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Serum Albumin Modifies the Effect of Peripheral Blood Monocytes on Severity of Diabetic Nephropathy in an Adult Population

      Abstract

      Background

      Our aim in this study was to characterize clinical associations between peripheral blood immune populations and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus.

      Methods

      We queried hospital records from an outpatient diabetes primary care clinic between 2018 and 2019 for clinical and laboratory data, including complete blood counts with differentials, serum albumin and globulin, glycated hemoglobin (A1C) and urine albumin-to-creatinine ratio. One hundred ninety-eight patients had complete cross-sectional data with temporally proximate complete blood counts and urine albumin-to-creatinine ratios. After univariable correlation assessment, we used a forward multivariable linear regression model to test the hypothesis that higher numbers of circulating innate immune populations would be associated with DKD, while accounting for known demographic, clinical and laboratory risk factors. We defined DKD as an albumin-to-creatinine ratio of >3 mg/mmol or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 from the Chronic Kidney Disease Epidemiology Collaboration.

      Results

      Adjusted analyses demonstrated significant (p<0.01) associations between higher urine albumin-to-creatinine ratio and peripheral circulating monocytes, independent of other established significant risk factors, including blood pressure, A1C, age and sex. We also identified serum albumin as a potentially important modifying factor of albuminuric kidney disease, which interacts with monocytes in more advanced disease. In contrast, the variable most strongly predictive of eGFR was age.

      Conclusions

      Circulating monocytes and serum albumin are significantly associated with albuminuria, but not eGFR in DKD. These results support the potential role of the innate immune system in diabetic microvascular end-organ damage and urinary protein loss, and may be readily translatable clinical markers to incorporate into risk-assessment models for prognostication in diabetes.

      Résumé

      Introduction

      L’objectif de notre étude était de décrire les associations cliniques entre les populations de cellules immunitaires dans le sang périphérique et la néphropathie diabétique (NPD) chez les patients atteints du diabète sucré de type 2.

      Méthodes

      Nous avons interrogé les dossiers médicaux électroniques d’un service de consultations externes (soins primaires) pour les diabétiques entre 2018 et 2019 pour trouver des données cliniques et de laboratoire, y compris les formules sanguines complètes avec différentielle, l’albumine et la globuline sériques, l’hémoglobine glyquée et le ratio albuminurie:créatinurie. Cent quatre-vingt-dix-huit patients avaient des données transversales complètes qui regroupaient des formules sanguines complètes et des ratios albuminurie:créatinurie proches dans le temps. Après l’analyse de corrélation univariée, nous avons utilisé un modèle de régression linéaire multiple ascendante pour vérifier l’hypothèse selon laquelle un plus grand nombre de populations de cellules immunitaires innées circulantes seraient associées à la NPD, tout en tenant compte des facteurs de risque démographiques, cliniques et de laboratoire connus. Nous avons défini la NPD en fonction d’un ratio albumine/créatinine > 3 mg/mmol ou un débit de filtration glomérulaire estimé (DFGe) de < 60 mL/min/1,73 m2 de la Chronic Kidney Disease Epidemiology Collaboration.

      Résultats

      Les analyses ajustées ont démontré des associations significatives (p < 0,01) entre un ratio albuminurie:créatinurie plus élevé et les monocytes périphériques circulants, indépendamment des autres facteurs de risque significatifs établis, dont la pression artérielle, l’hémoglobine glyquée, l’âge et le sexe. Nous avons aussi déterminé que l’albumine sérique est un paramètre modificateur potentiellement important de néphropathie albuminurique, qui interagit avec les monocytes dans la phase plus avancée de la maladie. En revanche, la variable la plus prédictive du DFGe était l’âge.

      Conclusions

      Les monocytes circulants et l’albumine sérique sont associés de façon significative à l’albuminurie, mais non au DFGe lors de NPD. Ces résultats confirment le rôle potentiel du système immunitaire inné dans les lésions aux organes cibles associées au diabète et la perte urinaire de protéines, et peuvent être des marqueurs cliniques facilement transposables aux modèles d’évaluation des risques pour le pronostic du diabète.

      Keywords

      Mots clés

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