PubMed Health⌕ Search

Biomedical subjects

Dick de Zeeuw

Publications and source records attributed to Dick de Zeeuw.

96 records · Page 6Linked to original sources
PubMed2002

Between-patient differences in the renal response to renin-angiotensin system intervention: clue to optimising renoprotective therapy?

Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II (Ang II), AT(1)-receptor blockers (ARB) is the cornerstone of renoprotective therapy. Still, the number of patients with end-stage renal disease is increasing worldwide, prompting the search for improved renoprotective strategies. In spite of proven efficacy at group level, the long-term renoprotective effect of RAAS blockade displays a marked between-patient heterogeneity, which is closely linked to between-patient differences in the intermediate parameters of blood pressure, proteinuria and renal haemodynamics. Of note, the between-patient differences by far exceed the between-regimen differences, and thus may provide a novel target for exploration and intervention. The responsiveness to RAAS blockade appears to be an individual characteristic as demonstrated by studies applying a rotation-schedule design. The type and severity of renal disease, obesity, insulin-resistance, glycaemic control, and genetic factors may all be involved in individual differences in responsiveness, as well as dietary factors, such as dietary sodium and protein intake. Several strategies, such as dietary sodium restriction and diuretic therapy, dose-titration for proteinuria, and dual RAAS blockade with ACE-I and ARB, can improve the response to therapy at a group level. However, when analysed for their effect in individuals, it appears that these measures do not allow poor responders to catch up with the good responders, i.e. in spite of their efficacy at group level, the available measures are usually not sufficient to overcome individual resistance to RAAS blockade. We conclude that between-patient differences in responsiveness to renoprotective intervention should get specific attention as a target for intervention. Unravelling of the underlying mechanisms may allow development of specific intervention. Based on the currently available data, we propose that response-based treatment schedules, with a multidrug approach titrated and adapted at individual responses rather than fixed treatment schedules, may provide a fruitful strategy for more effective renoprotection.

Chronic Disease↗
PubMed2002

Renal function as a predictor of prognosis in chronic heart failure.

The incidence of chronic heart failure (CHF) has been increasing, particularly because of the aging of the population and the improved survival of patients with coronary artery disease. Therefore, the current pathophysiological and clinical considerations in the diagnosis and treatment of CHF will need further improvement in terms of cardiovascular risk profiling, preventive measures, earlier intervention, and patient-tailored disease management. To date, the role of the kidney in CHF is mainly considered within the context of excessive salt and water retention, due to reduced renal blood flow. However, recent data indicate that the kidney may play a more decisive role in the progression and prognosis of the disease. It has been demonstrated that renal function is independently associated with an increased risk for all-cause mortality and cardiovascular morbidity. Furthermore, moderate renal insufficiency is a common phenomenon in this patient population and, for example, left ventricular ejection fraction, glomerular filtration rate, and New York Health Association class are not only prognostically important but are also acting independently, and support the hypothesis that cardiac function, clinical status, and renal function represent, in part, different prognostic entities of CHF. It could be questioned why an impaired renal function adds prognostic risk to develop CHF? A subclinically decreased renal function is unlikely to be the direct cause. Renal function is known to correlate with a variety of cardiovascular risk factors. Similar risk factors could contribute to the pathogenesis of intrarenal disease. Furthermore, a large number of metabolic abnormalities are related to impaired renal function and induce myocardial dysfunction and damage. Finally, neurohormonal activation is apparent in patients with chronic heart failure. Angiotensin II, the central product of the renin-angiotensin system, may play a central role in the pathophysiology and progression of cardiovascular and renal diseases. In conclusion, to prevent cardiovascular morbidity and mortality, new therapeutic strategies might be triggered by focussing on increasing our knowledge concerning adaptive and maladaptive mechanisms of the kidney involved in CHF.

Clinical Trials as Topic↗
PubMedDate not supplied

Approaches and methods in gene therapy for kidney disease.

Renal gene therapy may offer new strategies to treat diseases of native and transplanted kidneys. Several experimental techniques have been developed and employed using nonviral, viral, and cellular vectors. The most efficient vector for in vivo transfection appears to be adenovirus. Glomeruli, blood vessels, interstitial cells, and pyelum can be transfected with high efficiency. In addition, electroporation and microbubbles with ultrasound, both being enhanced naked plasmid techniques, offer good opportunities. Trapping of mesangial cells into the glomeruli as well as natural targeting of monocytes or macrophages to inflamed kidneys are elegant methods for site-specific delivery of genes. For gene therapy in kidney transplantation, hemagglutinating virus of Japan liposomes are efficient vectors for tubular transfection, whereas enhanced naked plasmid techniques are suitable for glomerular transfection. However, adenovirus offers the best opportunities in a renal transplantation setup because varying parameters of graft perfusion allows targeting of different cell types. In renal grafts, lymphocytes can be used for selective targeting to sites of inflammation. In conclusion, for both in vivo and ex vivo renal transfection, enhanced naked plasmids and adenovirus offer the best perspectives for effective clinical application. Moreover, the development of safer, nonimmunogenic vectors and the large-scale production could make clinical renal gene therapy a realistic possibility for the near future.

Animals↗
PubMedDate not supplied

Endothelial dysfunction in chronic kidney disease: determinant of susceptibility to end-organ damage and therapeutic response.

Endothelial dysfunction (ED) seems to be a crucial mediator of increased cardiovascular risk observed among patients with chronic kidney disease (CKD). Importantly, systemic ED does not only occur in patients with severe renal failure, but also in individuals with earlier stages of CKD. Close association between microalbuminuria and systemic ED renders renal vascular function an important marker for the severity of cardiovascular damage. Furthermore, changes in renal endothelium might be actively involved in the progression of renal end-organ damage. Recently, experimental evidence showed that interindividual variability in endothelial function of healthy rats predicts susceptibility to renal damage and the efficacy of renoprotective treatment. Therefore, a specific manipulation of renal and systemic ED might provide benefits in various stages of CKD. ED thus may represent an ideal therapeutic target not only for treatment, but also for primary prevention of renal disease.

Cardiovascular Diseases↗