Nephrology Flashcards
Normal anion gap ( = hyperchloraemic metabolic acidosis)
gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula renal tubular acidosis drugs: e.g. acetazolamide ammonium chloride injection Addison's disease
Raised anion gap
actate: shock, sepsis, hypoxia
ketones: diabetic ketoacidosis, alcohol
urate: renal failure
acid poisoning: salicylates, methanol
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
IgA Nephropathy
what is it?
(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.
IgA Nephropathy
associated diseases
alcoholic cirrhosis
coeliac disease/dermatitis herpetiformis
Henoch-Schonlein purpura
Pathophysiology of IgA Nephropathy
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
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
Differentiation 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
Management of IgA Nephropathy
Isolated hematuria, no or minimal proteinuria (less than 500 to 1000 mg/day), and a normal glomerular filtration rate (GFR)
no treatment needed, other than follow-up to check renal function
persistent proteinuria (above 500 to 1000 mg/day), a normal or only slightly reduced GFR
initial treatment is with ACE inhibitors
if there is active disease (e.g. falling GFR) or failure to respond to ACE inhibitors
immunosuppression with corticosteroids
Prognosis of IgA Nephropathy
25% of patients develop ESRF
markers of good prognosis: frank haematuria
markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD
Post streptococcous 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.
Post streptococcous glomerulonephritis
features
general headache malaise visible haematuria proteinuria this may result in oedema hypertension oliguria bloods: low C3 raised ASO titre
Post streptococcous glomerulonephritis
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’ appearance
Carries a good prognosis
histology of IgA nephropathy
histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3
membranoproliferative glomerulonephritis (type I) histology
Subendothelial immune complex deposits with ‘tram-track’ appearance on electron microscopy
membranous glomerulonephritis histology
Thickened basement membrane with subepithelial electron dense deposits creating a ‘spike and dome’ appearance
Mechanism of action: Spironolactone
aldosterone antagonist which acts in the cortical collecting duct.
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
Aetiology of Faconi’s syndrome
Generalised disorder of renal tubular transport in the proximal convoluted tubule
Features of Anti-Glomerular Basement Membrane Disease
pulmonary haemorrhage
rapidly progressive glomerulonephritis
this typically results in a rapid onset acute kidney injury
nephritis → proteinuria + haematuria
Investigation findings in Anti-glomerular basement membrane disease (Goodpasteurs)
renal biopsy: linear IgG deposits along the basement membrane
raised transfer factor secondary to pulmonary haemorrhages
Management of Anti-glomerular basement membrane disease
plasmaphoresis
steroids
cyclophosphamide
Risk factors for pulmonary haemorrhage in anti-glomerular basement membrane disease
smoking lower respiratory tract infection pulmonary oedema inhalation of hydrocarbons young males
urine sodium in acute tubular necrosis
> 40mmol
metabolic abnormalities caused by ammonium chloride injection
normal anion gap metabolic acidosis
normal anion gap metabolic acidosis causes
gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula renal tubular acidosis drugs: e.g. acetazolamide ammonium chloride injection Addison's disease
raised anion gap metabolic acidosis
lactate: shock, sepsis, hypoxia
ketones: diabetic ketoacidosis, alcohol
urate: renal failure
acid poisoning: salicylates, methanol
raised anion gap metabolic acidosis
lactate: shock, sepsis, hypoxia
ketones: diabetic ketoacidosis, alcohol
urate: renal failure
acid poisoning: salicylates, methanol
typical history: minimal change disease
a 15-year-old presents with nephrotic syndrome. Their blood pressure and renal blood tests are normal
typical history IgA nephropathy
a 25-year-old man presents with visible haematuria. He also complains of having a bad sore throat at the current time
Features of Henoch-Schonlein purpura
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 Henoch-Schonlein purpura
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.
treatment of Henoch-Schonlein purpura
analgesia for arthralgia
treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants
typical histories of streptococcus pyogenes
a 10-year-old boy boy presents after passing ‘brown’ urine. Two weeks ago he had a severe sore throat. On examination his blood pressure is high for his age and there is periorbital oedema
a 10-year-old presents with fever. They complain of fleeting large joint pain and ‘jerking’ movements of the hand and face. On examination a murmur is noted and subcutaneous nodules on the wrists
a 10-year-old presents with fever and a sore throat. Today they have a developed a fine, erythematous, ‘sand-paper’ rash which is more prominent in flexural areas.
Type 1 Membranoproliferative glomerulonephritis
accounts for 90% of cases
cause: cryoglobulinaemia, hepatitis C
renal biopsy
electron microscopy: subendothelial and mesangium immune deposits of electron-dense material resulting in a ‘tram-track’ appearance
Type 2 Membranoproliferative glomerulonephritis
- ‘dense deposit disease’
causes: partial lipodystrophy (patients classically have a loss of subcutaneous tissue from their face), factor H deficiency
caused by persistent activation of the alternative complement pathway
low circulating levels of C3
C3b nephritic factor is found in 70%
an antibody to alternative-pathway C3 convertase (C3bBb)
stabilizes C3 convertase
renal biopsy
electron microscopy: intramembranous immune complex deposits with ‘dense deposits’
Type 3 Membranoproliferative glomerulonephritis
causes: hep B and C
What is Alport’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.
typical question around Alport’s syndrome
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
Features of Alport’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
minimal change histology:
Effacement of foot processes on electron microscopy
CKD bone disease- basic problems
low vitamin D (1-alpha hydroxylation normally occurs in the kidneys)
high phosphate
low calcium: due to lack of vitamin D, high phosphate- due to reduced excretion
secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D
CKD bone disease - clinical manifestations
Osteitis fibrosa cystica aka hyperparathyroid bone disease Adynamic reduction in cellular activity (both osteoblasts and osteoclasts) in bone may be due to over treatment with vitamin D Osteomalacia due to low vitamin D Osteosclerosis Osteoporosis
Atypical haemolytic uraemic syndrome
encompasses many diseases with microangiopathic haemolytic anaemia with schistocytes and thrombocytopenia
No DIARRHOEAL syndromes
Haemolytic uraemic syndrome triad
Acute kidney injury
microangiopathic haemolytic anaemia
thrombocytopenia
Secondary causes of HUS
classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7 (‘verotoxigenic’, ‘enterohaemorrhagic’). This is the most common cause in children, accounting for over 90% of cases
pneumococcal infection
HIV
rare: systemic lupus erythematosus, drugs, cancer
Investigations of HUS
full blood count: anaemia, thrombocytopaenia, fragmented blood film U&E: acute kidney injury stool culture looking for evidence of STEC infection PCR for Shiga toxins
Management of HUS
Largely supportive
eculizumab (a C5 inhibitor monoclonal antibody) may be more beneficial than plasma exchange
Alports syndrome
hereditary nephritis due to a basement membrane disorder resulting in haematuria as a renal manifestation. Microscopic hematuria is persistent and invariable in males affected by Alport’s disease. Haematuria may present with/without bilateral anterior lenticonus and sensorineural hearing loss.
Genetics of Alports syndrome
X-linked dominant inheritance
Type IV collagen defect that leads to abnormal basement membrane
Features of Alport 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
Diagnosis of Alport syndrome
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
mechanism of action: Calcium resonium
Calcium and sodium cations are exchanged for hydrogen ions in the stomach. These hydrogen ions are then exchanged for potassium ions in the large intestine and the potassium ions are excreted from the bowel as part of the resin comple
What is cystinuria
Cystinuria is an autosomal recessive disorder characterised by the formation of recurrent renal stones. It is due to a defect in the membrane transport of cystine, ornithine, lysine, arginine (mnemonic = COLA)
Features of cystinuria
recurrent renal stones
are classically yellow and crystalline, appearing semi-opaque on x-ray
Diagnosis of cystinuria
cyanide-nitroprusside test
Management of cystinuria
hydration
D-penicillamine
urinary alkalinization
Glomerulonephritis and low complement
post-streptococcal glomerulonephritis
subacute bacterial endocarditis
systemic lupus erythematosus
mesangiocapillary glomerulonephritis
Glomerulonephritis with normal complement
levels
Goodpastures syndrome
rare condition associated with both pulmonary haemorrhage and rapidly progressive glomerulonephritis. It is caused by anti-glomerular basement membrane (anti-GBM) antibodies against type IV collagen
Complications of nephrotic syndrome
Anti-thrombin III deficiency (and plasminogen)- lost through glomerular basement membrane –> DVT/PE/renal vein thrombosis
Hyperlipidaemia
CKD
Increased infection risk - loss of urinary immunoglobulin loss
hypocalcaemia
Rapidly progressive glomerulonephritis
Rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.
Causes
Goodpasture’s syndrome
Wegener’s granulomatosis
others: SLE, microscopic polyarteritisR
Urine dip - protein positive
intra-renal AKI
Bacterial infections in Peritoneal dialysis
Coagulase-negative Staphylococcus species e.g. Staphylococcus epidermidis and Staphylococcus capitis peritonitis remains a common complication of peritoneal dialysis. Empiric antibiotic therapy usually aims to cover both gram-positive and gram-negative organisms.
Goodpastures accronyms
IgG deposits on renal biopsy
anti-GBM antibodies
Features of Goodpastures/anti-glomerular basement membrane disease
pulmonary haemorrhage
rapidly progressive glomerulonephritis
this typically results in a rapid onset acute kidney injury
nephritis → proteinuria + haematuria
Investigations in Goodpastures/ anti-glomerular membrane basement disease
renal biopsy: linear IgG deposits along the basement membrane
raised transfer factor secondary to pulmonary haemorrhages
Management of Goodpastures
plasma exchange (plasmapheresis)
steroids
cyclophosphamide
Risk factors for pulmonary haemorrhage in Goodpastures disease
smoking lower respiratory tract infection pulmonary oedema inhalation of hydrocarbons young males
Poor prognostic factors in IgA Nephropathy
male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD
Management of IgA nephropathy
isolated hematuria, no or minimal proteinuria (less than 500 to 1000 mg/day), and a normal glomerular filtration rate (GFR)
no treatment needed, other than follow-up to check renal function
persistent proteinuria (above 500 to 1000 mg/day), a normal or only slightly reduced GFR
initial treatment is with ACE inhibitors
if there is active disease (e.g. falling GFR) or failure to respond to ACE inhibitors
immunosuppression with corticosteroids
Differentiating between IgA Nephropathy and post streptococcous 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
Pathophysiology of IgA Nephropathy
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
What is diabetes insipidus
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)
Causes of cranial diabetes insipidus
idiopathic post head injury pituitary surgery craniopharyngiomas histiocytosis X DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome) haemochromatosis
Causes of nephrogenic diabetes insipidus
genetic: the more common form affects the vasopression (ADH) receptor, the 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
Features of HSP
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
Pre-renal or ATN - AKI
In prerenal uraemia think of the kidneys holding on to sodium to preserve volume
Pre-renal = urinary sodium excretion = 20%
Mechanism of action: Spironalactone
aldosterone antagonist which acts in the cortical collecting duct.
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
Prevention of calcium renal stones
high fluid intake low animal protein, low salt diet (a low calcium diet has not been shown to be superior to a normocalcaemic diet) thiazides diuretics (increase distal tubular calcium resorption)
prevention of oxalate renal stones
cholestyramine reduces urinary oxalate secretion
pyridoxine reduces urinary oxalate secretion
prevention of uric acid renal stones
allopurinol
urinary alkalinization e.g. oral bicarbonate
Genetic changes that cause nephrogenic diatbetes insipidus
the more common form affects the vasopression (ADH) receptor
the less common form results from a mutation in the gene that encodes the aquaporin 2 channel
Fibromuscular dysplasia
Young female, hypertension and asymmetric kidneys
Features of fibromuscular dysplasia
hypertension
chronic kidney disease or more acute renal failure e.g. secondary to ACE-inhibitor initiation
‘flash’ pulmonary oedema
Electron microscopy in minimal change disease
normal glomeruli on light microscopy
electron microscopy shows fusion of podocytes and effacement of foot processes
Membranoproliferative glomerulonephritis type 1
accounts for 90% of cases
cause: cryoglobulinaemia, hepatitis C
renal biopsy
electron microscopy: subendothelial and mesangium immune deposits of electron-dense material resulting in a ‘tram-track’ appearance
Membranoproliferative glomerulonephritis type 2
causes: partial lipodystrophy (patients classically have a loss of subcutaneous tissue from their face), factor H deficiency
caused by persistent activation of the alternative complement pathway
low circulating levels of C3
C3b nephritic factor is found in 70%
an antibody to alternative-pathway C3 convertase (C3bBb)
stabilizes C3 convertase
renal biopsy
electron microscopy: intramembranous immune complex deposits with ‘dense deposits’
AL amyloidosis
the most common form of amyloidosis
L for immunoglobulin Light chain fragment
due to myeloma, Waldenstrom’s, MGUS
features include: nephrotic syndrome, cardiac and neurological involvement, macroglossia, periorbital eccymoses
AA amyloidosis
A for precursor serum amyloid A protein, an acute phase reactant
seen in chronic infection/inflammation
e.g. TB, bronchiectasis, rheumatoid arthritis
features: renal involvement most common feature
Beta-2 microglobulin amyloidosis
precursor protein is beta-2 microglobulin, part of the major histocompatibility complex
associated with patients on renal dialysis
Magnesium ammonium phosphate, (also known as struvite) renal stones
caused by urea splitting bacteria e.g. proteus.
can cause staghorn calculi
Causes of papillary necrosis
chronic analgesia use sickle cell disease TB acute pyelonephritis diabetes mellitus
Features of papillary necrosis
fever, loin pain, haematuria
IVU - papillary necrosis with renal scarring - ‘cup & spill’
Nephrogenic diabetes insipidus
presents with polyuria and polydipsia. The kidneys are not responding to antidiuretic hormone (ADH) and so osmolality remains low post-water deprivation, as they fail to concentrate urine. Osmolality remains low after administering desmopressin, as the kidneys cannot res
Tolvaptan mechanism of action
action of vasopressin at the V2 receptor. This receptor is found on the basolateral membrane of the principal cells in the collecting ducts of the kidney. This reduces water absorption (through decreased aquaporin 2) and increases aquaresis without sodium loss. Desmopressin is a synthetic analogue of vasopressin that exerts agonism at the V2 receptor.
V1 receptors
found on vascular smooth muscle and when activated cause vasoconstriction. V3 receptors are expressed in the pituitary gland and modulate ACTH secretion.
Mechanism of action Abiraterone acetate
selective androgen synthesis inhibitor that works by blocking cytochrome P450 17 alpha-hydroxylase. It blocks androgen production in the testes and adrenal glands, and in prostatic tumour tissue. Abiraterone is administered orally in combination with prednisolone
paraneoplastic hepatic dysfunction syndrome
Also known as Stauffer syndrome. Typically presents as cholestasis/hepatosplenomegaly. It is thought to be secondary to increased levels of IL-6
