Kidneys Flashcards
What is the pathophysiology of Alport’s Syndrome?
It is an X-linked genetic disease and therefore seen in males
There is a defect in the ALPHA CHAIN of TYPE 4 COLLAGEN
This collagen is present in 2 main regions- The Glomerular Basement Membrane and the Eyes and Ears (Cochlea, Retina and Cornea)
So there would be haematuria, proteinuria AND hearing/ visual loss or defects
What are the 5 signs of Nephritic Syndrome seen in Alport’s Syndrome?
What are the visual, auditory and behavioural symptoms also seen in Alport’s Syndrome
Proteinuria
Microscopic or gross haematuria
Hypertension
A PERIPHERAL oedema
Fatigue and Dyspnoea
Opthalmological- Cataracts, Corneal Dystrophy, Lenticonus (the lens protrude into the anterior chamber)
Auditory- Sensorineural Hearing Loss
Behavioural- Learning disability
What 5 investigations should be conducted if Alport’s Syndrome is suspected?
Assess for Sensorineural Hearing Loss
Urinalysis- check for Proteinuria and Haematuria
U&Es- Check for signs of Renal Failure- High Creatinine and Low eGFR
Renal Ultrasound to exclude structural abnormalities
Renal Biopsy- when viewed under Electron Microscopy, you’d see the Longitudinal Splitting of the Lamina Densa with short stubs of Fibrils- forming a BASKET WEAVE APPEARANCE
What is the 2 step management plan for Alport’s Syndrome?
Why may transplantation fail?
ACE inhibitor- used as a Renoprotective drug if Haematuria or Proteinuria is present
Renal Replacement Therapy- Dialysis and Transplantation may be needed in an advanced disease
But- after transplantation, transplant failure may occur due to the presence of Anti-GBM Antibodies- which results in a clinical picture similar to Goodpasture’s Syndrome
What determines whether a patient has Chronic Kidney Disease?
If there are abnormalities in either the kidney structure or function occuring for more than 3 months
Or any marker of kidney injury, or a GFR<60 measured on 3 different occasions- separated by at least 90 days
What are the 2 most common causes of Chronic Kidney Disease?
Diabetes and Hypertension
Chronic Kidney Disease can result in Glomerular Scarring- what are the 3 things this can typically result in?
Metabolic derangement- due to HYPERKALAEMIA and URAEMIA
Anaemia- due to the reduced ERYTHROPOEITIN
CKD Mineral Bone Disease
Why is Chronic Kidney Disease a risk factor for Cardiovascular Health?
It results in Hypertension, Hypercholesterolaemia and Heart Failure
What are the 7 risk factors for Chronic Kidney Disease?
Age>50
Afro-Caribbean
Diabetes
Hypertension
Glomerular Nephritis
Nephrotoxic Drugs (such as NSAIDs)
Enlarged PROSTATE
What are the 8 signs of Chronic Kidney Disease?
Lethargy
Pruritus
Frothy Urine
Swollen Ankles (Peripheral Oedema)
Fluid Overload
Hypertension
Anorexia
Uraemic Sallow (yellow or pale brown skin colour)
What 7 investigations are to be considered in Chronic Kidney Disease?
Urine Dip for Proteinuria and Haematuria
Work out the Urine Albumin:Creatine Ratio (a ratio that is 3 or above suggests Proteinuria)
FBC- Normocytic Normochromic Anaemia- due to the reduced Erythropoeitin
Bone Profile and PTH- The patient is at risk of (3)- Hypocalcaemia, Hyperphosphataemia and Secondary or Tertiary Hyperparathyroidism
Renal Ultrasound- Bilateral Kidney Atrophy can be seen
CT scan if an obstructive cause is suspected
Renal biopsy if an intrarenal cause is suspected- such as Nephritic or Nephrotic Syndrome
What is the 6 step management plan for Chronic Kidney Disease
Stop SMOKING
Avoid Nephrotoxic Drugs (such as NSAIDs)
Have a low salt/ potassium diet with FLUID RESTRICTION
Manage the Cardiovascular Risk Factors (2)
- Hypertension- Give an ACE Inhibitor (first line) if the AC Ratio is raised (a sign of proteinuria). But stop if Creatinine rises higher than 30% or if the eGFR falls more than 25%. If AC ratio is not raised- then normal Hypertension management
- Hypercholesterolaemia- Give a Statin- Like Atorvastatin
Anaemia- target 10-12 Hb
- Iron Replacement
- Then Erythropoeisis Stimulating Agents (such as Erythropoeitin or Darbepoetin)
Renal Replacement Therapy (if eGFR<10 or if there are signs of Uraemia)
- Dialysis then Renal Transplant
What are the 7 Complcations of Chronic Kidney Disease?
Heart Failure- due to the Fluid Overload and the Anaemia
Chronic Kidney Disease- Mineral Bone Disease
Secondary and Tertiary Hyperparathyroidism
Anaemia- Normocytic Normochromic
Hyperkalaemia
Uraemia
Metabolic ACIDOSIS
What is CKD mineral bone disease?
A bone disease which occurs in patients with Chronic Kidney Disease
It is characterised by the widespread bone pain
What 3 metabolic changes does CKD Mineral Bone Disease result in?
Reduced 1-Alpha Hydroxylase activity leads to REDUCED VITAMIN D ACTIVATION
Reduced renal excretion of Phosphate results in HYPERPHOSPHATAEMIA. This stimulates bone resorption and leads to OSTEOMALACIA
HYPOCALCAEMIA
The Low Calcium, High Phosphate and Low Vitamin D leads to Secondary Hyperparathyroidism
What 5 bone conditions can CKD Mineral Bone Disease manifest as?
Osteoporosis
Osteosclerosis
Osteomalacia (due to the low VITAMIN D)
Osteitis Fibrosa Cystica- The Hyperparathyroid Bone Disease
Adynamic Bone Disease- due to the reduction in Osteoblast and Osteoclast activity
What are the 4 metabolic changes seen in the bloods of Secondary Hyperparathyroidism
LOW or NORMAL CALCIUM
HIGH or NORMAL PHOSPHATE
LOW VITAMIN D
HIGH PTH
What are the 4 signs of CKD Mineral Bone Disease?
Asymptomatic in early stages
Bone and Joint Pain
Bone Fractures and Deformation
Reduced Mobility
What are the 5 investigations to be ordered if Chronic Kidney Disease Mineral Bone Disease is suspected (if eGFR is less than 30 in a patient with bone pain)?
Hypocalcaemia
Hyperphosphataemia
Low Vitamin D
Secondary or Tertiary Hyperparathyroidism
Measure their eGFR
What is the aim and 5 step management plan for CKD Mineral Bone Disease?
The Aim is to reduce the levels of SERUM PHOSPHATE and PTH
First line- Reduce DIETARY PHOSPHATE- reduce MEAT and FISH and NUTS/ BEANS and DAIRY PRODUCTS
Vitamin D Replacement- as the 1-Alpha Hydroxylase Enzyme is still functioning. Give CHOLECALCIFEROL. In Later Stages, give ALFACALCIDOL or CALCITROL
Give Phosphate-Binders to tackle the high phosphate levels.
- Calcium-based phosphate binders can be used (CALCIUM ACETATE is first line) but can result in VASCULAR CALCIFICATION and HYPERCALCAEMIA.
- Non-calcium-based phosphate binders can be used if the calcium-based binders are ineffective- such as SEVELAMER, LANTHANUM and ALUMINIUM (Sevelamer also tackles HYPERCHOLESTEROLAEMIA)
Bisphosphonates given to Prevent and Treat Osteoporosis if eGFR<30
Parathyroidectomy in Tertiary Hyperparathyroidism
What us the pathophysiology of IgA Nephropathy
It is the deposition of IgA immune complexes in the MESANGIUM of the GLOMERULUS- which results in nephritic syndrome and end-stage kidney failure
Deposition in the MESANGIUM results in MESANGIUM PROLIFERATIVE GLOMERULONEPHRITIS due to TYPE 3 HYPERSENSITIVITY
This activates the ALTERNATIVE COMPLEMENT PATHWAY- C3 is converted to C3a and C3b which triggers glomerular injury
(This has a significant overlap with Henoch-Schonlein Purpura)
This typically happens after an infection of the mucosal lining- such as a URTI or Gastroenteritis
What are the 2 main risk factors for IgA Nephropathy?
Having a URTI or Gastroenteritis
What are the 7 signs of IgA Nephropathy
Very similar to Post-streptococcal Glomerulonephritis
- Haematuria- macroscopic in younger patients and microscopic in older patients
- Foamy urine- proteinuria
- Pink, red, coke urine- haematuria
- Sore Throat- Sign of URTI
- Loose stools and abdominal pain- Gastroenteritis
- OEDEMA due to PROTEINURIA
- Cervical Lymphadenopathy suggests URTI
What 4 investigations should be ordered if IgA Nephropathy is suspected?
Proteinuria and Haematuria
U&Es- baseline renal function to be measured as well as the deterioration
C3 and C4- C4 levels will be normal (C4 is associated with the Classic Complement Pathway)- C3 may be normal or low
Renal biopsy- Mesangial Hypercellularity with positive immunofluorescence for IgA and C3
What are the 4 steps for IgA Nephropathy Management?
Statins
ACE Inhibitor/ ARB- offer it immediately if Protein:Creatine ratio>100
Corticosteroids- if Proteinuria continues despite the ARB/ACE Inhibitor
Omega 3 Fatty Acids- Offer with the Corticosteroids
What organism causes Post-streptococcal Glomerulonephritis?
Strep Pyogenes
What are the differences between IgA Nephropathy and Post-streptococcal Glomerulonephritis?
IgA Nephropathy occurs 1-2 days after URTI/ Gastroenteritis
Post-streptococcal Glomerulonephritis occurs 1-2 weeks after URTI/ Pharyngitis/ Skin Infections
IgA Nephropathy- C3 levels are normal or reduced
Post-streptococcal Glomerulonephritis- C3 and CH50 levels are always reduced
IgA Nephropathy- Mesangial IgA deposits on Renal Biopsy
Post-streptococcal Glomerulonephritis- Positive Streptozyme test
IgA Nephropathy- ACE Inhibitor/ ARB for treatment
Post-streptococcal Glomerulonephritis- Furosemide for treatment
What is the pathophysiology of Lupus Nephritis?
What is the most common form of Lupus Nephritis?
It occurs in patients with SLE and involves the deposition of antigen-antibody complexes in the kidney
The most common form of Lupus Nephritis is Diffuse Proliferative Glomerulonephritis which presents with Nephritic Syndrome
What are the 6 main classes of Lupus Nephritis? And 2 facts about each
Class 1- Minimal Mesangial
- Normal renal function. Mild or Incidental
Class 2- Mesangial Proliferative
- Microscopic HAEMATURIA (with or without PROTEINURIA)
- Hypertension and Nephrotic Syndrome are rare here
- Typically responds to Steroids
Class 3- Focal Segmental
- Usually Nephrotic Syndrome
- Typically responds to high-dose Steroids
Class 4- Diffuse Proliferative (Most Common)
- Nephritic Syndrome
- Treated with Steroids and IMMUNOSUPPRESSANTS
Class 5- Diffuse Membranous
- Nephrotic Syndrome- Extreme Oedema
- May have hypertension
Class 6- Sclerosing
- Slowly progressing Renal Failure and Proteinuria
What are the 4 investigations to be ordered if Lupus Nephritis is suspected?
RENAL BIOPSY- GOLD STANDARD
Check for signs of SLE
Haematuria and Proteinuria in Urinalysis
Reduced eGFR
What are the findings on Biopsy for Light Microscopy (5), Electron Microscopy (1) and Immunofluorescence (1) for Diffuse Proliferative Glomerulonephritis (most common form of Lupus Nephritis)?
Light Microscopy-
- Hypercellular glomerulus
- Thickened basement membrane
- Endothelial and Mesangial Proliferation
- Wire-loop appearance
- Capillary wall thickening in SEVERE DISEASE
Electron Microscopy- Subendothelial IMMUNE COMPLEX DEPOSITION
Immunofluorescence- Granular Appearance
What is the 5 step management for Lupus Nephritis?
Corticosteroids
Immunosuppressive Agents
- Cyclophosphamide
- Azathioprine
Hydroxychloroquine
Renal Replacement Therapy if eGFR continues to deteriorate (Dialysis or Transplant)
ACE Inhibitor preferred in patients with Hypertension and Renal Disease
What is the pathophysiology of Membranoproliferative Glomerulonephritis?
It involves Mesangial Cell proliferation and Thickening of Glomerular Capillaries
What are the 3 types of Membranoproliferative Glomerulonephritis?
What 5 conditions is Type 1 associated with?
Type 1 (Most Common)- Associated with (5)-
- SLE
- Hepatitis B and C
- Chronic Lymphocytic Leukaemia
- Lymphoma
- Cryoglobulinaemia
Type 2 (Dense Deposit Disease)
- Activation of the Alternative Complement Pasthwya and therefore LOW levels of C3
- Associated with (2)- Factor H Deficiency and Partial Lipodystrophy
Type 3-
- Subendothelial and subepithelial deposits
- Associated with (2)- Hepatitis B and C
- ALL of them have LOW C3 levels (HYPOCOMPLEMENTAEMIA) and Mesangial Cell Proliferation
What are the 3 main risk factors for Membranoproliferative Glomerulonephritis?
Infections- HIV/ Hepatitis B and C/ Endocarditis
Chronic Lymphocytic Leukaemia/ Cryoglobulinaemia
Acquired Partial Lipodystrophy- loss of Fat- Associated with Type 2 Membranoproliferative Glomerulonephritis
What are the 4 signs of Membranoproliferative Glomerulonephritis?
Foamy Urine (Proteinuria)
Pink, Red or Coke tinged urine (Haematuria)
Oedema (due to Hypogammaglobuminaemia)
Oliguria (<0.5)
What 4 things are observed in Renal Biopsy for Membranoproliferative Glomerulonephritis?
PAS Staining on Light Microscopy shows Mesangial Cell Proliferation and Capillary Thickening
Type 1- Subendothelial and mesangial immune deposits result in Tram Track Appearance
Type 2- Intramembranous immune complex deposits with Dense Deposits
Immunofluorescence reveals C3 deposition
What 4 investigations are conducted in Membranoproliferative Glomerulonephritis?
Most children with Nephrotic Syndrome have Minimal Change Disease which would not show up on Renal Biopsy- so treat them with the treatment for MCD which is CORTICOSTEROIDS before the renal biopsy
- Haematuria and Proteinuria
- Type 1- Low C3 and C4 is Low or Normal
- Type 2- Low C3 and C4 is Normal
- Renal Biopsy is the definitive diagnosis
What is the 2 step approach to treating Primary Membranoproliferative Glomerulonephritis and 3 steps for treating Membranoproliferative Glomerulonephritis in general?
Primary Membranoproliferative Glomerulonephritis-
- Oral Cyclophosphamide
- Oral Mycophenolate Mofentil and Oral Corticosteroids
General-
- ACE Inhibitor/ ARB offered to all patients with Proteinuria generally
- Statins are offered to all patients with Nephrotic Syndrome after they are evaluated for having Dyslipidaemia
- Oral Warfarin- check their Serum Albumin. Patients with low Serum Albumin are at a higher risk of thrombosis
What are the three main symptoms of Nephritic Syndrome and Nephrotic Syndrome?
Nephritic-
- Haematuria (mainly)
- Hypertension
- Oedema
Nephrotic-
- Proteinuria (mainly)>3.5
- Hypoalbuminaemia<30
- Oedema
(may not always have hypertension)
What are the 4 main causes of Nephritic Syndrome?
Post-streptococcal Glomerulonephritis
Alport’s Syndrome
IgA Nephropathy
Rapidly-Progressive Glomerulonephritis
What are the 5 main causes of Nephrotic Syndrome?
Minimal Change Disease
Membranous Glomerulonephritis
Focal Segmental Glomerulosclerosis
Amyloidosis
Diabetic Nephropathy
What 2 conditions cause both Nephrotic or Nephritic Syndrome?
Diffuse Proliferative Glomerulonephritis
Membranoproliferative Glomerulonephritis
What are the 5 main investigations that show signs of Nephrotic Syndrome?
Proteinuria >3.5
Hypoalbuminaemia<30- which causes an OEDEMA
Hyperlipidaemia- liver increases synthesis of lipids in response to Low Albumin
Hypogammaglobuminaemia- due to loss of Immunoglobulins in the urine
Hypercoagulability- due to loss of Antithrombin 3, Protein C and S
What are the Light Microscopy Findings for Minimal Change Disease, Focal Segmental Glomerulosclerosis, Membranous Nephropathy, Diabetes and Amyloidosis?
Minimal Change Disease- Normal glomeruli
Focal Segmental Glomerulosclerosis- Focal and Segmental Glomerulosclerosis
Membranous Nephropathy- Thick Glomerular Basement Membrane
Diabetes- Mesangial Sclerosis and Kimmelstiel-Wilson Nodules
Amyloidosis- Apple-green Birefringence under Polarised Microscopy with Congo Red Stain
What are the Electron Microscopy Findings for Minimal Change Disease, Focal Segmental Glomerulosclerosis, Membranous Nephropathy and Membranoproliferative Glomerulonephritis?
Minimal Change Disease- Effacement of Foot Processes
Focal Segmental Glomerulosclerosis- Effacement of Foot Processes
Membranous Nephropathy- Subepithelial Immune Complex Deposition
Membranoproliferative Glomerulonephritis-
- Type 1- Subendothelial Immune Complex Deposition
- Type 2- Intramembranous Immune Complex Deposition
What is the most common cause of Nephrotic Syndrome in children, adults and the elderly respectively? And what diseases are they associated with (1, 4, 4) ?
Minimal Change Disease in children
- Hodgkin’s Lymphoma
Focal Segmental Glomerulosclerosis in adults
- HIV
- Heroin
- SLE
- Sickle Cell Anaemia
Membranous Nephropathy in elderly
- Malignancy
- Hepatitis B
- NSAIDs
- SLE
What are the three types of Rapid Progressive Glomerulonephritis caused by?
Type 1- Autoantibodies (Anti-GBM antibodies)
Type 2- Immune Complexes
- Such as from (3)- SLE, IgA Nephropathy, Henoch Schonlein Purpura
Type 3- ANCA-associated Vasculitides
What is the presentation for Rapid Progressive Glomerulonephritis?
Nephritic Syndrome (Haematuria with Red Cell Casts, Proteinuria, Hypertension and Oliguria)
What features of the underlying cause of Rapid Progressive Glomerulonephritis should be looked out for? (2)
Anti-GBM disease- Goodpasture’s
- Associated with Haemoptysis
Granulomatosis with Polyangiitis (Wegener’s) presents with a Vasculitis Rash or Sinusitis
How do you treat Rapid Progressive Glomerulonephritis?
Steroids and Cyclophosphamides
