Subclinical kidney damage hypothesis

Hypothesis

In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Acute Sequelae of SARS-CoV-2 infection (long Covid), endothelial dysfunction is posited to compromise the glomerular filtration apparatus, leading to a renal response characterized by elevated renin secretion. This initiates a cascade resulting in chronic immune system activation and the induction of sickness behaviors.

A comparable clinical entity exhibiting occult renal involvement is scleroderma, which may also impact the renal filtration system, albeit through the mechanism of reduced glomerular filtration efficiency secondary to the deposition of extracellular matrix components, rather than direct compromise of afferent arteriolar perfusion.

The renal system plays a critical role in blood pressure regulation. The initiation of renin secretion, indicative of renal distress, is detected by the central nervous system, given the heart's vital role in systemic perfusion. The central nervous system interprets these renal signals as indicative of pathology, leading to immune system activation in an attempt to identify the inciting agent. As renal dysfunction progresses, the corresponding increase in renin secretion further potentiates immune activation, potentially culminating in a state of heightened immune activation. Given the potential irreversibility of the underlying renal pathology, this immune hyperactivation may persist. Eventually, responsiveness to sustained renin signaling may attenuate, prompting the compensatory activation of alternative blood pressure regulatory mechanisms.

Concise Summary (Technical):

Endothelial dysfunction precipitates renal involvement and subsequent renin release. The heart secretes B-type natriuretic peptide (BNP) to signal the central nervous system regarding hemodynamic dysregulation. The central nervous system initiates immune system activation. The persistent nature of renal damage leads to chronic immune hyperactivation and potential immunopathology, exacerbating the overall physiological state.

Rationale

A persistent observation in both ME/CFS and long Covid research is the lack of a definitive biomarker. Current research efforts are largely focused on elucidating an etiology rooted in downstream immune system dysregulation, with limited consideration for the proposed renal-mediated mechanism.

Measurement of B-type natriuretic peptide (BNP) levels is infrequent in this context. Acute myocardial infarction, a common cardiac emergency, is typically assessed using alternative diagnostic markers. When BNP is measured, it is primarily indicated in the context of overt heart failure, rather than as a marker of hemodynamic signaling in these conditions.

Assessment of plasma renin activity (PRA) is also infrequent. Blood pressure is typically assessed noninvasively via sphygmomanometry. Despite markedly elevated renin levels, the body employs various compensatory mechanisms to mitigate hypertension, resulting in a potentially subclinical presentation.
Currently, there are no curative pharmacotherapies or interventions for reversing chronic kidney disease (CKD). Current management strategies primarily focus on blood pressure control. There is a paucity of histological analysis of renal tissue from deceased individuals with long COVID and ME/CFS, and any observed renal damage may be attributed to alternative etiologies

Validation Experiment

* Quantify plasma renin activity (PRA) to assess for elevated levels.
* Subsequently, measure plasma B-type natriuretic peptide (BNP) concentrations.

 

It is my own thoughts from my own experience. I hope I got it in a correct section.

Normally I have a more terse and folksy writing style. I wasn't attempting to deceive, but to put it into a more clinical language rather than relating my own experience.

 

I am afraid I don't think this works. Renovascular problems with renin hypersecretion do not stimulate an immune response. In scleroderma it is the other way around - an immune response damages renal vessels with a renin response. The brain and immune system do not look for an inciting agent. Signalling systems are triggered according to biochemical rules that have no concepts of 'inciting agents'. Renal artery stenosis does not produce an immune response.