Renal Deafferentation Improves Renal Function and Blood Pressure, but Not Cardiac Parameters in an Experimental Model Chronic Kidney Disease.

Chronic kidney disease is highly prevalent and its mortality is associated with cardiovascular disease. Experimental evidence shows that the renal nerves contribute to arterial hypertension and renal sympathetic hyperactivity worsening the disease; renal denervation has shown renoprotective and cardioprotective effects. However, renal sympathetic innervation plays a fundamental role in renal homeostasis and its removal is associated with impaired compensatory mechanisms during hemodynamic changes. Thus, the aim of this work was to investigate the effects of selective renal denervation of afferent fibers on renal and cardiovascular repercussions in chronic kidney disease (CKD) induced by 5/6 nephrectomy in Wistar rats. The use of animals was approved by the Federal University of São Paulo Animal Care and Use Committee and performed according to the National Institutes of Health guidelines for the conduct of experiments in animals. After five weeks of nephrectomy, denervation of renal afferent fibers with a periaxonal application of 33 mM capsaicin was performed. Cardiovascular and renal function parameters were evaluated three weeks after deafferentation.ResultsCKD induced increase in blood pressure (CTL 113±7.2 × CKD 185±14 mmHg), creatinine plasma levels (CTL 0.5±0.1 × CKD 1.2±0.5 mg/dl) and proteinuria (CTL 14±10 × 300±129 mg/24h). It was also observed an increase in cardiac hypertrophy, reduction in baroreflex sensitivity and in parasympathetic tone after autonomic double blockade. Afferent renal denervation reduced blood pressure (165±21 mmHg), improved creatinine plasma levels (0.8 ±0.2 mg/dl) and proteinuria (178±102 mg/24h). No alterations were observed after deafferentation over baroreflex sensitivity, cardiac hypertrophy and autonomic control to the heart. Together these results suggest that renal deafferentation improves blood pressure and renal function, without, however, improving the cardiac changes found in this CKD model. It is possible that the time expected after deafferentation or the stage of the disease in which it was performed was not sufficient to induce cardiac improvements. Further studies are necessary to elucidate this question.Support or Funding InformationCoordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001; by the São Paulo Research Foundation (FAPESP 18/02671‐3) and by the Brazilian National Research Council (CNPq)