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)