Emerging Treatments of Cardiorenal Syndrome: An Update on Pathophysiology and Management

Abstract

Cardiorenal syndrome refers to combined cardiac and renal dysfunction that adversely impacts both organs and is also associated with severe clinical outcomes. The pathophysiology is believed to be multifactorial and complex. Increased central venous pressure and intra-abdominal pressure, overactivation of the Renin-Angiotensin-Aldosterone System (RAAS), systemic illnesses like sepsis, amyloidosis, diabetes are important factors in developing the cardiorenal syndrome. Our review article attempts to review the pathophysiology and treatment aspect of cardiorenal syndrome and explores potential therapeutic strategies that can be adopted for the management.We searched PubMed, EMBASE, Google Scholar for relevant articles using different keywords and Medical Subject Headings, and finalized 38 articles to be included in our study. Cardiorenal syndrome management aims to eliminate venous congestion and fluid retention, which leads to improved cardiorenal status. This is usually achieved using pharmacologic agents like diuretics, vasodilators, inotropes, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), neprilysin inhibitors, and extracorporeal methods like ultrafiltration. The use of therapeutic agents such as sodium-glucose co-transporter 2 inhibitors and tolvaptan (a vasopressin V2 receptor antagonist), and cardiac resynchronization therapy has also been shown to have potential benefits in managing the disease. These agents can be instrumental in the management and require large-scale clinical trials specifically aimed at improving cardiorenal outcomes based on severity and type of cardiorenal syndrome.

Renal Dysfunction in Patients with Left Ventricular Assist Device

“… 3 Advanced heart failure is characterized by increased pressures in the right and left atria with decreased cardiac output leading to increased glomerular pressure, which in turn leads to decreased filtration rate. 4 , 5 , 6 Recent research shows CRS is a broad term describing an aberrancy in either renal or cardiac function that leads to dysfunction in the other organ. Neurohormonal activation, low systemic blood pressure, and increase intraperitoneal pressures also contribute to the pathophysiology of CRS.…”

Right Heart Function in Cardiorenal Syndrome

“…Reduction of RV overload, CVP, and renal venous pressure lead to increased renal perfusion and to improved RV/LV interaction, cardiac and kidney function [4,107]. Loop diuretics are frequently used for fast natriuresis with subsequent extracellular volume reduction [107][108][109]. There are no differences in outcome, symptom relief, or changes in renal function when loop diuretics are administered as bolus or continuous therapy [4, 42,106].…”

“…SGLT2 inhibitors are recommended for the treatment of HFrEF patients with and without type 2 diabetes mellitus [53]. Regardless of the presence of diabetes, SGLT2 inhibitors showed beneficial effects on cardiorenal outcome in HFrEF and HFpEF [108,[144][145][146][147]. These cardio-reno-protective benefits render SGLT2 inhibitors a promising drug in CRS prevention and treatment [148].…”

“…Selective blockade of the SGLT2 transporter increases renal excretion of glucose and sodium by inhibiting their reabsorption in the renal proximal tubules [149][150][151]. Reno-protective effects are mainly mediated by reduction in albuminuria, inflammation, hypoxic stress, renal artery stiffness, and restoration of tubuloglomerular feedback [108,148]. Reinforced diuresis may further contribute to advantageous effects of SGLT2 inhibitors on kidney function [108,152].…”

“…Ultrafiltration is another decongestive strategy in decompensated HF and concomitant renal dysfunction, although it does not lead to better outcome or renal function compared to pharmaceutical care only [ 42 , 111 ]. Ultrafiltration is associated with a higher rate of adverse events [ 111 ] and is not an effective therapy in CRS [ 108 ]. Future studies on individually titrated ultrafiltration patients are warranted [ 45 , 115 ], especially in HF and CRS.…”