Glomerulonephritis Flashcards
Definition
Glomerular injury, most often, not always inflammatory in nature. May involve all or part of glomerular apparatus.
Commonest causes of end stage renal
- Diabetes
- Hypertension
- GN
Etiology (8)
- Infections (group A beta-haemolytic Streptococcus, respiratory and GI infections, hepatitis B and C, endocarditis, HIV, toxaemia, syphilis, schistosomiasis, malaria, and leprosy)
- Systemic inflammatory conditions such as vasculitides (SLE, rheumatoid arthritis, and antiglomerulobasement disease, Wegener’s granulomatosis, microscopic polyarteritis nodosa, cryoglobulinaemia, Henoch-Schonlein purpura, scleroderma, and haemolytic uraemic syndrome)
- Drugs (penicillamine, gold sodium thiomalate, NSAIDs, captopril, heroin, mitomycin C, and ciclosporin)
- Metabolic disorders (diabetes mellitus, hypertension, thyroiditis)
- Malignancy (lung and colorectal cancer, melanoma, and Hodgkin’s lymphoma)
- Hereditary disorders (Fabry’s disease, Alport’s syndrome, thin basement membrane disease, and nail-patella syndrome)
- Deposition diseases (amyloidosis and light chain deposition disease).
- Idiopathic
Primary GN->causes
Primary disease: the pathological glomerular injury is limited to the kidney and not part of a systemic disease manifestation. The injury may or may not be idiopathic. Any systemic symptoms are a result of renal injury.
Post-infectious GN
IgA nephropathy
Anti-glomerular basement membrane (anti-GBM) GN
Idiopathic crescentic GN
Focal segmental glomerulsclerosis
Rapidly progressive.
Secondary disease->causes
Secondary disease: renal pathology in this group is a result of systemic disease such as vasculitis, which also has other organ involvement.
SLE Henoch-Schonlein purpura Wegener's granulomatosis Microscopic polyangiitis Cryoglobulinaemia Thrombotic microangiopathies Deposition diseases (amyloidosis, light chain deposition disease) Malignancies (Hodgkin's lymphoma, lung and colorectal cancer).
Nephrotic diseases
Nephrotic syndrome (nephrotic-range proteinuria, hypoalbuminaemia, hyperlipidaemia, and oedema)
Deposition diseases
Minimal change disease (number 1 cause in children)
Focal and segmental glomerulosclerosis (second most common cause in children)
Membranous nephropathy
Membranoproliferative GN.
Neprhitic diseases
Nephritic syndrome (haematuria, sub-nephrotic-range proteinuria, and HTN)
IgA nephropathy Postinfectious GN Rapidly progressive GN Vasculitis Anti-GBM GN.
Risk factors
Strong
group A beta-haemolytic Streptococcus respiratory infections GI infections hepatitis B hepatitis C infective endocarditis HIV SLE systemic vasculitis Hodgkin's lymphoma lung cancer colorectal cancer non-Hodgkin's lymphoma leukaemia thymoma haemolytic uraemic syndrome drugs
Clinical presentation
haematuria (common) oedema (common) hypertension (common) oliguria (common) anorexia (common) nausea (common) malaise (common) weight loss (common) fever (common) skin rash (common) arthralgia (common) haemoptysis (common) abdominal pain (common) sore throat (common)
First investigations and interpretations
FBE->normocytic, normochronic
UEC-> +Cr
LFTs->may be + if cause hepatitis/HIV/medications
Albumin->low in nephrotic
24 urine protein
Lipids->hyperlipidemia in neprhotic
Kidney USS may be warranted in some instances
Management in mild
May need salt and water restriction Daily weight Monitor BP, fluid input and output Phenoxymethylpenicillin Regular paracetamol if in pain
Management in moderate
moderate-severe disease Salt/water restriction Monitor BP ACE inhibitors and/or angiotensin-II receptor antagonists Phenoxymethylpenicillin Furosemide -->with nephrotic syndrome= prednisolone
Management with anti-GBM
Methylprednisilone
Cyclophosphamide
Electrophoresis
Phenoxymethylpenicillin
Management with immune complex
Methylprednisilone
Cyclophosphamide
Phenoxymethylpenicillin
Patient instructions
- Adhere strictly to diet and medication regimens to avoid long-term consequences
- Diet should be low in salt, water, and fat. Protein restriction, if advised, should be done cautiously to avoid malnutrition.
- Frequent follow-ups will be required to achieve aggressive BP goals and to monitor disease progression by protein in urine and renal functions (every 3-6 months, then less frequently)
Mechanism of Focal segmental glomerulosclerosis
Hyalinosis: amorphous plasma protein deposition--> obliterates capillary lumen \+injury of vessel wall--> focal glomerulosclerosis
Sclerosis: accumulation of collagen
seen +in diabetic nephroscleorsis
obliteraion of capillary lumen
Mechanism of BM thickening
+Protein synthesis
Deposition->immune complexes, amyloid
Progression of injury to glomerulosclerosis
Reduction in renal mass due to injury
- Systemic HTN->mesangial mass/ECcoagulation
- Glomerular hypertrophy->endothelial injury= + permeability to proteins, podocytes cant proliferate following injury->proteinuria.
Mechanism of fibrosis
Ischemia, chronic inflammation
lose pericapillary blood supply
Proteinuria= direct injury and
activates tubular cells–>+adhesion molecules, cytokine, GF–>fibrosis
Pathogenesis of immune mediated GN
- Cytotoxic antibodies
- Circulating immune complex
deposition= DNA/tumor antigens,
infectious products - In situ immune complex
deposition–>intrinsic tissue antigens
(anti-GBM), planted antigens (exogenous, endogenous=DNA, proteins, immunoglobuline, immune complexes, IgA) - Cell mediated->activates compliment
a. Neutrophils and monocytes--> activation complement, proteases, ROS, +cytokines b. Macrophages, T cells, NK= antibody/CMI= epilethial cell injury, +mediators c. mesangial cells= +ROS, cytokine, chemokines, grwth factors, NO, ET d. Platelets aggregate
Causes of nephritic syndrome
Post-infectious IgA nephropathy Membranoproliferative SLE Infetcive endocarditis HSP Vasculitic-> Polyangitis, churg-strauss
Clinical presentation of nephritic syndrome
Proteinuria Hematuria Azootemia RBC casts Oliguria Hypertension Edema
Pathogenesis of PSGN
Activation of compliment
Antigen-antibody deposition–>
+neutrophils, cytokines, etc=
damage
Few weeks following streptococcal infectioins
Laboratory findings: Urine, creatinine, UEC, LFT, albumin, ANA, USS, biopsy, complement
Urine: Oliguria, 2+ protein, RBC ++++, RBC & WBC casts.
24h urine: 0.5 g protein in 24h
Serum: creatinine = 0.14 (slightly elevated)
LFT, electrolytes, Full blood counts – Normal.
Serum albumin – normal ;
Antinuclear antibody (SLE) - Negative
Ultrasound of kidneys: normal
Renal biopsy – Glomerulonephritis*
Triad in neprhotic syndrome
Proteinuria
Hypoalbuminemia
Edema
Mechanism of edema, proteinuria in neprhotic
+glomerular permeability->proteinuria, reversal of protein:albumin, cannot compensate->reduced oncotic pressure= edema
Pathogenesis of hyperlipidemia and + infections in nephrotic, and +thrombosis
1. Lipids +: liver response to reduced oncotic pressure, altered transport of lipids, reduced catabolism. Lipiduria when lipoproteins leak 2. +Infections->loss of immunoglobulins 3. Thrombosis->loss of anticoagulants
Histological pathology on renal biopsy in neprhotic
glomerular pathology on renal biopsy:
minimal change disease (or minimal lesion disease or nil disease) – i.e. glomeruli appear
normal on light microscopy
membranous glomerulopathy
focal segmental glomerulosclerosis (FSGS)
membranoproliferative glomerulonephritis
nodular glomerulosclerosis
Causes of minimal change
Hodgkins lymphoma
NSAIDs
Steroids
Define minimal change disease
complete effacement of
podocyte foot process, lose
negative charge (lymphokines
reduce anion production).
In an adult what do you need to be mindful of in MCD
Association with Hodgkin’s lymphoma
Pathogenesis of IgA nephropathy
Deposition of polymeric IgA in mesangium w/
adherence of compliment–>activation
May have +IgA following GIT/Respiratory infection
In what group is IgA nephropathy more common
Celiac
Ankylosing spondylitis
Alcoholic liver disease->reduced clearance
What is FSGN
Sclerosis of some, not all glomeruli (focal) and within glomerulus only part of it has sclerosis (segmental)
Etiology of FSGN
Etiology>idipathic, HIV/heroin/sickle cell, reflux nephropathy scarring of previously necrotising, adaptive response (-ve renal mass, intrarenal compensation, membrane damage, ECM expansion), inherited
Comparison between MCD and FSGN
compared to MCD: +hematuria, -ve GFR, HTN \+non selective proteinuria Xresponse to steroids \+chronic development 50% in ten years seen more in adults
Pathogenesis of diabetic nephrosclerosis
PKC, AGE, polyol pathways=
thickening, +BM proliferation,
-ve fibrinolysis
initially +GFR-->+intraglomerular pressure, +glomerular proliferation/hypertrophy, +glomerular filtration area. In response to ablation of renal mass.
Pathogenesis of hypertensive neuropathy
Hyaline-->hyaline thickening w/ luminal narrowing--> hemodynamic stress and injury--> plasma protein leakage. Hyperplastic-->in malignant HTN--> smooth muscle cell proliferation, fibrinoid deposits and vessel wall necrosis
Causes of Rapidly progressive glomeruloneprhitis
Type 1- anti-GBM antibody–> renal limited, Goodpasture (associated pulmonary hemorrhage) IgG deposits on renal antigen + C3–>injury–>formation of crescents
Type 2 immune complex= idiopathic, post infectious, lupus nephritis, Henoch-schonlein–> granular pattern of immune complex deposition, cellular proliferation and crescents
Type 3 pauci immune Xanti-GBM antibodies ANCA +ve, wegeners, microscopic polyangtis
Management of neprhotic->general measures
- Admit to hospital. Discuss with renal
- Monitor UEC, BP, fluid balance and weight
- Determine and treat underlying cause
- Salt restriction and fluid restriction, daily weights
- IV 20% albumin + Frusemide if IV depletion, severe/symptomatic edema
- ACEi to reduce proteinuria!!!
- Treat infections->give pneumococcal vaccination + phenoxymethylpenicillin prophylaxis
- Avoid prolonged bed rest, give DVT prophylaxis if immobile
- Smoking, alcohol, diet, exercise
- Statins
- Iron and vitamin D may be needed
- Tight glycemic control
- Ranitidine
- Prednisilone to introduce remission, then wean
- Family education->urine protein testing every morning, give booklet
- After remissison->urine protein checked daily 1-2 years to ID a relapse
- If relapse, prednisilone prior to edema
- 80% chance of relapse, usually respond well
- Most common trigger is intercurrent infection
Prognosis in nephrotic
- Relapses are common
- If child steroid resistant->biopsy and consider cyclophosphamide
- Long term good prognosis
Assessment of neprhotic in children
- History:
Oedema, weight gain, poor urine output, dizziness, or discomfort as a result of the oedema (including abdominal pain).
a. Mild (subtle peri-orbital region, scrotum or labia)
b. Moderate with peripheral pitting oedema of the limbs and sacrum.
c. Severe with gross limb oedema, ascites and pleural effusions. - Investigations
Heavy proteinuria (dipstick 3-4+ or urine protein/creatinine ratio >0.2g/mmol)
Hypoalbuminaemia (12y
Systemic symptoms of fever, rash, joint pains (SLE).
Persistent hypertension (can have mild hypertension first 1-2 days) - Rule out any nephritic features (requiring entirely different management)
Macroscopic haematuria (INS may have microscopic haematuria)
Hypertension
Raised serum creatinine (INS may have mild elevation with mod-severe volume depletion) - Assess for severity and complications of INS
a. Intravascular volume depletion
Dizziness, abdominal cramps
Peripheral hypoperfusion (cold hands or feet, mottling, capillary refill time > 2 seconds), tachycardia, oligoanuria, low urinary sodium, hypotension (late sign)
Severe/symptomatic oedema – potential skin breakdown/cellulitis, gross scrotal/vulval oedema, increased work of breathing from pleural effusion
b. Infection (at increased risk in nephrotic state)
Cellulitis from gross oedema with skin compromise
Spontaneous bacterial peritonitis – abdominal pain, fever, nausea/vomiting, rebound tenderness
c. Thrombosis (at increased risk in nephrotic state)
Deep vein thrombosis, pulmonary embolus
Renal vein thrombosis – macroscopic haematuria, palpable kidney, loin tenderness, raised creatinine, hypertension
Cerebral vein thrombosis - headache, vomiting, impaired conscious state or focal neurology
Investigations in nephrotic
1. Urine Dipstick Microscopy Spot urine pro:cr Sodium (volume depletion) 2. Bloods FBC UEC, LFT (albumin) C3 and 4 (low in SLE and MPGN) ANA (SLE) Hep B if risk factors Varicella serology
Define a relapse of neprhotic
- Proteinuria 3+ or 4+ for 3 consequetive days
Need prompt administration of prednisilone
Considerations for steroid dependence in children/relpase of nephrotic
- Infections->need additional booster
- Vitamin D deficiency (lost in urine)
- Hyperlipidemia
- Hypothyroid->lost in urine
- BMD
- Eye examination after 12 months
