Glomerulonephritis

Question 1

Definition

Answer 1

Glomerular injury, most often, not always inflammatory in nature. May involve all or part of glomerular apparatus.

Question 2

Commonest causes of end stage renal

Answer 2

1. Diabetes
2. Hypertension
3. GN

Question 3

Etiology (8)

Answer 3

1. Infections (group A beta-haemolytic Streptococcus, respiratory and GI infections, hepatitis B and C, endocarditis, HIV, toxaemia, syphilis, schistosomiasis, malaria, and leprosy)
2. 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)
3. Drugs (penicillamine, gold sodium thiomalate, NSAIDs, captopril, heroin, mitomycin C, and ciclosporin)
4. Metabolic disorders (diabetes mellitus, hypertension, thyroiditis)
5. Malignancy (lung and colorectal cancer, melanoma, and Hodgkin’s lymphoma)
6. Hereditary disorders (Fabry’s disease, Alport’s syndrome, thin basement membrane disease, and nail-patella syndrome)
7. Deposition diseases (amyloidosis and light chain deposition disease).
8. Idiopathic

Question 4

Primary GN->causes

Answer 4

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.

Question 5

Secondary disease->causes

Answer 5

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).

Question 6

Nephrotic diseases

Answer 6

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.

Question 7

Neprhitic diseases

Answer 7

Nephritic syndrome (haematuria, sub-nephrotic-range proteinuria, and HTN)

IgA nephropathy
Postinfectious GN
Rapidly progressive GN
Vasculitis
Anti-GBM GN.

Question 8

Risk factors

Answer 8

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

Question 9

Clinical presentation

Answer 9

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)

Question 10

First investigations and interpretations

Answer 10

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

Question 11

Management in mild

Answer 11

May need salt and water restriction
Daily weight
Monitor BP, fluid input and output
Phenoxymethylpenicillin
Regular paracetamol if in pain

Question 12

Management in moderate

Answer 12

moderate-severe disease
Salt/water restriction
Monitor BP
ACE inhibitors and/or angiotensin-II receptor antagonists
Phenoxymethylpenicillin
Furosemide
-->with nephrotic syndrome= prednisolone

Question 13

Management with anti-GBM

Answer 13

Methylprednisilone
Cyclophosphamide
Electrophoresis
Phenoxymethylpenicillin

Question 14

Management with immune complex

Answer 14

Methylprednisilone
Cyclophosphamide
Phenoxymethylpenicillin

Question 15

Patient instructions

Answer 15

1. Adhere strictly to diet and medication regimens to avoid long-term consequences
2. Diet should be low in salt, water, and fat. Protein restriction, if advised, should be done cautiously to avoid malnutrition.
3. 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)

Question 16

Mechanism of Focal segmental glomerulosclerosis

Answer 16

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

Question 17

Mechanism of BM thickening

Answer 17

+Protein synthesis

Deposition->immune complexes, amyloid

Question 18

Progression of injury to glomerulosclerosis

Answer 18

Reduction in renal mass due to injury

1. Systemic HTN->mesangial mass/ECcoagulation
2. Glomerular hypertrophy->endothelial injury= + permeability to proteins, podocytes cant proliferate following injury->proteinuria.

Question 19

Mechanism of fibrosis

Answer 19

Ischemia, chronic inflammation
lose pericapillary blood supply
Proteinuria= direct injury and
activates tubular cells–>+adhesion molecules, cytokine, GF–>fibrosis

Question 20

Pathogenesis of immune mediated GN

Answer 20

1. Cytotoxic antibodies
2. Circulating immune complex
   deposition= DNA/tumor antigens,
   infectious products
3. In situ immune complex
   deposition–>intrinsic tissue antigens
   (anti-GBM), planted antigens (exogenous, endogenous=DNA, proteins, immunoglobuline, immune complexes, IgA)
4. 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

Question 21

Causes of nephritic syndrome

Answer 21

Post-infectious
IgA nephropathy
Membranoproliferative
SLE
Infetcive endocarditis
HSP
Vasculitic-> Polyangitis, churg-strauss

Question 22

Clinical presentation of nephritic syndrome

Answer 22

Proteinuria
Hematuria
Azootemia
RBC casts
Oliguria
Hypertension
Edema

Question 23

Pathogenesis of PSGN

Answer 23

Activation of compliment
Antigen-antibody deposition–>
+neutrophils, cytokines, etc=
damage

Few weeks following streptococcal infectioins

Question 24

Laboratory findings: Urine, creatinine, UEC, LFT, albumin, ANA, USS, biopsy, complement

Answer 24

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*

Question 25

Triad in neprhotic syndrome

Answer 25

Proteinuria Hypoalbuminemia Edema

Question 26

Mechanism of edema, proteinuria in neprhotic

Answer 26

+glomerular permeability->proteinuria, reversal of protein:albumin, cannot compensate->reduced oncotic pressure= edema

Question 27

Pathogenesis of hyperlipidemia and + infections in nephrotic, and +thrombosis

Answer 27

``` 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 ```

Question 28

Histological pathology on renal biopsy in neprhotic

Answer 28

glomerular pathology on renal biopsy: ƒƒminimal change disease (or minimal lesion disease or nil disease) – i.e. glomeruli appear normal on light microscopy ƒƒmembranous glomerulopathy ƒƒfocal segmental glomerulosclerosis (FSGS) ƒƒmembranoproliferative glomerulonephritis ƒƒnodular glomerulosclerosis

Question 29

Causes of minimal change

Answer 29

Hodgkins lymphoma NSAIDs Steroids

Question 30

Define minimal change disease

Answer 30

complete effacement of podocyte foot process, lose negative charge (lymphokines reduce anion production).

Question 31

In an adult what do you need to be mindful of in MCD

Answer 31

Association with Hodgkin's lymphoma

Question 32

Pathogenesis of IgA nephropathy

Answer 32

Deposition of polymeric IgA in mesangium w/ adherence of compliment-->activation May have +IgA following GIT/Respiratory infection

Question 33

In what group is IgA nephropathy more common

Answer 33

Celiac Ankylosing spondylitis Alcoholic liver disease->reduced clearance

Question 34

What is FSGN

Answer 34

``` Sclerosis of some, not all glomeruli (focal) and within glomerulus only part of it has sclerosis (segmental) ```

Question 35

Etiology of FSGN

Answer 35

``` Etiology>idipathic, HIV/heroin/sickle cell, reflux nephropathy scarring of previously necrotising, adaptive response (-ve renal mass, intrarenal compensation, membrane damage, ECM expansion), inherited ```

Question 36

Comparison between MCD and FSGN

Answer 36

``` compared to MCD: +hematuria, -ve GFR, HTN +non selective proteinuria Xresponse to steroids +chronic development 50% in ten years seen more in adults ```

Question 37

Pathogenesis of diabetic nephrosclerosis

Answer 37

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. ```

Question 38

Pathogenesis of hypertensive neuropathy

Answer 38

``` 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 ```

Question 39

Causes of Rapidly progressive glomeruloneprhitis

Answer 39

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

Question 40

Management of neprhotic->general measures

Answer 40

1. Admit to hospital. Discuss with renal 2. Monitor UEC, BP, fluid balance and weight 2. Determine and treat underlying cause 3. Salt restriction and fluid restriction, daily weights 4. IV 20% albumin + Frusemide if IV depletion, severe/symptomatic edema 5. ACEi to reduce proteinuria!!! 6. Treat infections->give pneumococcal vaccination + phenoxymethylpenicillin prophylaxis 7. Avoid prolonged bed rest, give DVT prophylaxis if immobile 8. Smoking, alcohol, diet, exercise 9. Statins 10. Iron and vitamin D may be needed 11. Tight glycemic control 12. Ranitidine 13. Prednisilone to introduce remission, then wean 14. Family education->urine protein testing every morning, give booklet 15. After remissison->urine protein checked daily 1-2 years to ID a relapse 16. If relapse, prednisilone prior to edema 17. 80% chance of relapse, usually respond well 18. Most common trigger is intercurrent infection

Question 41

Prognosis in nephrotic

Answer 41

1. Relapses are common 2. If child steroid resistant->biopsy and consider cyclophosphamide 3. Long term good prognosis

Question 42

Assessment of neprhotic in children

Answer 42

1. 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. 2. 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) 5. 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) 6. 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

Question 43

Investigations in nephrotic

Answer 43

``` 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 ```

Question 44

Define a relapse of neprhotic

Answer 44

1. Proteinuria 3+ or 4+ for 3 consequetive days | Need prompt administration of prednisilone

Question 45

Considerations for steroid dependence in children/relpase of nephrotic

Answer 45

1. Infections->need additional booster 2. Vitamin D deficiency (lost in urine) 3. Hyperlipidemia 4. Hypothyroid->lost in urine 5. BMD 6. Eye examination after 12 months