Beneficial effects on arterial stiffness and pulse-wave reflection of combined enalapril and candesartan in chronic kidney disease--a randomized trial.

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent in patients with chronic kidney disease (CKD). Inhibition of the renin-angiotensinsystem (RAS) in hypertension causes differential effects on central and brachial blood pressure (BP), which has been translated into improved outcome. The objective was to examine if a more complete inhibition of RAS by combining an angiotensin converting enzyme inhibitor (ACEI) and an angiotensin receptor antagonist (ARB) compared to monotherapy has an additive effect on central BP and pulse-wave velocity (PWV), which are known markers of CVD. METHODS: Sixty-seven CKD patients (mean GFR 30, range 13-59 ml/min/1.73 m(2)) participated in an open randomized study of 16 weeks of monotherapy with either enalapril or candesartan followed by 8 weeks of dual blockade aiming at a total dose of 16 mg candesartan and 20 mg enalapril o.d. Pulse-wave measurements were performed at week 0, 8, 16 and 24 by the SphygmoCor device. RESULTS: Significant additive BP independent reductions were found after dual blockade in aortic PWV (-0.3 m/s, P<0.05) and in augmentation index (-2%, P<0.01) compared to monotherapy. Furthermore pulse pressure amplification was improved (P<0.05) and central systolic BP reduced (-6 mmHg, P<0.01). CONCLUSIONS: Dual blockade of the RAS resulted in an additive BP independent reduction in pulse-wave reflection and arterial stiffness compared to monotherapy in CKD patients. TRIAL REGISTRATION: Clinical trial.gov NCT00235287.

Long-term haemodialysis survival.

Haemodialysis (HD) treatment for end-stage renal disease bears a poor prognosis. We present a case of a patient who, apart from two transplant periods lasting 8 months in all, was treated with conventional in-centre HD three times a week and who survived for 41 years. Patients should be aware that there is no theoretical upper limit for patient survival on HD.

Possibly enhanced Gd excretion in dialysate, but no major clinical benefit of 3-5 months of treatment with sodium thiosulfate in late stages of nephrogenic systemic fibrosis.

BACKGROUND: Gd-related nephrogenic systemic fibrosis was successfully treated with intravenous sodium thiosulfate according to a recent case report. METHODS: Four haemodialysis patients with severe Gd-related nephrogenic systemic fibrosis were treated with intravenous sodium thiosulfate for 3-5 months. Symptoms and patients' experiences were investigated. The dialysate Gd content was monitored. RESULTS: We observed no major clinical improvements in any patient. In one patient, we found slightly improved joint motion. Two patients had a subjective impression of slight improvements of joint motion and skin abnormalities. The dialysate Gd content was raised by the treatment, up to fivefold. CONCLUSIONS: We could not confirm that sodium thiosulfate treatment results in marked and rapid improvement in late stages of Gd-related nephrogenic systemic fibrosis. However, dialysate contents of Gd seemed to increase. It is unknown whether increased Gd excretion will lead to long-term clinical improvements in late stages of nephrogenic systemic fibrosis.

Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease.

BACKGROUND: Indices of central arterial stiffness, derived by use of applanation tonometry, have shown to be strong independent predictors of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the intra- and inter-observer and day-to-day reproducibility of pulse-wave analysis (PWA) and pulse-wave velocity (PWV) in pre-dialysis patients with CKD stages 3-5 using applanation tonometry with the SphygmoCor software and hardware. METHODS: Double recordings of the radial pressure waveform and the aortic and brachial PWV were performed under standardized conditions in 19 CKD patients with a mean GFR 25.3 ml/min/1.73 m(2) (range 9.9-42.2) by two trained observers and repeated by one of the observers within a week. RESULTS: The mean inter-observer and day-to-day differences (+/-2 SD) for the augmentation index (AIx) were 0.9 +/- 15.8% and 2.6 +/- 11.2%, for subendocardial viability ratio (SEVR) -0.9 +/- 15.5% and -0.4 +/- 24.7%, for aortic pulse pressure (PP) 1.4 +/- 13.3 mmHg and 0.3 +/- 20.9 mmHg and for aortic PWV 0.3 +/- 3.2 m/s and -0.7 +/- 1.9 m/s, respectively. Intra-observer differences were calculated for each of three sets of double measurements and showed good reproducibility as well. Calculations on sample size needed in a clinical trial showed a limited number of patients needed in a clinical study over time. CONCLUSIONS: PWA and PWV based on applanation tonometry using the SphygmoCor software and hardware are highly reproducible in pre-dialysis patients with CKD with the day-to-day variation being in accordance with the intra- and inter-observer variation. Thus, applanation tonometry using the SphygmoCor system is a simple, non-invasive method to assess central haemodynamics in clinical trials in patients with pre-dialysis CKD with only a limited number of patients needed to detect significant differences.

Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats.

The present study investigated the effect of circulating versus locally present renin on cerebral blood flow (CBF) and its autoregulation in rats. CBF was measured repetitively with the intracarotid 133Xe injection method, whereas blood pressure was lowered to determine the lower limit of autoregulation. To remove renin from the blood, rats were bilaterally nephrectomized and kept alive with peritoneal dialysis for 48 h. Five groups of animals were studied: 1) nephrectomized dialyzed rats, 2) nephrectomized dialyzed rats given a single intravenous dose of the angiotensin-converting enzyme inhibitor captopril (10 mg/kg), 3) sham nephrectomized and dialyzed rats, 4) rats receiving drugs as dialyzed rats but no surgery, and 5) rats given the same diet as the other groups but no drugs and no surgery. Baseline blood pressure was significantly lower in nephrectomized rats compared with controls. Nephrectomy, captopril, sham operation, or dialysis did not influence baseline CBF. The lower limit of CBF autoregulation was significantly lower in nephrectomized (53 +/- 4 mmHg) and sham-operated (58 +/- 4 mmHg) rats compared with diet control rats (78 +/- 3 mmHg). Captopril significantly decreased the lower limit in nephrectomized rats (35 +/- 2 mmHg). Thus removal of circulating renin caused no change in the lower limit of autoregulation. By contrast, captopril lowered the lower limit even in the absence of circulating renin and hence appeared to exert its effect on components of the renin-angiotensin system in the cerebral resistance vessel walls.

Nephrectomy and peritoneal dialysis eliminates circulating renin and controls uraemia in the rat.

OBJECTIVE: The aim of the present study was to develop a rat model for in vivo studies of the local effects of the renin-angiotensin system (RAS) following elimination of circulating renin. METHODS: Sprague Dawley rats were bilaterally nephrectomised and had a peritoneal dialysis catheter implanted. The rats were maintained on dialysis continuously for 48 hours, using Dianeal PD4 3.86% glucose dialysis solution. The peritoneal catheter and an automated system for dialysate exchange were made in our laboratory. A sham nephrectomised control group of rats was also dialysed. RESULTS: Nephrectomised and sham-operated rats remained active and in good general condition during peritoneal dialysis. At 48 hours, in nephrectomised, dialysed rats, peritoneal urea clearance was 4.14+/-0.52 ml/hour, plasma urea was 40.0+/-7.7 mmol/L, plasma creatinine was 0.423+/- 0.070 mmol/L and plasma renin was below the limit of detection. CONCLUSIONS: In conclusion, it was possible to sustain bilaterally-nephrectomised rats on continuous peritoneal dialysis for 48 hours, pending elimination of renin from the circulation. The nephrectomised dialysed rat model should be useful for investigation of the physiological effects of the circulating versus the local RAS.

Renal graft failure after addition of an angiotensin II receptor antagonist to an angiotensin-converting enzyme inhibitor: unmasking of an unknown iliac artery stenosis.

Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to achieve a more complete blockade of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. The present report describes a case of acute renal graft dysfunction following the addition of an ARB to existing ACE inhibition. This unmasked an unknown iliac artery stenosis. The case indicates a possible important role of Ang II generated by non-ACE pathways in this situation.