Urinary excretion of kidney damage biomarkers in hypertensive patients with chronic kidney disease, chronic heart failure, and with combined antihypertensive therapy and cardiac glycosides

Background. The combination of renal and heart failure is characterized as cardiorenal syndrome (CRS) and represents a significant clinical problem associated with an unfavorable prognosis for patients with arterial hypertension (HTN). Combination therapy, including antihypertensive and antiproteinuric drugs, as well as lipidlowering and antiplatelet agents, theoretically has the potential to improve cardiovascular and renal outcomes in patients with nephrosclerosis and chronic kidney disease (CKD). However, there is currently conflicting information regarding the role of cardiac glycosides (CGs) in promoting renal protection in patients with hypertension, stage C2 CKD, and chronic heart failure (CHF), and the safe administration of these drugs in patients with comorbid conditions is often challenging. Objective. To evaluate the effect of antihypertensive therapy with secondand third-generation beta-blockers (BB) in combination with angiotensin-converting enzyme inhibitors (ACE inhibitors) and diuretics with the addition of glycemic control (GCU) on signs of subclinical glomerular and tubular damage in patients with essential and nephrogenic hypertension, stages C2 and C3a of CKD, and persistent atrial fibrillation (PAF) combined with CHF with preserved ejection fraction (pEF) in functional classes I and II, based on the dynamics of albuminuria and excretion of urinary biomarkers of tubular damage, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), over a 3and 6-month follow-up. Design and methods. The observational study included 44 patients (12 men and 32 women, aged 42 to 76 years, mean age 56,8 ± 9,4 years) with essential and nephrogenic hypertension (with chronic pyelonephritis outside of exacerbation), with C2 and C3a stages of CKD and with PAF in combination with CHFpEF (FC I-II). All patients were divided into 2 groups according to clinical indications. In the 1st group (n = 18), combined antihypertensive therapy with ACE inhibitors, β-blockers and diuretics was carried out with simultaneous administration of CG for heart rate (HR) control. In the 2nd group (comparison, n = 26), similar antihypertensive therapy was carried out without CG, and HR was controlled by β-blockers. At baseline, 3, and 6 months, the impact of the prescribed therapy on tubulointerstitial and glomerular kidney damage was assessed in both groups based on changes in urinary concentrations of the biomarkers NGAL, KIM-1, and albumin. Results. In the group of patients with hypertension, CKD, and PAF with CHFpEF receiving CGs, an increase in mean glomerular filtration rate (GFR) and a decrease in serum creatinine levels were observed after 3 and 6 months, compared with the comparison group. Moreover, CG therapy was associated with an increase in albuminuria in all patients, which was not observed in patients receiving combination antihypertensive therapy (ACE inhibitors, beta-blockers, and diuretics) without CGs. Conclusion. The use of CGs in combination with antihypertensive therapy had a positive effect on renal nitrogen excretion in patients with hypertension and pulmonary fibrosis with CHF and was characterized by a decrease in serum creatinine and, accordingly, an increase in mean GFR. However, it was also accompanied by an increase in albuminuria. These data indicate the need for an individualized approach to CGs prescribing in patients with pulmonary fibrosis and CHF combined with HTN and CKD.

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