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Innovative Medicines & Omics Current approach in the management of kidney disease

sickness, immunosuppression in transplant recipients express. These associations, observed in laboratory
with suspected or confirmed COVID-19 should be altered models of sepsis, are supported by plasma cytokine levels
promptly. After the onset of ARDS, significant AKI in patients with sepsis-associated AKI. Human COVID-
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frequently manifests in COVID-19 patients, indicating 19 infection is caused by the interaction of the viral spike
that lung-kidney crosstalk is the primary mechanism protein’s receptor-binding domain with the cell surface
causing kidney injury. 17,18 ACE2. The spike protein is then cleaved by proteases, such
as TMPRSS2, in a proteolytic manner. When the virus
2.5. Role of SARSCoV2 in KD interacts with CD147, which is expressed on the proximal
Angiotensin-converting enzyme 2 (ACE2), a homolog convoluted tubules of the nephron and inflammatory
of ACE, reduces vasoconstriction induced by the cells; it can cause acute tubular necrosis, collapsing
renin-angiotensin system by converting Angiotensin glomerulopathy, protein leakage from Bowman’s capsule,
II to angiotensin 1 – 7. There are two types of and mitochondrial dysfunction. 24
ACE2: membrane-bound ACE2 and soluble ACE2. SARS-
CoV-2 attaches to ACE2 on the host cell membranes. The 2.6. Impaired renal reflex in AKI
ability of coronaviruses to enter cells depends on their The pathophysiology of renal disorders is thought to
ability to attach to cellular receptors and prime their S be influenced by renal sympathetic nerve activity. The
proteins for entry by host cell proteases. As a result, the intrarenal release of adenosine, triggered by tissue
activity of the protease transmembrane protease, serine ischemia, increases the activity of both afferent renal
2 (TMPRSS2) to cleave the viral spike protein and the sensory neurons and efferent renal sympathetic nerve
expression of ACE2, are essential for cell invasion. Both activity. Equally significant in the etiology of AKI is the
podocytes and the apical brush borders of the proximal effects of efferent RSNA, which include decreased renal
tubules in the kidneys express ACE2. ACE is expressed blood flow and oxygen delivery, as well as increased
in renal endothelial cells, whereas ACE2 is not. Recent renal workload. In hypotensive and hypovolemic
human tissue RNA-sequencing data show that the conditions, an elevation in RSNA causes acute renal
expression of ACE2 in kidney tissue is about 100 times vasoconstriction. This results in glomerulotubular
higher than in pulmonary tissue. The proximal tubules dysfunction, hormonal changes, and the development of
of the kidney have been shown to express TMPRSS2. renal ischemia. In contrast to angiotensin-converting
19
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Antibodies against ACE2 are produced when ACE2 enzyme inhibitor (ACEI)/angiotensin II receptor blockers
binds to the SARS-CoV-2 spike protein, causing a (ARB) monotherapy, short-term use of mineralocorticoid
conformational shift in proteins that serve as a target for receptor antagonists (MRAs) in combination with ACEIs/
autoantibody development. After antigen-presenting cells ARBs was not associated with a lower risk of cardiovascular
process complexes of SARS-CoV-2 and soluble ACE2, or renal outcomes in patients with diabetic KD and
antibodies may cause type 2/3 hypersensitivity reactions, hypertension. A real-world clinical problem for MRA-
in addition to Type 4 hypersensitivity reactions. Type 2 ACEI/ARB combination therapy is indicated by the risk
hypersensitivity responses during SARS-CoV-2 infection of hyperkalemia and the brief duration of the combination
trigger the production of immunoglobulin M against medication. Numerous pathophysiological conditions,
ACE2, which targets ACE2 in kidney cells and causes renal including diabetes, hypoxia, ureteral blockage, cirrhosis,
impairment. Recent research revealed that SARS-CoV-2 and renal IRI, have been linked to this defective inhibitory
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entered host cells through the novel CD147-spike protein renorenal reflex. Nitric oxide (NO), which functions
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pathway. The transmembrane glycoprotein CD147, as both a neurotransmitter and neuromodulator, is one
which is widely expressed, has been linked to numerous of the several neurotransmitters in the brain that alter
kidney illnesses, including CKD. It is significantly sympathetic nerve activity. Inducible nitric oxide synthase
expressed on inflammatory cells and proximal TECs. 21,22 (iNOS) and neuronal NO synthase (nNOS)-induced
According to Legrand et al., the enhanced production of endogenous NO synthesis seem to affect blood pressure
inflammatory cytokines by resident and immune kidney and sympathetic nervous system activity differently. This
cells is likely a factor contributing to tissue damage is thought to be caused, at least in part, by the differential
in COVID-19 patients. In COVID-19, nuclear factor release of neurotransmitters in the rostral ventrolateral
erythroid 2-related factor 2 (Nrf2) and its downstream medulla, including inhibitory gamma-aminobutyric acid
signaling components are likewise suppressed in the and sympatho-excitatory glutamate. Cyclic 3′-5′ guanosine
lungs. Inflammatory mediators such as tumor necrosis monophosphate-dependent processes are suggested in the
factor (TNF) and FAS can directly harm renal endothelial control of neuronal activity by microinjection of exogenous
and epithelial cells by binding to specific receptors they NO. The inhibition of Angiotensin II release also mediates

Volume 2 Issue 1 (2025) 39 doi: 10.36922/imo.4969