Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension Durability of Blood Pressure Reduction Out to 24 Months

Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension. Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure (BP) in patients with hypertension. Durability of effect beyond 1 year using this novel technique has never been reported. A cohort of 45 patients with resistant hypertension (systolic BP GT = 160 mm Hg on GT = 3 antihypertension drugs, including a diuretic) has been originally published. Herein, we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonrandomized manner. We treated 153 patients with catheter-based renal sympathetic denervation at 19 centers in Australia, Europe, and the United States. Mean age was 57 +/- 11 years, 39% were women, 31% were diabetic, and 22% had coronary artery disease. Baseline values included mean office BP of 176/98 +/- 17/15 mm Hg, mean of 5 antihypertension medications, and an estimated glomerular filtration rate of 83 +/- 20 mL/min per 1.73 m(2). The median time from first to last radiofrequency energy ablation was 38 minutes. The procedure was without complication in 97% of patients (149 of 153). The 4 acute procedural complications included 3 groin pseudoaneurysms and 1 renal artery dissection, all managed without further sequelae. Postprocedure office BPs were reduced by 20/10, 24/11, 25/11, 23/11, 26/14, and 32/14 mm Hg at 1, 3, 6, 12, 18, and 24 months, respectively. In conclusion, in patients with resistant hypertension, catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to GT = 2 years of follow-up, without significant adverse events. (Hypertension. 2011;57:911-917.

Erythrocyte Salt Sedimentation Assay Does Not Predict Response to Renal Denervation

Renal denervation (RDN) has recently been shown to be effective in patients without antihypertensive medication. However, about 30% of patients do not respond to RDN, and therefore, there exists a need to find predictors of response. Individuals are either salt-sensitive (SS) or non-salt-sensitive (NSS) in terms of their blood pressure (BP) regulation. The sympathetic nervous system can influence water and salt handling. RDN reduces sympathetic drive and has an impact on salt excretion. The present study was conducted to test the influence of salt sensitivity in terms of the BP reducing effect after RDN procedure. Salt sensitivity was estimated using the in vitro Erythrocyte Salt Sedimentation Assay (ESS). In 88 patients with resistant hypertension, RDN was performed. Office BP and lab testing were performed at baseline and at month 1, 3, 6, 12, 18, and 24 after RDN. A responder rate of 64.7% has been observed. Salt sensitivity measurements (ESS-Test) were completed in a subgroup of 37 patients with resistant hypertension. In this group, 15 were SS and 17 were salt-resistant according to the in vitro assay, respectively. The responder rate was 60% in SS patients and 59.1% in NSS patients, respectively. Electrolytes as well as aldosterone and renin levels did not differ between the two groups at baseline and in the follow-up measurements. The present study showed that salt sensitivity, estimated using the ESS in vitro test, did not affect the outcome of RDN and, therefore, does not help to identify patients suitable for RDN

Aldosterone-Mediated Sodium Retention Is Reflected by the Serum Sodium to Urinary Sodium to (Serum Potassium)2 to Urinary Potassium (SUSPPUP) Index

The serum sodium to urinary sodium ratio divided by the (serum potassium)2 to urinary potassium ratio (SUSPPUP formula) reflects aldosterone action. We here prospectively investigated into the usefulness of the SUSPPUP ratio as a diagnostic tool in primary hyperaldosteronism. Parallel measurements of serum and urinary sodium and potassium concentrations (given in mmol/L) in the fasting state were done in 225 patients. Of them, 69 were diagnosed with primary aldosteronism (PA), 102 with essential hypertension (EH), 26 with adrenal insufficiency (AI) and 28 did not suffer from the above-mentioned disorders and were assigned to the reference group (REF). The result of the SUSPPUP formula was highest in the PA group (7.4, 4.2–12.3 L/mmol), followed by EH (3.2, 2.3–4.3 L/mmol), PA after surgery (3.9, 3.0–6.0 L/mmol), REF (3.4 ± 1.4 L/mmol) and AI (2.9 +/− 1.2 L/mmol). The best sensitivity in distinguishing PA from EH was reached by multiplication of the aldosterone to renin-ratio (ARR) with the SUSPPUP formula (92.7% at a cut off > 110 L/mmol), highest specificity was reached by the SUSPPUP determinations (87.2%). The integration of the SUSPPUP ratio into the ARR helps to improve the diagnosis of hyperaldosteronism substantially

Everolimus in de novo kidney transplant recipients participating in the Eurotransplant senior program: Results of a prospective randomized multicenter study (SENATOR).

Early conversion to everolimus was assessed in kidney transplant recipients participating in the Eurotransplant Senior Program (ESP), a population in whom data are lacking. The SENATOR multicenter study enrolled 207 kidney transplant recipients undergoing steroid withdrawal at week 2 post-transplant (ClinicalTrials.gov [NCT00956293]). At week 7, patients were randomized (1:2 ratio) to continue the previous calcineurin inhibitor (CNI)-based regimen with mycophenolic acid (MPA) and cyclosporine or switch to a CNI-free regimen with MPA, everolimus (5-10 ng/mL) and basiliximab at weeks 7 and 12, then followed for 18 weeks to month 6 post-transplant. The primary endpoint was estimated GFR (eGFR). At week 7, 77/207 (37.2%) patients were randomized (53 everolimus, 24 control). At month 6, eGFR was comparable: 36.5±10.8ml/min with everolimus versus 42.0±13.0ml/min in the control group (p = 0.784). Discontinuation due to adverse events occurred in 27.8% of everolimus-treated patients and 0.0% of control patients (p = 0005). Efficacy profiles showed no difference. In conclusion, eGFR, safety and efficacy outcomes at month 6 post-transplant showed no difference between groups. The everolimus group experienced a higher rate of discontinuation due to adverse events. However, the high rate of non-randomization is highly relevant, indicating this to be a somewhat unstable patient population regardless of treatment

cDNA Microarray Analysis of Adaptive Changes after Renal Ablation in a Sclerosis-Resistant Mouse Strain

5 /6 nephrectomy (Nx) in susceptible animals causes glomerular sclerosis and interstitial fibrosis in the remnant kidney. Oxidative stress, transforming growth factor- _ (TGF- _ ), and the de novo synthesis of collagen seem to contribute to this process. However, these factors might also be required for tissue repair without fibrosis. Methods: W e examined dynamic changes after nephron loss in a mouse strain capable of complete recovery. C57BL/6 mice underwent single-session Nx and were followed for 40 weeks. Gene expression was monitored over 20 days using 22,000 cDNA microarrays. Results: The mice developed transient hypertension and glomerular hypertrophy after Nx but failed to progress to glomerular sclerosis or renal failure. Gene expression profiles revealed three stages of recovery, an early phase of injury response, an intermediate phase of extracellular matrix (ECM) production and a later phase of reconstitution. Surprisingly, oxidative stress responses and collagen production were strongly upregulated soon after Nx. Furthermore, TGF- _ 1 and connective tissue growth factor were rapidly upregulated and remained elevated. Conclusion: We suggest that oxidative stress, collagen production, profibrotic growth factors and ECM turnover are part of the comprehensive adaptation to nephron loss and not necessarily associated with progressive loss of renal function