Serotonine en bloeddruk

In dit proefschriftwordt enerzijds gepoogd een overzicht te geven van aan literatuur ontleende gegevens, die betrekking hebben op functie van serotonine bij de regulatie van de bloeddruk. Vooral wordt ingegaan op de mogelijke betekenis van serotonine bij de pathogenese van hypertensie. Anderzijds wordt in dit proefschrift verslag gedaan van eigen onderzoek, dat gericht is op de rol die serotonine mogelijkerwijs speelt bij het ontstaan en onderhouden van hypertensie. Bij dit onderzoek is vooral gebruik gemaakt van de nieuw ontwikkelde 5-HT2 receptor antagonist ketanserin, waarvan de effecten bij patienten met essentiele hypertensie bestudeerd werde

Atherosclerotic renovascular disease and renal impairment:Can we predict the effect of intervention?

Atherosclerotic renal artery stenosis (ARAS) is associated with hypertension, ischemic nephropathy, and high cardiovascular risk. We review the data on revascularization of the renal artery by percutaneous transluminal renal angioplasty (PTRA) and pharmacological therapy. In patients with severe ARAS and poorly controlled hypertension, PTRA can improve blood pressure control. In patients with rapid renal function loss and severe ARAS, PTRA can improve short-term renal function, but there is no evidence for long-term renoprotection. Recent evidence indicates that ARAS, and incidental renal artery stenosis, considerably increases cardiovascular risk, independent of blood pressure, renal function, and prevalent risk factors. This suggests that revascularization might potentially improve overall prognosis, but no data are available currently. The high cardiovascular risk warrants aggressive pharmacological treatment to prevent progression of the generalized vascular disorder. Ongoing trials will show whether revascularization has added, long-term effects on blood pressure, renal function, and cardiovascular prognosis

Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial

Objective To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention

The association of chronic kidney disease and dialysis treatment with foot ulceration and major amputation

Objective The objective of this study was to investigate the risk of chronic kidney disease (CKD) stage 4-5 and dialysis treatment on incidence of foot ulceration and major lower extremity amputation in comparison to CKD stage 3. Methods In this retrospective study, all individuals who visited our hospital between 2006 and 2012 because of CKD stages 3 to 5 or dialysis treatment were included. Medical records were reviewed for incidence of foot ulceration and major amputation. The time from CKD 3, CKD 4-5, and dialysis treatment until first foot ulceration and first major lower extremity amputation was calculated and analyzed by Kaplan-Meier curves and multivariate Cox proportional hazards model. Diabetes mellitus, peripheral arterial disease, peripheral neuropathy, and foot deformities were included for potential confounding. Results A total of 669 individuals were included: 539 in CKD 3, 540 in CKD 4-5, and 259 in dialysis treatment (individuals could progress from one group to the next). Unadjusted foot ulcer incidence rates per 1000 patients per year were 12 for CKD 3, 47 for CKD 4-5, and 104 for dialysis (P < .001). In multivariate analyses, the hazard ratio for incidence of foot ulceration was 4.0 (95% confidence interval [CI], 2.6-6.3) in CKD 4-5 and 7.6 (95% CI, 4.8-12.1) in dialysis treatment compared with CKD 3. Hazard ratios for incidence of major amputation were 9.5 (95% CI, 2.1-43.0) and 15 (95% CI, 3.3-71.0), respectively. Conclusions CKD 4-5 and dialysis treatment are independent risk factors for foot ulceration and major amputation compared with CKD 3. Maximum effort is needed in daily clinical practice to prevent foot ulcers and their devastating consequences in all individuals with CKD 4-5 or dialysis treatment

Selective cyclooxygenase-2 (COX-2) inhibition reduces proteinuria in renal patients

Background. Renoprotection is predicted by the antiproteinuric efficacy of a pharmacological agent. Nonsteroidal anti-inflammatory drugs (NSAIDs) interfering non-selectively in the prostaglandin system have strong antiproteinuric potency without reduction of systemic blood pressure. The effect of the selective COX-2 inhibitor rofecoxib in proteinuric patients is unknown, granted recently reported detrimental effects in non-renal patients. Shortterm effects of rofecoxib on proteinuria and blood pressure as compared to NSAID and RAAS blockade were studied. Methods. Sixteen stable patients [mean proteinuria 4.4 g/day; MAP 103 mmHg)] were included after a wash-out period. Hydrochlorothiazide 12.5 mg QD was given throughout. Additional blood pressure control was ensured by non-RAAS blocking antihypertensive agents. Patients received rofecoxib 25 mg QD, 50 mg QD and indomethacin 75 mg BID in randomized order for 4 weeks. Thereafter, a subset of the included patients (n = 11) received lisinopril 40 mg QD for 6 weeks preceded by a wash-out period. Results. Rofecoxib exerted a dose-dependent antiproteinuric effect. As compared to rofecoxib 25 and 50 mg, indomethacin was more effective [-18, -28 versus -49% (n = 16; P <0.05)]. As compared to rofecoxib 50 mg, lisinopril was more effective [-21 versus -51% (n = 11; P <0.05)]. No significant blood pressure changes were observed after rofecoxib and indomethacin, whereas lisinopril had a significant antihypertensive effect. Conclusion. Selective COX-2 inhibition reduces proteinuria without reduction of systemic blood pressure, pointing towards a specific renal effect, and may serve as a novel non-hypotensive adjunct antiproteinuric treatment

The association of chronic kidney disease and dialysis treatment with foot ulceration and major amputation

Objective\ud \ud The objective of this study was to investigate the risk of chronic kidney disease (CKD) stage 4-5 and dialysis treatment on incidence of foot ulceration and major lower extremity amputation in comparison to CKD stage 3.\ud \ud Methods\ud \ud In this retrospective study, all individuals who visited our hospital between 2006 and 2012 because of CKD stages 3 to 5 or dialysis treatment were included. Medical records were reviewed for incidence of foot ulceration and major amputation. The time from CKD 3, CKD 4-5, and dialysis treatment until first foot ulceration and first major lower extremity amputation was calculated and analyzed by Kaplan-Meier curves and multivariate Cox proportional hazards model. Diabetes mellitus, peripheral arterial disease, peripheral neuropathy, and foot deformities were included for potential confounding.\ud \ud Results\ud \ud A total of 669 individuals were included: 539 in CKD 3, 540 in CKD 4-5, and 259 in dialysis treatment (individuals could progress from one group to the next). Unadjusted foot ulcer incidence rates per 1000 patients per year were 12 for CKD 3, 47 for CKD 4-5, and 104 for dialysis (P < .001). In multivariate analyses, the hazard ratio for incidence of foot ulceration was 4.0 (95% confidence interval [CI], 2.6-6.3) in CKD 4-5 and 7.6 (95% CI, 4.8-12.1) in dialysis treatment compared with CKD 3. Hazard ratios for incidence of major amputation were 9.5 (95% CI, 2.1-43.0) and 15 (95% CI, 3.3-71.0), respectively.\ud \ud Conclusions\ud \ud CKD 4-5 and dialysis treatment are independent risk factors for foot ulceration and major amputation compared with CKD 3. Maximum effort is needed in daily clinical practice to prevent foot ulcers and their devastating consequences in all individuals with CKD 4-5 or dialysis treatment

Impact of incidental renal artery stenosis on long-term mortality in patients with peripheral arterial disease undergoing vascular procedure

ObjectiveIn peripheral arterial disease (PAD), mortality is high. Incidental renal artery stenosis (RAS) is a predictor of mortality in PAD patients undergoing angiography. This might be relevant for risk-benefit assessment when vascular surgery is considered, both in terms of perioperative risk, and in terms of life expectancy.MethodsWe studied the prognostic impact of incidental RAS in 488 subjects (334 men, 154 women; mean follow-up 6.0 ± 3.4 years) who underwent angiography for PAD in a single center between 1997 and 2000. Renal arteries were visualized and follow-up data concerning vascular procedures were analyzed.ResultsRAS (diameter reduction >50%) was present in 26%. Forty-six percent of study patients underwent a vascular procedure (85% vascular surgery, remainder underwent amputation). Patients that underwent vascular surgery had a better renal function at baseline, less history of stroke, and a larger proportion of smokers. Overall mortality was similar for patients that underwent surgery (54.5%) and those without surgery (49.6%). There was no difference in 90-day postoperative mortality for patients without or with RAS (7.2% vs 10.3%; NS). For subjects that underwent bypass surgery, long-term mortality was substantially and significantly higher among those with RAS (65.1%) vs those without RAS (43.5%). On Cox regression analysis, age was the only independent predictor of 90-day postoperative mortality. The well-known cardiovascular risk factors of age, diabetes mellitus, history of prior peripheral vascular disease, smoking, prior myocardial infarction, prior stroke, and amputation, as well as presence of RAS, were independent predictors for overall mortality.ConclusionIn PAD, incidental RAS predicts long-term mortality independent of other risk factors. The elevated mortality is not due to a higher postoperative risk. Subjects presenting with PAD and RAS can therefore undergo vascular procedures with the same risk as other patients