“Nephritic flares” are predictors of bad long-term renal outcome in lupus nephritis

Abstract

We retrospectively analyzed the courses of 70 patients with lupus nephritis followed for 5 to 30 years (median 127 months). Patients survival was 100% at 10 years and 86% at 20 years. The probability of not reaching the end point (persistent doubling of plasma creatinine) was 85% at 10 years and 72% at 20 years. A multivariate analysis of variables at presentation showed that male sex (P = 0.005) and hematocrit lower than 36% (P = 0.01) were associated with the end point (relative risk 7.5 and 14). We then analyzed for the role of renal flare-ups, defined either as a rapid increase in plasma creatinine or by an increase in proteinuria. Patients with renal flares of any type had more probabilities of reaching the end point than patients who never had flares (P = 0.03; relative risk 6.8). The hazard of the end point was 27 times higher in patients with flares along with rapid increased in plasma creatinine than in patients without flares or with flares with proteinuria alone (P < 0.00001). This hazard was higher when plasma creatinine did not return to the basal levels within two months after treatment (P < 0.00001).

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

“…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,…”

“…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.…”

“…A partial response was defined as a urinary protein:urinary creatinine ratio of 0.2-2.0 (15,24,32,47,(90)(91)(92). A complete response was defined as a urinary protein:urinary creatinine ratio of Ͻ0.2 (15,24,32,35,47,52,(89)(90)(91)(92)(93). Worsened was defined as a doubling of the urinary protein:urinary creatinine ratio (i.e., increased by 100%).…”

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

“…This belief is based on only a handful of published studies. Furthermore, the flare-associated risk of CKD or ESRD is thought to be mainly due to those flares that cause an increase in serum creatinine (SCr) and hematuria (so-called nephritic flares) (1,2). 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.…”

“…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).…”