Diseases Flashcards
Define AKI
An abrupt (<48hrs) reduction in kidney functions defined as;
- an absolute increase in serum creatinine by >26.4 micromol/L
- increase in creatinine by >50%
- a reduction in UO
note can only be applied following adequate fluid resuscitation and exclusion of obstruction
Name patient risk factors for AKI
- older age
- CKD
- diabetes
- cardiac failure
- liver disease
- PVD
- previous AKI
Name exposure risk factors for AKI
- hypotension
- hypovolaemia
- sepsis
- deteriorating NEWS
- recent contrast
- exposure to certain medications
What are the three categories of causes of AKI?
- pre-renal (functional|)
- renal (structural)
- post renal (obstruction)
Name pre-renal causes of AKI
- hypovolaemia; haemorrhage, volume depletion (e.g. D&V, burns)
- hypotension; cardiogenic shock, distributive shock (e.g. sepsis, anaphylaxis)
- renal hypoperfusion; NSAIDs/ COX2, ACEi / ARBs, hepatorenal syndrome
What is the basic pathogenesis of pre-renal AKI?
Reversible volume depletion leading to oliguria and increase in creatinine
Untreated pre-renal AKI can lead to what?
Acute tubular necrosis (histological diagnosis)
What is the commonest form of AKI in hospital?
Acute tubular necrosis
Name causes of acute tubular necrosis
- due to a combination of factors leading to decreased renal perfusion
- common causes include sepsis and severe dehydration
- other important causes include rhabdomyolysis and drug toxicity
Describe management of pre-renal AKI
- assess for hydration; clinical observations (BP, HR, UO), JVP, cap refill, pulmonary oedema
- fluid challenge for hypovolaemia;
> crystalloid (0.9% NaCl) or colloid (gelofusin)
> do not use 5% dextrose
> give bolus of fluid then reassess and repeat as necessary
> if >100mls IN and no improvement seek help
What is the basic pathogenesis of renal AKI?
- diseases causing inflammation or damage to cells causing AKI
- split by structure; blood vessels, glomerular disease, interstitial injury, tubular injury
Name causes of renal AKI
- vascular; vasculitis, renovascular disease
- glomerular; glomerulonephritis
- interstitial nephritis; drugs, infection (TB), systemic (sarcoid)
- tubular injury; ischaemia (prolonged renal hyperfusion), drugs (genatmicin), contrast, rhabdomyolysis
Name signs and symptoms of renal AKI
- Non specific symptoms
- constitutional; anorexia, weight loss, fatigue, lethargy
- nausea and vomiting
- itch
- fluid overload; oedema, SOB
Signs
- fluid overload including HTN, oedema, pulmonar oedema, effusions
- uraemia including itch, pericarditis
- oliguria
Name initial investigations for AKI
- U&Es; marker of renal function (Na, K, Ur, Cr), look at potassium
- FBC and coagulation screen; abnormal clotting, anaemia
- urinalysis; haematoproteinuria
- USS; ?obstruction ? size
- immunology; ANA, ANCA, GBM
- protein electroporesis and BJP (? myeloma)
Describe treatment of renal AKI
- establish good perfusion pressure; fluid resuscitate, once fluid restricted, if still not achieving adequate BP > inotropes/ vasopressors
- treat underlying cause; antibiotics if sepsis
- stop nephrotoxics
- dialysis if remains anuric and uraemia; can require urgent dialysis
Name the life threatening complications of AKI
- hyperkalaemia
- fluid overload
- severe acidosis (pH <7.15)
- uraemic pericardial effusion
- severe uraemia (Ur >40)
Describe the basic pathogenesis of post renal AKI
- AKI due to obstruction of urine flow leading to back pressure (hydronephrosis) and thus loss of concentrating ability
- causes; stones, cancers, strictures, extrinsic pressure
Describe treatment of post renal AKI
- relieve obstruction; catheter, nephrostomy (blockage further up)
- refer to urology is ureteric stenting required
What value of potassium is;
A) normal
B) hyperkalaemia
C) life threatening hyperkalaemia
A) 3.5 - 5.0
B) >5.5
C) >6.5
How is hyperkalaemia assessed (other than biochem)?
- ECG
- muscle weakness
What changes are seen on ECG for hyperkalaemia
- peaked / tented T waves
- flattened P wave
- prolonged PR interval
- ST depression
- sine wave pattern if severe
Describe medical management of hyperkalaemia
- cardiac monitor and IV access
- protect myocardium; 10mls 10% calcium gluconate (2-3mins)
- move K+ back into the cells; insulin (actrapid 10units) with 50mls 50% dextrose (30mins), salbutamol nebuliser (90mins)
- prevent absorption from GI tract; calcium resoniu (not in the acute setting)
Name indicated for urgent haemodialysis
- hyperkalaemia; >7 or >6.5 unresponsive to medical therapy
- severe acidosis; pH <7.15
- fluid overload
- urea >40, pericardial rub / effusion
40 year old male, presenting with general malaise and haemoptysis Urea is 28, creatinine 600, elevated ant-GBM) is a typical history of what?
Goodpastures syndrome
25 year old PWIJ found collapsed at home is a history typical of what?
Rhabdomyolosis
82 year old man admitted with BP 70/30, T 39, HR 140BPM, K+ 7.0, urea 48, Cr 789, CRP 250, CXR left basal consolidation is a history typical of what?
Acute tubular necrosis
72 year old man presenting with difficulty passing urine and reduced urine output is a history typical of what?
Obstructive uropathy
Name drugs that can cause hyperkalaemia
- spironolactone
- ramipril
- amiloride
- atenolol
What are the two types of polycystic kidney disease?
- autosomal dominant (most common)
- autosomal recessive
Describe autosomal dominant polycystic disease
- ADPKD is the most frequent life threatening hereditary kidney disease
- occurs worldwide and in all races and ethnic groups
- an important cause of ESRD
What are the common mutations in ADPKD?
- mutations in PKD gene 1 located on chromosome 16 (85% of cases)
- PKD2 mutation located on chromosome 4 (15% of cases)
- PKD1 patients develop end stage kidney failure at an earlier stage
Describe the pathology of ADPKD
- massive cyst enlargement > large kidneys
- epithelial lined cysts arise from a small population of renal tubules
- benign adenomas = 25% of kidneys
Describe the renal features of ADPKD
- reduced urine concentration ability
- chronic pain
- hypertension; common, early (31 yrs old mean age)
- haematuria; cyst rupture, cystitis, stones
- cyst infection (difficult to treat)
- renal failure
Describe the extra-renal features of ADPKD
- hepatic cysts; most common. present 10 yrs after renal cysts, liver function generally preserves, can result in SOB, pain, ankle swelling
- intra-cranial aneurysms; seen in clusters of family members, mainly in the anterior circulatory territory, screen if +ve family history
- cardiac disease; mitral/ aortic valve prolapse, valvular disease
- diverticular disease; diverticulitis and colonic perforation
- hernias; abdominal / inguinal hernias
Describe the diagnosis of ADPKD
- radiologic; ultrasound presence of multiple bilateral cysts, renal enlargement, CT/MRI when unclear on USS
- genetic; linkage analysis, mutation analysis
Describe ADPKD in children
- early onset, can be in utero or first year of life
- siblings at increased risk of early disease
- renal involvement similar to adults
- a single cyst in high risk pts is enough for diagnosis
- cerebral aneurysms rare in children
Describe management of ADPKD
- hypertensions rigorous control
- hydration
- proteinuria reduction
- cyst haemorrhage and cyst infection treated
- tolvaptan (ADH receptor antagonist)
- renal failure; dialysis, transplantation
Describe autosomal recessive kidney disease
- young children and associated with hepatic lesions
- rare
- renal involvement is bilateral and symmetrical
- urinary tract is generally normal
- histologically cysts are seen appearing from the collecting duct system
Describe the clinical presentation of ARPKD
- varies and depends on the renal / liver lesions
- relevance is distinguishing between severe forms and ones which survive the neonatal period
- kidneys always palpable
- hypertension
- recurrent UTIs
- slow decline in GFR; less than 1/3 reach dialysis
What is alports syndrome
- hereditary nephritis
- familial glomerular syndrome
- 1-2% pts with ESRD
- x linked inheritance
- disorder of type 4 collagen matrix
- mutation in COL4A5 gene leads to deficient collagenous matrix deposition
Describe the manifestations of alports syndrome
- haematuria; characteristic feature
- proteinuria seen later but confers bad prognosis
- extra renal; sensorineural deafness, ocular defects (anterior lenticonus), leiomyomatosis of oesophagus / genitalia rare
Describe the diagnosis of alports
- suspected in patients with microscopic haematuria +/- hearing loss
- renal biopsy; variable thickness (GBM characteristic feature)
Describe the treatment of alports
- no specific treatment
- standard aggressive treatment of BP, proteinuria
- dialysis / transplantation
What is anderson fabrys disease?
- inborn error of glycosphingolipid metabolism (deficiency of alpha-galactosidase A)
- x linked disease lysosomal storage disease
- affects kidneys, liver, lungs, erythrocytes
- uncommon
Describe the clinical features of anderson fabrys disease
- renal failure
- cutaneous; angiokeratomas
- cardiac; cardiomyopathy, valvular disease
- neuro; stroke, acroparaesthesia
- psychiatric
Describe the diagnosis of fabrys disease
- plasma / leukocyte a-GAL activity
- renal biopsy
- skin biopsy
- concentric lamellar inclusions with lysosomes - pathognomic
Describe the treatment of anderson fabrys disease
- enzyme replacement - fabryzyme
- management of complications
What is medullary cystic kidney?
- rare inherited cystic disease, autosomal dominant
- morphologically abnormal renal tubules leading to fibrosis
- affected; normal / small kidneys
- cysts are in the corticomedullary junction / medulla (not essential for diagnosis)
What is the macroscopic appearance of medullary cystic kidney?
- cortex and medulla are both shrunken
- presence of irregularly distributed cysts of variable size at the corticomedullary junction and in the outer medulla
Describe the diagnosis and treatment of medullary cystic kidney
- diagnosis; family history, ct scan
- presents average age 28 years
- renal transplantation
Describe medullary sponge kidney
- uncommon
- sporadic inheritance
- dilatation of collecting ducts
- severe cases; medullary are appears like a sponge
- cysts have calculi
- diagnosis is by excretion urography; to demarcate calculi
- renal failure unusual
Define CKD
A reduction in kidney function or structural damage (or both) present for more than 3 months, with associated health implications
CKD should be diagnosed in people with markers of kidney damage such as?
- a urinary albumin:creatinine ratio (ACR) greater than 3mg/mmol
- urine sediment abnormalities
- electrolyte and other abnormalities due to tubular disorders
- abnormalities detected by histology
- structural abnormalities detected by imagine
- a history of kidney transplantation
and / or
- a persistent reduction in renal function shown by a serum eGFR of less than 60ml/min/1.73m2
Define accelerated progression of CKD
- a persistent decrease in eGFR of 25% or more AND a change in CKD category within 12 months
or
- a persistent decrease of eGFR of 15mL/min/1.73m2 within 12 months
Name causes of CKD
- conditions associated with intrinsic kidney damage such as; hypertension, diabetes, glomerular disease
- current or previous AKI
- potentially nephrotoxic drugs
- causes of obstructive uropathy such as; structural renal tract disease, neurogenic bladder, benign prostatic hypertrophy, malignancy (bladder, prostate, ureteric), urinary diversion surgery, recurrent urinary tract calculi
- SLE, vasculitis, myeloma
- a Fhx of CKD stage 5
Renal anaemia may present with what?
- symptoms such as tiredness, shortness of breath, lethargy and palpitations
- may be due to reduced productions of erythropoietin by the kidney, reduced red blood cell survival and iron deficiency
Describe how renal mineral and bone disorder may present
- this may present with bone pain, increase bone fragility, or extra skeletal calcification such as in the skin or blood vessels
- give exogenous vitamin D
Peripheral neuropathy and myopathy may present with what?
- paraesthesia, sleep disturbance and restless legs syndrome
What is the initial treatment of CKD?
- treat the underlying condition
- diabetes > HbA1c target
- hypertension
- autoimmune / multisystemic conditions
- obstruction; relieve it
- nephrotoxins; stop
What is the blood pressure aims for CKD and CKD with diabetes?
CKD alone
- systolic below 140mmHg
- diastolic below 90mmHg
CKD and diabetes; (also in people with an ACR of 70mg/mmol or more)
- systolic below 130 mmHg
- diastolic below 80mmHg
What dietary advice is given to patients with CKD?
- phosphate restriction (if PO4 is high)
- salt reduction
- potassium restriction (if persistently elevated)
- fluid restriction to 1 - 1.5l per day
Describe the investigation and management of anaemia in CKD
- exclude other causes of anaemia
- check ferritin and iron stores, aiming for; ferritin >100, TSats >20%
- IV iron therapy; ferric carboxymaltose, iron sucrose
Name common presenting symptoms of kidney disease
- asymptomatic
- loin pain / urinary symptoms
- haematuria; microscopic, painless macroscopic
- proteinuria
- hypertension; asymptomatic, accelerated
- AKI
- chronic kidney disease
- nephrotic sndrome
- nephritic syndrome
What is a transplant?
- tissue taken from one person and placed in another
- either be taken from someone who has died or from a living donor
Name the different types of transplant
- decreased heart beating donors; brain stem death (DBD)
- non heart beating donors (DCD)
- live donation; directed and undirected, paired donation, financially procured
How are patients assessed for transplantation?
- immunology; tissue typing and antibody screening
- virology (exclude active infection)
- assess cardiorespiratory risk; ECG, echo, CXR etc
- assess peripheral vessels
- assess bladder function
- assess mental state
- assess any co-morbidity / PMHx which may influence transplant or be exacerbated by immunosuppression
Name some contraindications to transplant
- malignancy; known untreated malignancy, solid tumour in last 2- 5 yrs
- active HCV/HIV infection
- untreated TB
- severe IHD, not amenable to surgery
- severe airways disease
- active vasculitis
- severe PVD
- hostile bladder
What factors are looked at for tissue typing?
- blood group
- HLA A , B and DR
Name examples of sensitising events for transplant
- blood transfusion
- pregnancy or miscarriage
- previous transplant
How can patients be desensitised for transplantation?
- active removal of blood group or donor specific antibody
- plasma exchange
- and /or b cell antibody (rituximab)
Describe the transplant procedure
- extra peritoneal procedure
- transplant inserted in iliac fossa; attached to external iliac artery and vein, ureter plumbed into bladder with stent
- wound 15-20cm long
- average 2-3 hr operation
- 7-10 days in hospital
Name surgical complications of transplant
- bleeding
- arterial stenosis
- venous stenosis / kinking
- ureteric stricture and hydronephrosis
- wound infection
- lymphocele
Name the different types of rejection
- hyperacute rejection; due to preformed antibodies, unsalvageable, transplant nephrectomy require, should be a never event
- acute rejection; cellular or antibody mediated, can be treated with increased immunosuppression
- chronic rejection; antibody mediated slowly progressive decline in renal function. Poorly responsive to treatment
Describe immunosuppressive therapy
- induction treatment; basiliximab / dacluzimab
- prednisolone IV during operation
- maintainance treatment; prednisolone, tracrolimus, MMF or prednisolone, ciclosporin, azathioprine
Name anti-rejection treatments
- pulsed IV methylprednisolone (ACR)
- anti thymocyte globulin (ATG), (resistance ACR and AMR)
- IV immunoglobulin (AMR)
- plasma exchange (AMR)
- rituximab, bortezimab, eculizumab (AMR)
- intensification of immunosuppression
Describe CMV disease as a complication of transplant
- important cause of morbidity in immunosuppressed patients in first 3 months
- associated with early graft loss
- common if recipient is not immune but donor has evidence of previous infection
- causes; renal and hepatic dysfunction, oesophagitis, pneumonitis and colitis, increased risk of rejection
- evidence; IgM and PCR+ve
- treatment; prophylactic PO valganciclovir in higher risk patients, IV ganciclovir if evidence of infection
Describe BK nephropathy as a complication of transplantation
- prevalent and indolent in uroepithelium
- reflection of over immunosuppression
- can mimic rejection
- no effective anti-viral therapy
- treat by reducing immunotherapy
- monitor blood viral load by PCR
Name the commonest malignancies that occur due to complications of transplantation
- non melanoma skin cancers
- lymphoma (e.g EBV mediated PTLD)
- solid organs
Describe post transplant lymphoproliferative disease
- occurs in all forms of transplantation
- depends on immunosuppression level
- usually related to EBV infection
- reduce immunosuppression
- chemotherapy
- no role for antiviral therapy
Name causes of graft loss
- acute rejection
- death with a functioning graft
- recurrent disease
- chronic allograft nephropathy
- viral nephropathy
- PTLD
