval, 6.3 to 753.6; P,0.001) were independent predictors of the combined end point of developing new or progressive CKD. All four subjects over 35 years of age that spent over 30% of time in renal flare had a poor outcome. ConclusionIn patients with lupus nephritis, the relative duration of renal flare is an independent predictor of incident and progressive CKD.

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“…As shown, P-C and A-C were linearly related and highly correlated (r ϭ 0.99, slope ϭ 0.79, P Ͻ 0.0001). Shown in relationship to the regression of A-C on P-C is the minimum increase in proteinuria required to diagnose SLE proteinuric flare by the low- (18,19), intermediate- (19,20), and high-threshold criteria (22)(23)(24)(25)(26).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the use of high-threshold criteria for SLE proteinuric flare (22)(23)(24)(25)(26) may expose the kidney to greater nephrotoxicity than the use of the low-threshold criteria for SLE flare (18 -20). On this basis, it could be argued that, compared with the routine use of low-threshold criteria, the routine use of high-threshold criteria for proteinuric flare before triggering an increase in therapy will delay therapy and might increase the risk for irreversible kidney damage.…”

Section: Figure 2 Relationship Between P-c Ratio and The Proportion mentioning

confidence: 99%

Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis

Birmingham¹,

Rovin²,

Shidham³

et al. 2008

Clinical Journal of the American Society of Nephrology

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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 ؊ microalbumincreatinine 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 proteincreatinine 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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Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: Long‐term followup of a cohort of 145 patients participating in randomized controlled studies

Cited by 290 publications

References 31 publications

The American college of rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials

The American college of rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials

Renal Flare as a Predictor of Incident and Progressive CKD in Patients with Lupus Nephritis

Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis

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