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🌱 來自: Huppert’s Notes
Management of Complications Associated with Advanced CKDESRD🚧 施工中
Management of Complications Associated with Advanced CKD/ESRD
Blood pressure/volume
• Pathophysiology of hypertension in CKD: Complex and multifactorial, attributed to reduced nephron mass, increased Na+ retention, extracellular volume expansion, activation of hormones (RAAS) and the sympathetic nervous system, and endothelial dysfunction
• Goal blood pressure: Generally <130/80 mmHg. This may be more liberal when accounting for certain factors, such as the degree of kidney disease, dialysis tolerance, polypharmacy, adverse effects of medication, and history of transplant.
• Treatment:
- Sodium restriction is a key element of BP control. Fluid restriction becomes more important when GFR is severely reduced.
- Patients should monitor PO intake and weight. Dry weight is estimated by exam and maintained through diuresis or ultrafiltration during dialysis.
- Pharmacotherapy:
• Diuretics
- If a patient is still urinating, diuretics can assist with volume management
- Diuretics depend on reaching active concentrations in the tubule lumen; higher doses are required with worsening renal function as urea competitively binds to the Organic Anion Transporter 1 (OAT1) which transports the diuretics into the tubular lumen
- Most diuretics cause net fluid loss by preventing tubular sodium reabsorption
- Loop diuretics will often be necessary if eGFR <30 mL/min/1.73 m2 (Efficacy in reduced eGFR: bumetanide > furosemide > metolazone > chlorthalidone > hydrochlorothiazide).
• ACE inhibitors/ARBs
- First-line antihypertensive in CKD, especially with proteinuria and relatively preserved native kidney function
- Can cause hyperkalemia
- Increase in creatinine after starting agents is not necessarily indicative of kidney injury; generally should not be discontinued unless eGFR decreases by >30%
- Combination ACE/ARB associated with increased renal decline and generally contraindicated (ONTARGET study Lancet 2008)
• Calcium channel blocker (CCB)
- Do not need dose modification for renal clearance
- Relatively few adverse effects, can cause lower extremity edema
- Preferred class in CKD after ACE/ARB and diuretics; can reduce proteinuria
• Beta-blockers
- Typically used if secondary prevention of cardiac events is warranted
- Agents with combination alpha/beta antagonism are preferred to avoid metabolic effects of beta blockers, e.g., carvedilol and labetalol
- Nonrenal clearance is preferred, e.g., carvedilol
• Clonidine
- No renal dose adjustment
- Often used for hypertension on days between dialysis sessions
- Associated with rebound hypertension when discontinued or doses missed
Anemia
• Pathophysiology: Results from decreased erythropoietin (EPO) production, EPO resistance, and decreased RBC lifespan
• Treatment:
- Goal Hgb 10–11.5 g/dL
- Check iron studies in CKD patients with anemia
- Guidelines recommend for transferrin saturation >30%, ferritin >500 ng/mL, though practice patterns vary widely and less stringent targets may be used (e.g., transferrin saturation >20% and ferritin >100 ng/mL)
• Ferritin can be increased with inflammatory states too
• Rule out GI bleeding if you detect iron deficiency
- Iron supplementation
• IV iron is preferred in patients on hemodialysis. PO supplementation causes constipation, adds to pill burden, and is minimally absorbed compared to IV formulations.
• Iron sucrose (Venofer) and ferric gluconate (Ferrlecit) are the most commonly used formulations
• IV iron can cause anaphylaxis when first given; provide a test dose and administer slowly for patients who are IV iron naive
- Erythropoietin-stimulating agents (ESAs)
• Give if patient is iron replete but remains below Hgb goal
• Three formulations:
- Epoetin alfa (Epogen). 3× per week during HD or weekly in non-HD CKD.
- Darbepoetin alfa (Aranesp). Weekly during HD or monthly in non-HD CKD.
- Methoxy polyethylene glycol-epoetin beta (Mircera). Every 2 weeks.
- RBC Transfusion
• Uses:
- Consider pRBC transfusion if ESAs are contraindicated or unsuccessful
- Administer pRBCs if anemia is symptomatic or severe (Hgb <7 g/dL)
Bone mineral metabolism
• Pathophysiology: Mineral bone disorder is due to secondary hyperparathyroidism, which has two main contributing factors:
- Decreased 1-alpha-hydroxylase (made by the kidney) → decreased activation of 25-hydroxy vitamin D to 1,25-dihydroxy vitamin D → decreased Ca2+ absorption → decreased serum Ca2+ level → increased PTH
- Poor phosphate excretion → elevated phosphate → increased PTH and decreased 1,25-dihydroxy vitamin D
• Manifestations of CKD mineral bone disorder:
- Mineral and hormone abnormalities
• Increased phosphate
• Increased PTH
• Decreased 1,25-dihydroxy vitamin D
- Structural bone abnormalities
• Renal osteodystrophy: Range of abnormal bone pathology, bone turnover, and mineralization; includes osteomalacia, adynamic bone disease, and osteitis fibrosa cystica
• Increased alkaline phosphatase: Reflects osteoblast activity and bone turnover
• Increased FGF23: Secreted by osteocytes and involved in phosphate regulation
- Calcification of blood vessels and soft tissue
• Management of CKD mineral bone disorder:
- Phosphate
• Phosphate level should ideally be within the normal range, though levels <5.5 mg/dL are often tolerated by providers
• Phosphate binders are used to lower phosphate by preventing absorption of dietary phosphate
• Calcium-based phosphate binders (data below from ST. PETER et al. AJKD 2018)
- Calcium acetate (Phoslo) 667 mg/tablet; 34% of ESRD patients on this medication, cheap ($678/user-yr), strongest binder
- Calcium carbonate (Tums), cheap
• Non-calcium-based phosphate binders
- Sevelamer (Renvela) 800 mg/tablet; preferred by some due to absence of calcium, 54% of ESRD patients on this medication, expensive (4000/user-yr).
- Lanthanum carbonate (Carbrenol); 5% ESRD patients on this medication, expensive ($5000/user-yr).
- Iron-based phosphate binders: Ferric citrate and sucroferric oxyhydroxide. May be preferred if iron supplementation is needed.
- Calcium
• Keep corrected Ca2+ within normal range
• Dialysate can be adjusted to address low or high Ca2+ levels
• Consider measuring ionized calcium (iCa) in patients with significant hypoalbuminemia, acidemia, or hyperphosphatemia
- Vitamin D
• All CKD patients should be screened and treated for vitamin D deficiency or insufficiency (check 25-hydroxy vitamin D level). 1,25-dihydroxy vitamin D is not routinely measured in practice.
• Treat with cholecalciferol or ergocalciferol unless hypercalcemia or significant hyperphosphatemia is present
- PTH
• Guidelines recommend that PTH remain within 2–9× the upper limit of normal (~150–600 pg/mL) in HD patients
• Practice varies and treatment in non-HD patients is controversial
• Treatment: Active vitamin D analogs or calcimimetics are prescribed for severely elevated or rising PTH with replete 25-hydroxy vitamin D
- Active vitamin D: Analogs of 1,25-dihydroxy vitamin D
• Calcitriol (Rocaltrol). PO. Usually used for non-HD patients.
• Paricalcitol (Zemplar). Administered IV. Usually given with HD.
• Doxicalciferol (Hectorol). Administered IV. Usually given with HD.
- Calcimimetics: Competitive binder of Ca2+ sensing receptor, which regulates PTH release. Usually used when active vitamin D analogues are inadequate or contraindicated due to hypercalcemia. More expensive than active vitamin D analogues. Side effects: Can cause hypocalcemia, nausea and vomiting.
• Cinacalcet (Sensipar) – PO; in use since 2004
• Etelcalcetide (Parsabiv) – IV; given with HD
- Parathyroidectomy: Reserved for severe and refractory hyperparathyroidism in CKD