Which mutation(s) can result in congenital nephrogenic diabetes insipidus? Star the one seen in females.
- Mutation in V2 receptor (X-linked)
2. Mutation in AQP (non-X-linked)*
Patient with HT, hypokalemia, and metabolic alkalosis. (High/low) levels of (X) is classic for these findings.
High
X = aldosterone (via upregulation of ENaC)
Liddle’s syndrome: what’s the key mutation?
ENaC channel gain-of-function mutation that decreases its internalization (thus higher cell surface expression of channel)
Liddle’s syndrome presents with (high/low) BP, (hypo/hyper)-kalemia, and metabolic (acidosis/alkalosis). Aldosterone levels are (high/low).
High; hypo-kalemia; alkalosis
Low
Liddle’s follows which inheritance pattern?
AD
(X) syndrome is referred to as “pseudo-hyperaldosteronism” because (Y) levels are (low/high).
X = Liddle's Y = aldosterone and renin
Low (though presents with Sx of high aldosterone level due to up-regulated ENaC)
Treatment of Liddle’s syndrome includes:
- Low Na diet
2. ENaC channel inhibitors (amiloride, triamterene)
T/F: Liddle’s syndrome can be treated with spironolactone.
False - aldosterone inhibitors don’t work
Patients with Alport syndrome present with (proteinuria/hematuria) and (rapidly/slowly) progressive renal failure.
Hematuria (may have some proteinuria as podocytes become compromised);
Slowly
Majority of patients with Alport syndrome inherited mutation via (X) pattern of inheritance. This mutation is in (Y).
X = X-linked dominant (85%) Y = Collagen alpha-5
First-line Rx for uncomplicated cystitis
Trimethoprim/sulfamethoxazole
Second-line Rx for uncomplicated cystitis
- Fluoroquinolones
2. Beta-lactams
(X) diuretics ONLY block urinary diluting capacity by blocking (Y) at site where (Z) (reabsorption/secretion) makes urine hypo-osmotic.
X = thiazide
Y = NCC (Na/Cl cotransporter)
Z = Na
Reabsorption (Cortical diluting site of DCT)
(X) diuretics block BOTH urinary diluting capacity by blocking (Y) at which site?
X = loops Y = Na-K-2Cl cotransport
Thick ascending limb
(X) diuretics (increase/decrease) renin/aldosterone levels by messing with tubuloglomerular feedback.
X = loop
Increase
(X) diuretics are antagonized by NSAIDs. Why?
X = loops
Prostaglandin synthesis contributes to diuretic effect of these agents
List some drugs that reduce efficacy of loop diuretics by (stimulating/inhibiting) (X)-mediated tubular secretion.
Inhibiting;
X = oatp
- Probenecid (gout- blocks urate reabs)
- Penicillins
Which characteristic of a drug’s metabolite would allow it to antagonize effect of loop diuretic?
Anionic (decreases loops secretion by oatp)
How does chronic renal insufficiency affect efficacy of diuretics?
Decreased renal blood flow and increased anionic metabolites reduce diuretic renal excretion and efficacy
How does nephrotic syndrome affect efficacy of diuretics?
Hypoalbuminemia increases Vd of diuretics thus decreasing renal excretion and their efficacy
(X) diuretic is used in combo with Li to prevent development of Li-induced (Y). How does the drug do this?
X = amiloride Y = DI
Blocks Li uptake into principal cells via ENaC
Spironolactone is (agonist/antagonist) to (X) and affects which channels/transporters?
Antagonist
X = mineralocorticoid R
Decrease expression of ENaC, ser/thr kinase (activates ENaC), and NaK ATPase
T/F: spironolactone typically used in hyperaldosteronism.
True - antagonizes both renal and non-renal actions of aldosterone