Nephrology Flashcards
Give some secondary causes of glomerulonephritis
Haematological: myeloma, CLL Gastro: ALD, IBD, coeliac disease Resp: bronchiectasis, lung cancer, TB Infectious disease: hepatitis, HIV, malaria, Abx Rheum: SLE, RA, amyloid Drugs: bisphosphonates, NSAIDs, heroin
What is key to the clinical diagnosis of GN?
Kidney biopsy (need 10-12 glomeruli)
Describe Rapidly Progressing Glomerulonephritis (RPGN)
Crescenteric damage
Rapid increase in sCr over days
Aggressive - progresses to ESRF in 80-90% without treatment
Causes: ANCA vasculitis Goodpastures Syndrome (anti-GBM) Lupus nephritis Infection associated (strept/staph) - happens weeks after infection
Describe nephritic syndrome
Haematuria and proteinuria
High BP, raising sCR
Associated with IgA, SLE, post-infective
Describe nephrotic syndrome
Proteinuria (PCR >300 or >3.5g/d of protein)
Low serum albumin (<30)
Oedema
(+hyperlipidaemia)
What is the most common primary glomerular disease?
IgA nephropathy
Describe IgA nephropathy
Most common primary glomerular disease
May be secondary due to coeliac disease/cirrhosis
May be precipitated by an infection - synpharyngitic (strept. infection + blood in urine at same time)
Abnormal/overproduction of IgA –> proliferation of mesangial cells
What are the effects of IgA nephropathy?
Haematuria
HTN
Proteinuria (varies with prognosis)
How is IgA nephropathy managed?
ACEi (reduce permeability of GBM)
How many people with IgA nephropathy will develop ESRF?
1/3
Describe Membranous Glomerulonephritis
A disease of adults - effects podocytes
Presents with nephrotic syndrome
10% secondary to malignancy, drugs
What Auto-Ab is associated with membranous glomerulonephritis?
Anti-phospholipase A2 receptor Ab (70%)
What is the history of membranous glomerulonephritis like?
1/3 will spontaneously remit in 12-18 months
1/3 will progress onto ESRF in 1-2 years
1/3 will have persistent proteinuria with maintained eGFR
Describe the management of membranous glomerulonephritis
Treat underlying condition
ACEi, statins, diuretics, salt restriction
Cyclosporin, ritixumab, alkylating agents (cyclosphosphamide), steroids
Describe minimal change disease
The commonest GN in children (90% <10y)
Generally idiopathic but may be due to malignancy ie lymphoma
Presents with nephrotic syndrome
What changes are seen on:
A) light microscopy
B) electron microscopy
in minimal change disease?
A) no changes on light microscopy
B) foot process fusion on electron microscopy
How is minimal change disease treated?
High dose steroids
50% will relapse
Give some functions of the kidney
Metabolic waste excretion - urea, creatinine Endocrine functions - Vit D, EPO, PTH Drug metabolism/excretion Control of solutes/fluid balance BP control Acid/base balance
Describe the Glomerular Filtration Barrier
Negatively charged - no protein in filtrate
Large molecules are maintained within capillaries
What is the normal amount of protein in the urine?
<150mg/24 hours
What type of protein is detected by urine dipsticks?
Albumin
Define renal clearance
(Urine concentration of substance x urine volume) / plasma concentration of substance
How else can renal clearance be known as?
Glomerular Filtration Rate
When calculating eGFR, what parameters are taken into context?
Age
Gender
Race
Plasma creatinine
What is the unit for eGFR?
ml/min/1.73m^3
What things need to be taken into consideration when assessing a patient’s eGFR?
Assumes stable renal function - not useful for AKI
Can lose up to 50% renal function because eGFR starts to deteriorate
Useful for drug dosing
How does eGFR correspond to staging of CKD?
>/= 90% + abnormality = stage 1 60-89 + abnormality = stage 2 30-59 = stage 3 (moderate impairment) 15-29 = stage 4 (severe impairment) <15 = stage 5 (advanced renal failure)
What is the mechanism of inheritance for adult polycystic kidney disease?
Autosomal dominant
What gene mutations are involved in adult polycystic kidney disease?
PKD 1 (chromosome 16) - 85% PKD 2 (chromosome 4) - 15%
What do PDK 1 and 2 genes encode?
Polycystin 1 & 2
Membrane protein involved in calcium regulation
Present in renal tubular epithelia (+ liver and pancreas)
Overexprssed in cyst cells
What is the natural history of adult polycystic kidney disease?
Cysts enlarge
Kidney volume increases
Some compensation initially
eGFR starts to fall –> ~10y later kidneys fail
If a person has a FHx of adult polycystic kidney disease, how should they be investigated to see if they also have it?
Renal US at 21
Repeat at 30 if normal
Age 15-30: 2 unilateral/bilateral cysts
Age 30-59: 2 cysts in each kidney
Age >60: 4 cysts in each kidney
If a person doesn’t have a FHx of adult polycystic kidney disease, what is diagnostic for the condition?
> 10 cysts in each kidney
Renal enlargement
Liver cyst
What are some of the clinical consequences associated with adult polycystic kidney disease?
50% risk of ESRD by 50
Cyst accidents - rupture, bleeding, infection
Other: HTN Intracranial aneurysm Aortic incompetence Mitral valve prolapse Colonic diverticular disease Liver/pancreatic cysts Hernia
Describe the management of adult polycystic kidney disease
Supportive Early detection and management of HTN Treat complications Manage extra-renal associations Renal replacement therapy
Describe Von Hippel Lindau Syndrome
Autosomal dominant
Multiple benign and malignant tumours
Describe Autosomal Recessive PKD
Affects children
Results in hepatic fibrosis
Describe Tuberous Sclerosis
Autosomal dominant
Multiple benign tumours - brain, heart, eyes, kidney, skin
Epilepsy and learning difficulties
Describe Medullary Cystic Disease
Autosomal dominant
Cysts in medulla
Small to normal sized kidneys
Gout
Describe Alpert’s Syndrome
Usually X-linked
Second most common cause of inherited kidney disease
Collagen 4 abnormality (Alpha 3/4/5 gene mutation)
Deafness and renal failure (deafness first)
Microscopic haematuria, proteinuria, ESRF
Describe Fabry’s Disease
X-linked storage disorder
Alpha galactosidase A deficiency resulting in accumulation of Gb3 in the glomeruli (podocytes)
Proteinuria + ESRF (+neuropathy + cardiac and skin features)
Describe the diagnosis of Fabry’s Disease
Alpha-Gal A activity in leucocytes
Renal biopsy - inclusion bodies of G3b
How is Fabry’s Disease managed?
Enzyme replacement therapy
Describe the pathophysiology of diabetic nephropathy
Hyperglycaemia Volume expansion Intraglomerular hypertension Hyperfiltration (initially serum Cr decreases, so eGFR looks to improve) Proteinuria HTN + renal failure
How long does it take for diabetic nephropathy to occur following the development of diabetes?
Approximately 20 years
How should diabetic nephropathy be managed?
Tight glycemic control
Good BP control - ACEi/ARB
SGLT2 inhibitors
Describe renal artery stenosis
Stenosis of renal artery –> not enough blood supply to kidney –> kidney becomes fibrotic and shrinks down
What can cause progressive narrowing of the renal artery?
Atheroma
What happens if the renal perfusion has fallen to >20%?
GFR falls
Tissue oxygenation of cortex and medulla is maintained
What happens if the renal perfusion has fallen to >70%?
Cortical hypoxia –> microvascular damage and activation of inflammatory and oxidative pathways
Parenchymal inflammation and fibrosis –> becomes irreversible
Restoration of blood flow does not provide any benefit
Describe the management of renal artery stenosis
Good BP control (not with ACEi/ARB)
Statin
Good glycemic control if diabetic
Smoking cessation, increased exercise, reduce NaCl intake
Angioplasty
What are the indications for angioplasty in renal artery stenosis?
Rapidly deteriorating renal function
Uncontrolled HTN on multiple agents
Flash pulmonary oedema
Describe amyloidosis
Deposition of highly stable insoluble proteinous material in the extracellular space
What stain can be used to identify amyloid, and what will it stain?
Congo Red Stain
Apple green birefringence
What are the two types of amyloid?
AA amyloid: inflammation/infection
AL amyloid: immunoglobulin fragments - myeloma
How should amyloidosis be treated?
AA amyloid: treat underlying inflammatory/infection
AL amyloid: treat underlying haematological malignancy
In SLE, what can autoantibodies be directed against?
DNA
Histones
snRNPs
Transcriptional/translational machinery
Describe lupus nephritis
Auto-antibodies against dsDNA or nucleosomes
Form intravascular immune complexes or attach to GBM
Activates complement
Renal damage
How should lupus nephritis be managed?
Renal biopsy to confirm diagnosis + stage
Immunosuppression - steroids, retuximab, cyclophosphamide
Define Acute Kidney Injury
Decline of renal excretory function over hours/days which is recognised by an increase in serum urea and creatinine
What are the three classifications of AKI?
Pre-renal: circulatory failure
Renal: the cells of the kidney
Post-renal: obstruction
Give some pre-renal causes of AKI
Hypotension Hypovolaemia Hypoxic Hypoperfusion Sepsis Drugs/toxins
Give some causes of post-renal AKI
Obstruction: Calculi Tumours Lymph nodes Prostate
Give some causes of renal AKI
Acute tubular necrosis
GN
Rhabdomyolysis
Gentamicin
Describe acute tubular necrosis
Usually reversible Under-perfusion of tubules and/or direct toxicity Hypotension Sepsis Toxins
Give some endogenous toxins that can cause acute tubular necrosis
Myoglobin Haemoglobin Immunoglobin Calcium Urate
Give some exogenous toxins that can cause acute tubular necrosis
Drugs: ACEi, NSAIDs, gentamicin
Contrast
Poisons: metals, antifreeze
How does ACEi exacerbate AKI?
Inhibits production of ACE
Don’t get efferent arteriole constriction
How do NSAIDs exacerbate AKI?
Inhibits production of prostaglandins
Don’t get afferent arteriole dilation
What two drugs should always be stopped in a patient with AKI?
ACEi
NSAIDs
Describe the investigations required in a patient with suspected AKI
Bloods: urea, creatinine, potassium
Urine output
Clinical assessment: BP, JVP, oedema, heart sounds
Describe the initial treatment of a patient with AKI
Treat hyperkalaemia
Treat pulmonary oedema
Remove cause - NSAIDs, ACEi, sepsis
Exclude obstruction (renal US), and consider renal causes
What are some components of a GN screen?
ANCA
ANA
Immunoglobulins
Bence-Jones proteins
How should hyperkalaemia be managed?
Reduce reabsorption of K from gut - calcium resonium
Calcium gluconate - stabilises cardiac membrane
Insulin+dextrose - moves K into cells
What are the absolute indications of RRT in a patient with AKI?
Refractory K >/= 6.5mmol/L
Refractory pulmonary oedema
What are the relative indications of RRT in a patient with AKI?
Acidosis pH<7.1
Uraemia esp if urea >40
Pericarditis, endocarditis
Toxins (lithium)
Define CKD
Kidney damage or GFR >60ml/min/1.73m^3 for >3 months
Describe stable CKD
eGFR is not changing
Describe unstable CKD
eGFR is changing
What can cause a protein result of +1 on dipstick?
Fever, exercise, normal
How can proteinuria be quantified?
Comparing [protein] to [creatinine]
What is a normal ACR result?
<2.5
What is a normal PCR result?
<20
How does ACR relate to PCR?
ACR is around 2/3 of PCR result
Give some symptoms of CKD
Pruritis Nausea, anorexia, weight loss Fatigue Leg swelling Breathlessness Nocturia Joint/bone pain Confusion
Give some signs of CKD
Peripheral and pulmonary oedema Pericardial rub Rash/excoriation HTN Tachypnoea Cachexia Pallor/lemon yellow tinge
How can the progression of CKD be slowed down?
Aggressive BP control with ACEi and ARB Good glycemic control Diet Smoking cessation Lowering cholesterol - statins Treating acidosis
When is anaemia common in CKD?
When eGFR <30ml/min/1.73m^3
What should be replaced first if a patient with CKD has anaemia?
Folate, B12, iron
What is the target Hb in a patient with CKD?
100-120g/l
What phosphate binders can be used in secondary hyperparathyroidism?
Calcium: calcium carbonate/acetate
Non-calcium: aluminium
What is the target phosphate concentration in a patient with secondary hyperparathyroidism?
0.9-1.5mmol/L
If a patient has hyperparathyroidism secondary to CKD, what vitamin D replacement should they be given?
Alfacalcidol
