Diabetic kidney disease (DKD) is one of the most serious complications of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Current guidelines recommend a personalized approach in order to reduce the burden of DM and its complications. Recognizing sex and gender- differences in medicine is considered one of the first steps toward personalized medicine, but the gender issue in DM has been scarcely explored so far. Gender differences have been reported in the incidence and the prevalence of DKD, in its phenotypes and clinical manifestations, as well as in several risk factors, with a different impact in the two genders. Hormonal factors, especially estrogen loss, play a significant role in explaining these differences. Additionally, the impact of sex chromosomes as well as the influence of gene–sex interactions with several susceptibility genes for DKD have been investigated. In spite of the increasing evidence that sex and gender should be included in the evaluation of DKD, several open issues remain uncovered, including the potentially different effects of newly recommended drugs, such as SGLT2i and GLP1Ras. This narrative review explored current evidence on sex/gender differences in DKD, taking into account hormonal, genetic and clinical factors.

Diabetic kidney disease (DKD) is a major burden in elderly patients with type 2 diabetes (T2DM). Low estimated glomerular filtration rate (eGFR+, < 60 mL/min/1.73 m2) and albuminuria (Alb+) are essential for the diagnosis of DKD, but their association with clinical variables and quality of care may be influenced by ageing. Here we investigated the association of clinical variables and quality of care measures with eGFR+ and Alb+ in 157,595 T2DM individuals participating to the Italian Association of Clinical Diabetologists (AMD) Annals Initiative, stratified by age. The prevalence of eGFR+ and Alb+ increased with ageing, although this increment was more pronounced for low eGFR. Irrespective of age, both the eGFR+ and Alb + groups had the worst risk factors profile when compared to subjects without renal disease, showing a higher prevalence of out-of target values of HbA1c, BMI, triglycerides, HDL-C, blood pressure and more complex cardiovascular (CVD) and anti-diabetic therapies, including a larger use of insulin In all age groups, these associations differed according to the specific renal outcome examined: male sex and smoking were positively associated with Alb+ and negatively with eGFR+; age and anti-hypertensive therapies were more strongly associated with eGFR+, glucose control with Alb+, whereas BMI, and lipid-related variables with both abnormalities. All these associations were attenuated in the older (> 75 years) as compared to the younger groups (< 65 years; 65–75 years), and they were confirmed by multivariate analysis. Notably, Q-score values < 15, indicating a low quality of care, were strongly associated with Alb+ (OR 8.54; P < 0.001), but not with eGFR+. In T2DM patients, the prevalence of both eGFR and Albuminuria increase with age. DKD is associated with poor cardiovascular risk profile and a lower quality of care, although these associations are influenced by the type of renal abnormality and by ageing. These data indicate that clinical surveillance of DKD should not be unerestimated in old T2DM patients.