L35,36,37 CKD Pharmacology, Therapeutics, Labs

Three determinants of renin release:
1. Decreased ❌ sensed by kidney
2. Decreased BP or renal ❌
3. ❌ receptor activation

Diuretics for CKD:
1. Loop diuretics inhibit the activity of the Na-K-2Cl symporter in the ❌. Therefore maximum
effect is ~❌%.
2. Thiazide diuretics inhibit the activity of the Na-Cl symporter in the ❌. Maximum effect is ~❌%.
3. K-sparing diuretics inhibit the activity of epithelial Na+ channels in the ❌. Maximum effect is ~❌%.
4. Aldosterone antagonists competitively inhibit the binding of ❌ to the mineralocorticoid receptor. The only class of diuretics that do not enter the tubule cell from the apical (❌) side, and instead from the basolateral (❌) side.

Classification of CKD:
• Normal/ CKD 1: GFR >90 mL/min
• Mild/ CKD 2: GFR ❌ mL/min
• Moderate/ CKD 3: GFR ❌ mL/min
• Severe/ CKD 4: GFR ❌ mL/min
• End-stage/ CKD 5: GFR <15 mL/min

When using ACEIs and ARBs in CKD the target is a reduction in urine ❌ of 30-50%. Starting can ❌ GFR; start at a ❌ dose and titrate the dose slowly to effect. Other Important side effects to consider:
• ❌kalaemia
• ❌ renal impairment
• Dry cough (fairly ❌)
• Angioedema (❌, but serious)

Methods of estimating renal function:
1. Creatinine-based methods (CLcr, eGFR)
• Collection of 24 hour urine samples (❌ clearance)
• Cockcroft-Gault ❌ (an estimate of creatinine clearance)
• MDRD
• CKD-EPI
All these are reported by the lab as “❌”.
2. Cystatin C clearance
3. Clearance of a ❌: Inulin (NOT insulin), 51Cr EDTA (radioisotope)

Cockcroft & Gault equation:
CLcr = ( (140 - ❌) x ❌ x K* ) / ❌

* K = 1.23 for males, 1.04 for females

All creatinine-based methods;
• Are poor predictors of GFR if malnourished or low ❌ mass
• Over-estimate GFR in the elderly, ❌ (using total body weight), severe or end-stage renal disease
• Not for <❌ years old
• Unreliable when renal function ❌ rapidly (acute renal failure)
• Drugs ❌ tubular secretion can raise creatinine conc (e.g. probenecid, trimethoprim, spironolactone)

In CKD, K+ secretion is ❌ resulting in accumulation. Concentrations above ❌mmol/L become symptomatic. Hyperkalaemia is more likely to be observed in CKD 4 or 5, and is exacerbated by ❌ and K-sparing diuretics.

Match the ranges.
- Creatinine (plasma): Adult male: 50-❌ µmol/L, Adult female: 45-❌ µmol/L
- Urea (plasma): Adults: ❌ mmol/L
- Sodium (plasma) ❌ mmol/L
- Osmolality (plasma) 280-❌ mmol/kg
- Osmolality (urine) 300-❌ mmol/kg