Chronic Kidney Disease Flashcards
Why is it important that you obtain an early morning midstream urine sample?
Orthostatic proteinuria is a benign condition caused by changes in renal hemodynamics. It is present in a minority of (2-5%) otherwise normal individuals. It is caused by a period of prolonged standing.
When can there be proteinuria in the urine, outside of CKD?
- After physical exercise
- Fever
- Pregnancy
- UTI
- Abnormally high BP
- Nephrotic/Nephritic syndrome
What information can a urine dipstick tell you?
- Dipstick proteinuria = glomerular or tubulointerstitial disease
- Urine sediment with RBCs + RBC casts = proliferative glomerulonephritis
- Pyuria and/or white cell casts = interstitial nephritis (especially if eosinophils are present in the urine) or UTI
- Spot urine collection for total protein:creatinine ratio allows reliable estimation of total 24-hour urinary protein excretion.
- The degree of proteinuria correlates with the rate of progression of the underlying kidney disease and is the most reliable prognostic factor in CKD. - 24-hour urine collection for total protein and creatinine clearance.
- To detect and identify proteinuria, use urine albumin:creatinine ratio (ACR) as it has greater sensitivity than protein:creatinine ratio (PCR) for low levels of proteinuria.
- For quantification and monitoring of proteinuria, PCR can be used as an alternative. ACR is the recommended method for people with diabetes. - Initial urinalysis reveals non visible haematuria should have a urine culture performed to exclude a UTI.
- If a UTI is excluded, two further tests should be performed to confirm the presence of persistent non visible haematuria.
- If non visible haematuria persists then urological review is required
In addition to his diabetes blood test (HbA1C) what other tests should be performed at a diabetic review?
- BP
- Urinalysis
- BMI
- Foot exam (for peripheral neuropathy)
- Bloods for U+Es (renal function)
- Cholesterol levels
- Medication + lifestyle issues (i.e. smoking, sexual dysfunction)
Diabetic reviews occur annually!
Clearly cholesterol, blood pressure and diabetes all need addressing. Which is the most important factor that can be addressed which will reduce Mr Lewis’ risk of cardiovascular disease in the future?
Blood pressure
- Metformin reduced CVD in obese group
- Using Captopril or atenolol to lower BP, reducing risk of microvascular disease
Name some of the putative factors linking diabetes and cardiovascular disease
- Oxidative stress
- Poor glycemic control
- Markers of insulin resistance
- Low-grade inflammation
After metformin, what are the other drug options for combination therapy in type 2 diabetes?
- DPP-4 inhibitor (i.e. sitagliptin)
- Pioglitazone
- Sulphonylurea (i.e. glipizide)
When should pioglitazone not be used in type 2 diabetics?
- Heart failure
- Hepatic impairment
- DKA
- Bladder cancer history
- Macroscopic hematuria (uninvestigated)
What is proteinuria and how is it considered pathological?
Proteinuria >150mg/day is abnormal and is an important feature of increased glomerular permeability and therefore of early renal disease.
The dipstick tests commonly used to test for proteins usually detect albumin. Microalbuminuria (30-300mg/day) is an early feature of several renal diseases including diabetic nephropathy and other forms of glomerular or tubular diseases.
What is the most abundant normal protein excreted in the urine by the kidney?
Uromodulin/THP (Tamm-Horsfall glycoprotein)
- 150mg/day
What BP tablet would you recommend in someone with diabetes and some renal impairment?
Ramipril (ACE inhibitor)
How are ACE/ARBs renoprotective?
In type 1 diabetes:
- ACE reduce albuminuria + diabetic nephropathy
- ARBs reduce proteinuria
In type 2 diabetes:
- Reduce renal disease progression + albuminuria
- ACE reduce new nephropathy irrespective of BP
What are the cells in the glomerulus?
- Mesangial cells (impacted in diabetic nephropathy)
- Endothelial cells
- Glomerular basement membrane
- Podocytes foot processes
What is the pathophysiology of diabetic nephropathy?
- Increased glomerular pressure
- HTN (afferent arteriole -> vasoconstriction)
- RAS activation (efferent arteriole -> vasoconstriction) - Barotrauma of mesangium
- Release of cytokines -> inflammation
- Release of free radicals
- Mesangial expansion (produce collagen matrix)
- Mesangial expansion results in pushing on capillaries + thickens glomerular basement membrane + podocyte foot processes have increased fenestrations - Ischemia of nephron
- Atrophy + destruction (less blood flow from efferent arteriole vasoconstriction)
- Made worse from barotrauma of mesangium (i.e. cytokines + free radicals)
What are the clinical findings of diabetic nephropathy?
- Increased GFR
- Increasing glomerular pressure from afferent + efferent arterioles, which forces filtration to be increased (due to increased glomerular P) -> asymptomatic! - Detectable proteinuria
- Due to increased glomerular pressure + mesangial expansion
- Podocyte foot processes dilate = increased spaces so protein is able to escape out and isn’t reabsorbed
- Albumin is detected in the urine - Microhematuria
- Due to nephron ischemia (dying nephrons)
- The increased GFR in remaining nephrons compensates initially for those that are dying (thus GFR may still be increased then normal) - Kidney failure
- Kidney can no longer keep up with nephron destruction
- No longer can filter blood
- Decreased urine output
- Can lead to electrolyte imbalances, anemia, heart arrhythmias
What are the treatments for diabetic nephropathy?
Remember hyperglycemia activates RAS.
ACE inhibitors can allow for vasodilation of the afferent arteriole while also preventing RAS activation by acting on the efferent arteriole.
This overall prevents an increase of glomerular pressure and stops the progression to diabetic nephropathy.
What changes are seen on imaging of the kidneys in CKD?
Thinning of the renal cortex
What are the functions of the kidneys?
- Salt + water homeostasis (ADH + concentration of urine)
- Acid-base balance (reabsorption of HCO3- + excretion of H+)
- Endocrine organs (secrete EPO + renin)
- Regulation of BP
- Excrete waste products
- Activate vitamin D (second activation; first in liver)
What is the definition of chronic kidney disease?
Defined as abnormalities of kidney function or structure present for more than 3 months, with implications for health.
This includes all people with markers of kidney damage and those with a GFR < 60ml/min/1.73m2 on at least 2 occasions separated by a period of at least 90 days (with or without markers of kidney damage)
What is eGFR?
A creatinine-based estimate of GFR calculated in the lab.
It is an estimate and is prone to errors in certain patient groups.
Describe the mechanisms of ACE inhibitors and ARBs. How do they reduce proteinuria/albuminuria?
ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II, ARBs inhibit the angiotensin II receptor.
Angiotensin II is vasoconstrictive and salt retentive which underlies its pathophysiology in high blood pressure.
In terms of renal dysfunction Angiotensin II preferentially acts on the efferent arterioles to maintain the hydrostatic pressure at the glomeruli.
RAS overactivation and increased glomerular pressure has been implicated in diabetic nephropathy, Inhibiting the production of or the action of angiotensin II can therefore reduce glomerular hydrostatic pressure.
How would you counsel a patient on starting an ACE-i?
- Side effects:
- Dry cough (in 10% of patients)
- Angioedema
- Hypotension
- Hyperkalemia - These drugs must be stopped in AKI as they are nephrotoxic! In states of “pre renal” AKI the body wants to maintain the glomerular pressure by upregulating RAS and vasoconstricting the efferent arteriole. However if a patient is on ACE-I/ARB then this homeostatic system is blocked. (i.e. ACE/ARB is nephrotoxic in acute tubular necrosis)
- Contraindicated in pregnancy as they increase the risk of congenital malformations. Alternative hypertensive medications should be used during pregnancy
- instead use labetolol, nifedipine, or methyldopa
Why might there be an increase in creatinine and what increase is considered acceptable?
Due to the mechanism of action of ACE-I and ARBs a small increase in creatinine is acceptable following initiation of treatment. However after commencing the drug and after every dose change a blood test must be checked to ensure there has been no significant rise in creatinine. Commonly accepted increases are around 25-30% rise. If the creatinine does rise then blood should be checked regularly to ensure no further increase. A more significant rise may indicate underlying condition such as renovascular disease/renal artery stenosis.
What are the referral guidelines for nephrology?
Refer according to GFR:
30-59: Refer if progressive renal failure as defined by decreasing GFR of ≥ 25% over 12mo or decrease ≥15 ml/min/1.73m2 within 12 months
15-29: Usually require referal
< 15: Refer urgently
What 4 metabolic complications can occur in CKD?
- CKD mineral bone disease (hypocalcemia, hyperparathyroidism)
- Metabolic acidosis
- Hyperkalemia
- Renal anemia
How would you manage each of the following CKD complications, medically:
a) metabolic acidosis
b) renal anemia
c) hyperkalemia
d) secondary hyperparathyroidism
e) altered volume status
a) oral alkali (sodium bicarbonate)
b) EPO + IV iron; target ferritin > 200 in CKD
c) dietary restriction + if fails, decrease ACE-i dose
d) calcitriol/alphacalcidol (vitamin D analogue) ± calcium binders (i.e. bisphosphonates)
e) salt + fluid restricted diet; diuretics
How is CKD diagnosed?
- History + exam
- Immunology screen
- Renal biopsy ± MRA (magnetic resonance angiography)
What are the physical and metabolic complications of CKD?
- Anemia
- Metabolic acidosis
- Hyperkalemia
- Bone health (secondary parathyroidism)
- Fluid volume status
- Symptoms of uraemia
How can you reduce the progression of CKD?
- Control BP, cholesterol, UTI
2. Treat the underlying condition (i.e. diabetes)
What is azotaemia?
Elevation of nitrogenous metabolic waste in the blood due to failure of clearance by the kidneys
What is uraemia?
Clinical syndrome resulting from failing kidneys and progressive azotaemia
What is the normal range of GFR?
100-130ml/min/1.73m2
What is the difference between GFR and eGFR?
GFR:
- Non-creatinine based
- Inulin clearance
eGFR:
- Creatinine-based
- Creatinine clearance + serum creatinine
What are the stages of CKD based on?
Based on eGFR:
1 = kidney damage with normal/increased GFR (≥90)
2 = kidney damage with mild decrease in GFR (60-89)
3 = moderate decrease in GFR (30-59)
4 = severe decrease in GFR (15-29)
5 = established kidney failure (≤ 15)
What are the non-modifiable risk factors for CKD?
- Old age
- Family history
- Reduced kidney mass
- Low birth weight
- Ethnic minorities
- Low income
What are the modifiable risk factors for CKD that cause direct kidney damage?
- Diabetes
- High BP
- Autoimmune disease
- Systemic sepsis
- UTI
- Urinary stones
- Urinary obstruction
- Drug toxicity
When is an immediate referral made to nephrology regardless of GFR?
- Malignant HTN
- Hyperkalemia (>7mmol/l)
- Proteinuria with oedema + low serum albumin (nephrotic syndrome)
When is a routine referral to nephrology made?
- Dipstick proteinuria + urine PCR > 100mg/mmol
- Dipstick proteinuria + microscopic hematuria
- Macroscopic hematuria but urological tests negative
What are the 5 most common primary diseases affecting the kidney causing CKD?
- Diabetes
- HTN/renovascular disease
- Glomerulonephritis
- Pyelonephritis/reflux
- Systemic disease causing glomerulonephritis (vasculitis)
What is the nutritional management of CKD?
- Adequate calorie intake
- Adequate protein intake
- Salt restriction
- Fluid management
- Nutritional supplements
- Weight management
- Lipid control
What is the BP target with CKD?
130/80
125/75 or less in proteinuria states
How is BP controlled in CKD?
Use ACE/ARBs in all stages
- Check K+ and creatinine 2 weeks after starting/dose change/increasing diuretics
- If eGFR falls ≥ 15% STOP medication and review patient
- If eGFR < 30ml/min withdraw diuretic prior to starting ACE/ARB
- Stop ACE/ARB temporarily in acute hypovolemia
How does one prepare for renal replacement therapy?
- Stage 4 CKD
- Immunise (pneumococcal, influenza, hep B)
- Home based therapies have better outcomes
- Takes 3-6mo to set up dialysis care
Are there any changes to a patient’s prescription that you would want to make in view of his deteriorating eGFR? His current medications include Ramipril 10mg, amlodipine 5mg, metformin 1000mg bd, atorvastatin 40mg.
Metformin: “NICE recommends to avoid if eGFR less than 30mL/minute/1.73m2”
You have noted that Mr Lewis has been changed from simvastatin to atorvastatin. Research why this might have been done with reference to the MHRA guidance of August 2012?
Increased risk of myopathy and rhabdomyolysis in patients taking amlodipine and >20mg of simvastatin.
What side effect is associated with high doses of simvastatin?
Myopathy and/or rhabdomyolysis
Which drugs is simvastatin contraindicated for?
- Ciclosporin
- Danazol
- Gemfibrozil
What is the maximum dose for simvastatin when in conjugation with amlodipine or diltiazem?
20mg/day
Why might a CKD patient be breathless?
- Anaemia
- Fluid overload/pulmonary oedema
- Metabolic acidosis
- Associated heart failure
What occurs in renal failure biochemically?
- Increase in organic acids, particularly as a result of protein metabolism
- Increasing acidosis
- Falling bicarbonate
- Increasing potassium, urea, and creatinine
- Partial respiratory compensation
What are the 6 indications for dialysis?
- pH < 7.25
- K > 7mmol
- Fluid overload
- Toxins (SLIME)
- Creatinine > 400
- Uraemic pericarditis
Where along the nephron tubule is Na+ absorbed?
Proximal convoluted tubules (65-75%)
Ascending Loop of Henle
Distal convoluted tubules (5%)
Collecting Ducts (1%)
Where is HCO3- absorbed?
Proximal convoluted tubule
Where is water reabsorbed?
Collecting ducts
Descending Loop of Henle
List 3 osmotic diuretics and where they act
- Mannitol (IV)
- Urea (IV)
- Glycerol (oral)
- Act on proximal convoluted tubule
- Prevent the reabsorption of water from tubule into blood thus decreasing plasma volume + BP
- Increase the osmolality in the tubule + increase the excretion of all solutes!
List 2 loop diuretics and where they act
- Furosemide
- Bumetanide
- Act on thick ascending Loop of Henle
- Prevents sodium reabsorption (+ Cl + K + Ca + Mg)
- Acts on Na-Cl-K transporter in loop of Henle
- Can induce renin release due to plasma volume depletion
List 2 thiazide diuretics and where they act
- Hydrochlorothiazide
- Chlorothiazide
- Act on distal convoluted tubule
- Inhibit Na-Cl transporter
- Increases excretion of Na, K, Cl and H2O
- Increases reabsorption of urea in proximal convoluted tubule = increased plasmic uric acid = gout!
List 2 potassium sparing diuretics and where they act
- Spironolactone (aldosterone inhibitors) -> in collecting ducts
- Amiloride -> in distal convoluted tubule
- Work in distal convoluted tubules (end) + collecting duct
- Decrease the reabsorption of Na+ while preventing the excretion of K+
- Used in conjunction with other diuretics to prevent excretion of K+
- Increase excretion of Na, Cl, and H2O
What are the carbonic anhydrase inhibitors?
- Weakest diuretics
- Prevent reabsorption of NaHCO3- in the proximal convoluted tubule
- Used to treat glaucoma
- Examples: acetazolamide, methazolamide
What are the indications a patient should start renal replacement therapy?
- Fluid overload
- Refractory hyperkalemia
- Uraemic symptoms:
- nausea, vomiting, weight loss
- neurological symptoms
- uraemic pericarditis (rare)
What is created for hemodialysis? Peritoneal dialysis?
Hemodialysis = AV fistula (outside the body)
- 4h, 3x/week
- Fistula connects artery + vein in arm
- Often requires going to the hospital to get done
Peritoneal dialysis = Tenckhoff catheter insertion (inside the body)
- Can be done at home (4 exchanges/day for 30min)
- Tube close to bellybutton inserted + dialysate solution inserted into peritoneum
- Fluid is drained with waste then as waste products are diffused into the peritoneum
- CAPD (continuous ambulatory peritoneal dialysis) or APD (automated peritoneal dialysis - while sleeping for 7-10h)
What symptoms can guide you to indicate you need dialysis?
- Fatigue
- Decreased appetite
- Shortness of breath
- Nausea
What are contraindications to hemodialysis?
- Inability to achieve suitable vascular access
- Severe dementia
- Severe heart failure
- Bleeding disorder
- Low BP
- Severe active psychotic disorder
What are contraindications to peritoneal dialysis?
- IBD
- Ischemic bowel
- Acute diverticulitis
- Abdo abscess
- 3rd trimester pregnancy
- Abdo hernias
- Stomas/VP shunts
- Previous multiple abdominal surgeries
- Blind (unless having assisted APD)
- Poor manual dexterity (unless having assisted APD)
- Obesity
- Severe dementia
- Severe nephrotic range proteinuria
- Severe obstructive airway disease
- Poor hygiene
- Severe active psychotic disorder
What is dialysis?
Dialysis is a procedure to remove waste products and excess fluid from the blood when the kidneys stop working properly. It often involves diverting blood to a machine to be cleaned.
What are the side effects of dialysis?
- Itchy skin
- Muscle cramps
- Peritonitis (peritoneal dialysis)
- Low BP
- Sepsis
- Hernia (peritoneal dialysis)
- Weight gain (peritoneal dialysis)
What immunosuppression medications are used in kidney transplants?
- Cyclosporin
- Tacrolimus
Both act on T lymphocytes - Prednisolone
Works in the nucleus - MMF, Azathioprine
Affect cell cycle proliferation in B + T cells - Sirolimus
Stops proliferation of fibroblasts + tumour cells
How is tubulointerstitial transplant rejection treated?
IV steroids
What is the most severe form of transplant rejection?
Vascular rejection (treated with IV steroids)
Which 3 unusual infections are common in immunosuppressed patients?
- CMV -> tx with antivirals
- PCP
- Perforated diverticulitis (similar for cholecystitis + pancreatitis) -> “acute abdomen” presentation
What is the most common malignancy affecting immunocompromised patients?
Squamous cell carcinoma of the skin
What is fluconazole used to treat? How is it metabolised?
Treats candidiasis (thrush)
It’s metabolized in the liver - inhibits CYTP450 and thus prevents the metabolism of tacrolimus
What is the pathological classification of diabetic nephropathy?
Class 1: Thickening of the glomerular basement membrane
Class 2: Mesangial expansion
Class 3: Nodular sclerosis
Class 4: Advanced diabetic glomerulosclerosis
What happens to calcium and PTH in CKD?
Calcium drops and PTH rises. In addition, phosphate rises which can cause pruritus
What is the role of PTH?
Reabsorption of calcium and decreases reabsorption of phosphate
Activity of parathyroids are regulated by serum Ca2+ levels
What is the role of vitamin D?
Vitamin D (active form in kidney) reabsorbs Ca2+ and phosphate from the gut + releases Ca2+ from bone
What should you look for during a fistula examination?
- Where is the fistula?
- Radiocephalic/Brachiocephalic/Brachiobasilic - Is there any evidence of any previous fistulae?
- Is there evidence of any recent use? Dressings? Needle sites?
- Any signs of aneurysms? Haematomas? Infection?
- Is there any evidence of swelling of the fistula arm or collateral veins that may suggest central vein stenosis?
- Is there any evidence of cold/blue hands distal to the fistula which may suggest steal syndrome
What should you feel and listen to in a fistula?
Listen:
- listen along length for fistula bruit
Feel:
- Thrill?
- If the fistula is pulsatile this may suggest an outflow problem
What is the most common complication leading to death of ESRD?
Cardiovascular disease
- Sudden arrhythmic events
- Heart failure related to LVH
- Coronary vascular calcification
- Electrolyte disturbances
What are 3 symptoms/signs of CKD?
- Fatigue
- Hypertension
- Pruritis
What are the 2 most common causes of ESRD in the UK?
- Diabetes
2. HTN
Name absolute contraindications to renal transplant?
- Concurrent/recurrent infection
- Active malignancy
- Severe respiratory disease
- Severe peripheral vascular disease
- Severe ischemic heart disease
- Cirrhosis
- Severe cognitive impairment
- Drug/alcohol addiction
- Non-adherence to therapy
- Multiple non-successful transplants
His Vitamin D level (Vitamin D2/D3 is normal). He takes maximum dose of Lanthanum (a non calcium based phosphate binder). What treatment might help his CKD-MBD?
Parathyroidectomy
Mr Jones has evidence of tertiary hyperparathyroidism. Cholecalciferol is the inactive form of vitamin D produced by the skin from sunlight. We are told that this is normal in Mr Jones’ case therefore he does not require supplementation. Calcichew can be considered a calcium supplement (when taken between meals) or as a phosphate binder (when taken with meals). Calcium supplementation or using a calcium based phosphate binder would be inappropriate because Mr Jones has a high calcium. Similarly a vitamin D analogue such as alphacalcidol would increase the calcium and phosphate.
Management options therefore include a partial or total parathyroidectomy or using a calcimimetic such as cinacalcet. Cinacalcet is a medication that mimics calcium at calcium sensing receptors. Some of these receptors are found on the parathyroid gland and thus this new expensive drug can reduce PTH. It provides an alternative to patients who are unwilling to undergo a surgical parathyroidectomy.
Claire Bennett has been diagnosed with a metastatic gastric squamous cell carcinoma.
Claire is 38years old 173cm and weighs 70kg, therefore her body surface area is 1.84m²
The oncologist has decided from looking at the histology EOX chemotherapy is the most appropriate choice.
The dose for Capecitabine in EOX is detailed below. Please calculate the number of tablets which should be prescribed for one cycle.
Capecitabine 625mg/m2 Orally twice a day for 21 days
What is the total quantity of tablets that should be prescribed?
Body surface area is 1.84m² - 625mg x 1.84m2 = 1150mg
Cycle is 21 days
Each dose is taken twice daily, so 42 doses in total.
One dose is: 2 x 500mg tablets and 1 x 150mg tablet.
So 42 x 1 = 42 150mg tablets And 42 x 2 = 84 500mg tablets.
What is the mechanism of action of calcitonin? Where does it act?
Calcitonin decreases the level of Ca2+ in the blood.
It is released from the parafollicular C cells of the thyroid gland when there are high levels of Ca2+ in the blood.
It acts on the:
- Bone -> decreases bone reabsorption (decreases osteocyte arm formation)
- Kidney -> decreases reabsorption from proximal convoluted tubule
What is the mechanism of action of PTH? Where does it act?
PTH is released when Ca2+ levels are low.
It is released from the parathyroid glands which are located posterior to the thyroid gland.
It acts on:
- Bone -> increases osteoclast formation + bone reabsorption
- Kidney -> increases reabsorption from distal convoluted tubule
- Intestine -> activates vitamin D (25-cholecalciferol to 1,25-dihydrocholecalciferol) which acts on enterocytes in small intestine to increase absorption of dietary calcium
What is the mechanism of action of vitamin D? Where does it act?
Vitamin D acts with PTH to increase Ca2+ levels.
It acts on:
- Bone -> increases bone reabsorption + osteoclast formation
- Kidneys -> increases reabsorption from proximal + distal convoluted tubule
- Intestine -> increases absorption of dietary calcium
