Jens Dam Jensen

No significant effect of angiotensin II receptor blockade on intermediate cardiovascular end points in hemodialysis patients

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.

Increased serum erythropoietin level during azathioprine treatment in renal transplant recipients.

One hundred and six renal transplant patients were studied. During the first 12 months after renal transplantation all patients were treated with cyclosporine (Cy) and prednisone. At 12 months after transplantation the patients were randomly allocated to either conventional treatment with azathioprine (Az) and prednisone (group Az) or to continued treatment with Cy and prednisone (group Cy). Serum erythropoietin (s-EPO), glomerular filtration rate (GFR) and hematocrit (Hct) were measured at 12, 18 and 24 months after transplantation. s-EPO rose in the group Az from 19 U/l (mean) at 12 months to 28 U/l (p < 0.01) at 18 months and remained elevated at 24 months at 29 U/l compared with baseline level and with healthy subjects without anemia 18 U/l (p < 0.01). There was no significant change in s-EPO in group Cy during the study. The Hct in the two groups was not significantly different. GFR was the same in the two groups at 12 months and after 24 months. In conclusion, a switch from Cy to Az 1 year after renal transplantation results in a sustained rise in s-EPO which may in part represent a compensatory phenomenon to bone marrow suppression.

Aortic pulse wave velocity results depend on which carotid artery is used for the measurements.

Objective: Aortic pulse wave velocity (aPWV) is a gold standard noninvasive marker of arterial stiffness. aPWV is usually obtained as carotid–femoral pulse wave velocity by measurements on the common carotid artery and the femoral artery. The carotid arteries branch slightly differently from the aorta towards the right and left side of the neck. Theoretically, using the right or left carotid artery could influence aPWV results and there are no clear guidelines to support the choice of side. The aim of this study was to investigate whether aPWV results depend on right or left side carotid artery measurements in a group of healthy individuals. Methods and results: Two different observers examined 50 individuals without known cardiovascular disease between 23 and 66 years of age. The measurements were performed with the SphygmoCor equipment using both right and left carotid arteries. We found that use of the right carotid artery provided significantly higher aPWV values compared with the left carotid artery, also when using different methods to estimate the travel length of the pulse wave (pooled data, subtracted distance: 0.2 ± 0.4 m/s, P = 0.003; direct distance: 0.2 ± 0.5 m/s, P = 0.001). Conclusion: Using right or left carotid artery affects aPWV, as right-side measurements provided higher values. Attention to this side difference and use of the same carotid artery will increase the strength of intervention studies using aPWV as a surrogate endpoint.

Effects of High Dose Atrial Natriuretic Peptide on Renal Haemodynamics, Sodium Handling and Hormones in Cirrhotic Patients with and Without Ascites

To elucidate and to try to reverse the antinatriuretic mechanisms in liver cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus dose (2 micrograms per kg body weight) to 14 cirrhotic patients, and as a control to 14 healthy subjects. The nine patients with ascites had baseline values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure (BP) similar to controls. Their distal tubular fractional reabsorption of sodium (DFRNa), estimated by the lithium clearance technique, was higher than in controls, and so were plasma values of aldosterone (564 vs. 119 pmol l-1 medians), endothelin (1.23 vs. 0.63 pmol l-1), ANP (7.5 vs. 3.6 pmol l-1) and cyclic GMP (8.8 vs. 4.6 nmol l-1); p < 0.01 for all. The five patients without ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls. After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52 mmol min-1, p < 0.01), while GFR increased (108 to 117 ml min-1, p < 0.05), and DFRNa decreased (93 to 89%, p < 0.01). In cirrhotics with ascites sodium excretion was unaltered (0.12 to 0.11 mmol min-1), and so was GFR (84 to 83 ml min-1). Proximal tubular fractional reabsorption of sodium increased after 90 min, whereas DFRNa decreased immediately (97 to 96%, p < 0.01) though less markedly than in controls. Sodium excretion increased in four of five patients without ascites (0.23 to 0.27 mmol min-1, medians). In patients with ascites, endothelin in plasma decreased after ANP (p < 0.05). Plasma levels of angiotensin II, aldosterone and vasopressin were unchanged in all groups. In conclusion, although hyper-reabsorption of sodium occurred in the distal rather than the proximal part of the nephron in cirrhotic patients with ascites, ANP had no natriuretic effect. This was most probably due primarily to the lack of increase of GFR and blunted inhibition of DFRNa, attributed to high aldosterone. The effect of ANP in suppressing the high endothelin did not seem to improve sodium excretion.

Preserving residual renal function in dialysis patients: an update on evidence to assist clinical decision making

It has been documented that preservation of residual renal function in dialysis patients improves quality of life as well as survival. Clinical trials on strategies to preserve residual renal function are clearly lacking. While waiting for more results from clinical trials, patients will benefit from clinicians being aware of available knowledge. The aim of this review was to offer an update on current evidence assisting doctors in clinical practice.

Reliability of endogenous markers for estimation of residual renal function in haemodialysis patients

Residual renal function in haemodialysis patients is of increasing interest. However, reproducibility and agreement between methods to measure and estimate glomerular filtration rate (GFR) require further elucidation. The aim of this study was to evaluate the accuracy and reproducibility of GFR estimates based on endogenous markers in haemodialysis patients.

Quality of life development during initial hemodialysis therapy and association with loss of residual renal function

Introduction: Health related quality of life (HRQOL) is markedly reduced in hemodialysis patients compared to the general population. We investigated the course of self‐reported HRQOL over time and the association with selected factors, focusing on changes in glomerular filtration rate (GFR).

Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartan on Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIR Study)

Background and Aim Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan. Design Randomized, double-blind, placebo-controlled, one-year intervention trial. Setting and Participants Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year. Intervention Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients. Outcomes and Measurements Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension. Results At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters. Conclusion Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen. Trial registration Clinicaltrials.gov NCT00791830

Long-term effects of angiotensin II blockade with irbesartan on inflammatory markers in hemodialysis patients: A randomized double blind placebo controlled trial (SAFIR study).

Introduction: Low‐grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti‐inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients. Methods: Adult HD patients were randomized for double‐blind treatment with the ARB irbesartan 150–300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C‐reactive protein (hsCRP), interleukin (IL)−1β, IL‐6, IL‐8, IL‐18, and transforming growth factor‐β (TGF‐β) were measured using Luminex and enzyme‐linked immunosorbent assay (ELISA) technology. Findings: Eighty‐two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2–23.4)/2.7(0.2–29.6) μg/mL; IL‐1β 1.1(0.0–45.9)/1.1(0.0‐7.2) pg/mL; IL‐6 10(1–90)/12(1–84) pg/mL; IL‐8 31(9–134)/34(5–192) pg/mL; IL‐18 364(188–1343)/377(213–832) pg/mL; TGF‐β 3.2(0.8–13.9)/3.6(1.3–3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL‐6, IL‐8, and TGF‐β between placebo and ARB‐treated patients during the study period, and hsCRP, IL‐6, IL‐8, and TGF‐β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL‐1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL‐18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB‐treated (P ≥ 0.51 in tests for parallel curves and equal levels). Discussion: Inflammatory biomarkers were neither acutely, nor in the long‐term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti‐inflammatory effects.