Renal Denervation Mitigates Hypertension and Improves Glomerular Filtration Rate in an Adult Rat Model of Polycystic Kidney Disease

Abstract Background and Aims In autosomal dominant polycystic kidney disease (ADPKD) is frequent to find low urinary citrate levels. Recently it has been suggested that urinary citrate could be a marker of covert metabolic acidosis. Our aim was to analyze relationship between urinary citrate levels and renal functionality in ADPKD patients. Method We determined citrate, calcium and uric acid in 24-hour collected urine from 91 ADPKD patients Results Urinary citrate/creatinine ratio was 214±158 (range 5.3-678) mg/g Cr with levels significantly higher in females. When considering chronic kidney disease (CKD) stages we observed a progressive decrease in urinary osmolality and in urinary citrate, calcium and uric acid elimination. Low levels of citrate (<300 mg/g Cr) were present in 40% in CKD-1 stage, in 69.7% in CKD-2 stage, 92% in CKD-3 stage and 100% in CKD-4 + 5 stages. Urinary citrate was correlated with serum creatinine (r= -0.66, p<0.001) and eGFR (r= 0.56, p<0.001). Urinary citrate significantly correlated with urinary calcium but correlation with urinary uric acid was weaker. We did not find any correlation with serum bicarbonate. Using multiple lineal regression analysis we found as predictors of urinary citrate to glomerular filtration rate, female gender and urinary calcium levels. In a subgroup of patients we measured total kidney volume and we found an inverse correlation with urinary citrate levels that dissappeared when it was corrected with glomerular filtration rate. We did not also find a relationship between urinary elimination of calcium or uric acid and TKV after adjusting with eGFR. Conclusion Urinary citrate is very frequently reduced in ADPKD patients being present from very early CKD stages. Their levels are inversely correlated with glomerular filtration rate and directly with urinary calcium excretion. We did not found a relathionship with serum bicarbonate. We think that it would be interesting to study urinary citrate in other nephropathies and verify if it could be a marker of covert metabolic acidosis.

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Increase in Bioavailability of Nitric Oxide After Renal Denervation Improves Kidney Function in Sheep With Hypertensive Kidney Disease

Hypertension ◽

10.1161/hypertensionaha.120.16718 ◽

2021 ◽

Vol 77 (4) ◽

pp. 1299-1310

Author(s):

Reetu R. Singh ◽

Zoe M. McArdle ◽

Lindsea C. Booth ◽

Clive N. May ◽

Geoff A. Head ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Kidney Function ◽

Filtration Rate ◽

Renal Denervation ◽

Healthy Sheep ◽

No Bioavailability

Overactivity of renal sympathetic nerves and nitric oxide (NO) deficiency occur in hypertensive chronic kidney disease (CKD). In sheep with hypertensive CKD and NO deficiency, renal denervation (RDN) reduces blood pressure and improves kidney function (glomerular filtration rate). We hypothesized that this improvement in glomerular filtration rate after RDN is associated with increased NO bioavailability. In this study, glomerular filtration rate response to systemic inhibition of NOS (NO synthase) was examined in healthy and CKD sheep at 2 and 30 months after a sham (intact nerves) or RDN procedure. Basal urinary total nitrate (nitrate+nitrite) excretion was examined at 2 and 30 months, and kidney protein expression of endothelial and neuronal NOS was assessed at 30 months. Urinary nitrate+nitrite in CKD-RDN and healthy sheep was ≈50% to 70% greater than in CKD-intact. During NOS inhibition, the fall in glomerular filtration rate in CKD-RDN sheep was ≈20% greater than in CKD-intact. These effects in CKD-RDN sheep were similar to those in healthy sheep. Endothelial NOS protein expression was lower in CKD-intact sheep compared with healthy sheep and compared with CKD-RDN. In summary, RDN normalizes NO bioavailability and restores contribution of NO to renal hemodynamics in CKD. These changes may promote improvements in kidney function and sustained blood pressure lowering after RDN in hypertensive CKD.

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