A number of kidney diseases can lead to end stage kidney failure requiring renal replacement therapy in the form of dialysis or kidney transplantation. The underlying immunology and treatment options of some of these kidney diseases can introduce confounding factors into laboratory tests.
Acute Glomerulonephritis
Acute Glomerulonephritis (Acute GN) is a renal disease which results from an immunologic trigger of inflammation and proliferation of glomerular tissue, resulting in damage to the basement membrane, mesangium or capillary endothelium.
The pathophysiology involves glomerular lesions resulting from deposition or in situ formation of immune complexes. The kidneys may be enlarged by up to 50%.
The causal factors can be broadly divided into infectious and non-infectious groups (such as primary renal disease and conditions or agents).
Acute Kidney Injury (AKI)
Acute Kidney Injury (AKI) is a sudden and rapid decline in renal function which clinically manifests as a reversible acute increase in blood urea nitrogen and serum creatinine levels over the course of hours to weeks.
The pathophysiology involves reduction in renal blood flow resulting in decreased glomerular filtration rate (GFR) – Normal GFR = 90 to 120 mL/min/1.73m2. Suitable transplant candidates are added to the waiting list if GFR <= 15
There are 3 main causes of AKI:
- Prerenal failure caused by compromised renal perfusion
- Intrinsic renal failure caused by diseases of the kidney itself, mainly the glomerulus and/or tubules
- Obstruction of the urinary tract
Acute Tubular Necrosis (ATN)
Acute Tubular Necrosis (ATN) is Acute Kidney Injury (AKI) in which the pathology lies within the kidney itself with tubule cell damage and cell death usually resulting from an acute ischemic (lack of oxygen) or toxic event.
The pathophysiology involves tubule cell damage and cell death.
ATN is caused for the most part by an acute event, either ischemic or toxic. Ischemic injury can be caused by heart failure, sepsis, anaphylaxis etc. Toxins that can cause ATN include cyclosporine and tacrolimus.
Alport’s Disease
Alport’s Disease is a group of inherited, heterogeneous disorders involving the basement membranes of the kidney and frequently affecting the cochlea and eye as well. Alport’s Disease is characterised by Haematuria (blood in the urine), Proteinuria (protein in the urine) and Hypertension.
The pathophysiology involves aberration of basement membrane.
Alport’s Disease is caused by defects in the genes encoding alpha-3, alpha-4, or alpha-5 chains of type IV collagen of the basement membranes.
Antiglomerular Basement Membrane Disease (anti-GBM)
Antiglomerular Basement Membrane Disease (anti-GBM) is an autoimmune disorder characterized by the presence of circulating pathogenic autoantibodies directed against proteins in the glomerular basement membranes which can lead to rapidly progressive glomerulonephritis.
The pathophysiology involves anti-GBM antibodies binding to an epitope of type IV collagen in glomerular and alveolar basement membranes. Complement is activated, proinflammatory cells and CD4+ and CD8+ cells are recruited to the site and subsequently, proinflammatory cytokines, chemokines and proteolytic enzymes are released. This results in endothelial damage with endothelial cell detachment from the underlying GBM and fibrin accumulation under the disrupted endothelial cells.
An environmental factor such as smoking or hydrocarbon exposure is presumed to be required to unmask the cryptic collagen antigen in the basement membrane.
In the laboratory, patients with anti-GBM tend to be auto crossmatch positive which can potentially lead to wrong interpretation of the crossmatch in the absence of an auto tests. However, treatment with Cyclophosphamide can cause a loss of B cells which makes B cell auto crossmatching impossible.
Diabetic Nephropathy
Diabetic nephropathy is a serious kidney related complication of type 1 and 2 diabetes characterized by persistent albuminuria, progressive decline in the glomerular filtration rate (GFR) and elevated arterial blood pressure.
The pathophysiology involves three major histological changes in the glomeruli:
- Mesangial expansion directly induced by hyperglycaemia
- Thickening of the glomerular basement membrane (GBM) occurs
- Glomerular sclerosis caused by intraglomerular hypertension
The exact aetiology of diabetic nephropathy is unknown. Proposed mechanisms include hyperglycaemia causing hyperfiltration and renal injury, advanced glycation products and activation of cytokines.
Focal Segmental Glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is characterised by a segmental solidification of the glomerular tuft and segmental obliteration of glomerular capillaries (scarring or hardening of the glomeruli) which causes asymptomatic proteinuria or nephrotic syndrome with or without renal insufficiency.
The pathophysiology primarily involves injury inherent within or directed to podocytes. Involves podocyte fat process effacement, proliferation of mesangial, endothelial and epithelial cells in the early stages, followed by shrinkage or collapse of glomerular capillaries, all lead to scarring or glomerulosclerosis.
Proposed aetiology includes viral- or toxin-mediated damage or intrarenal hemodynamic changes such as glomerular hyperperfusion and high intraglomerular capillary pressure.
Treatment with Cyclophosphamide can cause a loss of B cells which makes B cell auto crossmatching impossible.
Goodpasture Syndrome (GS)
Goodpasture Syndrome (GS) is a renal disease in which anti-GBM antibodies cause glomerulonephritis and also act against the alveolar basement membrane leading therefore in addition, to pulmonary haemorrhage.
The pathophysiology involves autoantibodies (anti-GBM antibodies) directed against the glomerular and alveolar basement membranes. These autoantibodies bind and activate the complement cascade, resulting in tissue injury.
The aetiology is likely due to environmental insult such as smoking, exposure to solvents or hydrocarbons, infections, in a person with genetic susceptibility.
Treatment with Rituximab will cause the B cell crossmatch to be positive or will cause sufficient loss of B cells to make B cell auto crossmatching impossible. Treatment with Cyclophosphamide can cause a loss of B cells which makes B cell auto crossmatching impossible.
Haemolytic Uremic Syndrome (HUS)
Haemolytic Uremic Syndrome (HUS) is a disease characterized by haemolytic anaemia (anaemia caused by destruction of red blood cells), acute kidney failure (uraemia) and a low platelet count (thrombocytopenia). It predominantly, but not exclusively, affects children.
Hyperoxaluria
Hyperoxaluria is excessive urinary excretion of oxalate (kidney stones).
IgA Nephropathy
IgA Nephropathy (also known as Berger’s disease) is characterized by IgA deposition in the glomerular mesangium causing glomerulonephritis, a condition in which there is inflammation and proliferation of glomerular tissue, resulting in damage to the basement membrane, mesangium or capillary endothelium.
The pathophysiology comprises the formation of immune complexes which are deposited in renal mesangium and the production of autoantibodies. These induce glomerular injury through the release of pro-inflammatory cytokines and through chemokine secretion, leading to the migration of macrophages into the kidney.
In the laboratory, patients with IgA Nephropathy tend to be flow crossmatch positive due to auto antibodies. It is advisable to always set up an auto crossmatch test to exclude auto antibodies.
Membranous Glomerulonephritis
Membranous Glomerulonephritis (MGN) is a kidney disease triggered by an immune response, leading to immune complexes being deposited in the subepithelial space.
Polycystic Kidney Disease
Polycystic Kidney Disease is an inherited disorder multisystemic and progressive disorder characterized by cyst formation and enlargement in the kidney and other organs (e.g. liver, pancreas, spleen).
Polycystic Kidney Disease has a genetic basis with two main type. An autosomal dominant type caused by mutations in either the PKD1 (polycystin 1) or PKD2 (polycystin 2) gene and an autosomal recessive type caused by mutations in in the PKHD1 (fibrocystin) gene.
Renal Artery Stenosis
Renal Artery Stenosis (RAS) also known as Renal Artery Emboli is a narrowing of one of the renal arteries, most often caused by atherosclerosis (build-up of plaque aka atheroma, inside the arteries) or fibromuscular dysplasia (abnormal growth within the wall of an artery).
Sickle Cell Nephropathy
Sickle cell nephropathy is a type of nephropathy (kidney disease or damage) associated with sickle cell disease which causes kidney complications as a result of sickling of red blood cells in the small blood vessels of the kidney.