Author + information
- Oliver Dörr, MD⁎ (, )
- Christoph Liebetrau, MD,
- Helge Möllmann, MD,
- Stephan Achenbach, MD,
- Daniel Sedding, MD,
- Sebastian Szardien, MD,
- Matthias Willmer, MD,
- Johannes Rixe, MD,
- Christian Troidl, PhD,
- Albrecht Elsässer, MD,
- Christian Hamm, MD and
- Holger M. Nef, MD
- ↵⁎Medizinische Klinik I, Department of Cardiology, University of Giessen, Klinikstrasse 33, 35392 Giessen, Germany
To the Editor:
Renal sympathetic denervation (RSD) is an interventional treatment option for resistant arterial hypertension (HT) (1). Previous investigations of RSD excluded patients with progressive chronic kidney disease because of potential RSD-related kidney damage (1,2). Diagnosis of acute kidney injury is a clinical challenge; because of the absence of clinical symptoms, the diagnosis is based on biomarkers. However, a critical problem is the diagnostic gap for commonly used biomarkers during the early period after acute kidney injury. Highly sensitive biomarkers, such as urinary neurophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1, are early, maybe even real-time, markers for the early detection of even minor structural and functional kidney damage.
The present study analyzed urinary NGAL and KIM-1 concentrations, in addition to serum creatinine (sCr), blood urea nitrogen, and estimated glomerular filtration rate (eGFR), in patients undergoing RSD. Patients with impaired renal function (eGFR <45 ml/min/1.73 m2) also were considered. Our objective was to detect potential RSD-related functional or structural kidney damage in patients with refractory hypertension during the early postprocedural period and after a 3-month follow-up.
From September 2011 through March 2012, 62 consecutive patients with resistant HT who were to undergo RSD were included in the study at 2 clinical centers. In all patients, renal artery stenoses and further secondary origins of the HT (3) were excluded, before RSD. RSD was performed according to the standard clinical practice using a transfemoral approach with a 6-F sheath via the femoral artery. All patients received 500 ml 0.9% NaCl intravenously before and after the procedure. Patients were followed up over 3 months, and venous blood samples were collected before and at 24 h, 48 h, and 3 months after RSD. Samples were processed immediately and were frozen at −80°C until assayed. Twenty-four–hour blood pressure measurement was obtained before and 4 weeks and 3 months after RSD. Written informed consent from all patients for each investigation, as well as approval from the Institutional Review Board of the University of Giessen (230/11), was obtained.
A total of 62 consecutive patients (33 men and 29 women, mean age 68.0 ± 10.4 years) were included. Tables 1, 2, and 3 show the clinical characteristics of all patients enrolled in the study. All RSD procedures were performed bilaterally in a single-session procedure. On average, 78.5 ± 39.0 ml of contrast fluid was administered. The average number of antihypertensive drugs was 5.4 ± 1.4 in different substance classes.
A significant systolic blood pressure reduction was observed at 4 weeks as well as at the 3-month follow-up (Table 2). Measurement of urinary NGAL and KIM-1 concentrations showed no significant changes 24 and 48 h after RSD compared with baseline. Furthermore, no significant changes were seen at the 3-month follow-up (Table 3). In addition, measurements of eGFR and the sCr levels showed no significant differences after RSD compared with baseline. Even 3 months after RSD, these values remained unaltered (Table 3). In particular, 8 patients (13%) had an impaired renal function, with eGFR of <45 ml/min/1.73 m2 (37.8 ± 4.3 ml/min/1.73 m2). Even these patients did not show any alterations regarding KIM-1 and NGAL levels either in the early postprocedural period or after 3 months.
The results of the present study indicate the nonappearance of RSD-related functional or structural kidney damage or decreases in the remaining renal function during the early postprocedural period and after the 3-month follow-up.
Previous investigations excluded patients with impaired renal function (GFR <45 ml/min/1.73 m2) or progressive chronic kidney disease, because no data were available regarding potential RSD-related functional or structural kidney damage, or both (1–3). We conducted serial measurements of urinary NGAL and KIM-1 concentrations after RSD, in addition to sCr and eGFR measurements, to look for procedure-related functional and structural kidney damage after RSD, also considering patients with impaired renal function (eGFR <45 ml/min/1.73 m2). Our results demonstrate that urinary NGAL and KIM-1 concentrations did not increased during the following 2 days after RSD or after 3 months follow-up. The same holds true when patients with a eGFR <45 ml/min/1.73 m2 were investigated. In accordance with this observation, we additionally did not observe alteration in sCR, blood urea nitrogen, or eGFR measurements.
To our knowledge, this study was the first to investigate biomarkers for functional or structural kidney damage, or both, at early time points after RSD. Urinary NGAL and KIM-1 assays provided incremental diagnostic information, especially in the early phase of kidney damage, which is not detected by conventional biomarkers. Furthermore, KIM-1 and NGAL correlated positively with the degree of structural kidney damage and negatively with renal function.
Although conventional biomarkers for acute kidney injury such as sCr and blood urea nitrogen can provide information about kidney impairment, they have a diagnostic gap that can range from the first hours to the first days after structural or functional kidney damage, or both. Therefore, we also analyzed urinary NGAL and KIM-1 concentrations for the early and highly sensitive detection of subsequent functional and structural kidney damage with the potential for progression within the first days, as well as 3 months after RSD.
Although KIM-1 is not detected in healthy kidneys, in the present study, concentrations of KIM-1 were increased moderately at baseline. This may be explained by the fact that all of the included patients had HT and more than one third of the cohort had diabetes, which is known to be associated with elevated KIM-1 levels.
A total of 88.7% of the RSD-treated patients had sufficient blood pressure reduction after 3 months. Even in patients in whom RSD was unsuccessful, there were no differences with regard to the measured markers.
The preserved renal function after RSD may indicate that the autoregulatory mechanisms of the kidneys are not disturbed by this interventional procedure. In particular, the RSD-related reduction in efferent sympathetic activity leads to decreased renin release, and the effect on the afferent sympathetic fibers results in modulation of the peripheral vascular tone and reduction in renal blood flow. In accordance with the safety of the RSD procedure, and as reported in the HTN-1 Trial (2), the present study found no evidence of procedure-related kidney damage.
The exclusion of RSD-related functional or structural kidney damage, or both, is of major clinical importance. Our results provide additional evidence that RSD in patients with resistant HT is safe and potentially could be used for patients with progressive chronic kidney disease.
Please note: Drs. Dörr, Liebetrau, and Möllmann, the first three authors contributed equally to this work. Dr. Hamm is a member of the Advisory Board to Medtronic. Dr. Möllmann is a proctor for Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2013 American College of Cardiology Foundation