Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

Abstract

Nowadays, type II diabetes mellitus, more specifically ensuing diabetic nephropathy, and severe COVID-19 disease are known to be closely associated. The exact mechanisms behind this association are less known. An implication for the angiotensin-converting enzyme 2 remains controversial. Some researchers have started looking into other potential actors, such as neuropilin-1, mitochondrial glutathione, vitamin D, and DPP4. In particular, neuropilin-1 seems to play an important role in the underlying mechanism linking COVID-19 and diabetic nephropathy. We suggest, based on the findings in this review, that its up-regulation in the diabetic kidney facilitates viral entry in this tissue, and that the engagement of both processes leads to a depletion of neuropilin-1, which was demonstrated to be strongly associated with the pathogenesis of DN. More studies are needed to confirm this hypothesis, and research should be directed towards elucidating the potential roles of all these suggested actors and eventually discovering new therapeutic strategies that could reduce the burden of COVID-19 in patients with diabetic nephropathy.

Coronavirus Disease (COVID)-19 and Diabetic Kidney Disease

“…Wu et al conducted a study in 49 hospitalized patients on dialysis in Wuhan, China, and found that the disease course was generally more severe in patients with kidney failure than in those without kidney failure [ 18 ]. Hemodialysis patients received more noninvasive ventilation than non-dialysis patients and had a higher rate of complications, including acute respiratory distress syndrome (ARDS), shock, acute cardiac injury, and arrhythmia [ 49 , 50 ]. These findings suggest atypical clinical presentations of COVID-19 in patients on dialysis.…”

“…These findings suggest atypical clinical presentations of COVID-19 in patients on dialysis. The symptoms of fatigue and anorexia make the diagnosis difficult, since these symptoms are also observed in uremia, suggesting the need for a more systematic screening approach and universal respiratory precautions [ 49 , 50 , 51 ].…”

“…The authors described that 32% of kidney transplant patients (13/41) required hospitalization, had a significantly higher rate of dyspnea (77% vs. 21%; p = 0.003) and had substantially more elevated baseline creatinine (median of 2.0 vs. 1.3 mg/dL; p = 0.02) compared to nontransplant patients [ 49 , 50 , 51 ]. A study describes a practical approach to manage kidney transplants in COVID-19 patients [ 52 ].…”

“…A study suggests that the majority (96%) of hospitalized patients had a clinical course consistent with viral pneumonia, with 39% receiving mechanical ventilation, 21% requiring renal replacement therapy (RRT) with dialysis, while 28% of the kidney transplant recipients and 64% of intubated patients died [ 50 ].…”

“…As kidney transplant and dialysis patients with COVID-19 often present atypically, it is even more important to practice universal respiratory precautions [ 50 , 53 ]. Even after vaccines against SARS-CoV-2 are widespread, the global pandemic is likely to be our “new normal”, due to several more infectious variants [ 54 , 55 , 56 ].…”