Acute Renal Injury

ACUTE RENAL INJURY Pre-renal causes of acute renal injury  Pre-renal failure usually arises from impaired perfusion of the kidneys with blood (for example from hypovolaemia, hypotension, impaired cardiac pump efficiency or vascular disease limiting renal blood flow, or the combinations of these factors). Usually the kidney is able to maintain glomerular filtration close to normal despite wide variations in renal perfusion pressure and volume status – by the process of 'autoregulation'. Therefore, drugs that impair renal autoregulation, such as ACE inhibitors and NSAIDs, increase the tendency to develop pre-renal uraemia (raised serum urea concentration). All causes of pre-renal uraemia may lead to established parenchymal kidney damage and development of acute renal failure Post-renal causes of acute renal injury  Post-renal failure usually results from an obstruction of the urinary tract, and the urinary tract may be obstructed at any point between the kidney and the urethral meatus. In addition, obstructing lesions may lie within the lumen, or in the wall of the urinary tract, or be outside the wall, causing obstruction by external pressure. (For example, Prostate disease, Calculus disease (stones) – usually unilateral, pelvo-uretric junction obstruction, retroperitoneal disease and pelvic masses – ovarian Renal causes of acute renal injury   The most common cause of injury to the renal parenchyma is due to acute renal tubular necrosis (ATN). This often occur when pre-renal failure is not correctable and leads to histological damage of the tubules (ischaemic), but it can often be due to toxic damage . ATN is also associated with the presence of casts in the urine. In normal circumstances, ATN is a reversible renal lesion, but it can potentially progress to acute cortical necrosis which is irreversible Other less common causes include: o Acute glomerulonephritis o Acute interstitial nephritis (often drug-induced) – usually reversible, where morphologically, inflammatory cell infiltrate can be seen, with eosinophils and tubular damage o Vascular disease/endothelial dysfunction (due to malignant hypertension, scleroderma, and preeclampsia) Clinical presentations of renal injuries      Nephrotic Syndrome o Proteinuria o Oedema – level of protein in body drops due to proteinuria  this lowers oncotic pressure hence oedema o Hypoalbuminemia – due to proteinuria  excessive loss of body protein (that is predominantly albumin) o Hypercholesterolemia – from hypoalbuminemia, liver compensates by increasing production of cholesterol Nephritic Syndrome o Haematuria and Hypertension (in an acute setting) o Usually presence of proliferative o Highly-inflamed lesions Asymptomatic urinary abnormalities (AUA) Chronic renal failure – Systemic manifestations Acute renal failure o Acute fluid overload o Acute hyperkalaemia o Acute acidosis o Polyuric or oliguric o Rapidly rising serum creatinine Acute Renal Failure Prerenal Tubular Renal Glomerular Sclerosing Mesangial Membraneous Postrenal Vascular Interstitial Inflammatory Capillary Subendothelial Subepithelial Periglomerular crescents Pathogenesis of glomerular injury  Little is known of the etiologic agents and triggering events of glomerular injuries, however it is clear that immune mechanisms underlie most forms of primary glomerulonephritis and many of the secondary glomerular disorders. Glomerulonephritis can be readily induced experimentally by antigen-antibody reactions. Furthermore, glomerular deposits of immunoglobulins, often with various components of complement, are found in the majority of patients. Cell-mediated immune reactions also clearly play a role, usually in concert with antibody-mediated events Direct antibody mediated damage  In this form of injury, antibodies react directly with intrinsic tissue antigen, or antigens "planted" in the glomerulus from the circulation. This occurs in diseases such as anti-glomerular basement membrane disease (sometimes referred to as Goodpasture’s disease). The glomerular injury is caused by the production of a complement-binding IgG antibody directed at a collagen epitope in the glomerular basement membrane. As such, it is an autoimmune disease, and is the only type of glomerulonephritis in which the glomerulus itself is the direct target of the underlying immune response. Because circulating IgG antibodies are pathogenic in this condition, part of the treatment involves removal of the antibody from the circulation using plasmapheresis Immune complex-mediated damage  Damage in these conditions occurs either as a consequence of the binding of antibodies to antigens “trapped” in the glomerulus as a result of filtration, or following the deposition of circulating antigen-antibody complexes (immune complexes) within the glomerular capillaries (e.g. in lupus nephritis). Glomerular damage occurs due to the activation of the complement and inflammatory pathways. Treatment involves the removal of the antigen, if possible, and reducing the antibody production with immunosuppressive treatment. Damage due to mesangial IgA deposition  This occurs in IgA nephropathy and Henoch-Schonlein Purpura (HSP), where glomerular damage is a result of the deposition of IgA within the glomerulus. There are abnormalities in the levels of circulating IgA, with an increased propensity for mesangial deposition in the individual. Glomerular injury in these diseases is believed to be linked to local activation of complement proteins by the deposited IgA. IgA is normally produced constitutively and IgA with multiple specificities (polyclonal IgA) is normally present in the circulation. Mucosal antigen stimulation (typically by bacteria or viruses) stimulates an increase in IgA production. This is thought to be the explanation behind the occasional occurrence of macroscopic haematuria in these patient occurring simultaneously with a bacterial or viral infection Damage due to immune vascular inflammation (vasculitis)  This involves inflammation occurring within the vascular compartment (i.e. vasculitis – for example Wegener’s granulomatosis). Can involve both the extraglomerular blood vessels and the glomerular capillaries themselves. Soluble inflammatory factors such as cytokines and growth factors also play a role in the glomerular injury. There is no significant complement or immunoglobulin deposition in the glomerulus, with a pauci-immune pattern (minimal inflammation) Disruption of glomerular filtration due to production of soluble ‘permeability factors’  Examples of these diseases include minimal change nephrotic syndrome and primary change focal segmental glomerulosclerosis (FSGS). In these diseases, an as yet unidentifiable soluble factor directly injures the glomerular epithelial cell. Although these diseases are not associated with direct evidence of glomerular inflammation, a number of lines of evidence suggest that their pathogenesis is related to the overactivity of the immune system (including the response of the minimal change nephrotic syndrome to corticosteroids). Hence, they are typically included in classification systems for glomerulonephritis