Diabetic Nephropathy and COVID-19: Fatal Connection?
People with diabetes and diabetic kidney disease exhibit higher mortality and risk of severe illness in connection with COVID-19. The worse prognosis of these patients likely has multiple reasons; in the following overview, we will focus mainly on the cellular receptor of the SARS-CoV-2 virus – angiotensin-converting enzyme 2 (ACE2).
Diabetes Mellitus = Immunosuppressive State
Immune dysfunctions associated with diabetes mellitus (DM) cause greater susceptibility to infections. Moreover, 30–40% of patients with DM develop chronic kidney disease, which induces chronic systemic inflammation, thereby contributing to an immunosuppressive state. Increased susceptibility to infectious complications also raises the overall morbidity and mortality of diabetics.
Kidneys – Organs with High Susceptibility to COVID-19 Infection. Why?
According to available studies, the kidneys are organs highly susceptible to damage due to the expression of ACE2. This protein serves as a receptor for the coronavirus to enter cells and simultaneously participates in the development of a cytokine storm, which can have fatal consequences for the body. ACE2 can be considered a sensitivity factor for COVID-19 infection. Earlier studies on animal models have also shown that in DM, there is early upregulation and increased activity of ACE2.
Data from patients hospitalized during the spring of 2020 in New York showed that out of 510 COVID-positive patients admitted to intensive care units, 23% required dialysis for acute kidney failure. Among 84% of surviving patients, there was a restoration of kidney function within 1 month of observation. Another study confirmed significantly higher overall mortality in patients with COVID-19 and chronic kidney disease, those on hemodialysis, or those awaiting kidney transplant.
ACE Inhibitors or Sartans and the Course of COVID-19
It is important to differentiate between ACE and ACE2 – they are enzymes with different active sites. ACE2 is primarily located in the proximal tubule cells. Angiotensin-converting enzyme inhibitors used in antihypertensive treatment do not act against ACE2. It appears that therapy with ACE inhibitors or sartans does not have a negative impact on mortality or morbidity in patients with cardiovascular disease during COVID-19 infection.
SARS-CoV-2 and the Onset of Ketoacidosis or Type 1 Diabetes
Some findings also suggest that the SARS-CoV-2 coronavirus could trigger acute diabetes complications (e.g., diabetic ketoacidosis). The pathophysiological basis likely also involves the ACE2 receptor, which is expressed, among other places, in the beta cells of the pancreas. Therefore, there is a potential risk of SARS-CoV-2 damaging these cells and disrupting insulin secretion, leading to hyperglycemia and ketoacidosis.
Based on data obtained from monitoring pediatric patients in the United Kingdom, it is also presumed that exposure to SARS-CoV-2 may accelerate the onset of Type 1 diabetes mellitus (DM1).
Key = Good Diabetes Management
Available analyses show that if diabetics are properly treated, COVID-19 disease has a mild course for them, similar to the majority of the population. Poor glycemic control can compromise an individual's defenses, thereby facilitating the development of infection.
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Sources:
1. Apicella M., Campopiano M. C., Mantuano M. et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol 2020; 8 (9): 782-792, doi: 10.1016/S2213-8587(20)30238-2.
2. COVID-19 and diabetes: a co-conspiracy? Editorial. Lancet Diabetes Endocrinol 2020; 8 (10): 801, doi: 10.1016/S2213-8587(20)30315-6.5.
3. D'Marco L., Puchades M. J., Romero-Parra M., Gorriz J. L. Diabetic kidney disease and COVID-19: the crash of two pandemics. Front Med (Lausanne) 2020; 7: 199, doi: 10.3389/fmed.2020.00199.
4. Stevens J. S., King K. L., Robbins-Juarez S. Y. et al. High rate of renal recovery in survivors of COVID-19 associated acute renal failure requiring renal replacement therapy. PLoS One 2020; 15 (12): e0244131, doi: 10.1371/journal.pone.0244131.
5. Ozturk S., Turgutalp K., Arici M. et al. Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey. Nephrol Dial Transplant 2020; 35 (12): 2083−2095, doi: 10.1093/ndt/gfaa271.
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