만성신부전증 환자의 투석효율성을 높이기 위한 연구계획서

Hank Park

Hypotension is a big problem!

• Hypotension during dialysis treatment is an unresolved issue.

• Delivery of an adequate dose of dialysis is essential to improve the prognosis of dialysis patients

• Low blood pressure during the hemodialysis procedure is expected to occur more frequently in patients with comorbidities because it compels a limit to dialysis time and dialysis efficacy.

- van der Zee S, Thompson A, Zimmerman R, et al: Vasopressin administration facilitates fluid removal during hemodialysis. - Davenport A: Intradialytic complications during hemodialysis.- Imai E, Fujii M, KohnoY, et al: Adenosine A1 receptor antagonist improves intradialytic hypotension.

IDH (Intradialytic Hypotension)• Definition: A fall in SBP by at least 20mmHg or SBP < 100mmHG

• Cause : Decline Cardiac Function and Systemic Vascular Resistance (SVR) during removed solute : A rapid reduction in Plasma osmolality: High Interdialytic weight gain: Anemia: Autonomic neuropathy: Decrease pressor response to Vasopressor agents: LV Hypertrophy & Decrease cardiac preload: Decrease cardiac reserve: Increase arterial stiffness: Impaired venous compliance: Meal: Use of low sodium/ Increase magnesium dialysate: Anti-hypertension medication before HD: Excessive release of vasodilators (Not Adrenomedullin and Adenosine): Imbalance in the synthesis of vasoconstrictors (Endothelin & Vasopressin)

Intradialytic Hypotension (IDH) mechanism?

Patient factors

Cardiac disease - Systolic dysfunction - Diastolic dysfunction Arrhythmias Pericardial disease Autonomic neuropathy Dietary excess Interdialytic weight gain Food ingestion in dialysis Antihypertensive agents Anemia (< Hb 7.0g/dL)

Cardiac disease - Systolic dysfunction - Diastolic dysfunction Arrhythmias Pericardial disease Autonomic neuropathy Dietary excess Interdialytic weight gain Food ingestion in dialysis Antihypertensive agents Anemia (< Hb 7.0g/dL)

Dialysis procedure factors

Ultrafiltration, solute removal Thermal amplication Sympathetic failure - Increased adenosine - Increased nitric oxide Dialysate composition Low sodium (<138mEq/L) Low calcium High magnesium Acetate

Ultrafiltration, solute removal Thermal amplication Sympathetic failure - Increased adenosine - Increased nitric oxide Dialysate composition Low sodium (<138mEq/L) Low calcium High magnesium Acetate

IDH ---> Hypertension

• Mechanism of therapy for intradialytic hypotension are of great interest (van der Zee. S et al.)

• Increase in adenosine generation during hemodialysis may cause vasodilation and decrease in cardiac output, which results in systemic hypotension (Imai. E et al.)

• Removal of excess extracellular fluid -> symptomatic decreases in arterial pressure -> intradialytic hypotension -> chronically volume-expanded -> Chronic Hypertension (van der Zee. S et al.)

Solution?Routine management

of IDH

Target dry weight Diet fluid counseling Medication adjustment Correct anemia High sodium dialysate Sodium modeling

Target dry weight Diet fluid counseling Medication adjustment Correct anemia High sodium dialysate Sodium modeling

Individualized therapy of IDH

High calcium dialysate Low-magenesium dialysate Carnitine Sertraline Cool dialysate Midodrine (A vasopressor /antihypotensive agent)

High calcium dialysate Low-magenesium dialysate Carnitine Sertraline Cool dialysate Midodrine (A vasopressor /antihypotensive agent)

How to increase BP?Farese S. et al. Am J Kidney Dis. 2008.

• TEMS : Transcutaneous muscle simulation , PCMs : Passive cycling movement

• For each patient, each procedure was performed only once weekly and never on the same weekday.

Patient Characteristics

TEMS & PCMs during dialysis show significant results in raising BP

Increased Cardiac Output!• Heart rate was unchanged during both treatment (TEMS & PCM)

modalities. • Therefore, the observed increase in blood pressure can only be

explained by an increase in either peripheral resistance or cardiac output.

• For TEMS and active exercise, decreased vascular resistance has been described. Miller BF et al. Phys Ther 80:53-60, 2000

• Thus, increased cardiac output is a more likely explanation for the increase in blood pressure, a contention supported because increased central blood and preload volume positively alter cardiac output. Hanft LM et al. Cardiovasc Res 77:627-636, 2008

• There is an evidence that electrical muscle stimulation increases venous backflow from the musculature. Clarke Moloney M et al. Eur J Vasc Endovasc Surg 31:300-305, 2006

Efficiency? Urea & Phosphate!

• Longer observation periods with more patients are needed to assess potential benefits of TEMS and PCMs on hypotensive episodes during dialysis sessions

Several Studies about Passive Training

• Passive movement of the lower leg has been found to result in an approximate three-fold increase in muscle blood flow, and stretch of the muscle tissue without an alteration in either EMG activity or muscle oxygen uptake. (Krustrup et al. 2004)

• Vascular endothelial growth factor (VEGF) is probably one of the most important factor for endothelial activation, proliferation and migration.

• The passive movement model induced an enhanced level of muscle interstitial VEGF protein and an increased endothelial cell proliferative effect of muscle interstitial fluid from the muscle as well as a higher expression of endothelial nitric oxide synthase (eNOS) mRNA in the muscle. (Hellsten et al. 2008, Am J Physiol Regul Integr Comp Physiol)

Capillarization and presence of proliferating endothelial cells in skeletal muscle before and after passive training of the leg

• B. Hoier et al. J Physiol 588.19 (2010) pp 3833–3845

Relationship with CVD ?

• Farese et al. (Am J Kidney Dis) : Blood flow in the Femoral Artery increased up to 40% with TEMS and PCMs (unpublished) : Increased Cardiac Output by electrical muscle stimulation increases venous backflow from the musculature (Increased venous return)

• Future direction : ABI (Ankle Brachial Index) : BP Function between Ankle and Brachial : FMD : specific to Femoral Arterial function : Heart Rate Variability : Autonomic dysfunction : Cardiac Function : Mitral Inflow Conventional Doppler, Mitral Annular Velocity Tissue Doppler

Thank you