Primary Renal Disease

PRIMARY RENAL DISEASE Disease classification    Primary renal diseases are defined as diseases in which the renal manifestations of the illness are: either the first to appear or the most important manifestation of a systemic process – e.g. renal disease due to an inherited process Secondary renal diseases are those for which the kidneys are damaged due to another primary process – e.g. renal disease due to diabetes (diabetic nephropathy). Work out whether the disease is acute or chronic o If chronic, then find out which part of the component is affected by disease e.g. glomerulus, tubules, vasculature, interstitium  Look into the clinical manifestations of the disease Clinical manifestations of renal disease     Majority of renal diseases are named based on their pathological appearance, however they may have widely varied clinical presentations. When considering clinical manifestations, it is useful to distinguish between symptoms, signs, syndromes and diagnose. Symptoms of kidney disease include change in urinary appearance, oedema, tiredness, loin pain, nausea and headache In medicine, signs are what can be observed or found on physical examination such as pallor (due to anaemia), sallow complexion (accumulation of urochromes), hypertension, fluid overload (increased JVP, oedema), dependent ‘pitting’ oedema, proteinuria, microscopic haematuria, and glycosuria. A syndrome is a cluster of symptoms/signs that collectively indicate or characterise a disease. For example, nephrotic syndrome involves significant proteinuria due to glomerular damage, as well as low albumin, oedema and high serum lipid levels. Nephritic syndrome is essentially a ‘worser nephrotic syndrome’ where glomerular inflammation leads to haematuria/proteinuria and reduced GFR Pathological mechanisms of disease  A useful way to consider chronic renal diseases (i.e. those that have been present for more than three months) is based on the anatomical components involved, and also based on the pathological mechanism of damage. The pathological mechanisms of disease include: Glomerular diseases  Manifestations of glomerular diseases vary according to disease severity, but in general includes: o Loss of filtration selectivity e.g. proteins/RBCs in urine o Loss of filtration e.g. increased toxins in body, fluid retention Autoimmune glomerular diseases         Glomerular injury caused by components of the immune system, such as antibodies, complement components and cytokines. It may respond to treatments that supress the immune system Primary forms of autoimmune glomerular disease include the following list below. ‘Minimal change’ disease – presents with sudden onset nephrotic syndrome, ‘minimal’ change on light microscopy while electron microscopy shows obliteration of podocyte foot processes FSGS (focal and segmental glomerulosclerosis) – as the name suggests, this is patchy fibrotic scarring within individual glomeruli Membranous nephropathy – antibody and immune deposits in the glomerulus causing inflammation IgA nephropathy - commonest form of glomerular disease on renal biopsy, results show a deposition of IgA within glomerulus. Flares during mucosal infections are also common due to increased IgA production Mesangiocapillary glomerulonephritis - an immune complex mediated inflammation, which maybe ‘idiopathic’, or related to immune stimulation by various infectious agents (e.g. chronic hepatitis C or bacterial infection), or secondary to systemic immune disease, related to acquired defect of complement pathway Anti-glomerular basement disease - – caused by IgG antibody deposited within glomerular basement membrane (GBM) of kidneys. This can product intense glomerular inflammation which show up as cellular ‘crescents’ Degenerative glomerular diseases  Degenerative glomerular disease is a partial explanation for the observed fall in GFR that occurs with normal ageing. Normal ageing is associated with a progressive loss of GFR due to vascular injury, or glomerulosclerosis (glomerular scarring which maybe ’global’ or ‘segmental’. The main clinical manifestation is a loss of GFR, with little proteinuria and haematuria is uncommon as glomerular filtration barrier is not injured in remaining glomeruli. However, renal injury can cause ‘accelerated ageing’ of the remaining glomeruli. Genetic glomerular diseases  Alports syndrome is the most important inherited glomerular disease. It is an X linked inheritance of a mutation resulting in abnormal collagen component of GBM. Clinical manifestations include glomerular haematuria and proteinuria, progressive loss of GFR (chronic renal failure), and deafness and ocular abnormalities (due to systemic effects of abnormal collagen). Primary vascular diseases       Manifestations of vascular diseases affecting the kidney vary according to the size of the blood vessel involved o Large and medium sized arteries – impair renal blood flow and may cause ischaemia, chronically lead to falling GFR and renal scarring o Smaller arteries and capillaries – as above, but acute diseases involving glomerular capillaries may disrupt glomerular filtration and cause the nephritic syndrome Types of renal vascular disease include the following list below Degenerative vascular diseases - Ageing and vascular damage (hypertension, smoking, cholesterol) associated with atherosclerotic disease of main renal arteries, intimal thickening of smaller arteries (especially hypertension), and hyalinosis of arterioles. Clinically reduced renal function without haematuria and proteinuria (no major disruption of glomerular filtration barrier) Metabolic vascular disease – secondary to diabetes, particularly smaller-medium sized arteries Autoimmune vasculitis - Clinical manifestations of small vessel vasculitis (inflammation of glomerular capillaries and arterioles) are very similar to more severe forms of ‘glomerular’ disease – Typically manifest as the ‘nephritic syndrome’ Idiopathic vascular disease – such as thrombotic microangiopathy where there is endothelial damage associated with capillary thrombosis Tubular and interstitial renal diseases   Manifestations of tubular and interstitial renal diseases include o Loss of GFR o Loss of renal concentrating capacity o Acidosis o Glycosuria and aminoaciduria due to impaired reabsorption o Uncommon to have proteinuria or haematuria as there is no disruption of the glomerular filtration barrier Pathological mechanisms of primary tubular and interstitial diseases include genetic (e.g. inherited tubular disease), iatrogenic / toxic (medication side effects, environmental poisoning), ischaemic and idiopathic