Chronic kidney disease Flashcards
What is ADPKD?
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians.
What are the two disease loci identified in ADPKD?
PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively.
What percentage of ADPKD cases are type 1?
85% of cases.
What percentage of ADPKD cases are type 2?
15% of cases.
On which chromosome is ADPKD type 1 located?
Chromosome 16.
On which chromosome is ADPKD type 2 located?
Chromosome 4.
How does ADPKD type 1 typically present compared to type 2?
ADPKD type 1 presents with renal failure earlier.
What is the screening investigation for relatives of ADPKD patients?
Abdominal ultrasound.
What are the ultrasound diagnostic criteria for ADPKD in patients aged < 30 years?
Two cysts, unilateral or bilateral.
What are the ultrasound diagnostic criteria for ADPKD in patients aged 30-59 years?
Two cysts in both kidneys.
What are the ultrasound diagnostic criteria for ADPKD in patients aged > 60 years?
Four cysts in both kidneys.
What is a potential management option for select ADPKD patients?
Tolvaptan (vasopressin receptor 2 antagonist).
Under what conditions is tolvaptan recommended for ADPKD treatment?
If patients have chronic kidney disease stage 2 or 3 at the start of treatment, evidence of rapidly progressing disease, and the company provides it with the discount agreed in the patient access scheme.
Extensive cysts are seen in an enlarged kidney
What is a significant factor causing anaemia in chronic kidney disease (CKD)?
Reduced erythropoietin levels.
CKD is associated with a decrease in the production of erythropoietin, a hormone produced by the kidneys that stimulates erythropoiesis in the bone marrow.
What type of anaemia is typically seen in CKD?
Normochromic normocytic anaemia.
When does anaemia in CKD become apparent?
When the GFR is less than 35 ml/min.
What should be considered if the GFR is greater than 60 ml/min?
Other causes of anaemia.
What is the impact of anaemia in CKD on left ventricular hypertrophy?
It predisposes to the development of left ventricular hypertrophy, associated with a threefold increase in mortality in renal patients.
What role does hepcidin play in anaemia related to CKD?
In CKD, hepcidin levels are often increased due to inflammation and reduced renal clearance, leading to decreased iron absorption and impaired release of stored iron.
How does metabolic acidosis affect iron absorption in CKD?
It can inhibit the conversion of ferric iron (Fe³⁺) to its absorbable form, ferrous iron (Fe²⁺), in the duodenum, reducing iron absorption.
What are some causes of reduced erythropoiesis in CKD?
Toxic effects of uraemia on bone marrow, anorexia/nausea due to uraemia, reduced red cell survival, and blood loss due to capillary fragility.
What is the target haemoglobin level suggested by the 2011 NICE guidelines for CKD management?
10 - 12 g/dl.
What should be done before administering erythropoiesis-stimulating agents (ESA)?
Determination and optimisation of iron status.
What is recommended for patients who are not on ESAs or haemodialysis?
Oral iron should be offered. If target Hb levels are not reached within 3 months, switch to IV iron.
What do patients on ESAs or haemodialysis generally require?
IV iron.
Which ESAs should be used in CKD management?
Erythropoietin and darbepoetin should be used in those likely to benefit in terms of quality of life and physical function.
What are the basic problems in chronic kidney disease?
Low vitamin D, high phosphate, low calcium, secondary hyperparathyroidism.
What causes low calcium in chronic kidney disease?
Due to lack of vitamin D and high phosphate.
What is secondary hyperparathyroidism?
It is due to low calcium, high phosphate, and low vitamin D.
What is osteitis fibrosa cystica?
Also known as hyperparathyroid bone disease.
What is adynamic bone disease?
A reduction in cellular activity (both osteoblasts and osteoclasts) in bone, may be due to over treatment with vitamin D.
What causes osteomalacia?
Due to low vitamin D.
What is osteosclerosis?
A condition characterized by increased bone density.
What is osteoporosis?
A condition characterized by reduced bone density and increased fracture risk.
X-ray of a Brown tumour caused by secondary hyperparathyroidism in a young female with chronic kidney disease
What is a common cause of chronic kidney disease?
Diabetic nephropathy
What is another common cause of chronic kidney disease?
Chronic glomerulonephritis
What is a third common cause of chronic kidney disease?
Chronic pyelonephritis
What condition related to blood pressure can cause chronic kidney disease?
Hypertension
What genetic condition can lead to chronic kidney disease?
Adult polycystic kidney disease
What is the purpose of estimating glomerular filtration rate (eGFR)?
To provide a more accurate estimate of renal function than serum creatinine alone.
What is the most commonly used formula for estimating eGFR?
The Modification of Diet in Renal Disease (MDRD) equation.
What variables are used in the MDRD equation?
Serum creatinine, age, gender, and ethnicity.
What factors may affect eGFR results?
Pregnancy, muscle mass (e.g. amputees, body-builders), and eating red meat 12 hours prior to the sample.
What is the GFR range for CKD stage 1?
Greater than 90 ml/min, with some sign of kidney damage on other tests.
What is the GFR range for CKD stage 2?
60-90 ml/min with some sign of kidney damage.
What is the GFR range for CKD stage 3a?
45-59 ml/min, indicating a moderate reduction in kidney function.
What is the GFR range for CKD stage 3b?
30-44 ml/min, indicating a moderate reduction in kidney function.
What is the GFR range for CKD stage 4?
15-29 ml/min, indicating a severe reduction in kidney function.
What is the GFR range for CKD stage 5?
Less than 15 ml/min, indicating established kidney failure - dialysis or a kidney transplant may be needed.
What are the normal kidney tests that indicate no CKD?
Normal U&Es and no proteinuria.
CKD stages & GFR
What is chronic kidney disease usually diagnosed by?
Chronic kidney disease is usually diagnosed following abnormal urea and electrolyte results.
Is chronic kidney disease typically symptomatic?
Chronic kidney disease is usually asymptomatic.
What are possible features of chronic kidney disease?
Possible features include:
- Oedema (e.g. ankle swelling, weight gain)
- Polyuria
- Lethargy
- Pruritus (secondary to uraemia)
- Anorexia (which may result in weight loss)
- Insomnia
- Nausea and vomiting
- Hypertension
What is a common symptom of oedema in chronic kidney disease?
Ankle swelling and weight gain.
Example: Patients may notice swelling in their ankles.
What is the treatment requirement for hypertension in patients with chronic kidney disease (CKD)?
The majority of patients with CKD will require more than two drugs to treat hypertension.
What is the first-line treatment for hypertension in CKD?
ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g. diabetic nephropathy).
What should be expected when using ACE inhibitors in CKD patients?
A small fall in glomerular filtration pressure (GFR) and rise in creatinine can be expected.
What does NICE suggest regarding acceptable changes in eGFR and creatinine levels?
A decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable, but any rise should prompt careful monitoring.
What may a rise greater than the NICE suggested levels indicate?
A rise greater than this may indicate underlying renovascular disease.
When is furosemide particularly useful as an anti-hypertensive in CKD patients?
Furosemide is useful when the GFR falls to below 45 ml/min.
What is an additional benefit of furosemide in CKD patients?
It has the added benefit of lowering serum potassium.
What should be considered if a patient on furosemide is at risk of dehydration?
Consideration should be given to temporarily stopping the drug.
What do the NKF K/DOQI guidelines suggest regarding GFR cut-off for furosemide use?
The NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min.
What is a basic problem in chronic kidney disease (CKD) related to vitamin D?
1-alpha hydroxylation normally occurs in the kidneys → CKD leads to low vitamin D
What happens to phosphate levels in chronic kidney disease (CKD)?
The kidneys normally excrete phosphate → CKD leads to high phosphate
What is the consequence of high phosphate levels in CKD?
High phosphate level ‘drags’ calcium from the bones, resulting in osteomalacia
What causes low calcium levels in CKD?
Low calcium is due to lack of vitamin D and high phosphate
What is secondary hyperparathyroidism and its causes in CKD?
Secondary hyperparathyroidism is due to low calcium, high phosphate, and low vitamin D
What is the aim of managing chronic kidney disease mineral bone disease?
The aim is to reduce phosphate and parathyroid hormone levels.
What is the first-line management for reducing phosphate in CKD?
Reduced dietary intake of phosphate is the first-line management.
What are some treatments used in the management of CKD mineral bone disease?
Phosphate binders, vitamin D (alfacalcidol, calcitriol), and parathyroidectomy may be needed in some cases.
What type of phosphate binders are less commonly used now?
Aluminium-based binders are less commonly used now.
What are the problems associated with calcium-based phosphate binders?
Problems include hypercalcemia and vascular calcification.
What is sevelamer?
Sevelamer is a non-calcium based binder that is now increasingly used.
How does sevelamer work?
Sevelamer binds to dietary phosphate and prevents its absorption.
What are the additional benefits of sevelamer in CKD?
Sevelamer appears to have other beneficial effects including reducing uric acid levels and improving the lipid profiles of patients with chronic kidney disease.
X-ray of a Brown tumour caused by secondary hyperparathyroidism in a young female with chronic kidney disease
What is proteinuria?
Proteinuria is an important marker of chronic kidney disease, especially for diabetic nephropathy.
What ratio does NICE recommend for identifying patients with proteinuria?
NICE recommends using the albumin:creatinine ratio (ACR) in preference to the protein:creatinine ratio (PCR) due to greater sensitivity.
Can PCR be used for quantification and monitoring of proteinuria?
Yes, PCR can be used as an alternative for quantification and monitoring, although ACR is recommended in diabetics.
Are urine reagent strips recommended for proteinuria testing?
Urine reagent strips are not recommended unless they express the result as an ACR.
What are the approximate equivalent values for ACR and PCR?
ACR 30 mg/mmol corresponds to PCR 50 mg/mmol, and ACR 70 mg/mmol corresponds to PCR 100 mg/mmol.
What is the benefit of collecting a ‘spot’ ACR sample?
Collecting a ‘spot’ sample avoids the need to collect urine over a 24-hour period to detect or quantify proteinuria.
What type of urine specimen should be used for ACR collection?
A first-pass morning urine specimen should be used for ACR collection.
What should be done if the initial ACR is between 3 mg/mmol and 70 mg/mmol?
It should be confirmed by a subsequent early morning sample.
What does NICE state about a confirmed ACR of 3 mg/mmol or more?
Regard a confirmed ACR of 3 mg/mmol or more as clinically important proteinuria.
What are the NICE recommendations for referral to a nephrologist?
Referral is recommended for an ACR of 70 mg/mmol or more, or an ACR of 30 mg/mmol or more with persistent haematuria after excluding a urinary tract infection.
What should be considered for referral to a nephrologist with an ACR between 3-29 mg/mmol?
Consider referral if there is persistent haematuria and other risk factors such as a declining eGFR or cardiovascular disease.
How often should eGFR be monitored for people with or at risk of CKD?
Frequency of monitoring varies by eGFR and ACR categories.
What is the first-line management for proteinuria in patients with hypertension and CKD?
ACE inhibitors (or angiotensin II receptor blockers) are key in the management of proteinuria.
When should ACE inhibitors be indicated regardless of blood pressure?
If the ACR is > 70 mg/mmol, they are indicated regardless of the patient’s blood pressure.
What is the role of SGLT-2 inhibitors in managing proteinuric CKD?
SGLT-2 inhibitors may benefit patients with proteinuric CKD by blocking glucose reabsorption and reducing sodium reabsorption.
ACR PCR approximate equivalent
What is minimal change disease?
Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.
What percentage of minimal change disease cases are idiopathic?
The majority of cases are idiopathic, but in around 10-20% a cause is found.
What are some potential causes of minimal change disease?
Causes include drugs (NSAIDs, rifampicin), Hodgkin’s lymphoma, thymoma, and infectious mononucleosis.
What is the pathophysiology of minimal change disease?
T-cell and cytokine-mediated damage to the glomerular basement membrane leads to polyanion loss, resulting in increased glomerular permeability to serum albumin.
What are the features of minimal change disease?
Features include nephrotic syndrome, normotension, highly selective proteinuria, and normal glomeruli on light microscopy.
What is observed in electron microscopy for minimal change disease?
Electron microscopy shows fusion of podocytes and effacement of foot processes.
What is the first-line management for minimal change disease?
Oral corticosteroids are the first-line treatment, with 80% of cases being steroid-responsive.
What is the next step for steroid-resistant cases of minimal change disease?
Cyclophosphamide is the next step for steroid-resistant cases.
What is the prognosis for minimal change disease?
Prognosis is overall good, although relapse is common.
What are the relapse statistics for minimal change disease?
Roughly: 1/3 have just one episode, 1/3 have infrequent relapses, and 1/3 have frequent relapses which stop before adulthood.
