Nephrology Flashcards
complications of peritoneal dialysis ?
Peritonitis - coagulase-negative staphylococci such as Staphylococcus epidermidis is the most common cause.
Abx given should cover both gram negative and gram positive organisms - he BNF recommends vancomycin (or teicoplanin) + ceftazidime added to dialysis fluid OR vancomycin added to dialysis fluid + ciprofloxacin by mouth
Sclerosis peritonitis
which patients are at risk of contrast induced nephropathy?
Risk factors include
known renal impairment (especially diabetic nephropathy)
age > 70 years
dehydration
cardiac failure
the use of nephrotoxic drugs such as NSAIDs
what is contrast induced nephropathy?
Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media. Contrast-induced nephropathy occurs 2 -5 days after administration.
how to prevent contrast induced nephropathy?
the evidence base currently supports the use of intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to support the use of isotonic sodium bicarbonate
N-acetylcysteine has been given in the past but recent evidence suggests it is not effective*
Patients who are high-risk for contrast-induced nephropathy should have metformin withheld for a minimum of 48 hours and until the renal function has been shown to be normal. This is due to the risk of lactic acidosis.
how to work out anion gap?
(Na+ + K+) - (Cl- + HCO-3).
what is a normal anion gap?
The normal range = 10-18 mmol/L
What causes metabolic acidosis with normal anion gap?
Normal anion gap ( = hyperchloraemic metabolic acidosis)
gastrointestinal bicarbonate loss:
prolonged diarrhoea: may also result in hypokalaemia
ureterosigmoidostomy
fistula
renal tubular acidosis
drugs: e.g. acetazolamide
ammonium chloride injection
Addison’s disease
what causes metabolic acidosis with a raised anion gap?
Raised anion gap
lactate:
shock
sepsis
hypoxia
ketones:
diabetic ketoacidosis
alcohol
urate: renal failure
acid poisoning: salicylates, methanol
what are the causes of metabolic acidosis due to raised lactate?
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
lactic acidosis type A: sepsis, shock, hypoxia, burns
lactic acidosis type B: metformin
what may happed to eGFR in body builders?
The eGFR is often inaccurate in people with extremes of muscle mass. Body builders often have an inappropriately low eGFR.
what are the stages of CKD?
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
Initial management of renal colic?
NSAIDs are the treatment of choice
the NICE guidelines suggest for patients who require admission: ‘Administer a parenteral analgesic (such as intramuscular diclofenac) for rapid relief of severe pain’
Alpha blockers - promote smooth muscle relaxation and dilatation of the ureter potentially easing stone assuage - consider if stone less than 10mm
Investigations for renal stone?
urine dipstick and culture
serum creatinine and electrolytes: check renal function
FBC / CRP: look for associated infection
calcium/urate: look for underlying causes
stone analysis should be considered once the stone has passed
also: clotting if percutaneous intervention planned and blood cultures if pyrexial or other signs of sepsis
Non-contrasr CT KUB - within 24 hours of admission
USS for pregnant woman and children
management of renal stones?
Simplified first-line NICE guidance (please see guidelines for more details) NICE
Renal stones
watchful waiting if < 5mm and asymptomatic
5-10mm shockwave lithotripsy
10-20 mm shockwave lithotripsy OR ureteroscopy
> 20 mm percutaneous nephrolithotomy
Uretic stones
shockwave lithotripsy +/- alpha blockers>< 10mm shockwave lithotripsy +/- alpha blockers
10-20 mm ureteroscopy
Stones < 5 mm will usually pass spontaneously. Lithotripsy and nephrolithotomy may be for severe cases.
what is shockwave lithotripsy?
A shock wave is generated external to the patient, internally cavitation bubbles and mechanical stress lead to stone fragmentation
The passage of shock waves can result in the development of solid organ injury
Fragmentation of larger stones may result in the development of ureteric obstruction
The procedure is uncomfortable for patients and analgesia is required during the procedure and afterwards.
What is ureteroscopy?
A ureteroscope is passed retrograde through the ureter and into the renal pelvis
It is indicated in individuals (e.g. pregnant females) where lithotripsy is contraindicated and in complex stone disease
In most cases a stent is left in situ for 4 weeks after the procedure.
what is percutaneous nephrolithotomy?
In this procedure, access is gained to the renal collecting system
Once access is achieved, intra corporeal lithotripsy or stone fragmentation is performed and stone fragments removed.
How are renal stones prevented?
Calcium stones may be due to hypercalciuria, which is found in up to 5-10% of the general population.
high fluid intake
add lemon juice to drinking water
avoid carbonated drinks
limit salt intake
potassium citrate may be beneficial NICE
thiazides diuretics (increase distal tubular calcium resorption)
Oxalate stones
cholestyramine reduces urinary oxalate secretion
pyridoxine reduces urinary oxalate secretion
Uric acid stones
allopurinol
urinary alkalinization e.g. oral bicarbonate
what conditions typically present with a nephritic syndrome?
Rapidly progressive glomerulonephritis - aka crescentic glomerulonephritis
rapid onset, often presenting as acute kidney injury
causes include Goodpasture’s, ANCA positive vasculitis
IgA nephropathy - aka Berger’s disease, mesangioproliferative GN
typically young adult with haematuria following an URTI
there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
What conditions may present with mixed nephritic/nephrotic presentation?
Diffuse proliferative glomerulonephritis
classical post-streptococcal glomerulonephritis in child
presents as nephritic syndrome / acute kidney injury
most common form of renal disease in SLE
Membranoproliferative glomerulonephritis (mesangiocapillary)
type 1: cryoglobulinaemia, hepatitis C
type 2: partial lipodystrophy
what conditions usually present with nephrotic syndrome?
Minimal change disease
typically a child with nephrotic syndrome (accounts for 80%)
causes: Hodgkin’s, NSAIDs
good response to steroids
Membranous glomerulonephritis
presentation: proteinuria / nephrotic syndrome / chronic kidney disease
cause: infections, rheumatoid drugs, malignancy
1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop chronic kidney disease
Focal segmental glomerulosclerosis
may be idiopathic or secondary to HIV, heroin
presentation: proteinuria / nephrotic syndrome / chronic kidney disease
What is the mechanism of action of spironolactone?
Spironolactone is an aldosterone antagonist which acts in the cortical collecting duct.
aldosterone antagonists lead to increased sodium (and water) excretion while conserving potassium
Indications for Spironolactone?
ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used
hypertension: used in some patients as a NICE ‘step 4’ treatment
heart failure (see RALES study below)
nephrotic syndrome
Conn’s syndrome
adverse effects of spironolactone?
hyperkalaemia
gynaecomastia: less common with eplerenone
What is fanconi syndrome?
Fanconi syndrome describes a generalised reabsorptive disorder of renal tubular transport in the proximal convoluted tubule
what does fanconi syndrome lead to?
type 2 (proximal) renal tubular acidosis
polyuria
aminoaciduria
glycosuria
phosphaturia
osteomalacia
Causes of Fanconi syndrome?
cystinosis (most common cause in children)
Sjogren’s syndrome
multiple myeloma
nephrotic syndrome
Wilson’s disease
features of HIV associated nephropathy?
There are five key features of HIVAN:
massive proteinuria resulting in nephrotic syndrome
normal or large kidneys
focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy
elevated urea and creatinine
normotension
what is Alpert’s syndrome?
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 are the features of Alpert’s syndrome?
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
How is Alpert’s syndrome Diagnosed?
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 causes acute interstitial nephritis?
drugs: the most common cause, particularly antibiotics
penicillin
rifampicin
NSAIDs
allopurinol
furosemide
systemic disease: SLE, sarcoidosis, and Sjogren’s syndrome
infection: Hanta virus , staphylococci
what is the pathophysiology of acute interstitial nephritis?
marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules
what are the features of acute interstitial nephritis?
fever, rash, arthralgia
eosinophilia
mild renal impairment
hypertension
what are the investigations for acute interstitial nephritis?
sterile pyuria
white cell casts
what is seen in membranous glomerulonephritis on renal biopsy?
Renal biopsy demonstrates:
electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a ‘spike and dome’ appearance
how does membrane glomerulonephritis present?
Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF). It usually presents with nephrotic syndrome or proteinuria.
causes of membranous glomerulonephitits?
idiopathic: due to anti-phospholipase A2 antibodies
infections: hepatitis B, malaria, syphilis
malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
drugs: gold, penicillamine, NSAIDs
autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
How is membranous glomerulonephritis managed?
all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB):
these have been shown to reduce proteinuria and improve prognosis
immunosuppression
as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression
corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used
consider anticoagulation for high-risk patients
good prognostic features in membranous glomerulonephritis ?
Good prognostic features include female sex, young age at presentation and asymptomatic proteinuria of a modest degree at the time of presentation.
genetics of autosomal dominant polycystic kidney disease?
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 - chromosome 16
ADPKD type 2 - chromosome 4
management of ADPKD?
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.
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
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
what is diabetes insipidus?
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).
investigation for diabetes insipidus?
high plasma osmolality, low urine osmolality
a urine osmolality of >700 mOsm/kg excludes diabetes insipidus
water deprivation test
management of diabetes Insipidus?
nephrogenic diabetes insipidus
thiazides
low salt/protein diet
central diabetes insipidus can be treated with desmopressin
pathophysiology of minimal change disease?
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
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
management of minimal change disease?
oral corticosteroids: majority of cases (80%) are steroid-responsive
cyclophosphamide is the next step for steroid-resistant cases
how is lupus nephritis classified?
WHO classification
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis
Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal biopsy characteristically shows the following findings:
glomeruli shows endothelial and mesangial proliferation, ‘wire-loop’ appearance
if severe, the capillary wall may be thickened secondary to immune complex deposition
electron microscopy shows subendothelial immune complex deposits
granular appearance on immunofluorescence
how is lupus nephritis managed?
Management
treat hypertension
initial therapy for focal (class III) or diffuse (class IV) lupus nephritis
glucocorticoids with either mycophenolate or cyclophosphamide
subsequent therapy
mycophenolate is generally preferred to azathioprine to decrease the risk of developing end-stage renal disease
endocrine effets of renal cell cancer?
may secrete erythropoietin (polycythaemia)
parathyroid hormone-related protein (hypercalcaemia), renin
ACTH
features of renal cell cancer?
haematuria
loin pain
abdominal mass
pyrexia
varicocele
majority are left-sided
caused by the tumour compressing veins
what is Stauffer syndrome?
Stauffer syndrome
a paraneoplastic disorder associated with renal cell cancer
typically presents as cholestasis/hepatosplenomegaly
it is thought to be secondary to increased levels of IL-6
how is renal cell cancer managed?
for confined disease a partial or total nephrectomy depending on the tumour size
patients with a T1 tumour (i.e. < 7cm in size) are typically offered a partial nephrectomy
alpha-interferon and interleukin-2 have been used to reduce tumour size and also treat patients with metatases
receptor tyrosine kinase inhibitors (e.g. sorafenib, sunitinib) have been shown to have superior efficacy compared to interferon-alpha
tumour markers associated with testicular cancer?
germ cell tumours
seminomas: seminomas: hCG may be elevated in around 20%
non-seminomas: AFP and/or beta-hCG are elevated in 80-85%
LDH is elevated in around 40% of germ cell tumours
what are the types of germ testicular cancers?
Around 95% of cases of testicular cancer are germ-cell tumours. Germ cell tumours may essentially be divided into:
seminomas
non-seminomas: including embryonal, yolk sac, teratoma and choriocarcinoma
Non-germ cell tumours include Leydig cell tumours and sarcomas.
features of testicular cancer?
a painless lump is the most common presenting symptom
pain may also be present in a minority of men
hydrocele
gynaecomastia
this occurs due to an increased oestrogen:androgen ratio
germ-cell tumours → hCG → Leydig cell dysfunction → increases in both oestradiol and testosterone production, but rise in oestradiol is relatively greater than testosterone
leydig cell tumours → directly secrete more oestradiol and convert additional androgen precursors to oestrogens
A mutation in the gene that encodes aquaporin 2 is most likely to result in:
nephrogenic diabetes insipidus
what is calciphylaxis?
Calciphylaxis is a rare complication of end-stage renal failure. The underlying mechanism is not clear, however it results in deposition of calcium within arterioles causing microvascular occlusion and necrosis of the supplied tissue. It most commonly affects the skin and presents with painful necrotic skin lesions.
how is calciphylaxis managed?
Treatment of calciphylaxis focuses on reducing calcium and phosphate levels, controlling hyperparathyroidism and avoiding contributing drugs such as warfarin and calcium containing compounds.
how may renal vascular disease present?
It may present as hypertension, chronic renal failure or ‘flash’ pulmonary oedema.
Another common presentation is a sharp rise in creatinine following the initiation of ACE inhibitor therapy (e.g. hypertension that may itself be linked to the underlying renal artery stenosis).
ACE inhibitors reduce angiotensin II levels, which normally constrict the efferent arterioles in the glomerulus to maintain glomerular filtration pressure, especially in states of decreased renal perfusion
- when an ACE inhibitor is introduced, the reduction in angiotensin II levels leads to dilation of the efferent arterioles
in patients with renal artery stenosis, this change can significantly reduce the glomerular filtration rate (GFR), causing a sharp rise in serum creatinine
investigations for renal vascular disease?
MR angiography is now the investigation of choice
CT angiography
conventional renal angiography is less commonly performed used nowadays, but may still have a role when planning surgery
what is suggestive of falcon syndrome?
a normal anion gap metabolic acidosis, reduced serum bicarbonate and potassium levels, alongside increased urinary excretion of amino acids, glucose, bicarbonate, and phosphate, are indicative of Fanconi syndrome. Fanconi syndrome is characterised by impaired reabsorptive function in the PCT leading to excessive urinary loss of these substances. Consequently, this dysfunction can result in renal tubular acidosis (RTA) type 2 due to diminished bicarbonate reabsorption causing metabolic acidosis.
what are the complications of nephrotic syndrome
increased risk of thromboembolism related to loss of antithrombin III and plasminogen in the urine
deep vein thrombosis, pulmonary embolism
renal vein thrombosis, resulting in a sudden deterioration in renal function
hyperlipidaemia
increasing risk of acute coronary syndrome, stroke etc
chronic kidney disease
increased risk of infection due to urinary immunoglobulin loss
hypocalcaemia (vitamin D and binding protein lost in urine)
stages of diabetic nephropathy?
Stage 1
hyperfiltration: increase in GFR
may be reversible
Stage 2 (silent or latent phase)
most patients do not develop microalbuminuria for 10 years
GFR remains elevated
Stage 3 (incipient nephropathy)
microalbuminuria (albumin excretion of 30 - 300 mg/day, dipstick negative)
Stage 4 (overt nephropathy)
persistent proteinuria (albumin excretion > 300 mg/day, dipstick positive)
hypertension is present in most patients
histology shows diffuse glomerulosclerosis and focal glomerulosclerosis (Kimmelstiel-Wilson nodules)
Stage 5
end-stage renal disease, GFR typically < 10ml/min
renal replacement therapy needed
