Session 11 Flashcards
What is CKF?
[*] In humans normal GFR is 90-120 ml/min/1.73m^2
- 2 x10^6 nephrons (~a million nephrons in each kidney)
- 40,000 (2%) sufficient to survive
[*] Chronic Kidney Failure is defined as the irreversible and sometimes progressive loss of renal function over a period of months to years. Renal injury causes functioning renal tissue to be replaced by extra-cellular matrix in response to tissue damage; histologically this gives rise to glomerulosclerosis and tubular interstitial fibrosis. As a result, there is progressive loss of both the excretory and hormone functions of the kidney. Kidneys shrink, cortexes atrophy and there is an irregular outline. NB: not all kidneys shrink e.g. polycystic kidneys disease.
[*] Most glomerular diseases that lead to chronic renal failure are characterised by the development of proteinuria and systemic hypertension.
Describe the incidence of CKD
[*] Incidence; difficult to define as CKD is often asymptomatic. However Centre for Disease Control (CDC) in the USA report that more than 10% of people, or more than 20 million, aged 20 years or older have CKD.
- CKD is more common among women than men.
- More than 35% of people aged 20 years or older with diabetes have CKD
- More than 20% of people aged 20 years or older with hypertension have CKD
- It is suggested in the UK that 80 people per million of the population under the age of 80, per year would benefit from renal replacement therapy. Clearly, the incidence of CKD in the UK must be much higher.
- More common in elderly, ethnic minorities and socially disadvantaged.
Describe the aetiology of CKD
[*] CKD Aetiology: in developed countries, CKD is often associated with old age, diabetes, hypertension, obesity and cardiovascular disease (CVD). CKD is caused by common conditions which are frequently seen by GPs, general physicians, cardiologists and surgeons.
- Arteriopathic renal disease
- Hypertension
- Immunologic e.g. glomerulonephritis
- Systemic diseases e.g. diabetes, myeloma
- Infection e.g. pyelonephritis
- Obstructive and reflux nephropathies
- Genetic, family history of Stage 5 CKD or hereditary kidney disease – e.g. polycystic kidney disease (PCK – autosomal dominant, most don’t develop end stage renal failure or need dialysis until their 50s or 60s and patients in their 20s generally have CKD1 with a slow decline over the decades), Alport’s (hereditary nephritis characterized by glomerulonephritis, end-stage kidney disease and hearing loss)
- Hypercalcaemia
- Multisystem diseases with potential kidney involvement – e.g. systemic lupus erythematous (SLE)
- Neoplasms
- Vascular e.g. atherosclerotic vascular disease.
- CAUSE UNKNOWN
[*] Less than 10% have a glomerulonephritis (they don’t have a renal disease – their renal disease is part of something else e.g. diabetes or other chronic diseases)
[*] 85% of patients with CKD will be identified by looking in registries for diabetes, hypertension and ischaemic heart disease.
What are the risk factors for progressive renal injury?
[*] Risk Factors: factors other than the underlying disease process that may cause progressive renal injury include the following
- Acute insults from nephrotoxins or decreased perfusion
- Proteinuria
- Increased renal ammonia formation with interstitial injury
- Hyperlipidaemia
- Hyperphosphataemia with calcium phosphate deposition.
What are the Symptoms of CKD?
- Tiredness
- Breathlessness
- Restless legs
- Sleep reversal
- Aches and pains
- Nausea and vomiting
- Itching
- Chest pain
- Seizure
How do you classify CKD according to GFR?
How do you classify CKD according to proteinuria?
[*] Renal Disease Classification according to ACR categories (albumin: creatinine ratio) - based on proteinuria.
[*] A person with an eGFR of 25 ml/min/1.73m^2 and an ACR of 15 mg/mmol has CKD G4A2
[*] A person with an eGFR of 50 ml/min/1.73m^2 and an ACR of 35 mg/mmol has CKD G3aA3
[*] An eGFR of less than 15 ml/min/1.73m^2 (GFR Category G5) is referred to as kidney failure.
[*] GPs keep a register of patients with CKD3 or worse. Management is guided by NICE guidelines.
Describe mortality including causes of mortality in CKD
[*] In some patients, CKD inexorably worsens with progressive loss of renal function. CKD is also associated with substantial cardiovascular morbidity (CKD is a significant risk factor for CVS disease) and mortality. Most patients will succumb to cardiovascular disease before they get to dialysis.
Most patients die from cardiovascular disease with CKD rather than of CKD. Risk of cardiovascular death with GFR <90ml/min/1.73m^2 in 30,000 longitduinal follow-up for 5 years
- Stage 2: (GFR 60-89): 19.5% (mean 61 years)
- Stage 3: (GFR 30-59): 24.3% (mean 72 years)
- Stage 4: (GFR 15-29): 45.7% (mean 72 years)
- NB: CVS risk factors such as hypertension can be managed. So by treating CVS complications, you are increasing a CKD patient’s quality of life and life expectancy.
Mortality starts to increase in CKD very early on – around a GFR ~75 (once you have lost ~20-25% of starting GFR)
- You can potentially move the slope to the right by detecting and managing CKD early – slow down/delay rate of progression and need of dialysis.
- NB: rates of renal disease progression are applicable to all patients irrespective of underlying pathology.
- Dialysis keeps patients alive but life expectancy is reduced. E.g. for normal people ate the age of 40, life expectancy is another 40 years. For patients on dialysis, life expectancy is 9.7 years.
- Therefore preserving renal function improves not only quality of life but also quantity of life. Transplant is considered the gold-standard treatment.
What are the general effects of Chronic Kidney Failure?
- Increase in total body sodium and water
- Metabolic Acidosis which may affect bone, muscle and accelerate decline in renal function progression. TREAT with ORAL NaHCO3 tablets.
- Carbohydrate intolerance
- Negative nitrogen balance
- Lipid abnormalities
- NB: endocrine function of the kidneys – Renin-angiotensin, 1-alpha calcidol (active Vitamin D metabolism) and erythropoietin are clinically important in CKD – less so in AKI.
What are the cardiovascular effects of Chronic Kidney Disease?
- Atherosclerosis
- Cardiomyopathy or Pericarditis
- E.g. Renal Artery stenosis (roughened edges can be seen due to atherosclerotic plaques)
- Patients with CKD are more likely to die from a CVS event than require dialysis.
What are the haematological effects of CKD?
- Anaemia (decreased erythropoietin production). Ureamic environment also increases bone marrow’s resistance to erythropoietin and decreases the life span of red blood cells (decreased RBC survival) all => blood loss.
- Treat by giving exogenous erythropoietin.
- Increased tendency to bleed (reduced platelet function)
- Contributes to tiredness and reduced exercise tolerance
What are the effects of CKD on Bone?
CKD-MBD (Metabolic Bone Disease) is a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:
- Abnormalities of calcium, phosphate, PTH or Vitamin D metabolism
- Abnormalities in bone turnover, mineralization, volume, linear growth or strength.
- Vascular or other soft-tissue calcification e.g. extra-articular
Renal osteodystrophy: an alteration of bone morphology in patients with CKD. It is one measure of the skeletal component of the systemic disorder of CKD-MBC that is quantifiable by histomorphometry of bone biopsy.
Decreased GFR leads to accumulation of phosphate in the blood (as kidneys are unable to excrete it). Phosphate then complexes with free Calcium, reducing its effective serum concentration. This stimulates the parathyroid to produce more PTH which leads to Osteoitis Fibrosa Cystica (bone disease due to hyperparathyroidism).
Decreased GFR also leads to decreased active Vitamin D production (2nd hydroxylation into active form) which contributes to low calcium in the blood and leads to Osteomalacia as well as triggering increased secretion of PTH.
- Hyperphosphataemia and Low-1-alpha-calcidol in blood.
Generally asymptomatic in pre-dialysis patients. Some patients have muscle and bone pains.
Classical appearances of Renal Osteodystrophy
- “Rugger jersey spine” – sclerosis of the end of the vertebrae
- Erosion to terminal phalanges and bone cysts (due to increased parathyroid hormone)
- Non-bone calcification e.g. calcified aorta, calcification around the shoulder is associated with high levels of phosphate and calciphylaxis (deposition of calcium and phosphate in blood vessels leading to ulceration and skin necrosis).
What are the CNS, GI, Endocrine and Dermatological effects of CKD?
[*] CNS effects
- Neuropathy
- Seizures
- Coma
[*] Gastro-intestinal effects:
- Dyspepsia
[*] Endocrine effects:
- Impotence and infertility
- Short statue
[*] Dermatological effects:
- Pruritus (itching) (80%)
What are Ureamic symptoms and describe what is meant by altered drug metabolism in CKD
[*] Accumulation of waste products (occurs in uraemia but urea itself doesn’t seem to be causing the symptoms) contribute to uraemic symptoms
- Reduced appetite
- Nausea and vomiting (taste buds change)
- Pruritus..
- Can also leads to comas, seizures and pericarditis
[*] Altered drug metabolism
- Lots of drugs require dose alteration with CKD / ESRD due to reduced metabolism and/ or elimination
- Drug sensitivity can be increased even if elimination is unimpaired meaning side effects more likely e.g. statins
What does measuring proteinuria predict?
[*] In managing CKD, we need to measure blood pressure and proteinuria.
[*] Proteinuria predicts development of End-Stage Renal Disease. End-Stage Renal Failure is when death is likely without renal replacement therap and eGFR
- For CKD1 patients, a positive dipstick proteinuria indicates future need for dialysis is much more likely compared to a negative dipstick proteinuria result.
How would you measure renal function?
- Serum Creatinine Normal Range: 80-120μmol/L
- Actual GFR is difficult to measure – very time consuming, requires specialist equipment and skills etc
Inulin (freely filtered) does not work in clinical practice as it is extremely time consuming and requires inulin infusion first 51^Cr EDTA clearance – expensive, radioactivity involved, very specialised Iohexol clearance also requires specialist equipment, not easy to do. Creatinine clearance (involves patient collecting their urine for 24 hours – low rate of patient adherence as it is very inconvenient)
- Serum Creatinine used to be used as a suggorate marker for GFR however it wasn’t very good as your GFR could be at 40% of normal GFR and still have a normal serum creatinine level.
- Creatinine comes from the non-enzymatic dehydration of creatine and thus creatinine concentration is determined by renal function AND muscle mass (affected by age, sex and race).
- NB: some patients also take creatine supplements (e.g. bodybuilders)
- Therefore eGFR is used to measure renal function as it has a straight line, linear relationship to “Gold Standard” GFR – eGFR is much more representative of the true GFR than serum creatinine
How would you investigate and assess the cause of CKD?
[*] Investigating CKD
- Define degree of (classify) renal impairment
- Define cause of renal impairment
- Provide patient with diagnosis and prognosis
- Identify complications of CKD
- Plan long term treatment (plan management to delay progression of decline in renal function and plan for dialysis and transplantation).
[*] Assessment of Cause of CKD
May be clues from history and examination: context of a relevant past medical history
- Auto Antibody Screen
- Complement
- Immunoglobulin
- ANCA
- CRP
- SPEP/UPEP
- Imaging of Kidneys (particularly if you suspect they have some kind of structural abnormality)
- Urinary Ultrasound looking at size and hydronephrosis (obstruction to urine drainage leading to dilated collecting duct systems => dilated kidneys)
- CT
- MRI
- If the kidneys are normal in size and the cause of CKD is not obvious, a renal biopsy could be considered.
Describe the principles of Peritoneal Dialysis
- Tube inserted into peritoneum
- Peritoneal dialysis fluid is put into the peritoneal cavity and the dialysis occurs across the peritoneal membrane (semi-permeable membrane). Fluid drags water across by osmosis. Waste products diffuse across the semipermeable membrane into the peritoneal space where dialysate is pumped into. Then waste products are drained from peritoneal space in the dialysate.
- The fluid is then drained away and disposed of.
[*] Peritoneal Dialysis: The Reality
- 2 options
- CAPD (Continuous Ambulatory Peritoneal Dialysis): 4-5 bags throughout day (30 min exchange)
- APD (Automated Peritoneal Dialysis): overnight (machine works overnight)
- You are responsible for your care
Describe the Contraindications and Complications for CAPD
Contraindications:
- Failure of peritoneal membrane
- Adhesions, previous abdo surgery, hernia, stoma
- Patient (or carer) unable to connect / disconnect e.g. due to problems with hands /eyes
- Obese or large muscle mass (relative Contraindication) – less efficient in bigger patients (works best in kids)
- ~Average life expectancy for patients on PD is 5 years (consider age of patient)
Complications:
- Peritonitis (causes dialysate fluid to become turbid due to presence of white blood cells), exit or tunnel site functions
- Ultrafiltration failure
- Leaks (scrotal, diaphragmatic) – can’t be repaired so can’t have PD anymore
- Development of herniae
Describe the principles of Haemodialysis
- A pump pushes blood around the circuit as arterial pressure alone isn’t enough
- Anti-coagulant prevents blood forming thrombosis
- Air trap and detector prevents air entering bloodstream and forming air-emboli.
- Blood and dialysate fluid move in opposite directions (i.e. flow in a countercurrent fashion) to maximize the clearance of solute.
- Unit-Based HD: 4 hours, 3 times per week, designated slot
Describe Fistulas in Haemodialysis
[*] HD requires the creation of an Arteriovenous (AV) Fistula, a connection between an artery and vein. The difference in pressure means that blood moves from the artery => vein, causing it to dilate and develop a muscular wall. This provides vascular access. Using this vascular access, the patient is connected up to a dialysis machine which contains highly purified water across a semi-permeable membrane. This allows for ‘filtering’ of the patient’s blood.
- Most patients have six possible fistulae available. Loops are used if the radiocephalic, brachiocephalic and transposed brachiobasilic are difficult to access.
- When a fistula is made, the arterial pressure increases the pressure in the vein forcing the vein to undergo vascular remodelling – becomes arterialised
- Fistulas can get quite big which has an impact on person’s body image, particularly in young people
- Need to consider where you start the fistula – if you start the fistula in the arm, its easier to hide by wearing sleeves but in the future, fistulas aren’t viable below this point so you’ve reduced possible options in the future
- Another option is a permanent dialysis catheter (into the internal jugular vein above right atrium) however there is an infection risk and these catheters generally have a 5-6 year lifespan. The vein may become fibrotic and then fistulae on that side of the body will no longer be possible.
Describe Renal Transplantation
[*] Renal Transplantation: all patients with progressive CKD or end-stage renal failure should be considered for transplantation. When a kidney is transplanted, it is not to the normal anatomical position but to the iliac fossa. This is because it can easily be connected both to the iliac vessels and the bladder
Describe how CKD affects water and salt handling in the kidney
[*] Amount of urine produced depends on:
- GFR: e.g. GFR of 20mls/min = 28.8 L/day
- ADH: makes distal collecting tubule and collecting duct permeable to water (V2 receptors and aquaporins). No ADH produces dilute urine up to 30L/day
[*] Effect of CKD on Water/Salt handling by kidney
- Reduced GFR: loses ability to maximally dilute and concentrate urine.
- Small glomerular filtrate but same solute load causes osmotic diuresis (reduces maximum concentrating ability and response to ADH)…nocturia (getting up at night to go to the toilet etc).
- Low volume of filtrate reduces maximum ability to excrete urine therefore maximum urine volume much smaller
[*] Acid-Base Balance Disturbance Electrolyte Disturbances
- Generally asymptomatic
- Can require additional medication (e.g. Sodium Bicarbonate) or alteration of medication (e.g. stopping ACE-inhibitors) etc.
- Acidosis worsens bone disease and can cause muscle wasting (if left untreated)
