Minimal_Change_Disease_Flashcards
What is minimal change disease and its prevalence?
Minimal change disease primarily presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.
What are some identified causes of minimal change disease?
Identified causes include certain drugs like NSAIDs and rifampicin, as well as conditions such as Hodgkin’s lymphoma, thymoma, and infectious mononucleosis, accounting for 10-20% of cases.
What is the pathophysiology of minimal change disease?
The disease involves T-cell and cytokine-mediated damage to the glomerular basement membrane, leading to loss of polyanion and increased permeability to serum albumin.
T-cell and Cytokine-Mediated Damage to the Glomerular Basement Membrane: The glomerular basement membrane (GBM) is a crucial structure in the kidney’s filtration system, composed of various proteins including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. T-cells are a type of lymphocyte (immune cell) that can be activated during immune responses, including autoimmune reactions. When activated, T-cells can release cytokines, which are signaling proteins that mediate and regulate immunity and inflammation. The release of cytokines can lead to inflammation and damage to the GBM.
Loss of Polyanions: One of the consequences of damage to the GBM is the loss of polyanions, such as those found in heparan sulfate proteoglycans. These polyanions contribute significantly to the negative charge of the GBM. The negative charge is essential because it repels negatively charged molecules, including many plasma proteins like albumin, thus playing a critical role in determining what is filtered out of the blood and what is retained.
Reduction of Electrostatic Charge: With the loss of these negatively charged polyanions, the overall electrostatic charge of the GBM diminishes. This reduction in electrostatic charge results in a less effective barrier to the filtration of negatively charged molecules.
Increased Glomerular Permeability to Serum Albumin: Serum albumin is the main protein found in blood plasma, and it is normally retained in the bloodstream during the filtration process due to the electrostatic barrier provided by the GBM’s negative charge. However, when this barrier is compromised due to reduced electrostatic charge, the permeability of the GBM to albumin increases. This condition is often referred to as albuminuria or proteinuria, where there is an abnormal amount of albumin in the urine, indicating a problem with kidney filtration.
What are the clinical features of minimal change disease?
Features include nephrotic syndrome with normotension, highly selective proteinuria, normal glomeruli on light microscopy, and podocyte effacement on electron microscopy.
How is minimal change disease managed?
The management involves oral corticosteroids, with most cases responding well. Cyclophosphamide is used for steroid-resistant cases.
What is the prognosis for patients with minimal change disease?
Prognosis is generally good, though relapse is common: about one-third have one episode, one-third have infrequent relapses, and one-third have frequent relapses that typically cease before adulthood.
summarise
Minimal change disease
Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.
The majority of cases are idiopathic, but in around 10-20% a cause is found:
drugs: NSAIDs, rifampicin
Hodgkin’s lymphoma, thymoma
infectious mononucleosis
Pathophysiology
T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss
the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin
Features
nephrotic syndrome
normotension - hypertension is rare
highly selective proteinuria
only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus
renal biopsy
normal glomeruli on light microscopy
electron microscopy shows fusion of podocytes and effacement of foot processes
Management
oral corticosteroids: majority of cases (80%) are steroid-responsive
cyclophosphamide is the next step for steroid-resistant cases
Prognosis is overall good, although relapse is common. Roughly:
1/3 have just one episode
1/3 have infrequent relapses
1/3 have frequent relapses which stop before adulthood
4.
A 5-year-old boy with minimal change disease has recently had a relapse of
Bronchiolitis
Whooping cough
nephrotic syndrome during which he became oedematous and required treatment with oral prednisolone. His parents have become concerned about the long-term complications of minimal change disease. Which of the following is a complication of minimal change disease?
intercranial haemorrhage
subarachnoid haemorrhage
deep vein thrombosis
chronic kidney disease
Urinary tract calculi
Deep vein thrombosis
Minimal change disease is the most common cause of nephrotic syndrome in children. Nephrotic syndrome presents with a triad of proteinuria, hypoalbuminaemia, and oedema. Although it usually responds to steroids, some
patients will experience relapses and may develop complications. There are three main complications of minimal change disease: increased risk of thrombosis, increased risk of infection, and hypercholesterolaemia. The loss of anti-thrombin III in the urine leads to a hypercoagulable state which may be further exacerbated by the thrombocytosis that is caused by steroid therapy. This can increase the risk of both venous thrombosis (e.g. deep vein thrombosis) and arterial thrombosis (e.g. myocardial infarction). The loss of immunoglobulins in the urine will increase the risk of infection, particularly by encapsulated bacteria (e.g. Streptococcus pneumoniae) so patients should receive appropriate vaccinations. The falling oncotic pressure due to urinary albumin losses is thought to trigger increased hepatic cholesterol synthesis resulting in hypercholesterolaemia. This will increase their cardiovascular risk.
Although minimal change disease affects the kidneys, it is rarely associated with chronic kidney disease or urinary tract calculi. Subarachnoid haemorrhage resulting from berry aneurysm rupture is associated with polycystic kidney disease. Furthermore, the hypercoagulable state in minimal change disease increases a patient’s risk of thrombosis rather than haemorrhage.
Nephrotic Syndrome management
Nephrotic Syndrome (BMJ Best Practice)
Minimal change disease is main cause in children
Initially give oral steroids (60 mg/m2 per day of prednisolone)
o After 4 weeks, the dose should be reduced or alternate days for 4 weeks
o Then it should be weaned or stopped
Fluid restricted and low-salt diet
May need albumin and furosemide if very advanced MCD
Children who don’t respond after 4-6 weeks of corticosteroid therapy or have atypical features
may have a more complex diagnosis and need a renal biopsy
o Given ciclosporin or tacrolimus and methylprednisolone
