Nephro Flashcards
(120 cards)
1
Q
What is a urinary tract infection?
A
A ‘lower’ urtinary tract infection is generally considered to be infection of the bladder (cystitis)
Normally caused by transurethral ascend of colonic commensals, most commonly E. coli.
2
Q
What are the clinical features of Cystitis (UTI)?
A
Urinary frequency
Dysuria
Urgency
Foul-smelling urine
Suprapubic pain
Clinical examination may be normal or may reveal suprapubic tenderness.
3
Q
What are key differentials for UTI?
A
The key differential is pylenopheritis (urinary tract infection affecting the kidneys).
The patient may be vomiting, febrile, and complain of loin pain.
Clinical examination will reveal pyrexia and renal angle tenderness.
4
Q
What are the investigations of UTI?
A
Urine dipstick is positive for leucocytes and nitrites in most cases.
In uncomplicated cystitis no further investigations are required.
In children, men, and pregnant women a mid-stream urine sample should be sent.
5
Q
What is the first line management of UTI?
A
Non-pregnant women aged 16 years and over:
First choice is Nitrofurantoin if eGFR more than or equal to 45ml/minute - 100mg modified release twice a day for 3 days
Trimethoprim - if low risk of resistance - 200mg twice a day for 3 days
Second choice if no improvement in lower UTI symptoms on first choice taken for at least 48 hours, or when first choice not suitable - Nitrofurantoin (if not first choice)
Pivmecillinam - 400mg initial dose, then 200mg three times a day for 3 days
Fosfomycin 3g single dose sachet
Children and young people under 16 years
First choice:
Trimethorpim
Nitrofurantoin
Second choice:
Nitrofurantoin if not first choice
Amoxicillin - 125mg up to 11 mont, 1 to 4 years 250mg, 5 to 15 500mg
Cefalexin
The patient should be advised on conservative measures to reduce the risk of further infection e.g. regular fluid intake, post-coital voiding.
6
Q
What is the definition of Pyelonephritis?
A
Pyelonephritis is urinary tract infection affecting the kidneys/renal pelvis.
Caused by trans-urethral ascent of colonic commensals, most commonly E. coli.
7
Q
What are the clinical features of pyelonephritis?
A
Fever/rigors
Malaise
Loin/flank pain
Vomiting.
Clinical examination reveals fever and loin/flank tenderness.
8
Q
What are the key differentials for pyelonephritis?
A
The key differential is cystitis.
In cystitis the patient will rarely be pyrexial or have loin/flank tenderness.
Abnormal vital signs are more indicative of pyelonephritis.
9
Q
What are the investigations for UTI?
A
Bedside tests include a urine dipstick which will typically be positive for leucocytes and nitrites.
After admitting the patient, bloods should be taken to include FBC (raised WCC), U&E (to check for renal impairment), and blood cultures.
Other investigations include a urine MSU for MC&S.
A renal ultrasound can be performed to look for hydronephrosis if severe infection occurs with acute kidney injury.
10
Q
What is the management of pyelonrphritis?
A
The patient should be admitted to hospital for intravenous antibiotics (broad-spectrum cephalosporin/a quinolone/gentamicin)
11
Q
What can present with the long term use of nitrofurantoin?
A
Pulmonary fibrosis - fev1 and FVC less than 80% Fev1/FVC ratio high ( as seen in restrictive lung disease) - Long-term use of nitrofurantoin may precipitate restrictive lung disease.
12
Q
What is Acute intersitial nephritis?
A
Acute interstitial nephritis is thought to be mediated by an interstitial hypersensitivity reaction.
13
Q
What are the features of Acute interstitial nephritis?
A
Patients with acute interstitial nephritis typically present with delayed (2-40 days) picture of rash, fever, acute kidney injury and eosinophilia after a triggering medication. A subset of patients also report transient arthralgia.
14
Q
What are the drug causes?
A
Most medication that cause acute interstitial nephritis are as a result of hypersensitivity reactions to drugs and are not mediated by direct toxicity. The most frequently implicated drugs are:
Antibiotics (e.g. penicillins, sulfa drugs, cephalosporins and quinolones)
NSAIDs
Diuretics
Rifampicin
Allopurinol
Proton Pump inhibitors
5P’s - pee (diuretics), pain (NSAIDs), penicillins (and cephalosporins), PPIs and rifamPin
15
Q
What is Acute Kidney Injury?
A
Acute kidney injury (AKI) is defined as a rapid (within 7 days) and sustained (lasting >24 hours) reduction in renal function resulting in oliguria (reduced urine output) and a rise in serum urea and creatinine.
Unlike chronic kidney disease, AKI is usually reversible.
16
Q
What is the classification of Acute Kidney Injury?
A
The KDIGO is a common classification system used to risk stratify AKI:
Stage 1: creatinine rise of 1.5x compared to baseline or urine output <0.5 ml/kg/hour for 6 hours.
Stage 2: creatinine rise of 2x compared to baseline or urine output <0.5 ml/kg/hour for 12 hours.
Stage 3: creatinine rise of 3x compared to baseline or urine output <0.3 ml/kg/hour for 24 hours (or anuria for 12 hours) or serum creatinine >354umol/dl
17
Q
What are the risk factors for AKI?
A
An increased risk of AKI is associated with:
Chronic kidney disease
Diabetes with chronic kidney disease
Heart failure
Renal transplant
Age 75 or over
Hypovolaemia
Contrast administration
18
Q
What are the causes of AKI?
A
Pre-renal Causes
Shock (hypovolaemic, cardiogenic, or distributive)
Renovascular disease (such as renal artery stenosis).
Pre-renal causes account for approximately 55% of cases.
Renal Causes
Dysfunction in the glomeruli (as in acute glomerulonephritis)
Tubules (as in acute tubular necrosis)
Interstitial (as in acute interstitial nephritis)
Renal vessels (as in haemolytic uraemia syndrome or vasculitides).
Renal causes account for approximately 35% of cases of AKI.
———
Post-Renal Causes
Caused by obstruction to urinary outflow
Luminal (e.g. a kidney stone)
Mural (e.g. a tumour of the urinary tract)
Due to external compression (e.g. being prostatic hypertrophy).
Post-renal causes account for approximately 20% of cases of AKI.
19
Q
What are the investigations of AKI?
A
Bloods: FBC, U&E, LFT, glucose, clotting, calcium, ESR
ABG: hypoxia (oedema), acidosis, potassium
Urine: dip, MCS, chemistry (U&E,
CRP, osmolality, BJP)
ECG: hyperkalaemia
CXR: pulmonary oedema
Renal US: Renal size, hydronephrosis
Glomerulonephritis screen may be required if the cause is unclear
20
Q
What is the management of AKI?
A
As with all acute presentations, the general approach to acute kidney injury should initially follow the DR ABCDE algorithm.
A: is the airway compromised?
B: Acute kidney injury can be associated with critical illness. It may also result in pulmonary oedema. This should be managed in section ‘B’ by sitting the patient up, giving high flow oxygen, and IV furosemide with diamorphine.
C: it is helpful to assess the fluid status in (C). If the patient is hypovolaemic they will require intravenous fluid resuscitation.
Any life-threatening complications should then be identified and treated e.g. hyperkalaemia, sepsis, pulmonary oedema.
The cause should then be identified and treated appropriately:
Pre-renal AKI: give fluids if the patient is hypovolaemic, give intravenous antibiotics if the patient is septic. Stop nephrotoxic drugs.
Renal AKI: A nephrology review is often required to identify less common causes of Acute Kidney Injury
Post-renal AKI: catheterisation and urology review.
The patient should be also monitored carefully with regular observations, fluid status, and measurement of urine output (usually with a catheter) and U&Es.
21
Q
What medications need to be reviewed in AKI?
A
In a patient with an acute kidney injury remember to review the drug chart.
Suspend nephrotoxic drugs: NSAIDs, aminoglycosides e.g. gentamicin, ACE inhibitors/ARBs, and diuretics.
Suspend renally excreted drugs: metformin, lithium, digoxin.
Adjust renally excreted drugs e.g. opioids.
22
Q
What are the indications for dialysis?
A
Indications for acute dialysis can be remembered by the mnemonic AEIOU:
Acidosis (severe metabolic acidosis with pH of less than 7.20)
Electrolyte imbalance (persistent hyperkalaemia of more than 7 mmol
Intoxication (poisoning)
Oedema (refractory pulmonary oedema)
Uraemia (encephalopathy or pericarditis).
23
Q
What is the most common complication of Haemodyalsis?
A
Dialysis-induced hypotension is the most common complication of haemodialysis. The mechanism of action is the rapid reduction of blood volume during ultrafiltration and the decrease in extracellular osmolality during dialysis. Patients require accurate fluid assessment and may require cautious replacement of intravascular volume in emergency settings
24
Q
What is the mechanism of haemodialysis and haemofiltration?
A
Haemodialysis works by creating a counter-current flow.
Blood and dialysate flow on opposite sides of the semi-permeable membrane, and solute transfer occurs by diffusion.
Haemofiltration enables fluid removal by decreasing hydrostatic pressure of the dialysate. Solute movement occurs via convection rather than diffusion. Haemofiltration is typically used in patients who cannot tolerate rapid changes in haemodynamic parameters, and is often given in the ITU setting.
Peritoneal dialysis works by administering the dialyse into the peritoneal cavity. Waste solutes diffuse into the dialysate across the peritoneum (which acts as a semi-permeable membrane). Ultrafiltration (to draw water from the peritoneal cavity) occurs by the addition of osmotic agents to the dialysate (typically 1.5% glucose solution).
25
What are the complications of haemodialysis?
Cardiovascular disease
Fistula complications: stenosis, aneurysm, infection, steal syndrome, heart failure
Hypotension
Amyloidosis (secondary to build up of B2 microglobulin)
Dialysis disequilibrium syndrome (acute cerebral oedema due to rapid extraction of osmotically active substances)
26
What are the complications of peritoneal dialysis?
Complications of peritoneal dialysis include peritoneal dialysis peritonitis.
This is typically caused by Staphylococcus epidermidis.
The patient presents with abdominal pain, fever, and a cloudy dialysis bag.
The peritoneal dialysis fluid should be sent for culture.
Management is with intraperitoneal and systemic antibiotics.
Other complications of peritoneal dialysis include catheter malfunction, obesity (due to absorption of glucose from the dialysate fluid), and hernias.
27
What is Alport syndrome?
Alport's syndrome is an X-linked dominant condition. It is due to the defect in the gene coding for type 4 collagen, which is present in the kidneys, cochlear, and retina. (bilateral hearing loss, retinal flecks and transient haematuria)
Progressive renal insufficiency leads to renal failure in men around the age of 30-40. Transplant is the definitive treatment
28
What is chronic kidney disease?
Chronic Kidney Disease (CKD) is defined as a gradual, irreversible decline in kidney function. The KDIGO 2012 guidelines outline the criteria for the presence of CKD.
This requires either a decreased GFR (below 60 ml/min/1.73m2) or markers of kidney damage (albuminuria, electrolyte abnormalities, structural or histological renal abnormalities) present for >3 months.
29
What is the staging of CKD?
Stage 1 CKD if eGFR is >90 ml/min/1.73m2 with demonstrable kidney damage (e.g. haematuria or proteinuria).
Stage 2 CKD if eGFR is 60-89 ml/min/1.73m2with demonstrable kidney damage (e.g. haematuria, proteinuria, or raised urine albumin/creatinine ratio).
Stage 3 CKD if eGFR is 30-59 ml/min/1.73m2.
Stage 4 CKD if eGFR is 15-30 ml/min/1.73m2.
Stage 5 CKD if eGFR is <15 ml/min/1.73m2.
NB: The patient is typically asymptomatic until stage 4 or stage 5 CKD.
30
What are the causes of CKD?
Glomerular causes can be primary (such as IgA nephropathy) or secondary (such as SLE).
Vascular causes include vasculitis and renal artery stenosis.
Tubulointerstitial causes include amyloidosis and myeloma.
Congenital causes include polycystic kidney disease and Alport syndrome
Systemic causes such as diabetes and hypertension.
Developmental causes such as vesico-urteric reflux causing chronic pyelonephritis.
The most common causes of chronic kidney disease include:
Diabetes
Hypertension
Chronic glomerulonephritis
Polycystic kidney disease
31
What are the complications of CKD?
The complications of chronic kidney disease (CKD) can be understood by considering the key functions of the kidney.
Waste excretion - Uraemia and hyperphosphataemia
Regulation of fluid balance - Hypertension and peripheral/pulmonary oedema.
Acid-base balance - Metabolic acidosis.
Erythropoietin production - Anaemia.
Activation of vitamin D - Hypocalcaemia.
CRF HEALS is a useful mnemonic to remember the complications of CKD:
CRF HEALS
Cardiovascular disease
Renal osteodystrophy
Fluid (oedema)
Hypertension
Electrolyte disturbance (hyperkalaemia, acidosis)
Anaemia
Leg restlessness
Sensory neuropathy
NB: Cardiovascular disease is the most common cause of death in chronic kidney disease.
32
What are the features of renal osteodystrophy?
Reduced bone density (Osteoporosis)
Reduced bone mineralisation (Osteomalcia)
Secondary/Tertiary Hyperparathyroidism
May get spinal osteosclerosis: Rugger Jersey spine
33
What is microalbuminuria in CKD?
Microalbuminuria can be caused by diabetic nephropathy.
Progression can lead to overt nephropathy and chronic kidney disease.
All patients with diabetes over the age of 12 should undergo regular urinary albumin:creatinine ratio to screen for microalbuminuria. If microalbuminuria is detected (>2.5 mg/mmol in men, >3.5 mg/mmol in women), patients should be started on an ACE inhibitor.
34
What is the management of Sequelae of chronic kidney disease?
For the management of oedema conservative measures include fluid and salt restriction. Medical management includes the use of diuretics e.g. furosemide.
For the management of anaemia patients should be administered monthly subcutaneous erythropoietin (with target haemoglobin of 10-12 g/dL).
For the management of hypocalcaemia and hyperphosphataemia patients should be advised to restrict dietary potassium (found in dairy products and eggs) and can be prescribed sevelamer (a phosphate binder) and alfacalcidol (a 1-hydroxylated vitamin D analogue. Parathyroidectomy is an option in patients with tertiary hyperparathyroidism (PTH >28 mmol/L).
35
What is Acute urinary retention?
Acute urinary retention can cause significant suprapubic pain and inability to pass urine.
In older patients it can cause confusion. The acute kidney injury has most likely resulted from an obstructed renal system and the development of hydronephrosis. This can result in a very significant rise in creatinine.
Benign prostatic hyperplasia is the most likely cause of his urinary retention
36
What is ADPKD
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease in adults.
85% of ADPKD cases are caused by mutations in the PKD1 gene (polycystin-1) on chromosome 16.
15% of ADPKD cases are caused by mutations in the PKD2 gene (polycystin-2) on chromosome 4.
Mutations in PKD1 are associated with more severe disease.
37
What are the clinical features ADPKD?
Renal:
Flank pain and haematuria is the classic presentation of cyst rupture
Patients may present with flank pain, fever and urinary symptoms if they have a cyst infection
Hypertension
Renal failure (slowly progressive CKD)
Extra-renal:
Extrarenal cysts e.g. liver, pancreas, spleen
Intracranial berry aneurysms commonly at the junction of the anterior communicating artery and anterior cerebral artery
Mitral valve prolapse, aortic regurgitation
Diverticular disease
38
What are the complications of ADPKD?
Cyst rupture
Cyst infection
CKD
Subarachnoid haemorrhage due to aneurysm
Intracerebral haemorrhage due to hypertension
39
What are the investigations for ADPKD?
The imaging investigation of choice is an ultrasound scan
15-39 years: >3 renal cysts, 40 - 59 years: >2 renal cysts bilaterally, >60 year: >4 renal cysts bilaterally
CT and MRI can be used to determine the extent of cystic disease
Genetic testing might be considered in atypical cases
40
What is the management of ADPKD?
Supportive management of CKD
Treatment of hypertension
Some patients will be eligible for treatment with Tolvaptan which has been shown to slow formation of cysts and decline in kidney function
41
What is Post-streptococcal glomerulonephritis?
Poststreptococcal GN is a type of glomerular nephritis that occurs 1-2 weeks after a streptococcal throat infection or 2-6 weeks after a streptococcal skin infection.
It is only caused by certain strains of group A beta-haemolytic streptococci.
Pathogenesis is not fully understood but main theory suggests that there is immune complex deposition, neutrophil infiltration and complement activation in the glomerulus causing inflammation and/or proliferation.
42
What are the clinical features of Post-streptococcal glomerulonephritis?
Patients typically present with sudden onset of haematuria, oliguria, hypertension and oedema (normally periorbital, due to salt retention in the loose skin).
This is a typical nephritic syndrome presentation.
43
What are the other differentials for P-S GN?
It is important to consider all conditions that can cause a nephritic picture. These can be remembered as:
SHARP AIM
SLE
Henoch-Schönlein purpura
Anti glomerular basement membrane (GBM) disease (AKA Goodpasture's disease)
Rapidly Progressive glomerulonephritis (GN)
Post-streptococcal GN
Alport's syndrome
IgA nephropathy
Membranoproliferative GN
44
What are the investigations for P-S GN?
First line investigation in these patients would involve a urinalysis and microscopy, culture and sensitivities (MC&S).
Urinalysis is typically positive for protein or blood or both. Urine MC&S would likely show presence of red blood cells (normally dysmorphic, which suggests bleeding from the glomerulus), white blood cells (neutrophil infiltration is one of the mechanisms of damage in nephritic syndrome) and associated casts.
Blood tests should include Full blood count (FBC) to look for raised white cells, suggestive of an infective process, Urea and Electrolytes (U&Es) which can suggest acute kidney injury.
Immunoglobulins, complement (low C3 levels commonly found) and autoantibodies (such as raised anti-streptolysin O titre , raised DNAse B titre) can help delineate an autoimmune process.
Blood cultures are also indicated in patients with fever. Imaging is rarely helpful. The gold standard method for diagnosis is renal biopsy.
45
What is the managment of PS-GN?
Management
Supportive measures
Complications
Chronic kidney disease
End stage renal disease
46
What is an important complication of AKI?
Hyperkalaemia is an important complication of acute kidney injury (due to failure to renally excrete potassium). 10 ml 10% calcium gluconate should be administered intravenously if there is evidence of ECG changes or K >6.5.
This stabilises the myocardium to reduce the risk of life-threatening arrhythmias (but does not lower potassium levels)
47
How does distribuitive shock lead to raised creatinine?
Sepsis causes release of cytokines and a massive inflammatory response.
This results in vasodilation and increased capillary permeability (distributive shock). In response to a fall in renal perfusion pressure the kidneys are normally able to maintain the glomerular filtration rate (GFR) via activation of the renin-angiotensin aldosterone system.
This is called autoregulation. In severe renal hypoperfusion the kidneys are unable to maintain the GFR through autoregulation, and pre-renal AKI follows
48
What is Nephrotic syndrome?
Nephrotic syndrome is a clinical syndrome that arises secondary to increased permeability of serum protein through a damaged basement membrane in the renal glomerulus.
49
What are the clinical features of nephrotic syndrome?
It is typically characterised by a proteinuria (>3-3.5g/day), oedema, hypoalbuminaemia and hyperlipidaemia and lipiduria.
50
What is the pathophsyiology of nephrotic syndrome?
Cytokines damage podocytes causing them to fuse together and destroy charge of the glomerular basement membrane.
This allows increased permeability to plasma proteins. This causes massive protein loss in the urine.
As a result of this, serum albumin levels are reduced beyond the synthetic ability of the liver.
Thus patients experience marked oedema as with less albumin in the blood stream, there is less oncotic pressure.
This lets fluid leak out into the interstitium.
As an attempt to maintain oncotic pressure, the liver tries to compensate by increased synthesis of lipoproteins, this is one of the mechanisms postulated to cause the hyperlipidaemia.
However, the full mechanism is not fully understood.
51
What are the causes of nephrotic syndrome?
The most common cause in adults is membraneous glomerulonephritis. The most common cause in children is minimal change disease.
Systemic Disease
Diabetes Mellitus (Glomerulosclerosis)
Systemic Lupus Erythematosus (Membranous)
Amyloidosis
Minimal Change Glomerulonephritis
Associated with upper respiratory tract infection
Biospy: normal light microscopy, fusion of podocytes on electron microscope
Treat with steroids
1% go on to have end-stage renal failure
Membranous nephropathy
Associated with cancers (Lung, Colon Breast), infections (SLE, thyroid disease), infections (Hepatitis B) and drugs (Penicillamine and Gold)
Biopsy: subepithelial immune complex deposits
40% have spontaneous remission
Focal segmental glomerulosclerosis
More common in Afro-caribbean population
Associated with Berger's disease, sickle cell, HIV
Biopsy: focal scarring, IgM deposition
Treat with steroids or cylophosphamide/ciclosporin
30-50% progress to end stage renal failure
Membranoproliferative/Mesangiocapillary
Less common
May present as both nephrotic or nephritic
Associated with Hepatitis B, Hepatitis C and Endocarditis
50% progress to End-Stage Renal Failure
52
What is the difference between nephritic and nephrotic syndrome?
The key with nephrotic syndrome is an excess amount of protein in the urine, whereas nephritic syndrome is where there is an excess amount of blood in the urine.
53
What is the clinical presentation of nephrotic syndrome?
Periorbital and peripheral oedema
54
What are the investigations of nephrotic syndrome?
Bedside investigation include urine dipstick which reveals proteinuria. Urine analysis reveals a raised albumin creatinine ratio.
Renal biopsy is indicated in all adults but should only be done in children with an atypical presentation (e.g. steroid unresponsive, haematuria, under 1 years old or over 12 years old).
55
What is the management and complications of nephrotic syndrome?
High dose steroids which should be tapered according to clinical response.
Complications:
Infection (due to urinary loss of immunoglobulins)
Venous thromboembolism (due to urinary loss of antithrombin III)
Hyperlipidaemia (due to increased hepatic production of lipids to restore the serum oncotic pressure)
56
What is Rhabdomyolysis?
Rhabdomyolysis is caused by skeletal muscle breakdown.
This causes the release of intracellular contents such as myoglobin and potassium into the blood stream.
Excess myoglobin can precipitate in the glomerulus causing renal obstruction, direct nephrotoxicity and acute kidney injury.
57
What are the causes of Rhabdomyolysis?
Trauma: prolonged immobilisation (e.g. long lie in elderly patients), crush injuries, burns, seizures, compartment syndrome.
Ischaemia: embolism, surgery
Toxins: Statins, fibrates, ecstasy, neuroleptics
NB: It can also present following very strenuous exercise (e.g. spin class).
58
What are the features of Rhabdomyolsis?
Muscle pain, swelling
Red/brown urine
Acute kidney injury 10-12 hours after initial pain/injury
59
What are the investigations of Rhabdomyolysis?
Creatine kinase - the most reliable indicator of muscle damage. A 5 fold rise from the upper limit of the reference range suggests rhabdomyolysis although the levels are often much higher.
Raised LDH (suggestive of muscle damage)
Hyperkalaemia (liberated from the damaged muscle)
Hyperphosphatemia (liberated from the damaged muscle)
Hyperuricaemia (liberated from damaged muscle)
Hypocalcaemia (calcium is taken into the damaged muscle by several mechanisms).
Urine tests will often be falsely positive for blood on dipstick with no red blood cells seen on microscopy. This is due to the myoglobinuria, which is the reason why the urine is typically described as tea- or cola-coloured urine
60
What is the management of rhabdomyolsis?
Patients are often treated with supportive therapy. This includes IV fluids and management of hyperkalaemia.
61
What sort of AKI are bowel surgery patients suspectible to?
Patients undergoing bowel surgery are particularly susceptible to pre-renal AKI, due to dehydration and hypovolaemia for a number of reasons, including being kept nil-by-mouth before surgery, bowel preparation for surgery removing water in the bowel and exposure of intra-abdominal contents during surgery. Other clues that indicate a patient's AKI is likely due to dehydration include hypernatremia (likely hypovolemic) and a prolonged capillary refill time.
The mainstay of management for a pre-renal AKI is fluid administration
62
What is glomerulonephritis?
Damage to the glomerulus, including the glomerular basement membrane and glomerular capillaries, usually caused by inflammatory change.
63
What are the types of glomerulonephritis?
Membranous glomerulonephritis
Minimal change disease
Focal segmental glomerulonephritis
IgA nephropathy
Rapidly progressing glomerulonephritis
Lupus nephritis
Post-infectious glomerulnephritis
Anti-glomerular basement membrane antibody (Anti-GBM) disease
64
What are the causes of glomerulonephritis?
Infection e.g. group A streptococcus, hepatitis B and C, respiratory and gastrointestinal tract infections, endocarditis, HIV
Systemic inflammatory conditions e.g. lupus, rheumatoid arthritis, anti-glomerular basement membrane disease, microscopic polyangiitis, granulomatosis polyangiitis
Drugs, in particular non-steroidal anti-inflammatory drugs, gold, anabolic steroids
Metabolic disorders e.g. diabetes, hypertension and thyroid disease
Malignancy
Hereditary disorders e.g. Alport's syndrome
Deposition diseases e.g. amyloidosis
65
What are the symptoms of glomerulonephritis?
May be asymptomatic
Haematuria (macroscopic or microscopic)
Proteinuria
Oedema
Hypertension
Joint pain
Rash
Fever
Weight loss
66
What are the investigations of glomerulnephritis?
Urinalysis - may show haematuria, proteinuria
Urine microscopy
Urea and electrolytes - may show reduced glomerular filtration rate (GFR) or elevated creatinine
Full blood count - may have evidence of anaemia or inflammatory response
Metabolic profile - may reveal underlying diabetes
Lipid profile - may show hyperlipidaemia
C-reactive protein
Testing for specific systemic causes e.g. erythrocyte sedimentation rate (ESR), rheumatoid factor, complement, anti-nuclear antibody, anti-double-stranded DNA, antineutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane (GBM) antibodies
Renal tract ultrasound - to assess kidney size and any evidence of obstruction
Renal biopsy - definitive test for diagnosis of glomerulonephritis
67
What is the management of glomerulonephritis?
Management of glomerulonephritis depends on cause and may include
Antibiotics if infection
Angiotensin converting enzyme inhibitors (ACEi) to decrease proteinuria
Corticosteroids
Furosemide if hypertension and fluid overload
Immunosuppressant drugs
Plasmapheresis
68
What is Haemolytic uraemic syndrome?
Triad of features:
Microangiopathic haemolytic anaemia
Thrombocytopenia
Acute Kidney Injury
69
What are the causes of Haemolytic uraemic syndrome?
The enterohaemorrhagic E. coli O157 verotoxin acquired from undercooked meat or petting farms.
The verotoxin causes endothelial cell damage and thrombus formation within the renal arteries.
70
What are the symptoms of Haemolytic Uraemic syndrome?
Bloody diarrhoea
Vomiting
Abdominal pain
Low-grade pyrexia
Oliguria/anuria
Haematuria.
It is important to enquire about risk factors e.g. recent farm visits.
71
What are the signs of Haemolytic Uraemic syndrome?
The patient may appear pale (secondary to anaemia) or jaundiced (secondary to haemolysis).
There may be bruising (secondary to thrombocytopenia).
There may be abdominal tenderness.
72
What are the investigations of Haemolytic Uraemic syndrome?
Bedside: urine dipstick may show haematuria/proteinuria (non-nephrotic range).
Bloods: FBC shows a normocytic anaemia (secondary to haemolysis), thrombocytopenia, and possibly a raised neutrophil count. U&E shows a raised urea and creatinine. Clotting is typically normal. The blood film will reveal reticulocytes (secondary to haemolysis) and schistocytes (fragmented red cells).
Other investigations: stool culture for E. coli.
73
What is the management of Haemolytic Uraemic Syndrome?
Typically managed conservatively with supportive measures e.g. fluids for hypovolaemia.
If there is severe renal impairment haemodialysis may be necessary.
It is important to not administer antibiotics (this can induce expression and increase release of the verotoxin).
74
What is the first line management of Anaemia in CKD?
Features of anaemia include fatigue, shortness of breath on exertion and tachycardia
The kidneys produce erythropoietin, which stimulates the production of red blood cells.
In CKD, reduced levels of erythropoietin result in a normocytic, normochromic anaemia. The first-line management of anaemia in CKD is to replace erythropoietin with regular subcutaneous injections. However, EPO should not be given if there is iron deficiency anaemia as it can exacerbate this
75
What is the mechanism behind Acute Tubular Necrosis?
Muddy brown casts in the urine represent collections of dead renal tubule epithelial cells and are pathognomonic for acute tubular necrosis (ATN). This is an intra-renal cause of acute kidney injury. Common causes of ATN include hypotension and the use of nephrotoxic drugs.
A patient could develop chest sepsis, resulting in increased vascular permeability, hypotension, and subsequent ATN.
In ATN, renal tubules responsible for sodium reabsorption are impaired, thereby leading to a high fractional excretion of sodium in the urine (>1%)
76
What is Nephritic syndrome?
It is important to distinguish between nephritic and nephrotic syndrome in examination questions. Nephritic syndrome is more likely to present with haematuria and non-nephrotic range proteinuria (+/++ on the urine dipstick). Hypertension is also more common.
77
What is the presentation of Nephritic syndrome?
The syndromes do, however, typically present as a spectrum:
Pure nephrotic syndrome: minimal change disease.
Nephrotic syndrome with some haematuria: membranous glomerulonephritis, focal segmental glomerulosclerosis.
Nephritic syndrome with nephrotic-range proteinuria: membrano-proliferative (also known as mesangio-capillary) glomerulonephritis.
Pure nephritic syndrome: post-streptococcal glomerulonephritis, IgA nephropathy/Henoch-Schonlein purpura, infective endocarditis, Goodpasture's disease, vasculitis.
Questions concerning nephritic syndrome often require you to distinguish between post-streptococcal glomerulonephritis and IgA nephropathy. The key distinguishing factor is that post-streptococcal glomerulonephritis typically presents 3-4 weeks after a sore throat/skin infection whereas IgA nephropathy typically presents 3-4 days after a mild URTI.
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What are the possible differentials in a nephritic picture?
It is important to consider all conditions that can cause a nephritic picture. These can be remembered as:
SHARP AIM
SLE
Henoch-Schönlein purpura
Anti glomerular basement membrane (GBM) disease (AKA Goodpasture's disease)
Rapidly Progressive glomerulonephritis (GN)
Post-streptococcal GN
Alport's syndrome
IgA nephropathy (AKA Berger's disease)
Membranoproliferative GN
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When should an ACE-I be started in diabetic patients at risk of CKD?
All patients with diabetes over the age of 12 should undergo regular urinary albumin:creatinine ratio to screen for microalbuminuria. If microalbuminuria is detected (>2.5 mg/mmol in men, >3.5 mg/mmol in women), patients should be started on an ACE inhibitor
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What is Acute Tubular Necrosis?
Acute Tubular Necrosis is the most common cause of intrinsic acute kidney injury (AKI). It involves damage to the tubular epithelial cells within the renal tubules of the kidney due to either ischaemia or direct toxicity
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What is the clinical presentation of Acute Tubular Necrosis?
Acute kidney injury:
Oliguria
Uraemia
Electrolyte imbalance
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What are the causes of Acute Tubular Necrosis?
ISCHAEMIC CAUSES:
Hypotension
Shock:
- Haemorrhagic
- Cardiogenic
- Septic
Direct vascular injury:
- Trauma
- Surgery
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NEPHROTOXIC CAUSES:
Drugs:
Aminoglycocide antibiotics e.g.
Gentamicin
Antifungal drugs e.g. Amphoteracin
Chemotherapy agents e.g. Cisplatin
Non-steroidal anti-inflammatory drugs e.g. Ibuprofen
Angiotensin converting enzyme inhibitors (ACEi) e.g. Ramipril
Angiotensin receptor blocker e.g. Candesartan
Statins
Contrast
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What is the management of Acute Tubular Necrosis?
Correction of underlying cause
E.g. fluid resuscitation
Removal of nephrotoxins
May require haemofiltration or haemodialysis
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In CKD patients, what is the most underlying mechanism for low Vitamin D?
Vitamin D is obtained through both the skin (majority) and diet (minority).
When vitamin D is made it requires to go through two activations to produce the active product (1,25 vitamin D, Calcitriol).
The first is in the liver to produce 25-hydroxyvitamin D and then further hydroxylation in the kidney.
This latter reaction is catalysed by alpha-1 hydroxylase .
In advanced CKD endocrine functions of the kidney are lost which results in failed conversion of vitamin D. Therefore patients should receive activated vitamin D and phosphate binders in order to minimise the development of secondary hyperparathyroidism
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What should be assumed if painless haematuria occurs?
Painless haematuria should be considered bladder cancer until proven otherwise
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What is the investigation for bladder cancer?
Painless intermittent haematuria in a male smoker is suggestive of transitional cell carcinoma of the bladder. Clot retention, tumour growth, or tumour prolapse can cause acute retention. Cystoscopy is the investigation of choice in the diagnosis of bladder cancer
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What is IgA nephropathy?
A type of glomerulonephritis (GN) characterised by IgA deposition in the mesangium.
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What is IgA nephropathy?
A type of glomerulonephritis (GN) characterised by IgA deposition in the mesangium.
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What are the causes of IgA nephropathy?
IgA is the most common immunoglobulin in mucosal secretions.
In certain genetically predisposed people, there is an increased synthesis of a particular type of IgA secondary to a respiratory or gastrointestinal infection.
These types of IgA form immune complexes that are more easily lodged in the mesangium of the glomerulus causing proliferation.
This combined with activation of the alternative complement pathway causes glomerular injury.
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What are the clinical features of IgA nephropathy?
Typically patients present with recurrent gross or microscopic haematuria following (12-72h) an upper respiratory tract infection.
Mild proteinuria may also be present. On examination, hypertension may be present. Rare cases may present with rapidly progressive GN where they rapidly progress to acute renal failure.
Slow progression to chronic renal failure occurs in 15 - 40% of patients.
For differentials think SHARP AIM
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What are the investigations for IgA nephropathy?
First line investigation in these patients would involve a urinalysis and microscopy, culture and sensitivities (MC&S).
Urinalysis is typically positive for blood +/- protein. Only 5% of patients will present with nephrotic range proteinuria (>3-3.5g/24hr).
Urine MC&S would likely show presence of red blood cells (normally dysmorphic, which suggests bleeding from the glomerulus), white blood cells (neutrophil infiltration is one of the mechanisms of damage in nephritic syndrome) and associated casts.
Patients can be diagnosed histologically, with immunofluorescence typically showing IgA deposited in a granular pattern in the mesangium.
The gold standard method for diagnosis is renal biopsy.
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How can you distinguish between IgA nephropathy vs PSGN
IgA nephropathy occurs 1-2 days post-infection (vs. 1-3 weeks post-infection in PSGN)
Renal biopsy in IgA nephropathy shows IgA immune complex deposits (vs. IgG immune complex deposits in PSGN)
Blood tests should include Full blood count (FBC) (To look for raised white cells, suggestive of an infective process), Urea and Electrolytes (U&Es) to look for raised urea and creatinine suggesting acute kidney injury (This only occurs in less than 5% of patients). Blood cultures are also indicated in patients with fever.
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What is the management of IgA nephropathy?
Conservative: Monitoring and optimising fluid balance
Medical:
Optimise blood pressure
Angiotensin Converting Enzyme (ACE) inhibitor/Angiotensin Receptor Blocker reduce proteinuria and protect renal function
Corticosteroids can also help to decrease proteinuria
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What are absolute indications for renal replacement therapy?
A potassium level of 6.9mmol/L, with minimal response to insulin + dextrose treatment
Absolute indications for dialysis include refractory hyperkalaemia (as mentioned above),
severe intractable metabolic acidosis,
intractable fluid overload and pulmonary oedema,
presence of uraemic complications such as pericarditis, encephalopathy and seizures
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What is the treatment of UTI in the final trimester?
NICE recommends an immediate treatment with antibiotic for 7 days. Since the woman is near term, amoxicillin is considered a safe choice
96
What could cause raised urea with normal creatinine?
A high urea is indicative of a 'protein meal', as urea is a major nitrogenous waste product of protein metabolism within the liver.
Seeing that the patient is highly muscular, and in light of the patient not reporting any melaena (which could point to an upper gastrointestinal bleed, another cause of an elevated urea with normal creatinine), protein supplement use is the most likely cause
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What are Renal stones?
Urinary tract stones are usually formed due to over-saturation of urine. Certain stone types that form may also be caused by a specific underlying pathology. They may start small and not cause any issues. However, these stones can grow larger in size, fill the hollow structures of the kidney or even travel down the ureter. Lodging of the stone in the ureter blocks the flow of urine and my result in pain.
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What is the presentation of renal stones?
Severe, intermittent loin pain, which can radiate to the groin.
The patient often is restless.
Haematuria – either macroscopic (visible) or microscopic (on dipstick only) - although a negative dipstick would not exclude a renal stone.
Nausea and vomiting is common.
Secondary infection of a stone may cause fever or signs of sepsis – this is a surgical emergency requiring urgent decompression.
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What are the types of renal stones?
Calcium - Usually made of calcium oxalate (more common) or calcium phosphate (less common). 80%
Uric Acid - Usually there are no predisposing factors but gout can increase the risk of uric acid stones. 5-10%
Struvate - Often lead to large, staghorn calculi.
Staghorn calculi involve the renal pelvis and extend into at least 2 renal calyces.
Predisposing factors: Recurrent upper urinary tract infections.
Most common organism: Proteus infection —> causes alkalinisation of the urine which leads to staghorn calculi. 5-10%
Cysteine - Predisposing factor: Homocysteinuria- an autosomal recessive inherited metabolic disorder which predisposes to recurrent renal stones and urinary tract infections.
Indinavir - Rare forms e.g. Indinavir (HIV medication) – these are radio-lucent – often not visible on X ray, ultrasound or CT scans.
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What are the investigations for renal stones?
Bloods including renal function
Non-contrast CTKUB (CT Kidneys, ureters and bladder)
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What is the management of Renal stones?
Watchful waiting – this may be the best option in patients who have stones <5mm with no signs of obstruction, or if they are not keen to have any further interventions
Medical expulsive therapy (e.g. tamsulosin) - may be possible for those with calculi <5mm which are in the distal ureter.
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Percutaneous nephrolithotomy
Used for patients with large (>2cm) stones or complex calculi such as staghorn calculi, cysteine stones
Retrograde ureteral catheter inserted using a cystoscope, then an 18-gauge needle is used to access the renal collecting system under fluoroscopic guidance.
Calculi are extracted using forceps. They may be fragmented using ultrasonic or pneumatic probes.
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Ureteroscopy
Treatment of choice for management of distal or middle ureteric stones
Treatment of choice for pregnant women
These can be flexible or rigid.
Sometimes JJ stents can be placed during ureteroscopy to prevent ureteric obstruction
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Shock wave lithotropsy
This involved high energy shock waves which are radiologically focused on the stone with the aid of fluoroscopy. The energy fragments the stone.
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Open stone surgery
There is now a limited role for this given the above options. <1% of patients undergo this procedure, and it is mainly reserved for patients who have failed the above options, patients with complex / staghorn calculi, morbid obesity, or complex renal / ureteral anatomy.
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Prevention of stone formation
In patients with recurrent renal stones, medical therapy can often be used to prevent recurrence
Thiazides for hypercalciuria
Allopurinol or potassium citrate for uric acid stones
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What is Anti-glomerular basement membrane disease?
Anti-glomerular basement membrane disease involves antibodies to the non collagenous domain (NC1) of the alpha-3 chain of collagen type IV.
These antibodies are directed against antigens that are found on the glomerular basement membrane in the kidneys and in the lung alveoli.
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What are the pillars of therapy for anti-glomerular basement membrane disease?
The pillars of therapy in anti-GBM disease involves:
1. Removing any circulating antibody
2. Immunosuppression of the individual with medications so as to stop further production of antibodies
The former is achieved with plasmapheresis which removes the pathogenic circulating antibodies.
Immunosuppression is normally achieved with high dose oral prednisolone or oral cyclophosphamide.
Patients who present with severe acute kidney injury can benefit from dialysis, however this is associated with a very poor prognosis.
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What are the indications for Dialysis?
Indications for dialysis can be remembered by the mnemonic AEIOU:
Acidosis - severe metabolic acidosis with a pH <7.2
Electrolyte imbalances - Persistent hyperkalaemia greater than 7
Intoxication - Poisoning
Oedema - Pulmonary oedema refractory to treatment
Uraemia - This can present with either uraemic pericarditis or uraemic encephalopathy
In patients with end stage renal disease, renal transplantation can also be considered. In these patients, optimal conditions for transplantation are achieved when anti-GBM antibodies are undetectable in the serum for 12 months and the disease has been in remission for at lease 6 months without the use of cytotoxic agents.
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Why does nephrotic syndrome occur in Wilson's disease?
Nephrotic syndrome can be caused by regular Penicillamine use.
Penicillamine is a copper-chelating agent in Wilson's disease, which can result in membranous nephropathy.
In nephrotic syndrome, podocytes which prevent the excretion of protein into the glomerular filtrate are disrupted, resulting in excess protein excretion.
The loss of proteins such as endogenous anti-coagulants like antithrombin III result in hypercoagulability, which can predispose patients to venous thromboembolic events
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What is Renal Tubular acidosis?
In Renal Tubular Acidosis (RTA), impaired acid excretion leads to hyperchloraemic metabolic acidosis.
This leads to activation of the Renin Angiotensin system leading to potassium wasting and hypokalaemia.
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What is Type 1 RTA?
Type 1 RTA is characterised by inability to excrete hydrogen ions.
Type 1 (Distal) Causes:
Hereditary: Marfan's, Ehler's Danlos
Autoimmune: Sjogren's, SLE, thyroiditis
Drugs
Type 1 (Distal) Features:
Rickets/osteomalacia (bone buffering)
Renal stones
Urinary tract infections
Nephrocalcinosis can lead to end stage renal failure
Type 1 (Distal) Diagnosis:
Failure to acidify urine (pH >5.5) despite acid load
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What is Type 2 RTA?
Type 2 RTA occurs due to a defect in HCO3 reabsorption in the proximal collecting tubule. Tubules can reabsorb some HCO3 so can acidify urine in systemic acidosis when HCO3 is low. It is usually associated with Fanconi Syndrome
Type 2 (Proximal) Diagnosis:
Urine will acidify with an acid load (pH <5.5)
Fanconi Syndrome:
Disturbance of Proximal Collecting Tubule (PCT) function leads to generalised impaired reabsorption of amino acids, K+, HCO3, phosphate and glucose. --->
Low pH, bicarbonate, carbon dioxide and potassium
Type 2 (Proximal) Causes:
Idiopathic
Inherited: inborn errors, Wilson's
Acquired: tubule damage (drugs, myeloma)
Type 2 (Proximal) Features:
Polyuria (osmotic diuresis)
Hypophosphataemic rickets (Vit D resistant)
Acidosis
Low potassium
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What is Renal Transplant?
Renal transplant is the treatment of choice in patients with End-Stage Renal Failure
110
What are the initial investigations prior to transplant?
Virology status: CMV, HCV, HBV, HIV, VZV, EBV
Tuberculosis testing
ABO and HLA haplotype
111
What are the contraindications to renal transplant?
Active infections
Cancer
Severe co-morbidity
112
What are the type of grafts in renal transplant?
Cadaveric
No heart beating donor
Live - related
Live - unrelated
Patients who receive renal transplants need to be on life-long immunosuppression. This is of relevance when examining patients during practical exams who may have signs of medication use
113
What complications occur due to renal transplant itself?
Early e.g. infection, urinary leak, haemorrhage, impaired graft function.
Late e.g. lymphocele, ureteric stenosis, renal artery thrombosis.
114
What complications occur due to rejection of transplant?
Hyperacute rejection (within minutes): caused by ABO incompatibility, presents with graft thrombosis/SIRS within minutes of the transplant and intra-operatively. This is managed by immediate graft removal. This can be prevented by pre-treatment ABO cross-matching.
Acute rejection (within 6 months): caused by cell-mediated autoimmunity, presents with fever, pain around the graft site, and impaired renal function. This is managed with additional immunosuppressive therapy.
Chronic rejection (after 6 months): the cause is unclear but it is characterised by interstitial fibrosis and tubular atrophy. This presents with a gradual reduction in renal function and hypertension. This is not responsive to immunosuppressive therapy, and is difficult to manage.
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What are complications due to immunosuppressive therapy after transplant?
Drug toxicity/side-effects:
Steroids: Cushing Syndrome, Avascular necrosis, Addisons
Ciclosporin : Gingival hypertrophy, hypertrichosis, nephrotoxicity
Tacrolimus: cardiomyopathy, peripheral neuropathy, diabetes
Mycophenolate mofetil (GI upset, myelosuppression).
Infection secondary to immunosuppression e.g. cytomegalovirus infection (presenting with a fever and disturbed LFTs a few weeks after the transplant operation. This can be managed with ganciclovir).
Malignancy secondary to immunosuppression: typically of the skin (e.g. squamous cell carcinoma) or lymphoma (secondary to EBV re-activation).
116
Which creatinine levels would warrant stopping ACE-I after 2 weeks?
ACE-inhibitor should be stopped if the creatinine rises to more than 30% of baseline values after 2 weeks
117
How do you differentiate CKD from AKI?
Chronic kidney disease (CKD) can be differentiated from acute kidney injury (AKI) using a renal ultrasound, which would show bilateral shrunken kidneys in end-stage renal disease (ESRD)
Renal function in ESRD can decompensate acutely, leading to features of an acute kidney injury - acute on chronic
118
What is the definitive diagnosis of CKD?
Renal biopsy should confirm chronic kidney disease and its underlying cause
119
What is the criteria for referral to nephrology from GP for CKD?
CKD is associated with cardiovascular disease, which is the main cause of mortality.
The kidneys are responsible for the production of renin, the start of the renin-angiotensin-aldosterone system (RAAS) which is extremely important in monitoring blood pressure.
Resistant hypertension is a complication of CKD and need to be monitored due to the increased cardiovascular risk.
Hypertension after a trial of 4 different anti-hypertensives warrants a referral to nephrology, who can investigate the cause of this patient's hypertension (e.g. with ultrasound scans or biopsies) to determine other possible causes such as abnormalities in kidney structure and function, or renal artery stenosis. Form there, they will be able to determine the best course of treatment, e.g. renal replacement therapy, additional anti-hypertensives.
Other criteria for referring a patient to nephrology from primary care include:
eGFR <30eGFR decreased by >5 in 1 year
Albumin:creatinine ratio (ACR) >70 (unless known to be associated with diabetes)
ACR >30 with persistence haematuria (must exclude UTI first)
Suspected rare or genetic causes of CKD
Suspected renal artery stenosis
Suspected complications of CKD e.g. anaemia, gout, secondary hyperparathyroidism
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What is the difference between primary, secondary and tertiary hyperparathryoidism
Secondary and tertiary likely to occur in CKD
In primary PTH high, Ca high, phosphate low, vit d low or normal
In secondary PTH high Ca low or normal, Phosphate high or normal, vit d very low
Tertiary, PTH very high, Ca high, Phosphate high vit d low or normal
