Chronic Kidney Disease/Pharmacology of CKD Flashcards
(34 cards)
What is the definition of Chronic Kidney Disease?
A permanent reduction in GFR (at least 3 months).
What are the 6 most common causes of CKD?
1) Diabetic nephropathy- most common
2) Hypertensive nephrosclerosis; Renal vascular disease
3) Glomerulonephritis
4) Polycystic kidney disease
5) Interstitial nephritis
6) Obstruction
What are the 5 stages of renal degeneration?
1 - GFR>90 2 - GFR 60-90 3 - GFR 30-60 4 - GFR 15-30 5 - GFR less than 15
**Drug dosage must be adjusted in stage 3-5
Nitric oxide, PGE2, PGI1 have this effect on the GFR and arterioles
Dilate the afferent arteriole, increase the GFR
Caffeine and dopamine do what to the GFR
Increase the GFR, dilate the afferent arteriole
** Caffeine is an adenosine agonist
Angiotensin II, Norepinephrine, and Adenosine have what effect on the arteriole and the GFR?
All three constrict the afferent arteriole, decrease in the GFR.
Ang II and NE also constrict the efferent which increases the GFR.
NSAIDS have what effect on the GFR and the afferent arteriole?
Decrease the GFR and constrict the afferent arteriole.
ACE inhibitors and ARBs have what effect on the GFR?
Decrease AngII levels which preferentially dilates the efferent arteriole and decreases the GFR.
If hypovolemic, which three drug classes can cause AKI?
NSAID
ARB
Ace inhibitors
Recommendations for diuretics in people with Stage 3+ CKD:
Thiazides may lose effectiveness as renal function declines; more potent loop diuretics (e.g., furosemide) are recommended
Avoid potassium-sparing diuretics
Recommendations for ACE inhibitors/ARBs in people with Stage 3+ CKD:
Used through all CKD stages; monitor for hyperkalemia and elevations in serum creatinine; may cause ARF in hypovolemic patients
Recommendations for Beta-blockers in people with Stage 3+ CKD:
Atenolol: Half-life prolonged
Metoprolol, Carvedilol: No adjustments necessary
Recommendations for Ca channel blockers in people with Stage 3+ CKD:
No adjustment necessary.
Recommendations for clonidine in people with Stage 3+ CKD:
No adjustment necessary.
Recommendations for alpha blockers in people with Stage 3+ CKD:
No adjustment necessary.
Recommendations for vasodilators in people with Stage 3+ CKD:
No adjustment necessary.
Describe the relationship between Calcium, Phosphorus, and Parathyroid Hormone (PTH) in chronic kidney disease. Include Active Vitamin D and FGF-23.
Serum Ca is tightly regulated, as is phosphorus. The maintenance of levels is dependent on the GFR. When the GFR falls, Ca levels drop and PO4 levels rise. To re-establish normal, the body increases secretion of PTH (PTH secretes PO4 and preserves Ca), this is called secondary parathyroidism. Active Vitamin D (1,25dihydroxyvitamin D) is produced by the kidney, and also regulates PTH. When GFR falls, so does production of Active vitamin D.
Fibroblast Growth Factor 23 (FGF-23) has a primary function of secreting PO4 (is a regulator of phosphate balance). However, it suppresses 1,25 Vitamin D production, which decreases Ca absorption from the gut.
So decreased renal functhion decreases 1,25 VD, which leads to decreased Ca, which leads to increased PTH.
Decreased renal function also causes a rise in PO4, which triggers increased levels of FGF-23, which suppresses 1,25 VD, which decreases Ca levels, which raises PTH.
**Starts at GFR below 60, but don’t really see this until the GFR is below 25%.
What is the negative clinical effect of high PTH (secondary parathyroidism).
Bone disease (osteitis fibrosa, demineralization, bone pain, fractures)
Systemic toxicity (nervous system, endocrine, immunologic, cutaneous, cardiac)
What is uremia?
Urea and other solutes accumulate in the blood (Urea is the marker). Also see overproduction of counter-regulatory hormones (PTH, for example). Underproduction of EPO and 1,25 Vitamin D also a result of kidney atrophy.
Clinical features: All organ systems. Patients always have anemia.
When GFR is low, what hematologic issue can arise?
Anemia. EPO markedly decreased, and marrow space fibrosis occurs due to secondary hyperparathyroidism.
Why is CKD progressive?
The intact nephron hypothesis. Compensatory changes actually damage the functioning nephrons.
-Glomerular hypertrophy, blood flow per nephron increases, intra-glomerular pressure increases, solute flow per tubule increases.
True/False: more patients die than make it to dialysis.
True. Only 20% of people in stage 4 CKD make it to dialysis, whereas 47% die (primarily of Cardiovascular disease). This is independent of all the traditional risk factors, so there is something unique.
**IF a patient has CKD, they are automatically in the highest risk category for cardiovascular disease. (Even higher than a previous MI).
What is the most important factor in slowing progression of CKD?
Controlling blood pressure. (Combine 3 or more drugs).
In addition to a diuretic, all CKD patients should be on an ACEi or ARB. There is a clear renal-protective benefit. Unknown why, but several studies show this.
Can also give bicarbonate and vitamin D (less well proven).
What happens to the distribution of drug (Vd) in CKD?
Decreases and increases in Vd have been observed but in each case it resulted in an increase in levels of free unbound drug and Cp
In CKD patients, the Vd has been shown to decrease by as much as 50% in stage 5 as a result of decreased tissue binding (mechanism uncertain). Thus, any given dose of digoxin will result in a higher Cp due to the smaller Vd and as CKD progresses it will be necessary to gradually reduce the daily dose of digoxin to prevent toxic accumulations.
The anticonvulsant phenytoin (Dilantin) is highly protein bound in patients with normal kidney function. In CKD, organic acids are excreted less efficiently and accumulate in plasma competing with phenytoin for albumin binding sites (analogous to protein-binding displacement drug-drug interaction). Hypoalbuminemia may also occur in CKD and these changes result in less phenytoin binding to proteins, greater levels of free phenytoin and greater ability to distribute outside of the plasma and greater potential for toxicity. Generally, these effects would be of potential clinical significance only in the acute initialization of dose phase.
