Chronic Kidney Disease Flashcards
What is chronic kidney disease (CKD)?
CKD is deteriorating kidney function and progressive impairment of any underlying cause for >3months
What are the congenital and inherited causes of chronic kidney disease?
Polycystic kidney disease
Medullary cystic disease
Tuberous sclerosis
Congenital obstructive uropathy
What are the primary and secondary glomerular disease causes of chronic kidney disease?
Primary glomerulonephritides
=> inc focal glomerulosclerosis
Secondary glomerular disease => systemic lupus => polyangiitis => granulomatosis with polyangiitis => amyloidosis => diabetic glomerulosclerosis => thrombotic thrombocytopenia purpura => systemic sclerosis => sickle cell disease
What are the vascular causes of chronic kidney disease?
Hypertensive nephrosclerosis (black african)
Renovascular disease
Small and medium sized vessel vasculitis
What are the tubulointersitial causes of chronic kidney disease?
Tubulointersitial nephritis due to i.e. idiopathic, drugs, immunologically mediated
Reflux nephropathy
Tuberculosis
Schistosomiasis
Nephrocalcinosis
Multiple myeloma
Renal papillary necrosis i.e. diabetes, sickle cell disease + trait, analgesic nephropathy
Chinese herb neuropathy
What are the most common causes of chronic kidney disease in the UK?
Diabetes
Glomerulonephritis
High BP / renovascular disease
How is chronic kidney disease staged?
- pg 1393 kumar&clarks
- pg 302 ox handbook
Patients are staged according to
=> eGFR
=> Albuminuria
Both these parameters correlate with progressive renal impairment and cardiovascular risk
Who does CKD affect?
Ethnic variation
End-stage kidney disease is much higher in:
i. Black African => hypertensive nephropathy more common in this group
ii. Asians => diabetes nephropathy more common in this group
iii. Middle eastern => schistosomiasis causing urinary tract obstruction most common in this group
iv. Elderly => CKD caused by atherosclerotic renal vascular disease
* >70% of CKD due to diabetes, hypertension and atherosclerosis
Patients with chronic glomerular disease tend to deteriorate more quickly than those with chronic tubulointerstitial nephropathies.
What does the rate of decline to end-stage renal disease depend on in CKD?
Underlying nephropathy
Control on BP
What is the underlying pathology as a result of CKD?
I. Each kidney has ~million nephrons. In CKD, many nephrons have scarred and failed => increased burden of filtration on a small number of nephrons
II. The small number of functioning nephrons undergo hyperfiltration (increased blood flow as flow hasn’t changed)
=> these nephrons adapt via glomerular hypertrophy and reduced arteriolar resistance
III. Increased flow, pressure and stress => raised intraglomerular capillary pressure => accelerates remnant nephron failure
IV. Increased flow/strain may be detected by new or increasing proteinuria
What is the role of angiotensin II in CKD?
i. Ang II produced locally modulates intraglomerular capillary pressure and GFR
=> vasoconstriction of postglomerular arterioles + increasing the glomerular hydraulic pressure
ii. Ang II indirectly upregulates TGF-b (fibrogenic cytokine)
=> increases collagen synthesis
ii. Ang II indirectly upregulates plasminogen activator inhibitor-1
=> inhibits matrix proteolysis by plasmin
=> accumulation of excessive matrix
=> scarring in glomeruli and interstitium
What does the prognosis of CKD depend on?
Reduced GFR and albuminuria independently assoc. with high risk of:
i. all cause mortality
ii. CVS mortality
iii. progressive kidney disease & kidney failure
iv. AKI
What do you need to ask the patient if suspecting CKD?
Previous UTI, lower urinary tract symptoms
PMHx of hypertension, diabetes, ischaemic heart disease, systemic disorder, renal colic
Drug Hx
Family Hx inc. renal disease and subarachnoid haemorrhage
System review i.e. rare causes
Current state: symptomatic CKD if GFR <30
i. symptoms of fluid overload i.e. peripheral oedema, shortness of breath
ii. anorexia
iii. nausea & vomiting
iv. restless legs
v. fatigue & weakness
vi. pruiritis
vii. bone pain
viii. amenorrhoea
ix. impotence
What peripheral signs might you notice on examination suggestive of CKD?
Periphery:
i. Peripheral oedema
ii. Signs of peripheral vascular disease or neuropathy
iii. Vasculitis rash
iv. Gout tophi
v. Joint disease
vi. Arteriovenous fistula
vii. Signs of immunosuppression i.e. bruising from steroids
viii. Uraemic flat / encephalopathy GFR <15
What facial signs might you notice on examination suggestive of CKD?
Face:
i. Anaemia
ii. Xanthelasma
iii. Yellow tinge (uraemia)
iv. Jaundice (hepatorenal)
v. Gum hypertrophy (ciclosporin)
vi. Cushingoid (steroids)
vii. Periorbital oedema (nephrotic syndrom)
viii. Taut skin/telangiectasia (scleroderma)
ix. Facial lipidystrophy (glomerulonephritis)
What neck signs might you notice on examination suggestive of CKD?
Neck:
i. JVP for fluid state
ii. scar from parathyroidectomy or lymphadenopathy
What cardiovascular signs might you notice on examination suggestive of CKD?
CVS:
i. BP
ii. Sternotomy
iii. Cardiomegaly
iv. Stigmata of endocarditis
* if right sided heart failure or tricuspid regurgitation, JVP doesn’t reflect fluid state
What respiratory signs might you notice on examination suggestive of CKD?
Pulmonary oedema or effusion
What abdomen signs might you notice on examination suggestive of CKD?
Abdomen:
i. Peritoneal dialysis catheter or scars from previous ones
ii. Signs of previous transplant
iii. Ballotable polycystic kidneys ± palpable liver
What general investigations are carried out for in CKD?
Bloods : => U&E (compare with previous) => Hb (normochromic, normocytic anaemia) => Glucose => Decreased Calcium ; increased phosphate & PTH (renal osteodystrophy)
=> Direct investigations of renal disease: ANA, ANCA, anti-phospholipid antibodies, paraprotein complement, cryoglobulin, anti-GBM (glomerular basement membrane)
Urine:
=> Dipstick (microscopy, culture and sensitivity),
=> Albumin/protein : creatinine ratio,
=> Bence jones
Ultrasound imaging
Histology
What imaging is carried out in CKD?
Ultrasound for size, symmetry, anatomy, corticomedullary differentiation and to exclude obstruction
=> In CKD kidneys may be small except in diabetes, infiltrative disorders (amyloid, myeloma), adult polycystic kidney disease
=> If asymmetrical, consider renovascular disease
=> Scarring may be seen on ultrasound but isotope scans more sensitive
When may a renal biopsy be needed in CKD?
Renal biopsy in progressive disease, nephrotic syndrome, systemic disease, AKI without recovery
What are the risk factors for decline in CKD?
High BP
Diabetes
Metabolic disturbance
Volume depletion
Infection
NSAIDs
Smoking
*All CKD has increased risk of superimposed AKI => needs monitoring
How often should CKD be monitored?
GFR & albuminuria should be monitored at least once a year or according to risk:
Very high risk : every 3-4 months
High risk : every 6 months
RENOPROTECTION
i) What are the goals of treatment?
ii) What are the treatment measures?
iii) What additional management is required?
i) Goal of treatment is to slow renal disease progression by maintaining
=> BP <130/80mmHg
=> Proteinuria <0.3g/24h
ii) Treatment measures
Patients with CKD and proteinuria >1g/24h
=> ACE-i or ARB
=> Addition of diuretic to prevent hyperkalaemia & help control BP or calcium channel blocker i.e. verapamil or diltiazem
iii) Additional management
=> Statins to lower cholesterol <4.5mmol/L
=> Smoking cessation (3x higher deterioration risk in CKD)
=> Treatment of diabetes (HbA1c <53mmol/mol / 7%)
=> Normal protein diet
Out of all the CKD patients, 50% have been transplanted, 42% are on haemodialysis and 8% are on peritoneal dialysis.
Dialysis aims to mimic the excretory function of normal kidneys.
What are the 4 main functions of the kidney?
- Eliminating (nitrogenous & small molecular) wastes
- Maintaining normal electrolyte concentrations
- Preventing systemic acidosis
- Maintaining normal extracellular volume
When should dialysis be initiated?
eGFR ~10ml/min
Long term dialysis is started when it’s necessary to manage one or more symptoms of renal failure:
=> inability to control volume status inc. pulmonary oedema
=> inability to control BP
=> serositis
=> acid base or electrolyte abnormalities
=> pruriitis
=> nausea / vomiting / deterioration in nutritional state
=> cognitive impairment
But should be according to individual patients needs, symptoms and life plans
*Frail & patients with multiple co-morbidities choose to not undergo renal replacement therapy
How does a haemodialysis work?
Anticoagulated blood from patient is pumped across a semi-permeable membrane - the dialyser, before being returned to the circulation.
In the dailyser, ultrapure dialysate flows in the opposite direction and is in close contact with blood.
Small solutes (not cells or larger molecular weight proteins) can cross the membrane and move by diffusion down a concentrate gradient.
Transmembrane pressure allows controlled fluid removal by ultrafiltration.
Over 4 hours session, 80L of blood is circulated through the dialyser.
3x/week or more
Effective dialysis requires blood flow between 250 - 450ml/min.
How is this achieved to allow access to dialysis?
Via a surgical fashioned arteriovenous fistula using radial or brachial artery and cephalic vein.
In patients with poor quality arteries i.e. diabetes patients, synthetic arteriovenous grafts can be put in
For many patients, a semi-permanent dual-lumen venous catheter is inserted into the jugular or femoral vein
=> although instant use, risk of bacteraemia, catheter malfunction, venous stenosis or occlusion
What are the aims of haemodialysis?
- Maintain euvolaemia
- Maintain electrolyte balance
=> a low dialysate K+ allows control of hyperkalaemia
=> dialysate sodium controlled to prevent fluid shifts - Prevent acidosis
=> dialysate is buffered with bicarbonate
=> bicarbonate diffuses into blood to correct acidosis during treatment - Balancing frequency & duration of dialysis with quality of life
=> 3-5h of treatment 5x / week is adequate in maintaining volume and solute balance - Deliver enough dialysis
=> symptoms of under-dialysis are non-specific i.e. insomnia, itching and fatigue (despite correction of anaemia), restlesss legs and a peripheral sensory neuropathy
What are haemodialysis specific complications?
- Access (arteriovenous fistula or catheter) malfunction, thrombosis, stenosis or bleeding
- Bloodstream infection => disseminate to soft tissue causing septic arthritis, endocarditis, vertebritis
- Dialysis disequilibrium
- Intra-dialytic hypotension due to rapid fluid removal from the extravascular spaces
- Dialysis related amyloidosis
=> failure of clearing beta2-microglobulin leads to amyloid deposition.
What is haemofiltration?
What is haemodiafiltration?
- Haemofiltration:
=> Plasma water with suspended solutes is removed by convection (+ve pressure) across a high flux semipermeable membrane.
=> Substitution fluid is infused to replace fluid losses.
=> Haemofiltration used in acute settings when patient not haemodynamically stable
=> Differs from haemodialysis as there is no dialysate
- Haemodiafiltration:
=> Combination of dialysis and haemofiltration
=> Increase middle molecule clearance
=> Prevent long term dialysis complications i.e. dialysis related amyloidosis
What is peritoneal dialysis?
How is it carried out?
It uses peritoneal membrane as a semi-permeable membrane => avoiding the need for extracorporeal circulation of blood.
=> Simple, low tech but effective
=> Soft catheter is placed through the skin into the peritoneal cavity through the midline of the anterior abdominal wall
=> Dialysate runs into the peritoneal cavity under gravity
=> Urea, creatinine, phosphate and other uraemic toxins pass into the dialysate down their concentration gradients
=> Water is attracted into the peritoneal cavity by osmosis
=> More hypertonic solution improves fluid removal
What are the complications specific to peritoneal dialysis?
- Bacterial peritonitis - fever, abdo pain and cloudy peritoneal dialysate effluent
=> caused by staph. epidermidis, E.coli, pseudomonas, staph. aureus, mycobacterium
- Constipation may impair flow of dialysate
- Hernias caused by raised intra-abdominal pressure
- Sclerosing peritonitis => long term patients develop progressive thickening of the peritoneal membrane
Who should renal transplant be offered to?
What are the benefits of renal transplant?
Every patient with or progressing towards stage G5 kidney disease => treatment of choice for end-stage kidney disease.
Benefits:
Successful renal transplantation provides complete rehabilitation in end-stage kidney disease.
=> Survival is better than dialysis
=> No dietary and fluid restrictions
=> Anaemia & infertility corrected
What type of kidney donors do you get?
1) Diseased donor kidney
=> donor after brain death (heart beating donor)
=> donor after cardiac death (non-heart beating donor) - increased risk of delayed graft function
2) Living related or unrelated donor kidney => best graft function and survival especially if HLA matched
80% of grafts survive 5-10 years and 50% survive 10-30 years.
Which factors have improved patient and graft survival?
Appropriate patient selection
Better donor-recipient compatibility (ABO & HLA)
Improved surgical technique
Efficient immunosuppressants
What are the contraindications of renal transplant?
Absolute contraindication:
i. Cancer with metastases
Temporary contraindication:
i. Active infection
ii. HIV with viral replication
iii. Unstable cardiovascular disease
Relative contraindication:
i. Congestive heart failure
ii. Cardiovascular disease
A combination of immunosuppression drugs are used at the minimal effective dose in CKD.
What are the different types of monoclonal antibodies used for CKD?
What is their mechanism of action?
- Daclizuman or Basiliximab => selectively block activated T-cell via CD-25
- Alemtuzumab => T & B cell depletion
- Monoclonal antibodies used at the time of transplantation => reduces acute rejection & graft loss ; increases infection risk if non-selective
A combination of immunosuppression drugs are used at the minimal effective dose in CKD.
What is the mechanism of action of calcineurin inhibitors?
What are some examples of calcineurin inhibitors?
What are its side effects?
- Tacrolimus ; cyclosporin
- Calcineurin inhibitors inhibit T-cell activation and proliferation
- High inter-individual variation and narrow therapeutic index => drug level monitoring required
i) Clearance is dependent on cytochrome p450 => beware of drug interaction i.e. macrolide antibiotics & anti-fungal - Side effects: nephrotoxicity of the graft, high BP, cholesterol and new onset diabetes after transplantation (NODAT)
A combination of immunosuppression drugs are used at the minimal effective dose in CKD.
What are some examples of anti-metabolites?
What are its side effects?
- Mycophenolic acid ; azathioprine
i) Mycophenolic acid (MPA) is used preferentially => better prevention of acute rejection and graft survival - Side effects: anaemia, leucopenia, GI toxicity and teratogenic DO NOT use in pregnancy
A combination of immunosuppression drugs are used at the minimal effective dose in CKD.
What is the mechanism of action of glucocorticoids?
What are its side effects?
- Reduces transcription of inflammatory cytokines
=> 1st choice treatment for acute rejection - Side effects: high BP, hyperlipidaemia, diabetes, impaired wound healing, osteoporosis, cataracts, skin fragility
Sig. side effects => withdrawal of steroid use => steroid free immunosuppression preferred
What are the complications of renal transplant?
- Surgical i.e. bleeding, thrombosis, infection, urinary leaks, lymphocyte, hernia
- Delayed graft function => common in donation after circulatory death (DCD)
- Acute or chronic rejection
- Infection : high risk of all infection esp hospital acquired or opportunistic infections within 6 months (prophylaxis for CMV and pneumocystis jirovecii given) ; community acquired after 6-12 months
- Malignancy : 25x increased risk of cancer with immunosuppression esp. skin, gynaecological and post-transplant lymphoproliferative disorders.
- CVD : 3.5x increased risk of premature CVD
What happens in acute rejection?
How do you treat acute rejection?
Acute rejection can be divided into:
1) Antibody mediated (rare unless known pre-sensitised recipient)
2) Cellular is the most common => causes low renal function diagnosed on graft biopsy
3) Treatment: high dose steroids and increase immunosuppression
What happens in chronic rejection?
Chronic antibody mediated rejection causes progressive dysfunction of the graft
*Most graft loss due to an immune response by donor-specific antibodies => causing damage to kidney microcirculation
What is the prognosis of renal transplant?
Acute rejection <15%
Longer term graft loss = rare ~4%/year
What are the factors contributing to graft loss?
- Donor factors: age, comorbidity, living/deceased, (donation brain death [DBD] / donation circulatory death [DCD]
- Rejection
- Infection
- BP/CVD
- Recurrent renal disease in graft
* Most common = death with a functioning graft => graft outlives the patient
What are the CKD related Complications?
Anaemia
Acidosis
Oedema
CKD-MBD (mineral bone disorders)
Restless legs/cramps
Cardiovascular disease
Skin disease i.e. pruritus
Metabolic abnormalities i.e. gout, insulin & lipid metabolism
CKD renal complications
i) What is the pathology underlying anaemia in CKD?
ii) How do you manage anaemia in CKD?
Normochromic, normocytic anaemia due to:
=> Erythropoietin deficiency
=> Increased blood loss (during haemodialysis, occult GI bleed, platelet dysfunction)
=> Iron, folate, B12 deficiency
=> Increased haemolysis (shortened RBC lifespan in uraemia ; haemodialysis)
=> ACE inhibitors
=> Bone marrow toxins
Management:
Synthetic erythropoiesis-stimulating agents (ESAs) IV or subcutaneously
Monitor Hb every 2 weeks
Hypertension major side effect of ESA => BP monitoring
CKD renal complications
Most patients with CKD have mixed bone disease by late stage 3 CKD
i) i) What is the pathology underlying mineral bone disorders in CKD?
ii) How do you manage mineral bone disorders in CKD?
Mineral bone disorder changes:
- High serum phosphate
- Reduced hydroxylation of Vit. D
- Secondary hyperparathyroidism => reduced activation of vitamin D in parathyroid gland => increase release of PTH
- PTH promotes reabsorption of calcium from bone to reverse hypocalcaemia caused by 1,25 dihydroxycalciferol deficiency and phosphate retention
=> increase in osteoclastic activity = cyst formation and bone marrow fibrosis => osteomalacia, osteoporosis, osteosclerosis, adynamic bone disease
- Biochemical findings: hypocalcaemia, hyperphosphataemia, high PTH, high ALP (increased bone turnover)
5. Longstanding 2nd hyperparathyroidism => tertiary hyperparathyroidism - hyperplasia of the glands and PTH release independent of calcium or 1,25 dihydroxycalciferol => high bone turnover leads to hypercalcaemia
Management:
- Treat if phosphate >1.5mmol/L with dietary restriction ± phosphate binders
- Vitamin D supplements i.e. cholecalciferol, if high PTH persists give Vit D analogues i.e. alphacalcidiol
CKD renal complications
i) How do you manage oedema in CKD?
Restrict fluid/sodium intake
High dose of loop diuretics
Loop and thiazide (inhibits distal tubule sodium excretion) diuretics combination
CKD renal complications
i) How do you manage acidosis in CKD?
Sodium bicarbonate supplements for patients with eGFR <30 and low serum bicarbonate
CKD renal complications
i) How do you manage restless legs/cramps in CKD?
Exclude iron deficiency as cause
Sleep hygiene advice
Severe cases : gabapentin / pregabalin
CKD other complications
i) What is the pathology underlying cardiovascular disease risk in CKD?
ii) How do you manage this?
CKD increases risk of CVD x16 due to:
=> high BP
=> vascular stiffness (due to uraemia + raised calcium, PTH & phosphate increases calcification)
=> inflammation
=> oxidative stress
=> abnormal endothelial function
Manage by:
i) Low dose anti-platelets i.e. aspirin
ii) Atorvastatin
