Table 1. Studies detailing the effects of the innate immune system in cardiorenal syndrome (CRS) type I.

ACE- angiotensin-converting enzyme, AKI- acute kidney injury, IL- interleukin, TLR- toll-like receptors, TNF- tumor necrosis factor, GM-CSF- granulocyte/monocyte-colony stimulating factor, G-CSF- granulocyte-colony stimulating factor. 

AUTHOR & YEAR OF PUBLICATION	TYPE OF STUDY	PURPOSE OF STUDY	CONCLUSION
Clementi et al. [1]   2019	Review	Neurohormonal, endocrine, immune dysregulation and inflammation in CRS	To insinuate the need for novel drug therapies that cover new mechanisms in CRS.
Virzì et al. [5] 2014	Review	The Hemodynamic and Non-hemodynamic Cross-talk in CRS type I	To elaborate molecular, cellular, and subcellular  features for advancing  treatments
Virzì et al. [18] 2014	Review	Heart--kidney cross-talk and role of humoral signaling in critical illness	Damaged cardiac myocytes and renal tubular epithelium promote activation of innate and adaptive immune systems strengthening the humoral response.
Pasare and Medzhitov [25] 2004	Review	Toll-like receptors: linking innate and adaptive immunity	TLRs are essential for immune cell maturation and the apt recognition of internal and  external  molecular pathogens
de kleijn and Pasterkamp [26] 2003	Review	Toll-like receptors in cardiovascular diseases	TLRs play a crucial role in initiating cardiovascular diseases especially atherosclerosis formation
Chao [27] 2009	Review	Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart	TLRs respond to tissue injury and are important sources of cardiac ischemia-reperfusion injury. These receptors also cardioprotectors regulating cell survival in heart.
Eissler et al. [28] 2011	Animal study	Hypertension augments cardiac Toll-like receptor-4 expressions and activity	Hypertension actives the innate immune system through TLR.  ACE inhibitors inhibit inflammation only at high doses
Allam et al. [29] 2012	In vitro study	Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4	Histone neutralization can reduce ischemia-reperfusion injury from dying renal epithelial cells.
Kinsey and Okusa [30] 2008	Review	Inflammation in Acute Kidney Injury	Ischemia-reperfusion injury stimulates the immune system. TLR, chemokines. Cytokines amplify this response. Further research is needed to categorize the function of each component of the immune system in AKI.
Dong et al. [31] 2007	Animal study	Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury	Renal dendritic cells are localized to renal peritubular space and respond to innate immunity enrolling further circulating immune cells into the kidney.
Virzì et al. [32] 2018	Review	The role of dendritic and endothelial cells in CRS	Heart and kidney dendritic cells are involved in tissue remodeling. Additionally, endothelial cells act as antigen-presenting cells and act as a bridge between innate and adaptive immune systems.
Zhang et al. [33] 1993	Animal study	Interstitial dendritic cells of the rat heart. Quantitative and ultrastructural changes in experimental myocardial infarction	These dendritic cells instigate additional lymphocytes and reduce in quantity with the formation of a scar.
Naito et al. [34] 2008	Animal study	Differential effects of GM-CSF and G-CSF on the infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction	Induction of MI in rat models is characterized by dendritic cells infiltration, increased interferon-gamma and TLR4 expression with decreased IL-10 levels
Vaduganathan et al. [35] 2013	Review	The immunological axis in heart failure: the importance of the leukocyte differential	High lymphocyte counts in acute and chronic heart failure patients are associated with unfavorable prognosis. In particular, elevated monocyte counts are also indicative of severe outcomes in heart failure
Wrigley et al. [36] 2011	Review	The role of monocytes and inflammation in the pathophysiology of heart failure	Persistent activation of monocytes during heart failure augments tissue injury and are implicated in disease progression
Satoh et al. [37]     2008	Review	Immune modulation: role of the inflammatory cytokine cascade in the failing human heart.	Cytokines and TNF-alpha induce changes in monocyte phenotype, myocardial cell death, and advanced matrix metalloproteinase activity to enhance ventricular remodeling
Pastori et al. [38]                     2015	In vitro study 40 patients	CRS type I: A Defective Regulation of Monocyte Apoptosis Induced by Pro-inflammatory and Proapoptotic Factors	Inflammatory cytokines in the plasma of CRS patients induce the production of more cytokines leading to unregulated apoptosis.