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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References
- IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045.Diabetes Res Clin Pract. 2018; (138;271–278)
- Update of pathophysiology and management of diabetic kidney disease.J Formosan Med Assoc. 2018; (117:662–675)
- The global epidemiology of diabetes and kidney disease.Adv Chronic Kidney Dis. 2018; (25:121–132)
- Progressive diabetic nephropathy. How useful is microalbuminuria?.Contra. Kidney Int. 2014; (86:50–57)
- Clinical predictive factors in diabetic kidney disease progression.J Diabetes Investig. 2017; (8:6–18)
Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes.2006;55:1832–1839.
- AGE, RAGE, and ROS in diabetic nephropathy.Sem Nephrol. 2007; (27:130–143)
- Use of the monocyte-to-lymphocyte ratio to predict diabetic retinopathy.Int J Environ Res Publ Health. 2015; 12 (10009–10019)
- Association of monocyte-to-high density lipoprotein-cholesterol ratio with peripheral neuropathy in patients with Type II diabetes mellitus.Biomarkers Med. 2018; 13 (907–915)
- Use of readily accessible inflammatory markers to predict diabetic kidney disease.Front Endocrinol. 2018; (9:225)
- Diagnostic performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at estimating glomerular filtration rate in adults with diabetes mellitus: A systematic review and meta-analysis protocol.BMJ Open. 2019; 9
- Nomenclature for kidney function and disease: Report of a Kidney Disease: Improving Global Outcomes (KDIGO) consensus conference.Kidney Int. 2020; 97 (1117–1129)
- Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline.Ann Intern Med. 2013; 158 (825–830)
- Peripheral total and differential leukocyte count in diabetic nephropathy: The relationship of plasma leptin to leukocytosis.Diabetes Care. 2005; 28 (1710–1717)
- Monocyte–lymphocyte ratio is a valuable predictor for diabetic nephropathy in patients with type 2 diabetes.Medicine. 2020; 99e20190
- Monocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathy.Biomarkers Med. 2018; (9:953–959)
- The relationship between monocyte to high-density lipoprotein cholesterol ratio and diabetic nephropathy.Pakistan J Med Sci. 2019; 35 (1081–1086)
- The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: A randomised trial.Lancet Diabetes Endocrinol. 2015; (3:687–696)
- Association between monocyte count and risk of incident CKD and progression to ESRD.Clin J Am Soc Nephrol. 2017; 12 (603–613.)
- Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.Nephrol Dial Transplant. 2018; 33 (986–992)
- Serum albumin concentration and risk of end-stage renal disease: The REGARDS study.Nephrol Dial Transplant. 2018; 33 (9:953–1777)
- Significant association of serum albumin with severity of retinopathy and neuropathy, in addition to that of nephropathy, in Japanese type 2 diabetic patients.Endocrine J. 2008; 55 (311–316)
- The level of serum albumin is associated with renal prognosis in patients with diabetic nephropathy.J Diabetes Res. 2019; (16:6–11)
- Biological effects of albumin unrelated to oncotic pressure.Aliment Pharmacol Ther. 2002; 16: 6-11
- Specific antioxidant properties of human serum albumin.Ann Intensive Care. 2013; 3: 1-7
- Redox-derived damage-associated molecular patterns: Ligand function of lipid peroxidation adducts.Redox Biol. 2013; 1 (:94–96)
- Human monocyte interactions with non-enzymatically glycated collagen.Diabetologia. 1992; 35 (160–164)
Article info
Publication history
Published online: June 07, 2021
Accepted:
June 2,
2021
Received in revised form:
May 29,
2021
Received:
July 6,
2020
Identification
Copyright
© 2021 Canadian Diabetes Association.