ABSTRACT
ABSTRACT Despite improvements in patient survival and quality of life, long-term renal survival has not changed significantly in the recent decades and nephritis relapses affect over 50% of patients with lupus nephritis. Renal fibrosis affecting the tubulointerstitial compartment is a central determinant of the prognosis of any kidney disease. Notwithstanding this evidence, the current 2003 ISN/RPS classification still focuses on glomerular pathology and does not include a mandatory score with clear subcategories of the tubulointerstitial injury in the biopsy. The pathogenesis, and the morphological and molecular characteristics of this process in patients with lupus nephritis will be considered, together with a discussion about the concepts the clinician needs to efficiently address in this injury during daily practice and in future clinical trials. Both tubulointerstitial inflammation and fibrosis are strongly correlated with poor renal outcomes in lupus nephritis, regardless of the extent of glomerular damage. Therefore, it is essential to develop reliable and noninvasive approaches to predict which patients are most likely to develop CKD so that appropriate interventions can be adopted before ESRD is established. Currently, no ideal method for monitoring kidney fibrosis exists, since repeated renal biopsies are invasive. Promising methods for assessing and monitoring fibrosis non-invasively include imaging techniques, such as magnetic resonance imaging or ex vivo confocal microscopy, integrated in computational and digital pathology techniques. Finally, beyond specific immunosuppressive treatment in Lupus Nephritis, identifying and treating cardiovascular risk factors should be a cornerstone of treatment in these patients.
RESUMEN A pesar de las mejoras en la sobrevida de los pacientes y su calidad de vida, la sobrevida renal en el largo plazo no ha cambiado significativamente durante las últimas décadas, y las recidivas nefríticas afectan a más del 50% de los pacientes con nefritis lúpica. La fibrosis renal, que afecta el compartimiento tubulointersticial, es un factor determinante central en el pronóstico de todas las patologías renales. A pesar de la evidencia, la actual clasificación ISN/RPS del 2003 todavía se concentra en la patología glomerular y no incluye un score obligatorio con claras subcategorías de la lesión tubulointersticial en la biopsia. Se hablará de la patogenia y las características morfológicas y moleculares de este proceso en pacientes con nefritis lúpica, así como de los conceptos que el clínico necesita para abordar esta lesión de manera eficiente en su práctica cotidiana y en los estudios clínicos a futuro. Tanto la inflamación tubulointersticial como la fibrosis se relacionan fuertemente con desenlaces renales pobres en la nefritis lúpica, con independencia de la extensión del dañío glomerular. Resulta por lo tanto esencial desarrollar sistemas confiables y no invasivos para predecir cuáles pacientes tendrán mayor probabilidad de desarrollar enfermedad renal crónica, a fin de realizar las intervenciones apropiadas antes de que se establezca la enfermedad renal terminal (ERT). En la actualidad, no existe un método ideal para monitorear la fibrosis renal, dado que las biopsias repetidas son procedimientos invasivos. Algunos de los métodos promisorios para evaluar y monitorear la fibrosis de manera no invasiva son las técnicas de imágenes, tales como la resonancia magnética o la microscopía confocal ex vivo, integradas en técnicas de patología computarizadas y digitales. Finalmente, más allá del tratamiento inmunosupresor específico para la nefritis lúpica, identificar y tratar los factores de riesgo cardiovascular deberá ser uno de los pilares de tratamiento en estos pacientes.
Subject(s)
Humans , Pathological Conditions, Signs and Symptoms , Pathologic Processes , Fibrosis , Lupus Nephritis , Female Urogenital Diseases , VaricoceleABSTRACT
BACKGROUND AND AIM: There are few studies of urinary biomarkers and histopathologic features in lupus nephritis (LN). The aim was to analyze the correlation between a wide panel of urinary biomarkers and serum concentrations of anti C1q antibodies with histological items of activity and chronicity on kidney biopsy in LN patients. METHODS: Patients with systemic lupus erythematosus (SLE) according to American College of Rheumatology (ACR) criteria were included. LN diagnosis was based on ACR criteria. Histologic features of activity and chronicity indices were analyzed according to the Austin classification. Serum Anti C1q levels were determined by commercial ELISA. Urinary levels of transferrin, ceruloplasmin (CP), VCAM-1, TWEAK, monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), and alpha-1-acid glycoprotein were measured by commercial ELISA. RESULTS: We included 120 SLE patients (81% female, mean age 33.1 ± 9.3 years, 59.4% Mestizo, 37.8% Afro-Latin American): 64% had LN. Kidney biopsy was performed in 55 patients, but only 37 were made in our center. Anti C1q antibodies were associated with endocapillary proliferation. In patients with cellular crescents, urinary concentrations of CP were significantly higher. In patients with a chronicity index (CI) ≥ 4, fibrous crescents, tubular atrophy, and interstitial fibrosis, urinary MCP-1 levels were higher. CONCLUSIONS: In SLE patients, serum anti C1q antibodies and urinary CP were associated with activity on kidney biopsy and MCP-1 with chronic damage. This panel of biomarkers could be validated in larger, multi-ethnic population as a complementary tool for better stratification of LN patients. Key Points ⢠Urinary biomarkers are complementary useful tools for the assessment of SLE patients. ⢠Urinary levels of CP correlated with activity findings on kidney biopsy in LN patients. ⢠Urinary levels of MCP-1 correlated with chronic damage, especially with fibrous crescents, tubular atrophy, and interstitial fibrosis.