Chronic kidney disease Flashcards
How does the UK kidney association define chronic kidney disease?
A patient is said to have chronic kidney disease (CKD) if they have abnormalities of kidney function or structure present for more than 3 months.
The definition of CKD includes all individuals with markers of kidney damage or those with an eGFR of less than 60 ml/min/1.73m2 on at least 2 occasions 90 days apart (with or without markers of kidney damage).
It is important to note that patient’s with an eGFR greater than 60mL/min/1.73m2 will not be diagnosed with CKD unless markers of kidney damage are present.
How does renal function differ in AKI and CKD?
Acute kidney injury is defined as a sudden loss of renal function. However this is reversible that with early identification , appropriate management and treating the underlying cause, the patient can be expected to return to or near pre-AKI renal function.
In chronic kidney disease however, the is gradual (over months to years), irreversible reduction of kidney function. This reduction in kidney function is progressive and at end stage the patient may require dialysis or transplantation.
What are some of the markers used to quantify CKD?
Albuminuria (ACR > 3 mg/mmol)
Haematuria (or presumed or confirmed renal origin)
Electrolyte abnormalities due to tubular disorders
Renal histological abnormalities
Structural abnormalities detected by imaging (e.g. polycystic kidneys, reflux nephropathy)
History of kidney transplantation
State the cause of CKD.
Following an AKI - delayed pharmacological management can cause irreversible intrinsic damage
Long-standing hypertension
Diabetic nephropathy
Glomerulopathies/Vasculitis/Polycystic kidney disease
What are the risk factors for CKD progression?
Cardiovascular disease
Proteinuria
Previous episode of acute kidney injury
Hypertension
Diabetes
Smoking
African, African-Caribbean or Asian family origin
Chronic use of NSAIDs
Untreated urinary outflow tract obstruction
Explain the pathophysiology of how long standing hypertension can result in CKD?
High blood pressure moving through the afferent arteriole into the glomerulus results in the hyperfiltration due to an increased pressure within the glomerulus capillaries.
To withstand the higher blood pressure within the glomerulus, thickening of the vessel wall occurs known as Hyaline arteriolosclerosis which causes luminal narrowing. Despite there being high blood pressure, this luminal narrowing reduces perfusion through the glomerulus, leading to activation of RAS, further constricting the afferent arteriole.
This results in a decreased oxygen delivery to tissue such as the mesangial cells and tubular cells, resulting in ischaemia. This results in the secretion of TGF-B resulting in the deposition of fibroblasts and ECM release, causing fibrosis of glomerulus, specifically known glomerulosclerosis, causing a loss of filtration ability.
Once glomerulosclerosis has occurred in a nephron, the blood is redirected to other nephrons but again hyperfiltration occurs, and the same process of glomerulosclerosis of nephrons that were still functioning.
Explain the pathophysiology of how diabetic nephropathy can result in CKD?
Glucose within the blood, combines with proteins and lipids resulting in the formation of pro-inflammatory molecules in a process known as non-enzymatic glycation. In patients with diabetes, hyperglycaemia means that this process occurs more frequently. Pro-inflammatory molecules damages the efferent arteriole leading to arteriolosclerosis both hyaline (protein deposition) or atherosclerosis (glucose promotes oxidisation of LDL particles). Both cause thickening of the efferent arteriole resulting in increased backpressure, initially increasing the GFR due to hyperfiltration. When the GFR is increased due to hyperfiltration once again the mesangeal cells are stimulated resulting again in the secretion of TGF-B stimulating ECM release, causing fibrosis of glomerulus, specifically known glomerulosclerosis, causing a loss of filtration ability.
Once glomerulosclerosis has occurred in a nephron, the blood is redirected to other nephrons but again hyperfiltration occurs, and the same process of glomerulosclerosis of nephrons that were still functioning.
How can diabetic nephropathy be distinguished as a cause of glomerulosclerosis?
Due to the characteristic appearance of Kimmelstiel-Wilson nodules. These are nodules result from the expansion of the mesangial matrix, from damage as a result of non-enzymatic glycosylation of proteins. These nodules usually form in the glomerular capillary loops.
Explain the pathophysiology of how glomerulonephritis can result in CKD?
Often occurs in auto-immune disease such as Lupus or secondary to infections, often chronic, such as HIV or Hepatitis. These auto-immune or infection responses producing abnormal antibody-antigen complex which deposit within the glomerular basement membrane activating an inflammatory reaction resulting an inflammatory destructive lesions causing damage to the endothelial cells of the glomeruli capillaries, the basement membrane and the inner lining of the Bowman’s capsule, the podocytes. This makes the basement membrane more porous and areas of destruction, again causing hyperfiltration. When the GFR is increased due to hyperfiltration once again the mesangeal cells are stimulated resulting again in the secretion of TGF-B stimulating ECM release, causing fibrosis of glomerulus, specifically known glomerulosclerosis, causing a loss of filtration ability.
Once glomerulosclerosis has occurred in a nephron, the blood is redirected to other nephrons but again hyperfiltration occurs, and the same process of glomerulosclerosis of nephrons that were still functioning.
Explain the pathophysiology of how vasculitis can result in CKD?
Vasculitis is a broad term categorised by inflammation of the blood vessels which can involve them becoming swollen and even bursting. This can occur in the glomerular as is known as glomerulonephritis.
As mentioned previously, once glomerulonephritis has occurred inflammatory destructive lesions can form causing damage to the endothelial cells of the glomeruli capillaries, the basement membrane and the inner lining of the Bowman’s capsule, the podocytes.
This makes the basement membrane more porous and areas of destruction, again causing hyperfiltration. When the GFR is increased due to hyperfiltration once again the mesangeal cells are stimulated resulting again in the secretion of TGF-B stimulating ECM release, causing fibrosis of glomerulus, specifically known glomerulosclerosis, causing a loss of filtration ability.
Once glomerulosclerosis has occurred in a nephron, the blood is redirected to other nephrons but again hyperfiltration occurs, and the same process of glomerulosclerosis of nephrons that were still functioning.
Explain the pathophysiology of how polycystic kidney disease can result in CKD?
Fibrocystin gene defects in PCKD cause the outward growth and cyst formation on tubular cells. Multiple cysts cause compression of adjacent arterioles leading to a reduction in blood flow to the glomerulus or to other parts of the kidney tubule. A reduction in oxygen delivery to the proximal convoluted tubular cells, this affects the function of the tubular cells (absorption, filtration etc). So as less blood is also moving into the glomerulus leads to ischaemia, necrosis of the tubular cells (tubular disease as previously mentioned) but also a reduction in the GFR stimulating the juxtaglomerular cells stimulating RAAS system, constricting the arterioles, leading to secondary hypertension and the effects that can cause.
What is the main aims of management of CKD patients?
Identifying those who are at known risk of CKD, and ensuring appropriate management of these conditions (HTN, DM)
Delaying the progression of CKD (slowing CKD progression)
Lowering your risk of cardiovascular disease (having a heart attack or stroke)
Treating any complications that you may have because of your CKD
State the main complications associated with CKD.
Water and electrolyte imbalance
Muscle dysfunction
Hypertension
Renal/Metabolic bone disease
Renal anaemia
Will all patients with CKD develop the complications and at a particular stage?
Not every patient with CKD will develop all the complications and it is possible to develop them at different stages.
However for most complication, increased prevalence of the complication does correlate to increased severity of CKD (for example renal anaemia has this strong correlation).
What are the different stages of chronic kidney disease as defined by eGFR?
Stage 1: normal eGFR ≥ 90 mL/min per 1.73 m2 and persistent albuminuria
Stage 2: eGFR between 60 to 89 mL/min per 1.73 m2
Stage 3: eGFR between 30 to 59 mL/min per 1.73 m2
Stage 4: eGFR between 15 to 29 mL/min per 1.73 m2
Stage 5: eGFR of < 15 mL/min per 1.73 m2 or end-stage renal disease
What are the main management strategies of CKD patients?
Conservative diets
Drug management to reduce the rate of decline of renal function but also symptom control due to presence of complications
In end stage renal disease dialysis and transplant
What is the basis of the nutritional guidelines for somebody with CKD?
Specific dietician led advice will be provided to each patient individual and is dependent on their stage of CKD, but most nutritional advice promotes:
Low salt or sodium diet (2300mg or less)
Eating smaller portions of protein
Foods that protect the heart
Low phosphate (later stage)
Low potassium (later stage)
What are some of the water and electrolyte imbalances seen in the early stages of CKD?
Polyuria (increased urination) and nocturia (frequent urination during the night).
Reduced excretion of urea results in osmotic diuresis when the urea level is greater than 40 mmol/L. The concentration of this urine is very dilute.
What are some of the water and electrolyte imbalances seen in the later stages of CKD?
Glomerulosclerosis which is fibrosis of the glomerulus and constriction of the afferent arteriole reduces renal perfusion and there is a drop in filtration where the patient is unable to excrete sodium and water. This leads to a backpressure in blood (volume dependent hypertension occurs in 80% of CKD patients) and fluid which leads to oedematous areas forming - peripheral, pulmonary and ascites can all occur in CKD patients.
What is the management strategy of unregulated water?
Fluid restriction as the first line strategy
If the therapeutic monitoring parameters have not been reached,
Use loop diuretics as the second line strategy
What are the fluid restriction targets for CKD patients?
If not yet on dialysis and still passing urine - 1L/day as a minimum
If on haemodialysis or not passing urine - 500mL daily
Fluids includes anything that is liquid at room temperature (ice cream, gelantin)
In addition to fluid restriction targets what other nutritional advice may be provided to these patients and why?
Restrict dietary sodium, due to inability of the kidney to excrete sodium and water so increasing serum sodium will further cause hypertension and lead to further fluid retention.
Restricting sodium/avoiding salt helps to combat thirst
What is the therapeutic monitoring parameter for fluid restriction?
Reaching an optimal drug weight target
Reaching target blood pressure (volume dependent hypertension)
If fluid restriction has failed to achieve the therapeutic monitoring parameter, what pharmacological treatment would you introduce?
Include dosing regimen, therapeutic and toxic monitoring parameters
Furosemide:
Dosing regimen up to 2g PO daily
Less than 80mg PO daily is not effective in advanced CKD patients (below 20mL/min).
Dose to be administered in the morning.
Monitoring: after 5-7 days in high risk patients (includes CKD 3 or higher)
Therapeutic monitoring parameter:
Achieving optimal dry weight (weight loss of /day )
Bp - reaching target
Toxic monitoring parameters:
Blood pressure – hypotension
Hyperglycaemia (less common than thiazides)
U & Es – hypokalaemia, hyponatremia, hypomagnesaemia, hypocalcaemia
Renal function - serum creatinine
Inadequate weight loss
When may Bumetanide be used in preference to Furosemide as first line diuretic?
Bumetanide may be useful in patients with oedematous gut as it is better absorbed in these circumstances in comparison to Furosemide.
Dosing regimen: 1mg or 500 mcg in the elderly repeat after 6-8 hours if required.
Therapeutic and toxic monitoring is the same as Furosemide.
If the patient has inadequate response to loop diuretics what is the appropriate pharmacological management?
Metalazone:
5–10 mg daily, dose to be taken in the morning; increased if necessary to 20 mg daily.
Caution in mild to moderate impairment (risk of electrolyte imbalance and reduced renal function); avoid in severe impairment (ineffective if creatinine clearance less than 30 mL/minute).
Therapeutic:
Optimal dry weight (weight loss of …. /day)
Blood pressure reaching target
Toxic:
U&E’s - hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia, hyperuricaemia [gout], altered lipids
Renal function
Glucose - hyperglycaemia
Bp - hypotension
Do diuretics stop when dialysis begins?
Normally they do, but not always and is usually dependent upon whether the patient is passing urine.
What are the two main complications/concerns associated with water and electrolyte disturbances in CKD?
Hyperkalaemia- Potassium is renally excreted, so when there is a reduced glomerular filtration rate in CKD there is less filtration of potassium, and of the phosphate ion, this leads to an increase in serum potassium levels.
Metabolic acidosis - the kidneys play an important role in maintenance of the acid/base balance.
In CKD, decreased nephron mass is insufficient of excreting the acid load, in addition to the inability of the nephron to produce enough ammonia to neutralise the acid load, resulting in metabolic acidosis.
What are some of the complications associated with hyperkalaemia?
Muscle weakness, nausea, vomiting, diarrhoea but most significantly ventricular fibrillation (cardiac arrest).
What are some of the long-term complications associated with metabolic acidosis?
Osteoporosis and increased fracture risk due to increased bone loss
Decreased growth in children due to prevention of growth hormone release
Progression of CKD due to continuous cycle of acid build up, further decreasing kidney function and so on
Muscle loss due to excess acid causing its breakdown
High blood sugar due to acid causing insulin resistance
Increased risk of death
What is the appropriate management of hyperkalaemia in CKD patients?
Review medications causing raised potassium levels and consider initiation of co-prescribing potassium binders
What is the main medication used in CKD patients that causes hyperkalaemia?
ACE inhibitors but due to their long-term benefit in CKD patients for slowing the progression of renal function decline, co-prescribing potassium binders which enables them to remain on ACE inhibitors for longer, at a higher dose and with better adherence.
Name a drug, dosing regimen and therapeutic and toxic monitoring parameters for the treatment of hyperkalaemia.
Sodium Zirconium Cyclosilicate:
Initially 10 g 3 times a day, for up to 72 hours, followed by maintenance 5 g once daily, adjusted according to serum-potassium concentrations.
Therapeutic:
Serum potassium levels within range 3.6-5.0 mmol/L
Toxic monitoring parameters:
U & Es - hypokalaemia, hypercalcemia
Fluid imbalance
Oedema
How does your selected drug in the treatment of hyperkalaemia work?
It is a non-absorbed cation-exchange compound (releases calcium ions) that acts as a selective potassium binder in the gastro-intestinal tract, resulting in its excretion.
What is a medication that is often co-prescribed with potassium binders?
Lactulose, due to potassium binders releasing calcium ions as part of the cation exchange to bind to potassium in the GI tract. This calcium ions cause constipation so laxatives are often required.
What is the target serum potassium levels in pre-dialysis in haemodialysis patients?
4-6 mmol/L
Name a drug, dosing regimen and therapeutic and toxic monitoring parameters for the treatment of metabolic acidosis.
Sodium bicarbonate:
500mg TDS PO***
Therapeutic:
Toxic:
