Renal vascular disease

Renal vascular disease typically occurs with progressive narrowing of the main renal artery or smaller arterial vessels. Often, both patterns of disease coexist and result in ‘ischaemic nephropathy’ with damage to renal tissue. Much less commonly, inflammatory vasculitis can affect small or medium vessels. Ninety per cent of renal vascular disease is caused by atherosclerosis. Patients with renal vascular disease have an increased risk of cardiovascular death from associated cerebrovascular and coronary heart disease. Less than 10% of renal vascular disease is caused by fibromuscular dysplasia. The cause is unknown, but smoking is a risk factor. The disease is often bilateral and multifocal. It tends to affect the mid-portion of the renal artery, while atherosclerosis tends to occur at points of stress, especially at the junction of renal arteries with the aorta. This chapter reviews the diagnosis and management of renal vascular disease.

New Targets for End-Stage Chronic Kidney Disease Therapy

Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a) not previously described in the kidney, b) highly upregulated during progression and returning to the normal levels during reversal, and c) producing proteins that are either circulating or membrane receptors. The involvement of the selected genes in the mechanisms of renal disease was confirmed in additional models of renal disease, initiated in other compartments of the kidney such as glomeruli (administration of nephrotoxic serum) or the tubular interstitium (unilateral ureteral obstruction). The potential of the therapy was tested using mice lacking the expression of these genes and by in vivo administration of antisense oligonucleotides which blocked the transcription of the targeted genes. This strategy allowed the identification of periostin, an extracellular matrix protein normally involved in bone and tooth development, in addition to the discoidin domain receptor1 (DDR1) as potential targets of therapy against renal inflammation and fibrosis.

Venous and arterial thrombosis in dialysis patients

SummaryWhether the risk of both venous and arterial thrombosis is increased in dialysis patients as compared to the general population is unknown. In addition, it is unknown which subgroups are at highest risk. Fur-thermore, it is unknown whether having a history of venous thrombosis or arterial thrombosis prior to dialysis treatment increases mortality risk. A total of 455 dialysis patients were followed for objectively verified symptomatic thrombotic events between January 1997 and June 2009. The incidence rates in dialysis patients as compared to the general population was 5.6-fold (95% CI 3.1–8.9) increased for venous thrombosis, 11.9-fold (95% CI 9.3–14.9) increased for myocardial infarction, and 8.4-fold (95% CI 5.7–11.5) increased for ischaemic stroke. The combination of haemodialysis, lowest tertile of albumin, history of venous thrombosis, and malignancy was associated with subsequent venous thrombosis. Increased age, renal vascular disease, diabetes, high cholesterol levels, history of venous thrombosis, and history of arterial thrombosis were associated with subsequent arterial thrombosis. The all-cause mortality risk was 1.9-fold (95% CI 1.1–3.3) increased for patients with a history of venous thrombosis and 1.9-fold (95% CI 1.4–2.6) increased for patients with a history of arterial thrombosis. A potential limitation of this study was that in some risk categories as-sociations with venous thrombosis did not reach statistical significance due to small numbers. In conclusion, dialysis patients have clearly elev-ated risks of venous thrombosis and arterial thrombosis and occurrence of venous thrombosis or arterial thrombosis prior to the start of dialysis is associated with an increased mortality risk.