Impact of aggressive blood pressure reduction on kidney function after renal denervation: long-term outcome

Objective. To investigate the dynamics of renal function in patients with resistant arterial hypertension after renal denervation depending on the degree of central and peripheral blood pressure (BP) reduction and the baseline state of the kidneys.

Design and methods. A total of 22 patients (mean age 56,1 ± 10,2 years, 9 males) with treated resistant hypertension undergoing bilateral renal denervation (RDN) (Symplicity RDN System, Medtronic, USA) were included. Office BP measuring, 24-hour ambulatory BP monitoring (ABPM) (SpaceLabs 90207, USA), applanation tonometry (SphygmoCor, AtCor Medical, Australia) with the calculation of central aortic blood pressure (CAP), Doppler ultrasonography (Vivid 7 dimension) were obtained at baseline and at 1, 3, 6, 12, 18 and 24 months after RDN. Urine levels of NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1), L-FABP (Liver-type fatty acid binding protein), albuminuria and serum levels of сystatin C (sCysC) and creatinine (sCr) were measured by quantitative enzyme immunoassay at baseline and at 1, 3, 6, 12, 18 and 24 months after RDN. Glomerular filtration rate was estimated by the level of sCr and sCysC by CKD-EPI formula.

Results. All patients were divided into 3 groups according BP reduction: 1 — BP increase above 0 mm Hg; 2 — BP reduction from 0 to –30 mm Hg; 3 — BP reduction by > 31 mm Hg. An increased sCysС was registered in a group with decreased 24-hour systolic BP (1,06 ± 0,41; 0,93 ± 0,18 and 1,22 ± 0,23 ng/mL; F = 2,882; р = 0,04) and increased urine KIM-1 level — in a group with decreased office diastolic BP (2,18 ± 1,94; 1,53 ± 1,02 and 4,41 ± 0,97 pg/mL; F = 3,663; р = 0,03) at 3-month follow-up. An increased sCr level was registered in a group with decreased 24-hour systolic BP (78,3 ± 3,7; 88,2 ± 6,8 and 142,00 ± 8,8 μmol/L; F = 61,987; p = 0,004) and diastolic CAP (83,4 ± 8,2; 82,0 ± 8,0 and 142,0 ± 9,4 μmol/L; F = 23,476; p = 0,01), also an increased urine L-FABP level — in a group with decreased office diastolic BP (3531,3 ± 1795,0; 997,5 ± 1096,8 and 7351,7 ± 3297,0 pg/mL; F = 12,103; p = 0,002) at 6-month follow up.

Conclusions. Renal function worsening in patients during the period of maximum BP lowering may be associated with an excessive BP reduction. Therefore, we can suggest the occurrence of the J-curve phenomenon in relation to the kidneys.

1. Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125(13):1635–1642. doi:10.1161/CIRCULATIONAHA.111.068064

2. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275–81. doi:10.1016/S0140-6736(09)60566-3

3. Damascelli B, Patelli G, Tichá V, Della Rocca F, Lattuada S, Sala C et al. Catheter-based radiofrequency renal sympathetic denervation for resistant hypertension. J Vasc Interventio Radiol. 2013;24(5):632–639. doi:10.1016/j.jvir.2013.01.491

4. Simplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011; 57(5):911–917. doi:10.1161/HYPERTENSIONAHA.110.163014

5. Esler MD, Böhm M, Sievert H, Rump CL, Schmieder RE, Krum H et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial. Eur Heart J. 2014; 35(26):1752–9. doi:10.1093/eurheartj/ehu209

6. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M. Renal sympathetic denervation in patients with treatment resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010; 376(9756):1903–9. doi:10.1016/S0140-6736(10)62039-9

7. Mountfort K, Mahfoud F, Schmieder R, Davies J, Kandzari DE, Weil J et al. Catheter-Based Renal Sympathetic Denervation — Long-Term Symplicity™ Renal Denervation Clinical Evidence, New Data And Future Perspectives. Intervent Cardiol Rev. 2013;8(2):118–123. doi:10.15420/icr.2013.8.2.118

8. Mahfoud F, Bohm M, Schmieder R, Narkiewicz K, Ewen S, Ruilope L et al. Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry. European Heart Journal. 2019; 40(42):3474–3482. doi:10.1093/eurheartj/ehz118.

9. Mironova SA, Zvartau NE, Konradi AO. Kidney injury in arterial hypertension: can we trust the old markers? Arterial’naya Gipertenziya = Arterial Hypertension. 2016;22(6):536–550. doi:10.18705/1607-419X-2016-22-6-536-550. In Russian.

10. Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;60(2):419–24. doi:10.1161/HYPERTENSIONAHA.112.193870

11. Dörr O, Liebetrau C, Möllmann H, Gaede L, Troidl C, Wiebe J et al. Long-term verification of functional and structural renal damage after renal sympathetic denervation. Catheter Cardiovasc Interv. 2016; 87(7): 1298–303. doi:10.1002/ccd.26355

12. Robles NR, Hernandez-Gallego R, Fici F, Grassi G et al. Does a blood pressure J curve exist for patients with chronic kidney disease? J Clin Hypertens (Greenwich). 2017;19(8):764–770. doi:10.1111/jch.13024

13. Tsioufis CP, Papademetriou V, Dimitriadis KS, Kasiakogias A, Tsiachris D, Worthley MI et al. Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN™ I first-in-human study using a multi-electrode ablation system. Int J Cardiol. 2015;201:345–350. doi:10.1016/j.ijcard.2015.08.069

14. Persu A, Gordin D, Jacobs L, Thijs L, Bots ML, Spiering W et al. European Network COordinating research on Renal Denervation (ENCOReD). Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis. J Hypertens. 2018;36(2):221–229. doi:10.1097/HJH.0000000000001582

15. Ott C, Franzen KF, Graf T, Weil J, Schmieder RE, Reppel M et al. Renal denervation improves 24-hour central and peripheral blood pressures, arterial stiffness, and peripheral resistance. J Clin Hypertens (Greenwich). 2018;20(2):366–372. doi:10.1111/jch.13193

16. Sanders MF, Reitsma JB, Morpey M, Gremmels H, Bots ML, Pisano A et al. Renal safety of catheter-based renal denervation: systematic review and meta-analysis. Nephrol Dial Transplant. 2017;32(9):1440–1447. doi:10.1093/ndt/gfx088