Urinary serpin-A3 is an early predictor of clinical response to therapy in patients with proliferative lupus nephritis
Por:
Martinez-Rojas, Miguel Angel, Sanchez-Navarro, Andrea, Mejia-Vilet, Juan Manuel, Perez-Villalva, Rosalba, Uribe, Norma, Bobadilla, Norma A.
Publicada:
1 oct 2022
Resumen:
We have previously reported that urinary excretion of serpin-A3
(uSerpA3) is significantly elevated in patients with active lupus
nephritis (LN). Here, we evaluated the course of uSerpA3 during the
first year of treatment and its association with response to therapy in
patients with proliferative LN. The observational longitudinal study
included 60 Mexican adults with proliferative LN followed during the
first year after LN flare. uSerpA3 was detected by Western blot analysis
at flare and after 3, 6, and 12 mo. The response to therapy was
determined 1 yr after the LN flare. We evaluated the correlation between
uSerpA3 and histological parameters at LN flare. The temporal
association between uSerpA3 and response to therapy was analyzed with
linear mixed models. uSerpA3 prognostic performance for response was
evaluated with receiver-operating characteristic curves. Among the 60
patients studied, 21 patients (35%) were class III and 39 patients
(65%) were class IV. uSerpA3 was higher in class IV than in class III
LN (6.98 vs. 2.89 dots per in./mg creatinine, P = 0.01). Furthermore,
uSerpA3 correlated with the histological activity index (r = 0.29, P =
0.02). There was a significant association between the temporal course
of uSerpA3 and response to therapy. Responders showed a significant drop
in uSerpA3 at 6 mo compared with LN flare (P < 0.001), whereas
nonresponders persisted with elevated uSerpA3. Moreover, uSerpA3 was
significantly lower at flare in responders compared with nonresponders
(2.69 vs. 6.98 dots per in./mg creatinine, P < 0.05). Furthermore,
uSerpA3 was able to identify nonresponders since 3 mo after LN flare
(area under the curve: 0.77). In conclusion, uSerpA3 is an early
indicator of kidney inflammation and predictor of the clin-ical response
to therapy in patients with proliferative LN. NEW & NOTEWORTHY LN
requires aggressive immunosuppression to improve long-term outcomes.
Current indicators of remis-sion take several months to normalize,
prolonging treatment regiments in some cases. Serpin-A3 is present in
urine of patients with proliferative LN. We evaluated the excretion of
serpin-A3 in serial samples of patients with proliferative LN during the
first year after flare. We found that uSerpA3 correlates with kidney
inflammation and its decline at early points predicts the response to
therapy 1 yr after flare.
Filiaciones:
Martinez-Rojas, Miguel Angel:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City, Mexico
Sanchez-Navarro, Andrea:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City, Mexico
Mejia-Vilet, Juan Manuel:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City, Mexico
Perez-Villalva, Rosalba:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City, Mexico
Uribe, Norma:
Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City, Mexico
Bobadilla, Norma A.:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City, Mexico
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