Renal (Glomerulonephritis) Flashcards
(38 cards)
Nephritis and glomerulonephritis
Nephritis describes damage to the kidneys due to inflammation.
Glomerulonephritis describes nephritis involving the glomerulus.
structure of the glomerulus
Ultrafiltration occurs at the glomerulus. Liquid and small molecules need to pass through 3 layers to enter the nephron tubules:
1) The capillary endothelium:
- Allows fluid, plasma proteins, and large substances through
- Does not allow red or white blood cells and some proteins through
2) The glomerular basement membrane:
- Allows fluid and solutes through
- Does not allow intermediate-large substances including some proteins through
3) The epithelium of the Bowman’s capsule (made of podocytes):
- Allows fluid and small solutes through
- Does not allow large molecules such as proteins through
These three layers filter the blood with each layer preventing increasingly large substances from passing through into the nephron tubule. Overall, cells (such as red blood cells or white blood cells) and large proteins are not passed through.
nephritic vs nephrotic sydrome : location of disorder
1) Nephritic syndrome describes the signs and symptoms generally seen due to dysfunction of the capillary endothelium. This usually refers to severe and acute presentations of glomerulonephritis.
2) Nephrotic syndrome describes the signs and symptoms generally seen due to the dysfunction of podocytes. It is less associated with inflammation.
summary of nephritis vs nephrotic syndrome
Nephrotic syndrome
Active urine sediments with or without renal insufficiency, with nephrotic range proteinuria (>3g in 24hrs)
- Diabetes
- Minimal changes disease
- Membranous
- FSGS (focal segmental glomerular sclerosis)
amyloid
Nephritic syndrome
Active urine sediments with or without renal insufficiency, with mild proteinuria – blood in urine
- IgA nephropathy
- Lupus
- Mesangial proliferative glomerulonephritis
- Vasculitis
Nephrotic syndrome overview
Damage and dysfunction of the podocytes can lead to a loss of protein in the urine. As mentioned above, the podocytes are the ‘last line’ of filtration where large molecules such as proteins are prevented from entering the nephron tubule. Nephrotic syndrome is defined as:
- Proteinuria (>3.5 g/24hr)
- Hypoalbuminaemia
- Oedema
Other features that may also be seen include:
- Hyperlipidaemia
- Hypercoagulability
- Immunodeficiency
presentation of nephrotic syndrome
- Swollen e.g. periorbital and oedema
- Proteinuria >3 g in 24s hours
- Low serum albumin
- Hyperlipidaemia
- Hypercoagulable state
cause of nephrotic syndrome
In children
- 90% minimal change disease
In adults
- Minimal change
- Membranous nephropathy
- Focal segmental glomerulosclerosis (35%)
- Membranoproliferative glomerulonephritis
- Amyloid
Pathophysiology of minimal change
Where podocyte become effaced -> losing the ability to control the amount of protein leaked into the urine
management of nephrotic syndrome
Oedema
- Diuretics, need large doses and may need to be I.v. if gut oedema
- Salt and fluid retention
ACE-i
- Anti-proteinuria but caution if intravascularly deplete or if renal function deteriorating acutely
Hypercholesterolaemia
- Atherogenic if long-term nephrotic
- Life style advice and statins
Treat underlying condition
- Steroids for Minimal change disorder, underlying cause of disease
Diabetic nephropathy (DN)
describes a chronic reduction in kidney function associated with diabetes mellitus. It is characterised by proteinuria and a progressive reduction in the estimated glomerular filtration rate (eGFR). It generally occurs around 5-10 years after the onset of diabetes mellitus and can lead to chronic kidney disease (CKD).
screening for diabetic nephropathy
Since the predominant feature in DN is proteinuria, and many patients may be asymptomatic, all patients with both type 1 or type 2 diabetes mellitus should be screened annually with a urinary albumin:creatinine ratio (ACR). An ACR ≥3 mg/mmol is considered clinically significant.
management of diabetic nephropathy
- Optimise control of diabetes mellitus
- If ACR ≥3 mg/mmol: ACE inhibitor or angiotensin-II receptor blocker (ARB): slows progression
- If ACR ≥30 mg/mmol: ACE inhibitor/ARB and offer dapagliflozin if relevant eGFR thresholds are met
- Consider adding dapagliflozin to ACE inhibitor/ARB if ACR between 3-30 mg/mmol and relevant eGFR thresholds are met
Minimal change disease (MCD)
is the most common form of nephrotic syndrome in children. Its exact pathogenesis is unclear and immunofluorescence and light microscopy testing on biopsies showed no or minimal changes, hence MCD’s name. However, with electron microscopy, a diffuse loss of podocytes is seen, explaining proteinuria and the development of nephrotic syndrome.
RF MCD
- Leukaemia – MCD is associated with leukaemia
- Hodgkin’s lymphoma (HL) – MCD is associated with HL and may be the initial presenting symptom in some
- Recent viral illness – a dysregulated immune system is thought to play a role in MCD
management of MCD
Most cases are responsive to steroids, therefore oral corticosteroids are first-line. Other options include:
Cyclophosphamide or ciclosporin if corticosteroids are ineffective
investigations for MCD
urinalysis
- proteinuria
- no signif haematuria
Urine microscopya nd culutre
- to rule out UTI
UEs
- urea and creatinine gernally normal
- eGFR normal
Serum albumin
- low
Serum lipids
- hypercholesterol
C3 and C4
- to rule out immune complex glomerulonephritis
LFT
- to rule out liver disease
Renal US
- structural abnormality
Kidney biopsy
- not generally performed in childer because MCD is so likely
complications of MCD
Infection:
Due to urinary loss of immunoglobulins or immunosuppressive treatment
Thrombosis:
Due to the loss of antithrombin III in the urine
treatment for most causes of nephrotic syndrome
- steroids
- blood pressure management
nephritic syndrome overview
Inflammation leads to damage to the capillary endothelium. As mentioned above, this layer prevents the leakage of red blood and white blood cells into the nephron tubules. Nephritic syndrome is defined as:
Active urine sediments e.g. blood with or without renal insufficiency with mild proteinuria <3 g per 24 hr
A triad of:
- Haematuria
- Reduction in GFR (renal impairment / oliguria)
- Hypertension
Other features
- Often some proteinuria but less than nephrotic syndrome
- Disruption of the endothelium results in inflammatory response & damage to the glomerulus
- Onset may be acute or rapidly progressive (RPGN)
- Rapidly Progressive / Crescentic GN - a fulminant form of nephritic syndrome
causes of nephritic syndrome
- Anti-glomerular basement membrane disease (Goodpastures syndrome)
- IgA nephropathy (most common form)
- Post streptococcal glomerulonephritis
- Lupus
- Mesangial proliferative glomerulonephritis
- Vasculitis e.g. Granulomarosis with polyangiitis
Management of nephritic syndrome
- Blood pressure control / reduction of proteinuria
– ACE-I or AIIR first line if renal function allows
– Salt restrict - Treatment of oedema
– As for nephrotic syndrome if adequate renal function - Disease specific treatments
– Generally immunosuppressants
– e.g. RPGN – prednisolone, cyclophosphamide or rituximab +/- plasma exchange - Cardiovascular risk management
– Stop smoking, statin etc - Dialysis (often short-term)
IgA nephropathy
Also known as Berger’s disease, IgA nephropathy describes the clinical manifestations of immunoglobulin A (IgA)-containing immune complex deposits in the mesangium of the glomerulus (type III hypersensitivity). It is closely related to IgA vasculitis (Henoch–Schönlein purpura), which can be thought of as the systemic form of IgA nephropathy. Its pathogenesis is not fully understood.
Most patients with IgA nephropathy present with recurrent haematuria following an upper respiratory tract infection (URTI) or gastroenteritis. Less than 10% of patients may present with rapidly progressive glomerulonephritis (RPG).
