T/F: ACEi/ARBs are prescribed to all diabetic patients to prevent nephropathy.
False - not in normotensive patients (only if HTive)
Diabetic patients should be screened for signs of nephropathy. How is this done?
Testing urine albumin levels
T/F: ACEi /ARBs affect mesangial cells.
True - inhibit AII-induced mesangial cell growth/matrix deposition
Central DI is treated with (X) drug, (selective/non-selective) for (Y).
X = desmopressin
Selective
Y = V2
How is desmopressin administered?
Oral or nasal
Nephrogenic DI is treated with (X) drug(s). What’s the mechanism?
X = diuretics (thiazides, amiloride)
Induce diuresis (counter-intuitive) but then V depletion enhances water absorption in proximal tubule
It’s important for nephrogenic DI patient to be on (X) diet.
X = low Na, low protein
What are the indications to use immunosuppressive drugs for renal disease?
- Type II or III HS reactions in kidney
2. Transplant (rejection prevention/treatment)
List the three mechanisms (classes) of immunosuppressives used for renal diseases.
- Ab against T-cell membrane Ag
- B/T cell replication inhibitors
- Intracellular T-cell signaling inhibition
Basiliximab structure and mechanism.
Anti-IL2 receptor monoclonal Ab;
Selective binding to CD25 on T cells
You prescribe your kidney transplant patient an Ab immunosuppressive that depletes T cells. He develops fever, chills, and hypotension due to (X) release. Which drug is responsible for this?
X = cytokine
Antithymocyte globulin (rabbit ATG)
T/F: Basiliximab causes T-cell depletion without cytokine release/side effects of antithymocyte globulin.
False - causes neither
Purine antimetabolite drugs cause side effects primarily due to:
Their inhibition of cell replication in other sites (non-target tissue)
(X) immunosuppressant is administered as prodrug, which is then converted to active carboxylate form, (Y). This drug is a very efficacious selective inhibitor of IMP dehydrogenase. Which class of drugs does this fall under?
X = mycophenolate mofetil Y = mycophenolate
Purine antimetabolites
Calcineurin inhibitors block which (X)-mediated action?
X = calcineurin
dephosphorylation of cytosolic transcription factors
The end result of calcineurin inhibitor action is to (up/down)-regulate (X) (transcription/translation/replication).
Down;
X = IL2
Transcription
List the drugs that are calcineurin inhibitors. Star the one with lower risk of side effects.
- Cyclophosphamide
2. Tacrolimus*
List potential side effects of calcineurin inhibitors.
- HT, hyperlipidemia
- Diabetes
- Neuro
- Nephrotoxicity!!!
It’s important to monitor drug levels of (mycophenolate/tacrolimus/basiliximab) in patient that’s slow CYP inducer.
Tacrolimus
Kidney transplant patient on (X) immunosuppressant presents with nephrotoxic decrease in GFR. What are the drug’s mechanisms for nephrotoxicity?
X = calcineurin inhibitor (cyclophosphamide, tacrolimus)
- Afferent arteriole constriction and obliterative vascular pathology
- Tubular vacuolization/atrophy
- Interstitial fibrosis
Sirolimus, aka (X) is (agonist/antagonist) of (Y).
X = rapamycin
Antagonist
Y = mTOR (“target of rapamycin”)
(X) immunosuppressant drug blocks mTOR activity, which is required for (Y).
X = sirolimus/rapamycin Y = cytokine-mediated shift from G1 to S phase in cell cycle
End result of rapamycin/sirolimus action is (stimulation/inhibition) of (X)-mediated activation of (Y) cells.
Inhibition
Y = IL-2
Y = B/T Cells
Sirolimus is (more/less) efficacious and (more/less) nephrotoxic than cyclophosphamide.
Less, less (though may be new warnings of nephrotoxicity)
Current drug protocols for renal transplant patients: induction with (X) drugs and then pre-adaptation with (Y) drugs.
X = anti-thymocyte globulin (ATG) or anti-CD25 Ab (IV)
Y = Combo PO Rx (calcineurin inhibitors, mycophenolate mofetil, prednisone)
Current drug protocols for renal transplant patients: post-adaptation regimen involves (mono/combo)-Rx with:
Combo; same drugs as pre-adaptation (calcineurin inhibitors, mycophenolate mofetil, prednisone), but lower doses
Taper off steroids
List four classes/examples of nephrotoxic drugs that cause ATN.
- Dyes/radioconstrast agents
- Chemotherapeutics (cisplatin)
- Aminoglycosides (gentamicin)
- Amphotericin B
Gentamicin has clearance most similar to (PAH/Creatinine/Inulin/Glucose/Urea).
Creatinine;
Over 90% eliminated by kidney BTW
Patients taking acetaminophen are at risk for nephrotoxicity. Specifically, which pathological changes?
- Chronic interstitial nephritis
- Papillary necrosis/calcification
Increase risk of ESRD
T/F: Analgesic nephropathy is dose-dependent.
True
NSAID/COX2i nephrotoxicity is related to their effect of (increase/decrease) in (X) synthesis.
Decrease;
X = Prostaglandin
You would be concerned about analgesic nephrotoxicity in patient with which risk factors?
- Age
- HT, diabetes
- Renal impairment
- On diuretics
List two examples of drugs/classes that have been shown to induce crystalluria.
- Sulfa antibiotics (ex: sulfadiazine)
2. Acyclovir (prodrug is valacyclovir)
Ethanol and (X) drug both (stimulate/inhibit) vasopressin actions. They do this by (similar/different) mechanism(s).
X = Li
Inhibit
Different (EtOH blocks ADH release from pituitary and Li blocks signaling via V2-R)
Lithium effect on (X) in distal tubule typically causes (diuresis/retention). What can be given to prevent this?
X = V2 receptor
Diuresis
Amiloride (ENaC blocker) - prevents Li uptake into tubular cell
List three drugs/classes that induce SIADH.
- Oral hypoglycemics
- Antineoplastics
- Psychoactive drugs
SIADH Treatment:
- Saline (correct serum Na)
- Furosemide (decrease medullary hypertonicity)
- V2-R antagonist
“-vaptan” drugs, such as conivaptan, have which action?
V2-R antagonists
What are the reasons behind reduction in ‘Nonrenal’
Clearance of a drug in Renal Disease?
- Impaired biotransformation by kidney
2. Impaired hepatic clearance (uremic toxins downregulate CYP and decrease oatp-mediated hepatic drug uptake)
For patients with renal impairment, use an opioid (with/without) (X).
Without;
X = an active metabolite
(if metabolite accumulates due to poor clearance, will have additional opioid effects)
(Codeine/fentanyl/morphine) is/are preferred opioids in patients with renal impairment.
Fentanyl (inactive metabolite)
Codeine and morphine active metabolite (morphine-6-glucuronide) has opioid effects and is cleared by kidney
Trimethoprim/sulfamethoxazole are used for (X) renal disease. Dose should be reduced by 50% if GFR is (Y) mL/min.
X = UTI (antibacterials) Y = 15-30
Trimethoprim/sulfamethoxazole are contraindicated in patients with GFR of (X) mL/min.
X = under 15
Dose adjustment for quinolones is required in patients with GFR of (X) mL/min.
X = under 50
Normal saline contains (X) mEq/L of Na and (Y) mEq/L of Cl. Thus, total osmolality is (Z) mEq/L.
X = Y = 154 Z = 308
Free Water Excess/Deficit equation:
0.6xTBWx(1-(serum Na/140))
Adrogue formula allows you to calculate (X). What’s the formula?
X = how much serum Na will drop with 1 L of IVF
Infusate Na - serum Na)/(TBW+1
When you give patient D5W/hypotonic fluid, (ECF/ICF) V rises.
Both BUT ICF more (most of the fluid will go into the cells - so if you give 1.5 L, 1 L to ICF, 0.5 L to ECF)
IVF in patient with SIADH and serum Na of 110 mEq/L should be given (X)% normal saline, which has osmolality of (Y) mOsm/L.
X = 3 (hypertonic) Y = 900