No abstract

Severe acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression to chronic kidney disease (CKD), financial burden, and high mortality rate. Continuous renal replacement therapy (CRRT) is a predominant form of renal replacement therapy (RRT) in the intensive care unit (ICU) due to its accurate volume control, steady acid-base and electrolyte correction, and achievement of hemodynamic stability. This manuscript reviews the different aspects of CRRT prescription in critically ill patients with severe AKI, sepsis, and multiorgan failure in ICU. These include the choice of CRRT versus Intermittent and extended hemodialysis (HD), life of the filter/dialyzer including assessment of filtration fraction, anticoagulation including regional citrate anticoagulation (RCA), prescribed versus delivered CRRT dose, vascular access management, timing of initiation and termination of CRRT, and prescription in AKI/sepsis including adsorptive methods of removing endotoxins and cytokines.

This study shows that neutralization of endogenous TNF-alpha is effective in preventing acute glomerular inflammation and crescent formation, and in treating established disease, in a rat model of crescentic nephritis. These results may have therapeutic implications for human glomerulonephritis.

Hepatitis C virus (HCV) infection is a significant health problem, as it can lead to chronic active hepatitis, liver cirrhosis, and hepatic carcinoma. Patients undergoing hemodialysis treatment are at increased risk of contracting HCV and other viral infections. This is primarily due to their impaired cellular immunity, underlying diseases, and blood exposure for a prolonged period. Transmission of viral hepatitis, and in particular HCV in dialysis units, has been showing a progressive increase worldwide, ranging between 5% in some western countries and up to 70% in some developing countries. The annual rate of HCV seroconversion in Saudi Arabia is 7% to 9%, while its prevalence is variable between 15% and 80%. This prevalence remained at almost 50% in recent years, despite the further increase in number of patients with end-stage renal disease and the expansion of dialysis services. The most prevalent genotypes in Saudi Arabia are genotype 4 followed by genotypes 1a and 1b, whereas genotypes 2a/2b, 3, 5, and 6 are rare. Genotypes 1 and 4 were associated with different histological grades of liver disease. Mixed infections with more than one genotype were observed in some studies. Isolation of dialysis machines and infected patients, together with strict application of infection-control policies and procedures and continuous education and training of nursing staff, remain the cornerstone in prevention and control of the spread of HCV infection in dialysis units. Interferon (INF)-alpha or pegylated INF, alone or in combination with ribavirin, have shown great promise in the treatment of chronic HCV in dialysis patients.

Goodpasture's, or anti-glomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis and lung haemorrhage, and is caused by autoimmunity to the NC1 domain of the alpha3 chain of type IV collagen (alpha3(IV)NC1). This study examines the development of crescentic nephritis and alveolar haemorrhage in a model of Goodpasture's disease, experimental autoimmune glomerulonephritis (EAG), induced in WKY rats by immunization with rat GBM in adjuvant. An increase in circulating anti-GBM antibodies and albuminuria was observed by week 2, which increased further by weeks 3 and 4, while a decrease in creatinine clearance was observed by week 2, which decreased further by weeks 3 and 4. The kidneys of animals with EAG showed linear deposits of IgG on the GBM and a transient glomerular infiltration by CD4+ T cells at week 2. By week 3 there were large deposits of fibrin in Bowman's space, and glomerular infiltration by CD8+ T cells and macrophages, accompanied by focal necrotizing glomerulonephritis with crescent formation. Ultrastructural studies showed glomerular endothelial cell swelling and epithelial cell foot process effacement at week 2. As the lesion progressed, capillary loops became occluded and the mesangium became expanded by mononuclear cells. By week 3 there was detachment of the endothelium from the GBM, and accumulation of fibrin beneath the disrupted endothelial cells and in Bowman's space. Occasional breaks were observed in the continuity of the basement membrane, and cytoplasmic projections from infiltrating mononuclear cells could be seen crossing the capillary wall between the lumen and the crescent. The lungs of animals with EAG showed patchy binding of IgG to the alveolar basement membrane (ABM) at week 2, and infiltration of the interstitium by CD8+ T cells and macrophages by weeks 3 and 4, accompanied by both interstitial and alveolar haemorrhage. Ultrastructural studies showed focal mononuclear cell infiltrates in alveolar walls at week 2. Occasional breaks were observed in the basement membrane and adjacent endothelium by weeks 3 and 4, together with accumulation of surfactant and erythrocytes within the alveolar spaces. This study defines for the first time the relationship between the immunological and pathological events during the evolution of EAG, and provides the basis for further work on the pathogenesis of Goodpasture's disease.