Renal Disease Flashcards
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ileus:
- inability of the intestine (bowel) to contract normally and move waste out of the body.
(AKI): Acute Kidney Injury-
- a sudden loss of kidney function due to a non-renal condition (e.g. drugs). Often reversible (temporary) but can be permanent if the precipitating condition is not corrected.
- A common cause is dehydration (can present with BUN:SCr > 20:1 plus decreased urine output, dry mucus membranes, tachycardia.
(CKD) Chronic Kidney Disease-
- a progressive loss of kidney function over months to years.
- The degree of kidney function is measured by the glomerular filtration rate (GFR) or creatinine clearance (CrCl), and by how much albumin is in the urine.
Kidney Failure [End-Stage Renal Disease (ESRD)]-
- Total and permanent kidney failure.
- Fluid and waste accumulate.
- Requires Dialysis (or transplant) is needed to perform the functions of the kidneys.
The most common causes of CKD are _______ and _________.
diabetes AND hypertension
Proximal Tubule: the area in nephron where maximal reabsorption occurs*
large amounts of _____________ are reabsorbed here.
Blood pH is regulated by the exchange of ___________ and _________ ions.
Other ions and substances reabsorbed from the proximal tubule back into the blood include:
Ca, Cl, Na, and H2O are reabsorbed into the blood.
hydrogen ions and bicarbonate (HCO3) ions
K+, glucose, amino acids, vitamins, urea, choline
Drugs that work here at the proximal tubule include:
SGLT2 inhibitors
Descending Loop of Henle:
- as filtrate moves down the descending loop of Henle, ________ is reabsorbed into the blood.
-Nothing else is reabsorbed at this point, so the concentration of Na and Cl in the filtrate increases.
” So in the descending limb, __________ is mainly being reabsorbed, which leads to the filtrate becoming more concentrated.”
water
water
Ascending Loop of Henle:
- as the filtrate moves up the ascending loop of Henle, ___1_______ is reabsorbed back into the blood but not _____2_____.
- If _______3_________ is present, water passes through the walls of the ascending limb and is reabsorbed into the blood; less water is then excreted into the urine
Electrolytes are reabsorbed at the ascending loop of Henle and are reabsorbed back into the blood, these include: _______4_______
1) Na, Cl ions are reabsorbed back into the blood
2) water usually.
3) (ADH) antidiuretic hormone
4) Na, Cl, Ca, K, Mg, NH4
Drugs that work at ascending limp of Henle:
Loop diuretics:
- inhibit the Na/K pump. by blocking the pump, this causes less Ca reabsorption back into the blood, leading to Ca depletion.
- less Na is reabsorbed back into the blood. This increases the filtrate concentration of Na causing less water to be reabsorbed.
- Long-term use of loop diuretics can decrease done density because of this.
Distal Convoluted Tubule:
- farthest point away from the entry point of nephron
- is involved in regulating K, Na, Ca and pH
Drugs that work at Distal Convoluted Tubule:
Thiazide diuretics:
- inhibit the Na-Cl pump in the distal convoluted tubule.
- only about 5% of Na is reabsorbed here, making thiazide diuretics weaker than loops.
- thiazide diuretics increase Ca reabsorption at the Ca pump in the distal convoluted tubule. “ So long term use of thiazide diuretics has a protective effect on bones.”
Potassium (K) sparring diuretics:
Aldosterone Antagonists:
Collecting Duct:
- is the final site of water and electrolyte balance
- is a network of tubules and ducts that connect the nephrons in each kidney to a ureters.
- is involved with water and electrolyte balance, which is affected by levels of ADH “antidiuretic hormone” also called vasopressin, and aldosterone.
Drugs that work in collecting duct:
Potassium (K) sparring diuretics:
Aldosterone Antagonists: spironolactone and eplerenone
- which do the opposite of aldosterone, decrease reabsorption of Na and H2O, and increase reabsorption of K.
Aldosterone:
Works in the distal convoluted tubule & collecting duct to increase ____________ and __________ reabsorption and decrease _________ reabsorption.
Na and water
potassium
Select Drugs that Cause Kidney Disease:
Aminoglycosides
Amphotericin B
Cisplatin
Cyclosporine
Loop Diuretics
NSAIDs
Polymyxins
Radiographic contrast dye
Tacrolimus
Vancomycin
Risk Factors for Drug Induced Kidney Disease:
- multiple nephrotoxic drugs
- existing kidney disease
- decreased blood flow to the kidneys (heart failure, dehydration, hypotension)
- elderly
Estimating Kidney Function:
Blood Urea Nitrogen (BUN): urea is a waste product of protein metabolism.
Creatinine: a waste product of muscle breakdown
normal serum creatinine (SCr) range is ________.
0.6-1.3mg/dL
As Kidney function declines:
BUN will ______________
CrCl will ________________
SCr will _____________
BUN will increase.
CrCl will decrease.
SCr will increase.
The accuracy of Creatinine-based estimation equations is decreased when a patient has __________.
very low muscle mass, which is often the case in frail elderly patients
(low muscle mass = low SCr)
This can lead to an overestimation of CrCl and inappropriate drug dosing for the patients true kidney function.
A GFR < 60 mL/min/1.73m2 and/or albuminuria (ACR or AER > or = to 30) indicates that the patient has ________
Chronic Kidney Disease
albumin creatinine ratio (ACR)
albumin excretion rate (AER)
An ACE inhibitor or ARB are 1st line for patient with CKD, hypertension and albuminuria (with or without diabetes).
Normal SCr increase up to 30%. This is expected, and treatment should not be stopped. If SCr increases by > 30% the treatment should be discontinued, and the patient will generally be referred to a nephrologist.
Do NOT Use ACE inhibitors and ARBs together.
They increase potassium (K), which can result in hyperkalemia.
Monitor SCr and K
The SCr and K should be monitored 1-2 weeks after initiating.
Patients should be counseled to avoid potassium supplements and salt substitutes (KCl).
ACE inhibitors and ARBs For albuminuria
Who?
All patients with albuminuria
Why?
To prevent kidney disease progression
How?
Inhibit RAAS causing efferent arteriolar dilation.
What?
Reduce pressure in the glomerulus.
Patients with advanced kidney disease require monitoring of _______________
(PTH) parathyroid hormone,
phosphorus (phosphate, PO4),
Ca, and
Vitamin D levels
The Complications of (CKD) Chronic Kidney Disease:
The interactions of Ca, PO4 and Vitamin D in CKD are complex.
- (PO4) phosphate levels increase (because the kidneys ________1________)
- Vitamin D cannot be activated by the kidney, causing ____2____
- Both high (PO4) phosphate and low calcium cause ___3__
In a patient with healthy kidneys, PTH would cause the kidneys to increase calcium resorption, but in CKD this is not possible, and calcium is pulled from the bones, leading to bone demineralization and increased fractures. Normally, when calcium levels return to normal, PTH release is shut down, but the chronically high PO4 levels continue to stimulate ____4____.
In CKD, the kidneys produce less ____5___ resulting in decreased ____6___ production in the bone marrow which causes anemia.
1- cannot eliminate excess PO4 absorbed from the diet.
“ Phosphate levels increase. These high levels of phosphate signal to the parathyroid gland to increase PTH.”
2- dietary calcium absorption to decrease.
“ since the kidneys cannot activate Vitamin D, there is decreased calcium levels in the blood serum. This signals again to the parathyroid gland, to increase PTH”
3- increased release of PTH
4- PTH release and hypercalcemia can persist, causing calcification and cardiovascular disease.
5- erythropoietin
6- RBC
In healthy kidneys, the kidneys activate vitamin D which helps us absorb calcium.
An increase in PTH, signals to the kidneys to reabsorb more ___1___.
In a patient with CKD, the kidneys cannot reabsorb more __2__. So instead, the PTH starts signaling to pull the ___3______ from the ____4_.
1- calcium into the blood, since the calcium in the blood is low.
2- calcium.
3-calcium
4- bones
” so patients with CKD can have bone fractures occur along with other complications if this is not corrected”
Hyperphosphatemia (PO4) Treatment:
- restrict diet (avoid dairy products, cola, chocolate and nuts)
Phosphate binders: (3 types)
- aluminum based
- calcium based: FIRST LINE
- aluminum and calcium free
Hyperphosphatemia contributes to chronically elevated PTH levels and must be treated to prevent ________ and _________
bone disease
fractures
Phosphate binders:
work by -
If a missed dose-
blocking the absorption of dietary PO4 by binding to it in the intestine.
They are taken prior to (or at the start of) each meal.
If a dose is missed (and the food is absorbed), the phosphate binder should be skipped, and the patient should resume normal dosing at the next meal or snack.
aluminum hydroxide
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aluminum based phosphate binder
Class: phosphate binder
Indications: hyperphosphatemia
MOA: drug blocks the absorption of dietary (PO4) phosphate by binding to it in the intestine.
Dosage forms: suspension
Dosing: 300-600mg PO TID with meals
treatment limited to 4 weeks or can get aluminum accumulation leading to aluminum toxicity, which is toxic to bone and CNS
Contraindications:
Warnings:
Side Effects:
aluminum intoxication, “dialysis dementia”, osteomalacia, constipation, nausea
Monitoring:
Ca, PO4, PTH, signs and symptoms of aluminum toxicity
Pearls/Notes:
- potent, use short term. “Rarely used due to the risk of aluminum accumulation (which can cause nervous system and bone toxicity). Treatment duration is limited to 4 weeks”**
- toxic to bone and CNS
- Used LAST LINE essentially
- typically used in hospital setting when there is a need to lower phosphate level to a safer range urgently
Drug-Drug/Food interactions:
*- levothyroxine
*- quinolones and tetracyclines
*- oral bisphosphonates
*- Others
Phoslyra
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Calcium (Ca) Acetate
Calcium-based phosphate binder: First line
Class: phosphate binder
Indications: hyperphosphatemia CKD
MOA: drug blocks the absorption of dietary (PO4) by binding to it in the intestine.
Dosage forms: tablet, capsule, solution
Dosing: 1334mg PO TID with meals, titrate based on (PO4) levels
Contraindications:
Warnings:
Side Effects:
Hypercalcemia, constipation, nausea
Monitoring:
Ca, PO4, PTH
Pearls/Notes:
- hypercalcemia, is especially problematic with concomitant use of vitamin D (due to increased calcium absorption)
- constipation
- Calcium acetate binds more dietary phosphorus on an elemental calcium basis compared to calcium carbonate
Drug-Drug/Food interactions:
*- levothyroxine
*- quinolones and tetracyclines
*- oral bisphosphonates
*- others
PhosLo*
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Calcium (Ca) Acetate
Calcium-based phosphate binder: First line
Class: phosphate binder
Indications: hyperphosphatemia CKD
MOA: drug blocks the absorption of dietary (PO4) by binding to it in the intestine.
Dosage forms: tablet, capsule, solution
Dosing: 1334mg PO TID with meals, titrate based on (PO4) levels
Contraindications:
Warnings:
Side Effects:
Hypercalcemia, constipation, nausea
Monitoring:
Ca, PO4, PTH
Pearls/Notes:
- hypercalcemia, is especially problematic with concomitant use of vitamin D (due to increased calcium absorption)
- constipation
- Calcium acetate binds more dietary phosphorus on an elemental calcium basis compared to calcium carbonate
Drug-Drug/Food interactions:
*- levothyroxine
*- quinolones and tetracyclines
*- oral bisphosphonates
*- others
Tums
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calcium carbonate
Calcium-based phosphate binder: First line
Class: phosphate binder
Indications: hyperphosphatemia
MOA: drug blocks the absorption of dietary PO4 by binding to it in the intestine
Dosage forms: tablet, chewable tablet
Dosing: 500mg PO TID with meals (Can vary with formulation), titrate based on PO4 levels
Max dose:
Contraindications:
Warnings:
Side Effects:
*Hypercalcemia, constipation, nausea
Monitoring:
Ca, PO4, PTH
Pearls/Notes:
total daily dose of elemental calcium should be less than < 2000mg (from diet and supplements)
Drug-Drug/Food interactions:
*- levothyroxine
*- quinolones and tetracyclines
*- oral bisphosphonates
*- others
Velphoro
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sucroferric oxyhydroxide
Class: Al free & Ca free Phosphate Binder
Indications: Hyperphosphatemia CKD
MOA:
drug blocks the absorption of dietary PO4 by binding to it in the intestine
Dosage forms: chewable tablet
Dosing: 500mg PO TID with meals, titrate based on PO4 levels
Contraindications:
Warnings:
Side Effects:
diarrhea, constipation, discolored stool(black)
Monitoring:
iron, ferritin, PO4, PTH
Pearls/Notes:
- iron based products, absorption is minimal with sucroferric oxyhydroxide
- no aluminum accumulation, less hypercalcemia, but more expensive
Drug-Drug/Food interactions:
*- levothyroxine should NOT be used with sucroferric oxyhydroxide
*- quinolones and tetracyclines
*- oral bisphosphonates
*- others
- doxycycline should be 1 hour before
-
Auryxia
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ferric citrate
Class: Al free & Ca free Phosphate Binder
Indications: Hyperphosphatemia CKD
MOA:
drug blocks the absorption of dietary PO4 by binding to it in the intestine
Dosage forms: chewable tablet
Dosing: 2 tablets (420mg) PO TID with meals, titrate based on PO4 levels
Contraindications:
Warnings:
Side Effects:
diarrhea, constipation, discolored stool(black)
Monitoring:
iron, ferritin, TSAT* (only with ferric citrate), PO4, PTH
Pearls/Notes:
- iron based products
- no aluminum accumulation,
-less hypercalcemia,
-but more expensive
Drug-Drug/Food interactions:
*- levothyroxine
*- quinolones and tetracyclines
*- oral bisphosphonates
*- others
*- doxycycline should be 1 hour before
*- ciprofloxacin should be separated by 2 hours from ferric citrate**
Fosrenol
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lanthanum carbonate
Class: Al free & Ca free Phosphate (PO4) Binder
Indications: hyperphosphatemia CKD
MOA: drug blocks the absorption of dietary PO4 by binding to it in the intestine. They are taken just prior to (or at the start of) each meal.
Dosage forms: chewable tablet, powder
Dosing: 500mg PO TID with meals, titrate based on PO4 levels. Must chew tablet thoroughly to reduce risk of severe GI adverse effects.
- Use powder if unable to chew tablets
Contraindications:
** GI obstruction, fecal impaction, ileus**
ileus (inability of the intestine (bowel) to contract normally and move waste out of the body.
Warnings:
GI perforation
Side Effects:
*Nausea/vomiting, diarrhea, constipation, abdominal pain
Monitoring:
Ca, PO4, PTH
Pearls/Notes:
Drug-Drug/Food interactions:
*- levothyroxine, separate by 2 hours from lanthanum
*- quinolones and tetracyclines, should be given one hour before or 4 hours after
*- oral bisphosphonates
*- others
- can bind to Al, Ca or Mg containing antacids; administration of these products should be separated from lanthanum by 2 hours**
Renvela
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sevelamer carbonate
Class: Al free & Ca free Phosphate Binder that is NOT systemically absorbed
Indications: hyperphosphatemia CKD
MOA: drug blocks the absorption of dietary PO4 by binding to it in the intestine
Dosage forms: tablet, powder
Dosing: 800-1600mg PO TID with meals, titrate based on PO4 levels
Contraindications:
Bowel obstruction
Warnings: can reduce dietary absorption of vitamins D, E, K and folic acid; consider vitamin supplementation
Side Effects: nausea/vomiting/diarrhea (all>20%), dyspepsia, constipation, abdominal pain, flatulence
Monitoring:
Ca, PO4, HCO3, Cl, PTH
Pearls/Notes:
- can lower total cholesterol :) and LDL by 15-30% :)
- sevelamer carbonate can maintain bicarbonate concentrations
Drug-Drug/Food interactions:
*- levothyroxine, should be given several hours before dose of sevelamer
*- quinolones and tetracyclines, should be given 2 hours before or 6 hours after the sevelamer dose
*- oral bisphosphonates
*- others
