Nephrology Flashcards
What are the causes of metabolic acidosis:
Normal anion gap (hyperchloraemic)
- GI bicarbonate loss - diarrhoea, uterosigmoidostomy, fistula
- renal tubular acidosis
- drugs e.g. acetazolamide
- ammonium chloride injection
- Addison’s
Increased anion gap
- lactate: shock, hypoxia
- ketonones: DKA, alcohol
- urate: renal failure
- acid poisoning: salicylates, methanol
Causes of metabolic alkalosis:
Loss of hydrogen ions or gain of bicarbonate due to kidney or GI problems:
- vomiting/aspiration
- diuretics
- liquorice, carbenoxolone
- hypokalaemia
- primary hyperaldosteronism
- Cushing’s syndrome
- Bartter’s syndrome
- congenital adrenal hyperplasia
Causes of respiratory acidosis:
- COPD
- decompensation other resp conditions
- sedatives: benzodiazepines, opiate overdose
Causes of respiratory alkalosis:
- anxiety
- PE
- salicylate poisoning
- CNS disorders: stroke, SAH, encephalitis
- altitude
- pregnancy
What causes type A lactic acidosis?
- sepsis
- shock
- hypoxia
- burns
What causes type B lactic acidosis?
metformin
What are the causes of acute interstitial nephritis?
Drugs:
- penicillin
- rifampicin
- NSAIDs
- allopurinol
- furosemide
- systemic: SLE, sarcoidosis, Sjogren’s
- infection: Hanta virus, staphylococci
What are the features and investigations of acute interstitial nephritis?
- fever, rash, arthralgia
- eosinophilia (casts)
- mild renal impairment
- HTN
- sterile pyuria and white cell casts
Pre-renal causes of AKI:
ischaemia: e.g. hypovolaemia secondary to diarrhoea/vomiting, renal artery stenosis etc.
Renal causes of AKI:
- intrinstc damage to glomeruli, renal tubules or interstitium
e. g. toxins (drugs, contrast), GN, ATN, AIN, rhabdomyolysis, tumour lysis syndrome
Postrenal causes of AKI:
obstruction to urine: e.g. stones, hydronephrosis, external compression etc.
Risk factors of AKI:
- CKD
- other organ failure/chronic disease e.g. HF, liver disease, diabetes
- history of acute AKI
- nephrotoxic drugs: NSAIDs, aminoglycosides, ACEi, ARBs and diuretics in past week
- iodinated contrast agent
- > =65yo
- oliguria (<0.5ml/kg/hr)
Symptoms and detection of AKI:
Symptoms:
- reduced urine output
- pulmonary and peripheral oedema
- arrhythmias (secondary to changes in K+)
- features of uraemia (e.g. pericarditis or encephalopathy)
Detection:
- creatinine increase by >=26micromol/L in 48 hours
- 50% or greater rise in serum creatinine or within 7 days
- reduced urine output <0.5ml/kg/hr for more than 6 hours
- urinalysis
- renal US within 24 hours
Drugs which should be stopped in AKI:
-NSAIDs
-aminoglycosides
-ACEi
-ARB
-diuretics
(metformin, lithium, digoxin)
How do you treat hyperkalaemia e.g. in AKI?
- IV calcium gluconate
- combined insulin/dextrose infusion
- nebulised salbutamol
- calcium resonium (oral or enema)
- loop diuretics
- dialysis
Criteria for diagnosing AKI:
- rise in creatinine of 26micromol/L or more in 48 hours OR
- > =50% rise in creatinine over 7 days OR
- fall in urine output to less than 0.5ml/kg/hour for more than 6 hours in adults (8 in children) OR
- > =25% fall in eGFR in children/young adults in 7 days
When do you refer AKI to a nephrologist?
- renal transplant
- ITU with unknown cause AKI
- vasculitis/GN/tuberointerstitial nephritis/myeloma
- AKI with no known cause
- inadequate response to treatment
- complications of AKI
- stage 3 AKI
- CKD stage 4 or 5
- qualify for renal replacement hyperkalaemia/metabolic acidosis/complications of uraemia/fluid overload (pulmonary oedema)
How can you differentiate between acute and chronic renal failure?
-renal US
-most chronic have bilateral small kidneys
EXCEPT ADPKD, diabetic nephropathy, amyloidosis, HIV associated nephropathy
-chronic has hypocalcaemia due to reduced vit D
What are the types of ADPKD?
Type I: -polycysitn-1 -85% of cases -chromosome 16 -presents with renal failure earlier Type II: -polycystin-2 -chromosome 4
Features and extra renal manifestations of ADPKD:
- HTN
- recurrent UTIs
- abdominal pain
- renal stones
- haematuria
- CKD
- extra-renal: liver cysts, berry aneurysms (SAH), mitral valve prolapse, mitral/tricuspid incompetence, aortic root dilation, aortic dissection
- cysts in other organs: pancreas, spleen, rarely thyroid, oesophagus and ovary
How do you manage ADPKD:
- tolvaptan (vasopressin receptor 3 antagonist)
- if CKD stage II or III, evidence of rapidly progressing disease
What is Alport’s syndrome? (incl features)
- x-linked dominant
- defect gene coding for type IV collagen (abnormal GBM)
- more severe in males
- presents in childhood
Features:
- mircoscopic haematuria
- progressive renal failure
- bilateral sensorineural deafness
- leticonus
- retinitis pigmentosa
- renal biopsy: splitting of lamina densa
What is Amyloidosis?
- extracellular deposition of insoluble fibrillar protein - amyloid
- also apolipoprotein E and heparin sulphate proteoglycans
- accumulation of amyloid fibrils - tissue/organ dysfunction
How do you diagnose amyloidosis?
- congo red staining - apple-green birefringence
- serum amyloid precursor scan
- biopsy of rectal tissue
What is an anion gap?
(sodium+potassium) - (bicarbonate+chloride)
normal: 8-14mmol/L
What is anti-GBM disease?
- Goodpasture’s
- rare, small vessel vasculitis
- associated with pulmonary haemorrhage and rapidly progressive GN
- antibodies against type IV collagen
- more common in men 2:1
- HLA DR2
How do you test for and manage anti-GBM disease?
- renal biopsy: linear IgG deposits along BM
- increased transfer factor secondary to pulmonary haemorrhages
- manage with: plasma exchange, steroids, cyclophosphamide
What increases the risk of pulmonary haemorrhage in anti-GBM?
- smoking
- lower RTI
- pulmonary oedema
- inhalation of hydrocarbons
- young males
What is ARPKD?
- autosomal recessive version
- much less common
- defect in gene on chromosome 6 which encodes fibrocytin
- end stage renal failure in childhood
- liver involvement (portal and interlobular fibrosis)
- renal biopsy shows multiple cylindrical lesions
- diagnosis on prenatal US: abdominal masses and renal failure, consistent with Potter’s syndrome secondary to oligohydramnios
Complications of AV fistulae?
- infection
- thrombosis (absence of bruit)
- stenosis (acute limb pain)
- steal syndrome
What is diabetes insipidus and what are the features and investigation?
- either deficiency of ADH (cranial) or insensitivity to ADH (nephrogenic)
- polyuria and polydipsia
- increased plasma osmolality and decreased urine osmolality
- urine osmolality >700mOsm/kg excludes DI
- water deprivation test
What causes cranial diabetes insipidus and what is the management?
-idiopathic
-post HI
-pituitary surgery
-craniopharyngiomas
-histiocytosis X
-DIDMOAD (Wolfram’s syndrome)
-haemochromatosis
manage with desmopressin
What are the causes of nephrogenic diabetes insipidus and the management?
-genetic (ADH receptor or aquaporin 2 channel)
-electrolytes (hypercalcaemia and hypokalaemia)
-drugs: demeclocycline, lithium
-tubulo-interstitial disease: obstruction, sickle cell, pyelonephritis
manage with thiazides, low salt/protein diet
Side effects of erythropoietin therapy and indication:
-used for anaemia associated with CKD can cause: -accelerated HTN - encephalopathy and seizures -bone aches -flu-like -skin rashes, urticaria -pure red cell aplasia -increased PCV - thrombosis -iron deficiency secondary to increased erythropoiesis
Why might someone be unresponsive to erythropoietin therapy?
- iron deficiency
- inadequate dose
- concurrent infection/inflammation
- hyperparathyroid bone disease
- aluminium toxicity
What is Fanconi syndrome, features and causes?
- generalised reabsorptive disorder of renal tubular transport in the proximal convoluted tubule
- polyuria, type II RTA, aminoaciduria, glycosuria, phosphaturia, osteomalacia
- causes: cystinosis, Sjogren’s, multiple myeloma, nephrotic syndrome, Wilson’s
What is fibromuscular dysplasia?
- renal artery stenosis secondary to atherosclerosis
- 90% female
- causes HTN, CKD and flash pulmonary oedema
Maintenance fluids:
- 25-30ml/kg/day water
- 1mmol/kg/day of potassium, sodium and chloride
- 50-100g/day of glucose to limit starvation ketosis
What is the risk of using large volumes of NaCl 0.9%?
increased risk of hyperchloraemic metabolic acidosis
In which patients is Hartmann’s contraindicated?
hyperkalaemic patients
What is focal segmental glomerulosclerosis and the causes?
- causes nephrotic syndrome and CKD
- young adults
- idiopathic
- secondary to other renal pathology
- HIV
- heroin
- Alport’s syndrome
- sickle cell
- high recurrence rate in renal transplants
What are the investigations and management for focal segmental glomerulosclerosis?
- renal biopsy: focal and segmental sclerosis and hyalinosis, effacement of foot processes
- manage with steroids (and immunosuppressants)
Causes of transient or spurious non-visible haematuria:
- UTI
- menstruation
- vigorous exercise (resolves in 3 days)
- sexual intercourse
Spurious causes of haematuria (red/orange urine)
- beetroot, rhubarb
- rifampicin
- doxorubicin
Urgen referral criteria for haematuria:
- > =45yo with unexplained visible haematuria without UTI or visible haemautria that persists after successful treatment of UTI
- > =65yo and unexplained non-visible haematuria and dysuria or increased WCC
Non-urgent referral criteria for haematuria:
- > =60yo with recurrent or persistent unexplained UTI
- <40yo with normal renal function, no proteinuria and normotensive (no referral - manage in primary care)
Presentation of HUS:
- triad: AKI, microangiopathic haemolytic anaemia, thrombocytopaenia
- bloody diarrhoea few days after onset
- most cases secondary to:
- shiga toxin producing e-coli (STEC) O157:H7 - most common in children
- pneumococcal infection
- HIV
- rare: SLE, drugs, cancer
- primary HUS - atypical - complement dysregulation
Management of HUS:
- supportive e.g. dialysis, fluids, blood transfusion
- no Abx
- eculixumab - C5 inhibitor monoclonal antibody
What is Henoch-Schonlein Purpura and the features?
- IgA mediated small vessel vasculitis
- some overlap with IgA nephropathy (Berger’s)
- usually in children following infection
- palpable purpuric rash (with localised oedema) over buttocks and extensor surfaces of arms and legs
- abdominal pain
- polyarthritis
- features of IgA nephropathy
- good prognosis - self-limiting
Treatment of HSP:
- analgesia for arthralgia
- supportive Tx for nephropathy
What is IgA nephropathy, associations, pathophysiology and presentation?
- Berger’s
- most common cause of GN
- associated with: alcoholic cirrhosis, coeliac disease/dermatitis herpetiformis, HSP
- mesangial deposition of IgA immune complexes, mesangial hypercellularity, positive immunofluorescence for IgA and C5
- typically young male with recurrent episodes of macroscopic haematuria following a RTI
- nephrotic range proteinuria rare
- renal failure unusual
IgA nephropathy vs post streptococcal:
- post strep results in low complement
- post strep main symptom proteinuria
- interval between URTI and post-strep onset (1-2 weeks)
Prognosis of IgA nephropathy:
- 25% ESRF
- frank haematuria - good prognosis
- male, proteinuria, HTN, smoking hyperlipidaemia, ACE genotype DD - poor prognosis
How does membranoproliferative GN/mesangiocapillary GN present?
- nephrotic syndrome, haematuria or proteinuria
- poor prognosis
- involves mesangium as well as BM (unlike membranous)
Type I membranoproliferative GN:
- 90% cases
- caused by cryoglobulinaemia, hepatitis C
- renal biopsy: sub endothelial and mesangium immune deposits of electron dense material - tram track appearance
Type II membranoproliferative GN:
- dense deposit disease
- caused by partial lipodystrophy and factor H deficiency
- persistent activation of alternative complement pathway
- low circulating levels of C3
- C3b nephritic factor found in 70%
- renal biopsy: intramembranous immune complex deposits with dense deposits
Type III membranoproliferative GN is caused by:
hepatitis B and C
How do you treat membranoproliferative GN?
steroids
Membranous GN
- most common type in adults
- presents as nephrotic syndrome or proteinuria
- renal biopsy: basement membrane thickened with sub epithelial electron dense deposits (spike and dome)
Causes of membranous GN:
- idiopathic: antiphospholipase A2 antibodies
- infections: hep B, malaria, syphilis
- malignancy: prostate, lung, lymphoma, leukaemia
- drugs: gold, penicillamine, NSAIDs
- autoimmune: SLE, thyroiditis, rheumatoid
Management of membranous GN:
- ACEi or ARB
- immunosuppression (corticosteroid and cyclophosphamide)
- consider anticoagulation
Prognosis of membranous GN:
1/3 spontaneous remission
1/3 remain proteinuric
1/3 ESRF
Minimal change disease (presentation, causes, features, biopsy, management)
- presents as nephrotic syndrome
- causes: idiopathic, drugs, Hodgkin’s lymphoma, thymoma, infectious mononucleosis
- T cell and cytokine mediated damage to GBM - polyanion loss
- normotension, high selective proteinuria (albumin and transferrin leak through glomeruli)
- renal biopsy: normal glomeruli on light microscopy, fusion of podocytes and effacement of foot processes on electron microscopy
- management: majority steroid responsive or cyclophosphamide if steroid resistant (do biopsy)
Prognosis of minimal change disease:
- 1/3 only 1 episode
- 1/3 infrequent relapses
- 1/3 frequent relapses which stops before adulthood
Features of nephrotic syndrome:
- triad: proteinuria, hypoalbuminaemia, oedema
- loss of antithrombin III, protein C and S and associated increase in fibrinogen predisposes to thrombosis
- loss of thyroxine - binding globulin decreased total but not free thyroxine
Complications of nephrotic syndrome:
- increased risk of thromboembolism due to loss of antithrombin III and plasminogen in urine
- hyperlipidaemia - increased risk of ACS, stroke etc.
- CKD
- increased risk of infection due to urinary immunoglobulin loss
- hypocalcaemia (vita and binding protein lost in urine)
Sign of nephrotoxicity contrast media:
25% increase in creatinine within 3 days of intravascular administration
Nephrotoxicity contrast media risk factors and prevention:
- know renal impairment
- > 70 yo
- dehydration
- cardiac failure
- use of nephrotoxic drugs
Prevention:
- IV 0.9% NaCl at 1ml/kg/hr of 12 hours pre- and post-op
- isotonic sodium bicarbonate
- N-acetylcysteine not effective
Complications of peritoneal dialysis:
- peritonitis: coagulase negative staph e.g. staph epidermis most common, also aureus
- sclerosing peritonitis
Post-streptococcal glomerulonephritis presentation and features:
- 7-14 days following group A beta haemolytic strep infection (usually pyogenes)
- immune complex deposition in glomeruli
- mostly young hcildren
- general headache, malaise, visible haematuria, proteinuria, oedema, HTN, oliguria, low C3 and raised ASO titre
- good prognosis
What does the renal biopsy show in post-streptococcal GN?
- acute diffuse proliferative GN
- endothelial proliferation with neutrophils
- electron microscopy: sub epithelial humps cause by lumpy immune complex deposits
Rapidly progressive glomerulonephritis causes and presentation:
- rapid loss of renal function with formation of epithelial crescents in majority of glomeruli
- causes: Good pasture’s, vasculitic rash or sinusitis with Wegener’s
Reflux nephropathy:
- chronic pyelonephritis secondary to vesico ureteric reflux
- commonest cause of chronic GN
- scanning first 5 year
- strong genetic component
- renal scars may produced increased quantities of renin - HTN
- diagnosis by micturating cystography
Renal artery stenosis:
- secondary to atherosclerosis (90% of renal vascular disease)
- HTN, CKD, flash pulmonary oedema
Renal papillary necrosis incl causes and features:
- coagulative necrosis of renal papillae due to variety of causes
- caused by: severe acute pyelonephritis, diabetic nephropathy, obstructive nephropathy, analgesic nephropathy, sickle cell anaemia
- visible haematuria, loin pain, proteinuria
Types of renal replacement therapy:
- haemodialysis
- peritoneal dialysis
- renal transplant
Haemodialysis:
- most common RTT
- most need 3 per week
- surgery to create AV fistula 8 weeks before commencing
Peritoneal dialysis:
- filtration within abdomen
- dialysis solution injected into abdominal cavity through a permanent catheter
- high dextrose concentration of solution draws waste products out
- 2 types: continuous ambulatory and automated peritoneal dialysis
Renal transplant:
- into groin and renal vessels connected to external iliac
- failing kidneys not removed
- life-long immunosuppressants
- average lifespan 10-12 years
Haemodialysis complications:
- site infection
- endocarditis
- stenosis at site
- hypotension
- cardiac arrhythmias
- air embolus
- anaphylactic reaction to sterilising agents
- disequilibration syndrome (cerebral oedema)
Peritoneal dialysis complications:
- peritonitis (staph epidermis)
- sclerosing peritonitis
- catheter infection
- catheter blockage
- constipation
- fluid retention
- hyperglycaemia
- hernias
- back pain
- malnutrition
Renal transplantation complications:
- DVT/PE
- opportunistic infection
- malignancies (particularly lymphoma and skin cancer)
- bone marrow suppression
- recurrence of original disease
- urinary tract obstruction
- CVD
- graft rejection
Hyperacute rejection of transplant:
- pre-existing Ab against ABO or HLA antigens
- type II hypersensitivity
- widespread thrombosis of graft vessels -ischaemia and necrosis
- remove graft
Acute graft failure of transplant:
- <6 mo
- usually mismatched HLA, cell mediated cytotoxic T cells
- or CMV infection
- may be reversible with steroids and immunosuppressants
Chronic graft failure of transplant:
- > 6 mo
- both AB and cell mediated mechanisms cause fibrosis to transplanted kidney
- recurrence of renal disease
Immunosuppression in renal transplantation:
- intial: ciclosporin/tacrolimus with monoclonal Ab
- maintenance: ciclosporin/tacrolimus with MMF or sirolimus
- add steroids if more than one steroid responsive acute rejection episode
Rhabdomyolysis features:
- AKI with disproportionately increased creatinine
- elevated CK
- myoglobulinuria
- hypocalcaemia (myoglobin binds calcium)
- increased phosphate (from myocytes)
- hyperkalaemia (before renal failure)
- metabolic acidosis
Causes of rhabdomyolysis:
- seizure
- collapse/coma
- ecstacy
- crush injury
- McArdle’s syndrome
- drugs: statins (especially with clarithromycin)
Management of rhabdomyolysis:
- IV fluids to maintain good urine output
- urinary alkalisation sometimes used
Causes of sterile pyuria:
- partially treated UTI
- urethritis e.g. chlamydia
- renal tuberculosis
- renal stones
- appendicitis
- bladder/renal cell cancer
- APKD
- analgesic nephropathy
SLE renal complications WHO classifications:
- class I: normal kidney
- class II: mesangial glomerulonephritis
- class III: focal and segmental proliferative GN
- class IV: diffuse proliferative GN
- class V: diffuse membranous GN
- class VI: sclerosis GN
class IV most common and severe
What produces hyaline casts:
- Tamm Horsfall protein secreted by distal convoluted tubule
- normal urine, exercise, fever or loop diuretics
What is visible in the urine in ATN?
brown granular casts
How does the urine appear in prerenal uraemia:
bland urinary sediment
What is visible in the urine with nephritic syndrome?
red cell casts
Symptoms of anaemia in CKD:
- tachycardia
- fatigue
- pallor
- aortic flow murmur
What causes anaemia in CKD:
- usually normochromic normocytic anaemia
- prediposes to left ventricular hypertrophy
- decreased erythropoietin
- reduced erythropoiesis due to toxic effects of uraemia on bone marrow
- reduced iron absorption
- anorexia/nausea due to uraemia
- reduced red cell survival
Management of anaemia in CKD:
- determination of iron status before erythropoiesis stimulation agents
- many patients esp haemodialysis requires IV iron
- ESAs e.g. erythropoietin and darbepoietin
Clinical manifestations of bone disease in CKD:
- osteitis fibrosa cystica (hyperparathyroid bone disease)
- adynamic: cellular activity decreased, may be due to over treatment with vit D
- osteomalacia
- osteoscelerosis
- osteoporosis
Management of bone disease in CKD:
- aim to decrease phos and PTH
- 1st line: decrease phosphate dietary intake
- phosphate binders (sevelamer, calcium based)
- vit D: alfacalcidol (does not require activation in kidneys), calcitriol
- sometimes parathyroidectomy
CKD stage I
- GFR greater than 90ml/min
- some sign of kidney damage
CKD stage II
- 60-90ml/min
- some sign of kidney damage
CKD stage IIIa and b
a -45-59ml/min -moderate reduction kidney function b -30-44ml/min -moderate reduction kidney function
CKD stage IV
- 15-29ml/min
- severe reduction in kidney function
CKD stage V
- less than 15ml/min
- establish kidney failure
- dialysis or kidney transplant needed
What can affect MDRD formula for calculating CKD stage?
- pregnancy
- muscle mass
- eating red meat 12 hours before sample
At what eGFR does a nephrologist need to be called?
<30ml/min
What ratio is used to determine proteinuria in CKD?
ACR over PCR (greater sensitivity)
How should a urine sample be collected for CKD?
- spot sample
- first pass morning urine
- if initial ACR 3-70mg/mmol, subsequent early morning sample (higher no repeat sample needed)
Which ACR values should be referred to a nephrologist?
- > =70mg/mmol unless caused by diabetes
- > =30mg/mmol with persistent haematuria (2 of 3 dipsticks) after exclusion of UTI
- 3-29mg/mmol with persistent haematuria and risk factors consider
Management of coexistent HTN and CKD:
- ACEi or ARB
- ACR >70mg/mmol regardless of BP
Which medication which CKD patients take can lead to abdominal pain, back pain, muscle weakness etc?
- calcium binders e.g. calcium acetate
- hypercalcaemia and vascular calcification
What kind of murmur can you hear with anaemia?
soft ejection systolic murmur (aortic flow murmur)
Maintenance fluid regime rate:
500ml 0.9% saline at 100ml/hr
Resuscitation fluids:
500ml 0.9% saline in 15 mins
What should you consider in young females who develop an AKI after taking ACEi? (string bead appearance)
fibromuscular dysplasia
How to distinguish primary and secondary aldosteronism:
high renin - secondary e.g. renal artery stenosis
Most common extra renal manifestation of ADPKD:
liver cysts
How do you treat nephrogenic diabetes?
chlorthiazide
How do you treat hypokalaemia?
- cardiac monitoring
- 3 x 1 litre bags of 0.9% saline with 40mmol KCL per bag over 24 hours
What variables does the MDRD equation include?
- creatinine
- age
- gender
- ethnicity
