Effects on albuminuria and blood pressure after radiofrequency renal denervation: two-year results from the Global SYMPLICITY Registry DEFINE

Background

Increased urinary albumin/creatinine ratio (uACR) is independently associated with renal disease progression, and all-cause mortality. uACR reduction improves cardiorenal prognosis. Data on the effect of renal denervation (RDN) on uACR in patients with uncontrolled hypertension and albuminuria is scarce.

Methods

The Global SYMPLICITY Registry DEFINE is a RDN registry of real-world patients undergoing radiofrequency (RF) RDN with Symplicity RDN system (Medtronic, Plc). Two groups of patients with either microalbuminuria (uACR 30-299 mg/g) or macroalbuminuria (uACR ≥300mg/g) at baseline were analysed. UACR, estimated glomerular filtration rate (eGFR), office systolic BP (OSBP) and prescribed number of antihypertensive medication classes (AH med classes) were assessed at 3, 6, 12, and 24 months after RDN. UACR values were log-transformed to compare changes from baseline using paired t-tests. Percentage change in geometric mean of uACR from baseline to follow-up was calculated. To evaluate the correlation between uACR and BP changes, a multivariable linear regression analysis with repeated measures was performed on uACR changes through 2 years with independent variables including OSBP changes.

Results

Five hundred-fifty-five patients had uACR spot measurements evaluable at baseline. Among these, 125 (23%) patients had microalbuminuria (median uACR 69 [IQR: 46-128] mg/g) with mean eGFR 77 mL/min/1.73 m², and 56 (10%) patients had macroalbuminuria (median uACR 829 [IQR: 437 - 1966] mg/g) with mean eGFR 56 mL/min/1.73 m². In the microalbuminuria group, OSBP was 168±23 mmHg, with 4.8±1.3 prescribed AH med classes, 42% had diabetes, and 45% had renal disease history. In the macroalbuminuria group, OSBP was 166±26 mmHg, with 5.1±0.9 prescribed AH med classes, 63% had diabetes, and 73% had renal disease history.

2 years after RDN, the uACR was significantly reduced by 50% (95% CI: -68%, -23%) and 66% (95% CI: -82%, -33%) in the micro- and macroalbuminuria groups, respectively (Figure). Log-transformed uACR showed significant reductions from baseline at all timepoints (p<0.05). OSBP reduced by 21.9 ± 26.6 mmHg and 16.0 ± 24.4 mmHg at 2 years in the micro- and macroalbuminuria groups, respectively. There were no major changes to AH med classes.

Multivariable linear regression showed a significant association between OSBP and uACR changes with a 10mmHg reduction in OSBP being associated with a 14% reduction in uACR (p<0.0001).

Conclusion

RF RDN was associated with significant uACR reductions in patients with uncontrolled hypertension and albuminuria. The magnitude of the UACR reduction was more pronounced than expected from the BP lowering effect per se, indicative of a potential additional nephroprotective effects of RF RDN. Further prospective study is warranted.Figure