Renal Flashcards
ADPKD
-How common is this?
-What disease loci have been identified?
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively
ADPKD type 1 and type 2
-Which is more common?
-Which chromosome corresponds to which type?
-Which presents with renal failure earlier
ADPKD type 1 ADPKD type 2
85% of cases 15% of cases
Chromosome 16 Chromosome 4
Type 1 - Presents with renal failure earlier
What is the screening investigation for ADPKD?
The screening investigation for relatives is abdominal ultrasound
What is the ultrasound diagnostic criteria for ADPKD
-if aged <30
-If aged 30-59
-If aged >60
Ultrasound diagnostic criteria (in patients with positive family history)
two cysts, unilateral or bilateral, if aged < 30 years two cysts in both kidneys if aged 30-59 years four cysts in both kidneys if aged > 60 years
What can be used for treatment in ADPKD? what are the criteria for treatment 3?
For select patients, tolvaptan (vasopressin receptor 2 antagonist) may be an option. NICE recommended it as an option for treating ADPKD in adults to slow the progression of cyst development and renal insufficiency only if:
they have chronic kidney disease stage 2 or 3 at the start of treatment there is evidence of rapidly progressing disease and the company provides it with the discount agreed in the patient access scheme.
What are 7 features of ADPKD?
Features
hypertension recurrent UTIs flank pain haematuria palpable kidneys renal impairment renal stones
What are 4 extra renal manifestations of ADPKD?
Extra-renal manifestations
liver cysts (70% - the commonest extra-renal manifestation): may cause hepatomegaly berry aneurysms (8%): rupture can cause subarachnoid haemorrhage cardiovascular system: mitral valve prolapse, mitral/tricuspid incompetence, aortic root dilation, aortic dissection cysts in other organs: pancreas, spleen; very rarely: thyroid, oesophagus, ovary
Give 5 causes of chronic kidney disease?
diabetic nephropathy
chronic glomerulonephritis
chronic pyelonephritis
hypertension
adult polycystic kidney disease
What may affect eGFR? 3
Factors which may affect the result
pregnancy muscle mass (e.g. amputees, body-builders) eating red meat 12 hours prior to the sample being taken
What CKD stage corresponds to what eGFR range?
1
2
3
4
5
CKD stage GFR range
1 Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests* are normal, there is no CKD)
2 60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no CKD)
3a 45-59 ml/min, a moderate reduction in kidney function
3b 30-44 ml/min, a moderate reduction in kidney function
4 15-29 ml/min, a severe reduction in kidney function
5 Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed
give 8 possible features of CKD
Possible features include:
oedema: e.g. ankle swelling, weight gain polyuria lethargy pruritus (secondary to uraemia) anorexia, which may result in weight loss insomnia nausea and vomiting hypertension
Describe the pathophysiology of CKD and bone disease?
Basic problems in chronic kidney disease (CKD):
1-alpha hydroxylation normally occurs in the kidneys → CKD leads to low vitamin D the kidneys normally excrete phosphate → CKD leads to high phosphate
This, in turn, causes other problems:
the high phosphate level 'drags' calcium from the bones, resulting in osteomalacia low calcium: due to lack of vitamin D, high phosphate secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D
What is the aim in management of renal bone disease?
The aim is to reduce phosphate and parathyroid hormone levels.
Overview
reduced dietary intake of phosphate is the first-line management phosphate binders vitamin D: alfacalcidol, calcitriol parathyroidectomy may be needed in some cases
What phosphate binders can be used for patients with renal bone disease?
Phosphate binders
aluminium-based binders are less commonly used now
calcium-based binders
problems include hypercalcemia and vascular calcification
sevelamer
a non-calcium based binder that is now increasingly used
binds to dietary phosphate and prevents its absorption
also appears to have other beneficial effects including reducing uric acid levels and improving the lipid profiles of patients with chronic kidney disease
What does ACR 30 / 70 correspond to in terms of PCR and total protein?
ACR 30 - PCR 50 - urinary protein exc. 0.5
ACR 70 - PCR 100 - urinary protein exc 1
How is ACR sample collected?
When would you need a repeat early morning sample?
What is a significant ACR?
Collecting an ACR sample
by collecting a ‘spot’ sample it avoids the need to collect urine over a 24 hour period in order to detect or quantify proteinuria
should be a first-pass morning urine specimen
if the initial ACR is between 3 mg/mmol and 70 mg/mmol, this should be confirmed by a subsequent early morning sample. If the initial ACR is 70 mg/mmol or more, a repeat sample need not be tested.
Interpreting the ACR results
the NICE guidelines state ‘regard a confirmed ACR of 3 mg/mmol or more as clinically important proteinuria’
In what 3 situations would you refer to a nephrologist ?
NICE recommendations for referral to a nephrologist:
a urinary albumin:creatinine ratio (ACR) of 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated
a urinary ACR of 30 mg/mmol or more, together with persistent haematuria (two out of three dipstick tests show 1+ or more of blood) after exclusion of a urinary tract infection
consider referral to a nephrologist for people with an ACR between 3-29 mg/mmol who have persistent haematuria and other risk factors such as a declining eGFR, or cardiovascular disease
Haematuria
-What is used to test for this?
-What is persistent, non-visible haematuria defined as?
-what other 3 things should be checked when haematuria is found?
Testing
urine dipstick is the test of choice for detecting haematuria
persistent non-visible haematuria is often defined as blood being present in 2 out of 3 samples tested 2-3 weeks apart
renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checked
urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected
in what 2 situations does haematuria require urgent referral within 2 weeks?
Aged >= 45 years AND:
unexplained visible haematuria without urinary tract infection, or
visible haematuria that persists or recurs after successful treatment of urinary tract infection
Aged >= 60 years AND have unexplained nonvisible haematuria and either dysuria or a raised white cell count on a blood test
What requires a routine referral to urology?
Aged 60 >= 60 years with recurrent or persistent unexplained urinary tract infection
Since the investigation (or not) of non-visible haematuria is such as a common dilemma a number of guidelines have been published. They generally agree with NICE guidance, of note:
patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care
what is nephritic syndrome?
haematuria and hypertension
What is nephrotic syndrome?
proteinuria, oedema
What accounts for 80% of nephrotic syndrome?
Primary glomerulonephritis accounts for around 80% of cases
minimal change glomerulonephritis (causes 80% in children, 30% in adults)
membranous glomerulonephritis
focal segmental glomerulosclerosis
membranoproliferative glomerulonephritis
What systemic disease can cause nephrotic syndrome?
Systemic disease (about 20%)
diabetes mellitus
systemic lupus erythematosus
amyloidosis
What drugs can cause nephrotic syndrome?
Drugs
gold (sodium aurothiomalate), penicillamine
What neoplasm and infections can cause nephrotic syndrome?
Others
congenital
neoplasia: carcinoma, lymphoma, leukaemia, myeloma
infection: bacterial endocarditis, hepatitis B, malaria
How does minimal change disease present? what 5 causes exist?
Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.
The majority of cases are idiopathic, but in around 10-20% a cause is found:
drugs: NSAIDs, rifampicin
Hodgkin’s lymphoma, thymoma
infectious mononucleosis
Describe the pathophysiology of minimal change disease?
Pathophysiology
T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss
the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin
Give 4 features of minimal change disease
nephrotic syndrome
normotension - hypertension is rare
highly selective proteinuria
only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus
renal biopsy
normal glomeruli on light microscopy
electron microscopy shows fusion of podocytes and effacement of foot processes
Describe the management of minimal change disease
Management
oral corticosteroids: majority of cases (80%) are steroid-responsive
cyclophosphamide is the next step for steroid-resistant cases
What is the prognosis of minimal change disease?
Prognosis is overall good, although relapse is common. Roughly:
1/3 have just one episode
1/3 have infrequent relapses
1/3 have frequent relapses which stop before adulthood
What is IgA nephropathy? how does this present?
IgA nephropathy (also known as Berger’s disease) is the commonest cause of glomerulonephritis worldwide. It classically presents as macroscopic haematuria in young people following an upper respiratory tract infection
What are 3 associated conditions with IgA nephropathy?
Associated conditions
alcoholic cirrhosis
coeliac disease/dermatitis herpetiformis
Henoch-Schonlein purpura
What is the pathophysiology of IgA nephropathy?
pathophysiology
thought to be caused by mesangial deposition of IgA immune complexes
there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3
Give 4 features of presentation of IgA nephropathy
Presentations
young male, recurrent episodes of macroscopic haematuria
typically associated with a recent respiratory tract infection
nephrotic range proteinuria is rare
renal failure is unusual and seen in a minority of patients
How to differentiate between IgA nephropathy and post-strep glomerulonephritis
-complement level
-symptoms
-duration of symptoms
Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis
post-streptococcal glomerulonephritis is associated with low complement levels
main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur)
there is typically an interval between URTI and the onset of renal problems in post-streptococcal glomerulonephritis
Post-strep glomerulonephritis
-When does this occur?
-what is this caused by?
-Who is usually affected?
Post-streptococcal glomerulonephritis typically occurs 7-14 days following a group A beta-haemolytic Streptococcus infection (usually Streptococcus pyogenes). It is caused by immune complex (IgG, IgM and C3) deposition in the glomeruli. Young children are most commonly affected.
What is seen on blood tests for post-strep glomerulonephritis?
bloods:
raised anti-streptolysin O titre are used to confirm the diagnosis of a recent streptococcal infection
low C3
Give 5 features of post-strep glomerulonephritis
Features
general -headache/malaise
visible haematuria
proteinuria - this may result in oedema
hypertension
oliguria
What is seen on renal biopsy in post-strep glomerulonephritis? 4
Renal biopsy features
-post-streptococcal glomerulonephritis causes acute, diffuse proliferative glomerulonephritis
-endothelial proliferation with neutrophils
-electron microscopy: subepithelial ‘humps’ caused by lumpy immune complex deposits
-immunofluorescence: granular or ‘starry sky’ appearanc
What is the prognosis of post-strep glomerulonephritis?
Carries a good prognosis
what is henoch-schonlein purpura? What is there an overlap with?
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger’s disease). HSP is usually seen in children following an infection.
Give 4 features of henoch schonlein purpura
Features
-palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs
-abdominal pain
-polyarthritis
-features of IgA nephropathy may occur e.g. haematuria, renal failure
What is the prognosis for HSP?
-What should be monitored
-what is the relapse rate?
Prognosis
usually excellent, HSP is a self-limiting condition, especially in children without renal involvement
blood pressure and urinanalysis should be monitored to detect progressive renal involvement
around 1/3rd of patients have a relapse
What is renal papillary necrosis?
Renal papillary necrosis describes the coagulative necrosis of the renal papillae due to a variety of causes.
What are 6 causes of renal papillary necorosis?
Causes
severe acute pyelonephritis
diabetic nephropathy
obstructive nephropathy
analgesic nephropathy - phenacetin was the classic cause but this has now been withdrawn
NSAIDs
sickle cell anaemia
Give 3 features of renal papillary necrosis
Features
visible haematuria
loin pain
proteinuria
What is alports syndrome? how is this inherited? does this affect males and females differently?
Alport’s syndrome is usually inherited in an X-linked dominant pattern*. It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM). The disease is more severe in males with females rarely developing renal failure.
What is commonly asked about in patients with alports syndrome?
A favourite question is an Alport’s patient with a failing renal transplant. This may be caused by the presence of anti-GBM antibodies leading to a Goodpasture’s syndrome like picture.
How does alport syndrome present?
-what features may be seen 6
Alport’s syndrome usually presents in childhood. The following features may be seen:
microscopic haematuria
progressive renal failure
bilateral sensorineural deafness
lenticonus: protrusion of the lens surface into the anterior chamber
retinitis pigmentosa
renal biopsy: splitting of lamina densa seen on electron microscopy
What are three investigations for alport syndrome?
Diagnosis
molecular genetic testing
renal biopsy
electron microscopy: characteristic finding is of the longitudinal splitting of the lamina densa of the glomerular basement membrane, resulting in a ‘basket-weave’ appearance
What is Diabetes insipidus? what are the two different types?
Diabetes insipidus (DI) is a condition characterised by either a decreased secretion of antidiuretic hormone (ADH) from the pituitary (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI).
Give 7 causes of cranial diabetes insipidus?
Causes of cranial DI
idiopathic
post head injury
pituitary surgery
craniopharyngiomas
infiltrative
histiocytosis X
sarcoidosis
DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram’s syndrome)
haemochromatosis
Give 5 causes of nephrogenic diabetes insipidus?
Causes of nephrogenic DI
genetic:
-more common form affects the vasopression (ADH) receptor
-less common form results from a mutation in the gene that encodes the aquaporin 2 channel
electrolytes
hypercalcaemia
hypokalaemia
lithium
lithium desensitizes the kidney’s ability to respond to ADH in the collecting ducts
demeclocycline
tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis
What are two features of Diabetes insipidus?
Features
polyuria
polydipsia
What are three investigations for diabetes insipidus?
Investigation
high plasma osmolality, low urine osmolality
a urine osmolality of >700 mOsm/kg excludes diabetes insipidus
water deprivation test
Describe the management of nephrogenic vs central diabetes insipidus?
Management
nephrogenic diabetes insipidus
-thiazides
-low salt/protein diet
central diabetes insipidus can be treated with desmopressin
Spironalactone - what is the mechanism of action? where does this act?
Spironolactone is an aldosterone antagonist which acts in the cortical collecting duct.
What is the classical triad of renal cell carcinoma?
-What can be found in men?
classical triad: haematuria, loin pain, abdominal mass
pyrexia of unknown origin
left varicocele (due to occlusion of left testicular vein)
endocrine effects: may secrete erythropoietin (polycythaemia), parathyroid hormone (hypercalcaemia), renin, ACTH
25% have metastases at presentation
When should a lower BP target be used for patients with CKD?
Aim for a lower blood pressure target (<130/80 mmHg) in patients with chronic kidney disease, hypertension and a urinary albumin:creatinine ratio (ACR) of 70 or more
