Session 11 Flashcards
(38 cards)
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
What are the caveats of eGFR?
- Only accurate in adults
- Correction needed for black patients (proportionally higher muscle mass compared to Caucasians) (not Asians)
- It defines CHRONIC KIDNEY disease (relies on renal function being relatively stable) and is not useful in acute kidney injury (intercurrent illness or haemodynamic problems)
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.
What are potentially modifiable risk factors to delay the progression of renal failure?
Lifestyle
- Stop smoking
- Obesity – lose weight (obesity increases risk of CVS disease)
- Lack of exercise increases risk of CVS disease
Treat diabetes (if present)
Treat high blood pressurewhich helps to slow kidney function decline and protect CVS system. 80-85% of patients are hypertensive. Fluid overloading can be treated by:
- Anti-hypertensives
- Diuretics
- Fluid restriction
ACE inhibitors / Angiotensin II receptor blockers in proteinuria
Lipid lowering – statins for high cholesterol levels.
Further to this the patient should be monitored by checking their eGFR and indications for initiation of dialysis.
Describe Conservative Care / End of Life
- Dialysis may not be better for everyone
- Dialysis prolongs survival for elderly (70 years or older) patients who have ESRD and significant comorbidity by approximately 2 years
- Patients who choose conservative care can survive a substantial length of time, achieving similar numbers of hospital-free days to patients who choose haemodialysis.
- Heart disease is especially associated with poor outcomes on dialysis
What are symptoms of ESRD with end of life care?
- Pain: may relate to ESRD e.g. bone pain, dialysis-related pain but often not related e.g. neuropathy, musculoskeletal
- Constipation
- Fatigue
- Nausea / Lack of appetite
- Pruritus
- Cramps / restless legs
- Sleep disturbance
- REDUCED QUALITY OF LIFE
Describe mortality in ESRD
- Patients with ESRD have increased mortality compared to age-matched patients without ESRD
- But majority of patients don’t die from renal failure – they die from cardiac disease, cerebrovascular, malignancy, infection amongst others. This is true in both dialysis and transplant patients. Transplant patients have increased risk of malignancy and mortality from malignancy.
- RRT patient aged 30-34 had a mortality rate 25x higher than general age-matched population.
- Average life expectancy of incident ESRD patient aged 25-29 years is 18 years from diagnosis.
- RRT patients aged 85+ had a mortality rate 2.7x higher than general population.
- Average life expectancy for incident ESRD patient aged 75 years is 3 years from diagnosis.
Consider quality of life of a patient on dialysis
- Fluid intake could be limited to 500ml a day
- Foods such as potatoes (apart from mashed), cheese, chocolate, coffee, toffee, avocado, bacon, chips, crisps etc) are prohibited due to their high phosphate and/or potassium content.
- Patients on dialysis are more likely to suffer from loneliness and isolation from friends (not able to go out and socialize etc)
What is meant by RRT, Dialysis and what are the indications for initiation of Dialysis?
[*] Renal Replacement Therapy is required when native renal function declines to a level no longer adequate to support health. Usually when eGFR 8-10 ml/min (Normal ~100 ml/min)
[*] Indications for Initiation of Dialysis
- Uraemic symptoms
- Acidosis
- Pericarditis
- Fluid overload
- Hyperkalaemia
[*] Dialysis is a process where there is a passage of molecules through a semi-permeable membrane down a concentration gradient.
