Fabry nephropathy. Role of nephrologist and clinical variables associated with the diagnosis

Abstract

Background: The early detection of Fabry nephropathy is of interest to us. Its treatment is more effective in early stages. It has been studied by analysing molecular and tissue biomarkers. These have certain disadvantages that hinder its routine use. The aim of this study is to describe the role of the nephrologist in the diagnosis of the disease, and to describe the clinical variables associated with nephropathy in affected patients. Material and methods: Cross-sectional study. Patients were included from three reference centers in Argentina. Results: Seventy two patients were studied (26.26 ± 16.48 years): 30 of which (41.6%) were men and 42 of which (58.4%) were women; 27 pediatric patients and 45 adults. Fourteen “index cases” were detected, 50% of which were diagnosed by nephrologists. Nephropathy was found in 44 patients (61%): 6 pediatric patients and 38 adults. Two types of clinical variables were associated with nephropathy: (i) peripheral nervous system compromise (P ≤ 0.001), angiokeratomas (P ≤ 0.001) and auditory compromise (P = 0.01–0.001), with these being early clinical manifestations of the most severe disease phenotype, and (ii) structural heart disease (P = 0.01–0.001) and central nervous system compromise (P = 0.05–0.01), which are major and late complications, responsible for increased morbidity and mortality and lower life expectancy. Conclusion: The nephrologist plays an important role in the diagnosis of Fabry nephropathy, although the detection thereof owing to its renal involvement would represent a late diagnosis, because nephropathy is associated with late complications of the most severe disease phenotype. Resumen: Antecedentes: La detección temprana de la nefropatía por enfermedad de Fabry es de interés, pues su tratamiento es más eficaz en estadios precoces. Ha sido estudiada por biomarcadores moleculares y tisulares, pero estos poseen desventajas que dificultan su uso rutinario. El propósito del presente trabajo es describir el rol del nefrólogo en el diagnóstico de la enfermedad y las variables clínicas asociadas a nefropatía en pacientes afectados. Material y métodos: Estudio transversal. Se incluyeron pacientes de tres centros de referencia de Argentina. Resultados: Se estudiaron 72 pacientes (26,26 ± 16,48 años): 30 (41,6%) varones y 42 (58,4%) mujeres; 27 pediátricos y 45 adultos. Se detectaron 14 «casos índice», el 50% diagnosticados por nefrólogos. Se halló nefropatía en 44 pacientes (61%): 6 pediátricos y 38 adultos. Dos tipos de variables clínicas se asociaron a nefropatía: a) compromiso del sistema nervioso periférico (p ≤ 0,001), angioqueratomas (p ≤ 0,001) y compromiso auditivo (p = 0,01-0,001), siendo estas manifestaciones clínicas tempranas del fenotipo más severo de la enfermedad, y b) cardiopatía estructural (p = 0,01-0,001) y compromiso del sistema nervioso central (p = 0,05-0,01), que son complicaciones mayores y tardías, responsables de la morbimortalidad aumentada y la menor expectativa de vida. Conclusión: El nefrólogo cumple un rol importante en el diagnóstico de la enfermedad de Fabry, ya que aunque la detección de esta por su compromiso renal significaría diagnóstico tardío, debido a que la nefropatía se asocia a complicaciones tardías del fenotipo más severo de la enfermedad. Keywords: Fabry disease, Nephropathy, Proteinuria, Early diagnosis, Palabras clave: Enfermedad de Fabry, Nefropatía, Proteinuria, Diagnóstico temprano