154 Second Examination

CKD, Asthma, Shock/Sepsis, Colorectal Cancer, GERD/PUD

KDIGO Category for AKI [table]

KDIGO Category for CKD [table]

• Cause

• GFR category

• Albuminuria category

basis of KDIGO 2013

• CGA staging

• Acid-base balance

• Water balance

• Electrolyte balance

• Toxin removal

• Blood pressure control

• Erythropoiesis

• vitamin D activation

vital process associated with the renal system

• AWETBED

• Glomerular filtration

• Tubular reabsorption

• Tubular secretion

3 major processes in urine formation

Renal Insufficiency → Azotemia → Uremia → End-stage Renal Disease

progression of CKD

• As GFR stage increases, the risk of the patient also increases

• As albumin leakage increases, the risk of the patient also increases

trends in CGA Staging [table]

• DM

• HTN

• Dyslipidemia

• Age

• Obesity

• Smoking

• Family history

• Male sex

• Protein-rich diet

• Pregnancy

risk factors for CKD

• edema

• ↑ blood levels of K, Mg, PO₄

• ↓ blood levels of Ca, albumin

• metabolic acidosis

clinical manifestations of CKD

mGFR (measured GFR)

gold standard for evaluating GFR

Creatinine or Cystatin C

eGFR estimates GFR using which parameters?

Renal ultrasound

which test is best used to detect structural abnormalities (e.g. obstruction)?

Perirenal hematoma

• caution in patients with high bleeding risks

primary precaution when doing a biopsy

protein (albumin)

principal marker of kidney damage

quantitative detection of urine protein/albumin [table]

Glomerular filtration rate (GFR)

Gold standard quantitative index of kidney function

Male: 107 to 147 mL/min/m²

Female: 98 to 138 mL/min/m²

Normal GFR levels (male and female)

< 60 mL/min/m²

GFR levels in CKD

Creatinine Clearance (CrCl)

Most widely used indirect measure of GFR

• age

• gender

• weight

• race

GFR estimation is based on which parameters?

• AGWR

Cockcroft and Gault

preferred equation for drug dosing

Modification of Diet in Renal Disease (MDRD)

recommended by National Kidney Foundation for CKD staging

effect of special populations on CrCl [table]

Increase:

• Decreased P-gp transport

• Mg(OH)₂ and NaHCO₃

  • increases solubility ➝‬ absorption of weakly acidic drugs

Decrease

• Gastroparesis

• Increased gastric pH

• Chelation

• Vomiting and diarrhea

• Bowel wall edema

Effect of CKD on absorption

Increase:

• Decreased albumin ➝‬ increased acidic drugs

Decrease:

• Increased alpha-1 acid glycoprotein ➝‬ decreased alkaline drugs

Effect of CKD on distribution

Liver:

• Slowed Phase I (CYP3A4)

• Slowed Phase II (slower conversion to a water-soluble compound)

Kidneys:

• Reduced renal metabolism ➝ accumulation

Effect of CKD on metabolism

Decrease:

• Glomerular filtration

• Tubular reabsorption

• Tubular secretion

• Metabolite excretion

Effect of CKD on excretion

• Digoxin ➝ altered tissue binding ➝ reduce the LD

• Edema ➝ increased Vd ➝ increase the LD

Most drugs require the normal loading dose. What are the exceptions?

• Prevent progression and complications

• Treat underlying cause

  • DM, HTN, Dyslipidemia

• Lifestyle modifications

• Renal dose adjustment

  • Avoid nephrotoxins

Reduce incidence of complications from potential infections

• Vaccination

Goals of Therapy

• PTLRR

• Add ACEi > ARB if with HTN or albuminuria

• Add SGLT2 > Metformin > GLP-1 > DPP4 if with DM or albuminuria

• Add statin if with ASCVD

  • Add-on: Antiplatelets > Ezetimibe / PCSK9i > Fenofibrate

Goals of Therapy for patients with DM, HTN, albuminuria, ASCVD

• Exercise 30 minutes 5x per week

• Weight loss if BMI > 25 kg/m²

• Smoking cessation

• Alcohol moderation (two/one drinks a day for men/women)

• Modified DASH diet

  • Low K⁺

  • Low Na⁺ if with HTN

Non-pharmacological recommendations

• EWSAM

• Adjust medication doses

  • D/C if eGFR < 60 mL/min/1.73 m² and hypovolemic

    • Metformin

    • RAAS blockers

    • Diuretics

    • NSAIDs

    • Lithium

    • Digoxin

• Avoid herbal supplements

• Updated vaccination

  • Influenza yearly

  • Pneumococcal if eGFR < 30 mL/min/1.73 m²

  • Hepatitis B if eGFR < 30 mL/min/1.73 m²

• Use aspirin for ASCVD

  • Unless bleeding risk

Pharmacological recommendations (general)

8.5 - 10.5 mg/dL

Normal Total Serum Ca²⁺ levels

4.4 - 5.4 mg/dL

Normal Ionized Serum Ca²⁺ levels

0.1 - 1% is in the ECF

• 99% of total body stores of Ca²⁺ is in skeletal bone

How much (in %) of the total body calcium (or phosphate) is reflected in plasma?

2.5 - 4.5 mg/dL

Normal Serum Phosphorus levels

• Calcium-sensing receptors

• Vitamin D receptors

• FGF-23 receptors

The parathyroid gland contains which 3 important receptors?

• Hypocalcemia

• Hyperphosphatemia

• Low calcitriol

3 stimuli that tells the parathyroid gland to release PTH?

Increase Ca²⁺ levels

• Bones: release calcium into the blood

• Kidneys: reabsorb calcium back into the blood

• Intestines: absorb more calcium from food or medicines

Action of PTH on different parts of the body

• Nephron loss

  • Impaired phosphate excretion = higher phosphate levels

  • More phosphate can complex with Ca²⁺ = lower Ca²⁺ levels

• Impaired vitamin D activation

  • Active form of vitamin D is calcitriol

    • Impaired vitamin D activation = lower calcitriol levels

  • Calcitriol stimulates intestinal calcium absorption

    • Lower calcitriol = lower Ca²⁺ levels

How does CKD lead to hypocalcemia?

Primary

• No underlying cause

• Hyperactive Parathyroid gland

Secondary

• With underlying cause

  • Usually CKD (nephron loss)

• Progressive and starts at GFR < 60 mL/min/1.73 m²

  • May lead to hyperplasia of parathyroid gland

  • More PTH = higher Ca²⁺ levels → Hypercalcemia

Tertiary

• Due to long-standing secondary hyperparathyroidism

  • Even if CKD is corrected, the parathyroid gland fails to return to normal and has become autonomous

  • More PTH

Differentiate the 3 types of hyperparathyroidism

converted from 25–(OH)–D₃ via 1–alpha hydroxylase in the kidneys

precursor of calcitriol

• Increase Ca²⁺ levels

• Suppress PTH production

Action of calcitriol

• Nephron loss

  • Lower total 1–alpha hydroxylase = lower calcitriol

• Common in CKD 4 - 5

  • Lower sunlight exposure, dietary intake, and dermal synthesis of vitamin D

How does CKD lead to lower calcitriol?

osteocytes

FGF-23 is produced by?

• Hyperphosphatemia

• High calcitriol

• High PTH

3 stimuli for FGF-23 production?

• Decrease phosphate reabsorption

• Inhibit PTH production

• Inhibit 1-alpha hydroxylase = lower calcitriol levels

Action of FGF-23