Renal Flashcards
(99 cards)
1
Q
Define AKI:
A
AKI is characterised by a decline in renal function that happens rapidly (over hours to days).
It is diagnosed based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria as below:
* Increase in serum creatinine by >26.5 mmol/l within 48 h, or
* Increase in serum creatinine > 1.5x the baseline within the last 7 days, or
* Urine output < 0.5 ml/kg/h for 6 hours
Unlike chronic kidney disease (CKD), AKI is typically reversible, at least in part.
2
Q
Who is at an increased risk of developing AKI?
A
- Patients with CKD
- Elderly patients
- Previous AKI
- Malignancy
- Medical conditions increasing risk of urinary obstruction (e.g. BPH)
- Cognitive impairment and disability (may be reliant on others for fluid intake)
- Medications: NSAIDs or ACE inhibitors
- Recent administration of iodine-containing contrast media
3
Q
What are the Pre-renal causes of AKI:
A
Pre-renal causes are the most common, and occur due to decreased renal perfusion e.g. due to:
- Hypovolaemia (e.g. dehydration, haemorrhage, gastrointestinal losses, burns)
- Renovascular disease (e.g. renal artery stenosis)
- Medications reducing blood pressure or renal blood flow (e.g. NSAIDs, ACE inhibitors, ARBs, diuretics)
- Hypotension due to reduced cardiac output (e.g. HF, sepsis)
4
Q
What are the Intra-renal causes of AKI:
A
Renal causes occur due to structural damage to the kidneys, which may affect:
- The glomeruli (e.g. acute glomerulonephritis, nephrotic syndrome)
- The tubules (e.g. acute tubular necrosis due to ischaemia or toxins, rhabdomyolysis)
*. The interstitium (e.g. acute interstitial nephritis secondary to drugs) - The renal vessels (e.g. renal vein thrombosis, vasculitis)
5
Q
What are the Post-renal causes of AKI:
A
Post-renal causes involve obstructed to urinary flow anywhere along the urinary tract, which may be:
- Luminal (e.g. ureteric stones or a blocked catheter)
- Intramural (e.g. urethral or ureteric strictures, ureteric carcinomas)
- Due to external compression (e.g. an abdominal or pelvic tumour, benign prostatic hyperplasia)
6
Q
What classifies as stage 1 AKI?
A
AKIs are staged according to the KDIGO criteria as follows:
Stage 1 - any of:
- Creatinine rise of 26 micromol/L or more within 48 hours
- Creatinine rise to 1.5-1.99x baseline within 7 days
- Urine output < 0.5 mL/kg/hour for more than 6 hours
7
Q
What classifies as stage 2 AKI?
A
Stage 2 - any of:
- Creatinine rise to 2-2.99x baseline within 7 days
- Urine output < than 0.5 mL/kg/hour for more than 12 hours
8
Q
What classifies as stage 3 AKI?
A
- Creatinine rise to 3x baseline or higher within 7 days
- Creatinine rise to 354 micromol/L or more with either
- Acute rise of 26 micromol/L or more within 48 hours or
- 50% or more rise within 7 days
- Urine output < than 0.3 mL/kg/hour for 24 hours
- Anuria for 12 hours
9
Q
What are sx of AKI?
A
An AKI may be asymptomatic and be detected on blood tests only, or may be diagnosed due to a fall in urine output.
Symptoms may be seen especially in severe cases where uraemia occurs, and include:
* Nausea and vomiting
* Fatigue
* Confusion
* Anorexia
* Pruritus
10
Q
What are the signs of AKI?
A
- Hypertension (a complication of AKI)
- Bladder distension due to urinary retention
- Hypotension and dehydration (in many pre-renal causes)
- Signs of fluid overload (e.g. raised jugular venous pressure, pulmonary and peripheral oedema) as a complication of AKI
- Signs related to the underlying cause (e.g., fevers in sepsis, rashes in vasculitis)
- Pericardial rub (in uraemic pericarditis)
11
Q
What are the Initial Ix of AKI:
A
Bedside tests:
* Urinalysis
* ECG to screen for complications of hyperkalaemia
* Blood gas to look for acidosis as a complication of AKI, allows rapid potassium measurement
Blood tests:
* U&Es to get creatinine for diagnosis (compare to baseline if available) and check for hyperkalaemia
* Full blood count may show anaemia in vasculitis or raised white cells in infection
* LFTs may be deranged in severe hypotension causing ischaemic hepatitis
* Clotting as a baseline in case a renal biopsy is later required (rare)
* Bone profile to screen for hypercalcaemia (seen in myeloma which can cause renal AKI)
* Creatinine kinase to look for rhabdomyolysis
* CRP may be raised in infection or vasculitis
Imaging:
* Bladder scan if urinary retention is suspected
* USS KUB (kidneys, ureters and bladder) if a post-renal cause is suspected, may show hydronephrosis.
* The next line of imaging would be a CT KUB as this is a more sensitive modality.
12
Q
What further tests can be done for AKI? (renal screen)
A
ANA
Double-stranded DNA
Anti-nuclear cytoplasmic antibodies
Anti-GBM antibodies
Erythrocyte sedimentation rate
Serum immunoglobulins
Serum electrophoresis
Serum free light chains
Complement levels (C3 and C4)
HIV screening
Hepatitis B and C serology
13
Q
Ix Intrarenal cause of AKI.
A
If the diagnosis is still unclear and a renal cause is suspected, a renal biopsy may be indicated.
14
Q
What is the most common cause of AKI and how would you treat it?
A
The most common cause of AKI is dehydration
IV fluid resuscitation will be required
15
Q
Tx AKI:
A
- Review regular medications and suspend any nephrotoxic drugs (e.g. NSAIDs, aminoglycosides, ACE inhibitors, ARBs) and review those that may cause complications in cases of renal impairment (e.g. opiates, metformin)
- Low-risk patients with an uncomplicated stage 1 or 2 AKI may be considered for discharge if there is an identifiable cause that can be managed in the community
16
Q
What factors will prompt referral for consideration of renal replacement therapy with dialysis or haemofiltration?
A
Remembered by the AEIOU mnemonic:
- Acidosis (severe metabolic acidosis with pH of <7.20)
- Electrolyte imbalance (resistant hyperkalaemia)
- Intoxication (AKI secondary to certain drugs or poisons)
- Oedema (refractory pulmonary oedema)
- Uraemia (uraemic encephalopathy or pericarditis)
17
Q
Define Renal Artery Stenosis:
A
A type of renovascular disease that occurs when the renal arteries (one or both) become narrowed, reducing the blood supply to one or both kidneys.
Renal hypoperfusion upregulates the renin-angiotensin-aldosterone system, causing hypertension
18
Q
What are the risk factors of developing Renal Artery Stenosis?
A
- Atherosclerosis of the renal arteries 90% cases
- Older age
- Hypertension
- Diabetes
- Smoking
- Obesity
- Hyperlipidaemia
- Hx of peripheral vascular, cerebrovascular or heart disease
- Fhx of CVD
- Fibromuscular dysplasia (FMD) is the commonest form of nonatherosclerotic RAS
19
Q
What are the causes of Renal Artery Stenosis:
A
- Atherosclerosis
- Non-atherosclerotic causes of RAS:
- Fibromuscular dysplasia
- Vasculitis (e.g. Takayasu’s arteritis, polyarteritis nodosa)
- Trauma
- Embolisation
- Arterial dissection (of the renal artery or aorta)
- Radiotherapy
- Renal arteriovenous malformation
- Post-transplant RAS
- Neurofibromatosis
20
Q
What are the sx and signs of Renal Artery Stenosis:
A
- Hypertension, which may be sudden onset, severe and treatment-resistant
- This may be asymptomatic or present with headaches, dizziness or blurred vision
- “Flash” pulmonary oedema may occur with no obvious precipitant and normal left ventricular function
- Asymptomatic, and identified after initiation of an ACE inhibitor or angiotensin-II receptor blocker (ARB) causes a significant deterioration in renal function
- An abdominal bruit may be heard on auscultation over the flank
- Evidence of risk factors for atherosclerotic disease may be seen on examination e.g., corneal arcus and xanthelasma due to hyperlipidaemia
21
Q
The complications of Renal Artery Stenosis?
A
- Hypertension causing end-organ damage (stroke, retinopathy, heart failure, renal failure)
- Pulmonary oedema
- Progressive chronic kidney disease
- Complications of intervention e.g. cholesterol embolisation
22
Q
The Ix of Renal Artery Stenosis:
A
- GOLD standard is renal arteriography.
23
Q
The management of Renal Artery Stenosis:
A
Medical management:
* Antihypertensives- ACE-inhibitors and ARBs can be used unless there is a solitary kidney, advanced CKD or severe bilateral RAS
* CCB and BB
* Dyslipidemia- (e.g. statin treatment)
* Optimise management of comorbidities
Interventional management:
* Angioplasty and stenting of the renal arteries is the first-line vascular intervention
24
Q
What are the indications for Revascularization as tx for Renal Artery Stenosis?
A
Indications for revascularization:
* >60% unilateral stenosis with any of the following: HF, recurrent acute decompensations, unexplained acute pulmonary oedema, unstable angina, failure/ intolerance to antihypertensive medication, accelerated HTN, single functioning kidney.
* 60% bilateral stenosis with progressive renal insufficiency.
25
Define Rhabdomyolysis?
Rhabdomyolysis is a potentially life-threatening condition that occurs when there is rapid breakdown of skeletal muscle.
Intracellular contents of muscle cells are released, including creatine kinase, myoglobin and potassium.
26
What are the causes of Rhabdomyolysis?
* Prolonged immobilisation
* Crush injuries
* Severe burns
* High-voltage electrical injury
* Prolonged seizures
* Compartment syndrome
* Medications (e.g. statins, fibrates, neuroleptic malignant syndrome)
* Recreational drugs (e.g. ecstasy, cocaine)
* Toxins (e.g. snake venom)
* Heatstroke
* Myositis (e.g. viral or autoimmune)
* Delirium tremens (alcohol withdrawal)
* Metabolic or genetic disorders
* DKA
* Thyroid storm
27
What are the sx of Rhabdomyolysis?
Muscle pain
Weakness
Tea-coloured urine
Malaise
Fevers
Anorexia
Nausea and vomiting
28
What are the signs of Rhabdomyolysis?
* Tender and swollen muscles (often disproportionate to the injury sustained)
* Altered mental state - agitation, delirium
* Oliguria or anuria
* rise in serum CK
* increase in release of metabolic products e.g., myoglobin which damages the glomeruli causing dark/ reduced urine output
29
What are the Ix of Rhabdomyolysis?
Bedside tests:
* Urine dipstick is falsely positive for blood due to myoglobinuria
* Urine microscopy shows no red cells in the urine
* VBG to rapidly obtain serum potassium; metabolic acidosis
* ECG changes due to hyperkalaemia/ hypocalcaemia
Blood tests:
* Creatine kinase is the key DIAGNOSTIC test - a CK > 5x the upper limit of normal is expected
* U&Es looking for renal impairment and hyperkalaemia; creatinine is raised out of proportion to urea
* Full blood count as a baseline; white cells may be raised if inflammation or infection is driving rhabdomyolysis
* Coagulation screen to monitor for disseminated intravascular coagulation
* Bone profile may show hypocalcaemia, high phosphate
* Liver function tests may show a liver injury; AST and ALT will be raised due to muscle damage
* Urate, lactate dehydrogenase and aldolase are raised (these are non-specific)
Imaging is not routinely required- MRI is the imaging modality of choice, and will show oedematous muscles with features of myonecrosis in severe cases
Special tests:
Muscle biopsy may also be considered; this should be delayed for at least a month after an acute episode of rhabdomyolysis
30
What is the management of Rhabdomyolysis?
Medical management:
* IV fluid rehydration - large volumes may be required to meet a target urine output of 200-300ml/hour (or 3 ml/kg/hour) until CK normalises
* Hyperkalaemia with calcium gluconate for myocardial protection and iV insulin/dextrose
* In some cases, IV sodium bicarbonate may be considered to correct acidosis
Interventional management:
* Intensive care admission for renal replacement therapy may be required in severe rhabdomyolysis
* Some causes of rhabdomyolysis may require surgical intervention e.g. fasciotomies for compartment syndrome
31
What are the complications of Rhabdomyolysis?
* AKI
* Arrhythmias including cardiac arrest may occur due to hyperkalaemia and hypocalcaemia
* Metabolic acidosis is common, often with an increased anion gap
* DIC
* Compartment syndrome
* Hypercalcaemia
* Liver injury
32
Define Nephritic Syndrome:
Nephritic syndrome refers to a collection of signs and symptoms that occur due to renal inflammation (nephritis), specifically glomerular inflammation (glomerulonephritis).
The key features are haematuria, proteinuria (usually non-nephrotic range i.e. < 3.5 grams/day), hypertension, oliguria and oedema.
33
Aietiology of Nephritic syndrome
* Lupus nephritis
* Henoch-Schonlein purpura
* Post-infectious glomerulonephritis (GN), for example: Post-streptococcal GN
* Other bacteria e.g. pneumococcal pneumonia
* Viral infections e.g. hepatitis B
* Parasitic infections e.g. malaria
* Anti-glomerular basement membrane (anti-GBM) disease
* IgA nephropathy
* Membranoproliferative glomerulonephritis (MPGN)
* Infective endocarditis
* ANCA-associated vasculitides e.g.
* Granulomatosis with Polyangiitis (GPA)
* Microscopic Polyangiitis (MPA)
* Eosinophilic Granulomatosis with Polyangiitis (EGPA)
* Cryoglobulinaemia
* Genetic causes e.g. Alport syndrome
34
Sx of Nephritic syndrome:
* Haematuria (often microscopic but may be macroscopic) - "cola-coloured" brown urine is typical
* Hypertension (may cause symptoms of headache and blurred vision)
* Non-nephrotic range proteinuria
* Peripheral and pulmonary oedema
* Oliguria
* Uraemic symptoms due to renal impairment, for example:
- Anorexia
- Nausea
- Fatigue
- Pruritus
- Lethargy
Patients may also have signs and symptoms of the underlying cause of nephritic syndrome, for example:
* Alopecia, rashes and arthralgia in systemic lupus erythematosus
* Haemoptysis and dyspnoea in anti-GBM disease
* Purpuric rash, arthritis and abdominal pain in Henoch-Schonlein purpura
35
The Ix of Nephritic Syndromes:
Bedside tests:
* Urine dip to confirm haematuria and proteinuria
* Urine MS&C shows dysmorphic rbc and rbc casts; culture is negative
* Urine protein:creatinine ratio to quantify proteinuria (usually below nephotic-range i.e. < 3.5 grams/day)
* Blood gas to rapidly check acid-base status and look for hyperkalaemia that may complicate renal impairment
Blood tests:
* FBC, U&Es, LFTs, CRP and ESR, Coagulation screen
* Anti-GBM antibodies for anti-GBM disease
* ANCA - pANCA is typically positive in EGPA and MPA, and cANCA is typically positive in GPA
* Complement may be low in systemic lupus erythematosus (SLE), cryoglobulinaemia or MPGN
* Antinuclear antibodies, anti-dsDNA and anti-Smith antibodies to screen for SLE
* Rheumatoid factor and cryoglobulin levels if cryoglobulinaemia is suspected
* Serology for post-infectious glomerulonephritis e.g. antistreptolysin titre, HIV and hepatitis B and C
3 sets of blood cultures if infective endocarditis is suspected
Imaging tests:
* Renal USS to rule out an obstructive cause of AKI, assess renal structure and plan a biopsy
* CXR and/or CT if there is clinical evidence of a renal-pulmonary syndrome (e.g. anti-GBM disease) or if pulmonary oedema is suspected
* Echocardiogram if infective endocarditis is suspected
Special tests:
* Renal biopsy is the key investigation to diagnose the cause of nephritic syndrome
* For example, post-streptococcal GN is characterised by granular staining of IgG and complement subepithelial deposits (sometimes referred to as a "starry sky" pattern)
36
Ix of Nephritic syndromes:
Conservative:
* Stop any causative medication
* Fluid and salt restriction may be advised to help control hypertension and oedema
* A low potassium diet may be required in patients with hyperkalaemia
Medical:
* Antihypertensives to control BP
* Diuretics (usually loop diuretics such as furosemide) may be required for oedema
Interventional:
* Patients with renal failure secondary to glomerulonephritis may require renal replacement with dialysis
* In some cases where patients progress to end-stage renal failure, renal transplantation may be considered
* Some causes of nephritic syndrome (e.g. anti-GBM disease) are treated with plasmapheresis
37
Define IgA Nephropathy (Berger’s disease):
This is the disease characterised by glomerular deposits of IgA.
38
What are the signs and sx of IgA Nephropathy:
* Asymptomatic
* Visible haematuria
* This usually occurs 12-72 hours after an URTI or GI infection
* Self-limiting within a few days
* Haematuria typically recurs with subsequent infections
* Loin pain (either unilateral or bilateral) may accompany episodes of haematuria
* Hypertension
* Oedema and frothy urine in patients presenting with nephrotic syndrome
39
What is the Diagnostic Ix of IgA Nephropathy:
Renal biopsy is the diagnostic test and shows diffuse mesangial IgA immune complex deposits
40
What is the management of IgA Nephropathy:
* control BP
* refer to secondary care
* Immunosuppression: Hydroxychloroquine and mycophenolate mofetil in Chinese patients
* Systemic steroids e.g. nephrotic syndrome or rapidly progressive glomerulonephritis
* Patients with end-stage renal disease require renal replacement therapy with dialysis or transplant
41
Define Nephrotic Syndrome?
Nephrotic syndrome occurs when there is excessive loss of protein in the urine, leading to hypoalbuminemia and peripheral oedema.
Other resulting features include hyperlipidaemia, abnormal coagulation and immunodeficiency.
42
What is the diagnostic criteria for Nephrotic syndrome?
The diagnosis of nephrotic syndrome requires the presence of all of:
Proteinuria > 3.5 grams/24 hours
Serum albumin < 30 grams/litre
Peripheral oedema
43
What are the sx of Nephrotic Syndrome?
Frothy urine due to proteinuria
Swelling of the face and body
Weight gain due to fluid retention
Fatigue
Lethargy
Anorexia
44
What are the signs of Nephrotic sysndrome?
Oedema - typically peripheral and periorbital
Muehrcke's lines refers to paired white transverse lines across the nails that may occur secondary to hypoalbuminemia
Signs of hyperlipidaemia such as xanthelasma (yellow plaques over the eyelids)
Signs of pleural effusion e.g. dull bases to percussion with decreased air entry
Patients may also present with signs and symptoms of complications e.g. infection, thrombosis.
45
What are the complications of Nephrotic Syndrome?
* Increased risk of infection as immunoglobulins are lost in urine
* Venous thromboembolism due to urinary loss of anti-thrombotic proteins such as antithrombin III
* Hyperlipidaemia
* AKI
* CKD
* Medication side-effects especially with chronic steroid use (e.g. osteoporosis, psychiatric effects)
* Hypothyroidism due to urinary losses of T4 and T3 with their binding proteins
* Vitamin D deficiency as this is also lost in urine
* Anaemia
46
Tx of Nephrotic syndrome?
- Urgent referral for biopsy
- Treatment depends on underlying cause but involves IS, BP management, diuresis and at least prophylaxis against VTE.
- Aim to reduce proteinuria (which is a rick for CKD progression)
47
Ix of Nephrotic Syndrome?
Bedside tests:
* Urine dipstick
* Urine protein:creatinine ratio
Blood tests:
* LFTs to confirm hypoalbuminemia
* U&Es for renal function
* FBC may show anaemia in persistent nephrotic syndrome
* Vitamin D may be low as this is lost in urine
* Bone profile may show hypocalcemia secondary to vitamin D deficiency
* Coagulation screen is usually normal although there is a hypercoagulable state with increased risk of thromboembolism
* HbA1c or fasting glucose for diabetes
* Lipid profile often shows dyslipidemia
* CRP and ESR may be raised
* Myeloma screen i.e. immunoglobulins and serum protein electrophoresis if myeloma is suspected
* Autoimmune screen e.g. for suspected systemic lupus erythematosus (antinuclear antibody, complement levels etc.)
* Infection screen i.e. hepatitis B and C serology, HIV testing
Imaging tests:
* CXR if signs of pleural effusion
* US KUB
* CT pulmonary angiogram for suspected pulmonary embolism or doppler ultrasound of the limbs for suspected DVT
Special tests:
* Renal biopsy is the key investigation to DIAGNOSE the cause of nephrotic syndrome - this is important both for prognosis and to guide management
48
What is the medical management of Nephrotic Syndrome?
* Corticosteroids first-line- should be weaned after remission is achieved ++ PPI
* Other immunosuppressive drugs (e.g. ciclosporin, cyclophosphamide, mycophenolate mofetil or rituximab)
* Diuretics are used to treat significant peripheral oedema, usually furosemide but potassium sparing and thiazide diuretics may be added as adjuncts
* Risk of thromboembolism should be assessed and prophylactic anticoagulation considered
* Antihypertensives
49
What is the conservative management of Nephrotic syndrome.
Conservative:
* Restrict salt intake to <2g/day
* Fluid restriction to <1.5L/day
* Weight should be monitored, with a target of 1-2 kg weight loss per day until the patient reaches their predicted "dry weight" (i.e. weight when not oedematous)
* Dietary changes (e.g. avoiding a high protein diet, limiting fat intake) may be advised and dietician input may be indicated
* Mechanical thromboprophylaxis (TEDS) to reduce risk of venous thromboembolism
50
Define Hydronephrosis?
An upper urinary tract dilation.
51
What are the sx of Hydronephrosis?
- Pain
- Haematuria
- Changes to urine volume
- Anuria (obstruction likely)
- Dysuria (stasis or urine precedes infection)
- Palpable bladder
- Loin tenderness
- Flank mass (palpable hydronephsosis)
52
What is the Ix of Hydronephrosis?
* Urine for MCS & urine dip
* Creatinine
* CRP, WBCs & blood cultures
* PSA in men
* Imaging not really helpful
* US- pelvis and calyces dilation, hydronephrosis, dilated ureter & hydronephrosis
* CT to look for cause of compression (if not on US)
53
What is the Tx for Hydronephrosis?
Treatment is determined by:
- Site of obstruction
- Presence of additional urinary infection
- Degree of metabolic disturbance
Prompt by relieving obstruction:
- Catheter
- Nephrostomy (stenting)
54
Define Reflux nephropathy?
Reflux of urine up ureters as bladder contracts during micturition.
55
What are the sx of Reflux nephropathy?
- prolonged bed wetting and frequent UTIs (kids).
- If has not resolved into adulthood will present as CKD or unexplained hypertension/proteinuria
56
Define Nephroblastoma (Wilms tumour):
Wilms' tumour is a malignant embryonic tumour originating from the developing kidney.
It represents the most common abdominal tumour in paediatric patients.
57
What are the sx of Nephroblastoma (Wilms tumour):
* A palpable abdominal mass that does not cross the midline, although it may be bilateral
* Abdominal distension
* Haematuria
* Hypertension
* Often asymptomatic unless the tumour grows sufficiently large to cause pain or disrupt other abdominal structures.
58
What are the Ix for Nephroblastoma (Wilms tumour)?
* Haematuria may be picked up on urine dipstick, and raised blood pressure will be noted on observations if tumour has progressed
* A CT scan of the chest, abdomen, and pelvis is indicated for patients with suspected nephroblastoma to identify the extent and potential spread of the disease.
* DEFINITIVE DIAGNOSIS = renal biopsy, which may reveal small round blue cells on histology.- not exclusive to this disease
59
Tx for Nephroblastoma (Wilms tumour)?
* Most children will have chemotherapy.
* Surgical resection, typically nephrectomy, is often the primary treatment following chemotherapy.
* Adjuvant radiotherapy may be needed depending on the type and stage of the tumour.
60
What are the complications of Nephroblastoma (Wilms tumour)?
* Hypertension
* Renal failure
* Treatment may cause heart failure, secondary malignancies and affect the child's growth
61
Risk factors for developing Wilms Tumour
* children <5 yrs
62
Risk factors for Diabetic Nephropathy:
Risk factors for diabetic nephropathy include:
* Hypertension
* Higher waist circumference
* Diabetic retinopathy
* Male gender
* Smoking
* South Asian ethnicity
* Dyslipidemia
63
Classification of Diabetic Nephropathy;
* Class I- Mild or nonspecific changes on light microscopy; glomerular basement membrane thickening on electron microscopy
* Class II- Diffuse mesangial expansion
* Class III- Nodular sclerosis (Kimmelstiel-Wilson lesions)
* Class IV- Advanced diabetic glomerulosclerosis affecting more than 50% of glomeruli
64
Sx of Diabetic Nephropathy
Fatigue
Anorexia
Weight loss
Nausea and vomiting
Taste disturbance
Itch
Breathlessness
Sleep disturbance
Bone pain
Foamy urine due to proteinuria
Polyuria or oliguria
65
Signs of Diabetic Nephropathy
Hypertension
Peripheral and/or pulmonary oedema
Encephalopathy
Cachexia
Pallor
Uraemic odour
66
Ix of Diabetic Nephropathy?
Bedside:
* All adults with diabetes - screened annually for diabetic nephropathy with an early morning UACR
* Urinalysis - rule out other causes
Bloods:
* Annual diabetic screening: U&Es (classify severity of CKD)
* HbA1c to assess glycaemic control
* LFTs may show hypoalbuminemia in patients with nephrotic syndrome
Imaging:
* Renal USS
* Doppler -assess for renal artery stenosis
Special tests:
Renal biopsy is not required in the majority of cases however if there is a suspicion of intrinsic renal disease or there is diagnostic uncertainty it may be indicated.
In diabetic nephropathy, a biopsy will reveal Kimmelstiel-Wilson nodules, which are nodules of pink hyaline material in regions of glomerular capillary loop.
67
What will Biopsy show in patient with Diabetic Nephropathy?
In diabetic nephropathy, a biopsy will reveal Kimmelstiel-Wilson nodules, which are nodules of pink hyaline material in regions of glomerular capillary loop.
68
Medical management of Diabetic Nephropathy:
* Optimisation of diabetic control
* Target HbA1c 53 mmol/mol
* ACEi are the FIRST LINE treatment for diabetic nephropathy- be started in all patients with an ACR of 3 mg/mmol or more
* ARBs if ACEi not tolerated
* SGLT2 inhibitors should be offered to patients with type 2 diabetes and an ACR of 30 mg/mmol or more
69
Define Autosomal Dominant Polycystic Kidney Disease (ADPKD):
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited renal disorder characterised by continuous formation and growth of cysts in the kidneys.
This leads to progressive renal impairment due to destruction of nephrons and may cause end-stage kidney disease.
ADPKD also has several extrarenal manifestations, including cyst formation in the liver and other organs and intracranial aneurysms.
70
Aietiology of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
The PKD genes cause mutations in polycystin 1 and 2, which lead to cyst formation and expansion
PKD1 is located on chromosome 16, and PKD2 is located on chromosome 4
Disease is typically more severe with PKD1 mutations
71
Sx of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
* Flank pain
- Acute, secondary to cyst haemorrhage, infection or urinary tract stones
* Chronic pain
*Haematuria (often due to cyst rupture)
* Fever and systemic illness due to infection i.e. malaise, nausea and vomiting
* May present with recurrent UTI
* Polyuria and nocturia
* CKD e.g. lethargy, peripheral oedema, pruritus
72
Signs of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
* Bilateral large masses in the flanks (palpable enlarged kidneys)
* Hepatomegaly (up to 70% have liver cysts)
* Hypertension
* Splenomegaly is rarer (5% have splenic cysts)
73
Ix of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
USS of the kidneys is the key DIAGNOSTIC test and is used for screening adult family members:
* 3+ renal cysts in total if aged 15-39 is sufficient to diagnose ADPKD
* 2+ cysts in each kidney if aged 40-59 is sufficient to diagnose ADPKD
* No cysts if aged 40+ is sufficient to exclude ADPKD
74
Medical management of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
* Tolvaptan for patients with stage 2/3 CKD with rapidly progressive disease, to slow cyst growth and renal impairment
* Antihypertensives may be required to maintain a blood pressure of < 130/80
* ACEi or ARBs are first-line
* Analgesia
* Antibiotics if UTI
75
Surgical management of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
* Drainage of painful or infected renal cysts may be done percutaneously, laparoscopically or via a laparotomy
* Nephrectomy e.g. very large cysts, uncontrolled haemorrhage, symptomatic mass effect
* For patients with ESRD requiring renal replacement therapy, renal transplant is preferred
* In some cases, removal of the native kidney may be required prior to transplantation to make space
* Symptomatic liver cysts may also require drainage or resection
* Intracranial aneurysms detected on screening may be treated prophylactically (e.g. clipping or coiling) - observation is also an option
76
Poor prognostic factors of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
Poor prognostic factors include:
- PKD1 genotype
- Younger age of onset
- Larger kidneys
- Hypertension
- Male sex
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Define CKD?
Reduction in kidney function or structural damage (or both); must be present for > 3 months with associated health complications.
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Risk F. of CKD:
* Family history of CKD
* Black or Hispanic ethnicity
* History of acute kidney injury (AKI)
* Older age
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Causes of CKD:
Diseases causing intrinsic kidney damage:
* Diabetes
* Hypertension
* Glomerulonephritis
* Conditions causing urinary tract obstruction:
* Recurrent urolithiasis
* Structural abnormalities (e.g. ureteropelvic junction obstruction)
* External compression (e.g. from a pelvic mass)
* Bladder voiding problems (e.g. benign prostatic hyperplasia, neurogenic bladder)
Iatrogenic causes:
* Radiotherapy
* Nephrotoxic drugs, e.g. aminoglycosides, lithium, NSAIDs
Renal involvement secondary to multisystem diseases:
* HIV
* Myeloma
* Vasculitis
* Systemic lupus erythematosus (lupus nephritis)
* Amyloidosis
* Genetic kidney diseases
* ADPKD
* Alport's syndrome
* Tuberous sclerosis
* Cystinosis
* Recurrent urinary tract infections
* Often secondary to vesico-ureteric reflux or other anatomical defects
* Leads to chronic pyelonephritis which may lead to end-stage renal disease
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Sx of CKD:
CKD is often asymptomatic, however especially in later stages patients may have non-specific symptoms such as:
* Lethargy
* Anorexia
* Headaches
* Weight loss (or gain due to fluid overload)
* Nausea and vomiting
* Itching (uraemic pruritus)
* Shortness of breath (due to anaemia, pulmonary oedema, pleural effusion or acidosis)
* Muscle cramps, especially at night
* Bone pain (due to renal osteodystrophy)
* Taste changes
* Cognitive impairment
* Urinary symptoms:
* Polyuria or oliguria may occur
* Nocturia
* Frothy urine (due to proteinuria)
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The signs of CKD:
* Hypertension
* Pallor (due to anaemia)
* Abnormal fluid status
* Fluid overload with peripheral and/or pulmonary oedema
* Dehydration
* Cachexia
* Ammonia-like smelling breath due to uraemia
* Tachypnoea (due to anaemia, pulmonary oedema, pleural effusion or acidosis
* Flank mass(es) may be palpable due to malignancy or renal cysts (e.g. in ADPKD)
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Stages of CKD:
- CKD 1 – GFR > 90 with a kidney problem
- CKD 2 – GFR 60 – 90 with a kidney problem
- CKD 3 – GFR 30 – 60
- CKD 4 – 15-30
- CKD 5 - < 15
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Define IgA Nephropathy:
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What are the causes of IgA Nephropathy:
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What are the Ix of IgA Nephropathy:
1st LINE urinalysis and MC&S:
* Urinalysis is typically positive for blood ± protein; it is rare for patients to present with nephrotic-range proteinuria
* Urine microscopy will usually show presence of dysmorphic red blood cells which suggests bleeding from the glomerulus
The GOLD-standard method for diagnosis is renal biopsy:
* This shows diffuse mesangial IgA immune complex deposition
* Serum IgA is elevated in approximately 50% of patients
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Clinical features of IgA Nephropathy:
* Patients present with recurrent gross or microscopic haematuria following 12–72 h of an upper respiratory-tract infection or GI infection
*Aaged 20–30
* Mild proteinuria may be present
* HTN may be present
* It can be associated with HSP/IgA vasculitis, chronic liver disease, inflammatory bowel disease (IBD) and skin and joint disorders, eg. psoriasis
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Tx IgA Nephropathy:
The mainstay of treatment is supportive and aimed at reducing cardiovascular risk:
* Dietary salt restriction
* Treatment of proteinuria (>0.5 g/day) with an ACE-i/ARB
* Treatment of HTN
Patients are risk stratified into those who are at low risk of progression to CKD and ESKD and those at high risk:
* Those at high risk of progression are considered for treatment with corticosteroids.
* Immunosuppresion should be offered for those who present with an RPGN.
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Define Post-streptococcal Glomerulonephritis (PSGN):
PSGN is a type of immune-complex-mediated GN that can occur 1–3 weeks after a streptococcal upper respiratory-tract infection. It is more common in children than adults.
GN can occur after other types of bacterial infection; however, PSGN or infective endocarditis are the most commonly encountered causes.
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Causes of Post-streptococcal Glomerulonephritis:
* It is caused by certain strains of group A β-haemolytic streptococci.
* Pathogenesis is not fully understood but main theories suggest that there is immune-complex deposition, neutrophil infiltration and complement activation in the glomerulus causing inflammation and/or proliferation.
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Clinical features of Post-streptococcal Glomerulonephritis:
* Patients typically present with sudden onset of haematuria, oliguria, HTN and/or oedema 1–3 weeks post-infection
* Patients may also be asymptomatic with microscopic haematuria
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What are the Ix of Post-streptococcal Glomerulonephritis:
* First-line investigation includes a urinalysis and MC&S
* An FBC may show raised white cells, suggestive of an infective process
* U&Es often show an AKI
* Immunoglobulins, complement (low C3 levels commonly found) and autoantibodies (such as raised anti-streptolysin titre, raised DNAse B titre) can help support the diagnosis
* Blood cultures are indicated in patients with fever
* The GOLD-standard method for diagnosis in adults is a renal biopsy: The classical finding is subepithelial 'humps' on electron microscopy
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Causes of Anti-GBM:
Anti-GBM disease is caused by antibodies to the non-collagenous domain (NC1) of the ⍺3 chain of type IV collagen.
These antibodies are directed against antigens found on the GBM in the kidneys and in the lung alveoli, leading to the presentation with pulmonary–renal syndrome.
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Clinical features of Anti-GBM:
* Haemoptysis and pulmonary haemorrhage
AKI, often severe and rapidly progressive, leading to renal failure
* It is more common in males
* There are two peaks in age of presentation: 20–30 years and 60–70 years
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Ix of Anti-GBM:
* Urinalysis and MC&S
* U&Es
* pH to assess degree of acidosis and whether dialysis is indicated
* CXR/CT -pulmonary haemorrhage
* An acute renal screen to identify the cause: anti-GBM should be specifically requested for patients presenting with pulmonary–renal syndrome; this will be positive; ANCA may be positive.
* Renal biopsy is the GOLD standard for diagnosis:
this will show focal and segmental necrotising crescents and linear IgG standing along the basement membrane
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Management of Anti-GBM:
Removal of the circulating antibody:
* achieved with plasma exchange which removes the pathogenic circulating antibodies.
Immunosuppression to stop further production of antibodies:
* normally achieved with high-dose oral prednisolone and cyclophosphamide.
* relapse of the disease is very rare and maintenance immunosuppression is not usually indicated.
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Eosinophilic granulomatosis with polyangiitis (EGPA)
Also known as Churg Strauss
The majority of patients with EGPA are pANCA positive (anti-MPO)
EGPA is characterised by allergic asthma, rhinitis and eosinophilia
Approximately 30% have renal involvement; 50% of these present with an RPGN
Kidney biopsy shows a focal and segmental necrotising GN with eosinophilic infiltration
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Granulomatosis with polyangiitis (GPA)
Also known as Wegners granulomatosis
The majority of patients with GPA are cANCA positive (anti-PR3)
GPA is characterised by upper respiratory-tract symptoms, pulmonary haemorrhage (70%), RPGN and signs of systemic vasculitis
Kidney biopsy shows a focal and segmental necrotising GN which is pauci-immune
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Microscopic polyangiitis (MPA)
The majority of patients with MPA are pANCA positive (anti-MPO)
MPA is characterised by pulmonary haemorrhage (30%), RPGN and signs of systemic vasculitis
Kidney biopsy shows a focal and segmental necrotising GN which is pauci-immune
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