Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), influenced by multiple factors, among which genetic factors play a key role, with variants in genes such as HLA-DRB1, IRF5, STAT4 and APOL1, associated with increased risk and severity of the disease, especially in populations of African and mixed-race ancesty.1 Likewise, socioeconomic status influences the evolution of the disease, since limited access to medical care, lack of adherence to treatments and living conditions, sometimes precarious, can aggravate the progression of LN. Environmental factors such as exposure to infections and chronic stress can also trigger dysregulated autoimmune responses in genetically predisposed individuals, thereby exacerbating kidney inflammation and promoting long-term organ damage.2
In this issue, Pazos Pérez et al. perform a cross-sectional analysis of a cohort of patients from the Hospital de Especialidades del Centro Médico Nacional Siglo XXI.3 It should be noted that about 50% of the patients started their SLE in the form of LN. These data are higher than those of other academic cohorts, including GLADEL, with an impact at the beginning of only 5%, or the International SLICC International Collaborative Group, with an impact in the form of LN of 38% at the beginning.4,5
In the present cohort, the low use of hydroxychloroquine (HCQ) in patients with LN (only 8% vs. 23% in patients without LN) is striking. The protective effect of the use of HCQ on various domains in SLE, especially as a factor for the prevention of end-stage chronic kidney disease (ESRD) demonstrated more than 15 years ago in the LUMINA cohort, is well known.6 In addition, a higher prevalence of infections in the group without LN draws attention, without a plausible biological explanation that accounts for this phenomenon, nor a greater leukopenia between groups, and with immunosuppression, as expected, greater in the LN group (higher use of cyclophosphamide, mycophenolate and methylprednisolone). Finally, another factor to highlight in the present Mexican cohort is a high prevalence of comorbidities in patients with LN, including hypertension and obesity in 40% and 15%, respectively.
LN affects a significant proportion of patients, especially in at-risk populations such as African-Americans, Asians, or mixed-race populations in Latin America. Several studies have demonstrated that mestizos develop kidney disease in a higher proportion and at an earlier age, compared to other ethnic groups.2 About 10% of patients can develop ESRD. In a Mexican mestizo cohort of patients with LN, a higher risk of developing ESRD was reported, particularly in those receiving maintenance treatment with azathioprine, those with more flares, or those with onset at younger ages.7
Economic, geographic and cultural barriers make it difficult timely access to specialized medical services for many mestizo patients. These limitations can delay diagnosis and initiation of appropriate treatment, resulting in faster progression of LN and a worse prognosis. In addition, the lack of resources and trained personnel in rural or disadvantaged areas aggravates this situation, which prevents comprehensive and continuous care.2
The development of chronic kidney disease in patients with LN is the result of multiple genetic and sociodemographic factors, factors inherent to the activity and characteristics of the disease, as well as good access and adherence to treatment and control of comorbidities, among others. Fig. 1 summarizes the main factors related to progression to chronic kidney disease in LN.
We are living through exciting years in the management of SLE and NL, with the arrival of new drugs such as voclosporin, and more recently obinutuzumab, but we cannot forget the importance of good management of conventional therapies with better adherence to HCQ, mycophenolate mofetil (MMF), calcineurin antagonists, and nephroprotective measures such as ACE inhibitors, weight control, reduction of salt intake, and even the use of the new sodium-glucose cotransporter type 2 (SLGT2) inhibitors.
Therefore, the ABCs and Ds of NL management should include: 1) better control of activity, with better implementation of sequential therapies (addition of belimumab), use of combination therapies (tacrolimus plus MMF or belimumab plus MMF or tacrolimus) and incorporation of new therapeutic targets (voclosporin, obinutuzumab); 2) reduction of the use of glucocorticoids to minimum possible doses, to minimize their adverse effects; 3) control of comorbidities, including hypertension, obesity, dyslipidemia, hyperuricemia, smoking, and excessive salt intake, which are related to a worse prognosis in LN and, if I may say so; 4) prevention of organ damage, particularly kidney damage with the use of ACE inhibitors, improved adherence to both immunosuppressive and nephroprotective treatment, and the use of other drugs such as SGLT2 inhibitors, such as dapagliflozin.
