2012-3-14 報告醫師：F1侯羿州 指導醫師：MA黃文宏 Journal Clubs 2012-3-14 報告醫師：F1侯羿州 指導醫師：MA黃文宏

Clin J Am Soc Nephrol 4: S30–S40, 2009.

LIFE magazine, April 28, 1947

In October 1989, the Dallas Dialysis Conference discussed the reasons that hemodialysis (HD) patients in the United States fared worse than those in other developed countries. Relative mortality risk for patients with ESRD in the United States was still 15% higher than in Europe and 33% higher than in Japan.

5 year survival rate in USA: 40%. USA: 150, 862; EDTA: 124,796; Japan: 66244 5 year survival rate in USA: 40%. Only the youngest patients in the US (less than 15 years) have longer survival than their counterparts in Europe and Japan. In non-diabetics: US vs EDTA: RR1.22 US vs Japan: 1.40 Am J Kidney Dis. 1990 May;15(5):451-7

Clin J Am Soc Nephrol 4: S2–S4, 2009. doi: 10.2215/CJN.04730709

In the past few years, many technological innovations in dialysis equipment have been developed, and new modalities and strategies have been introduced. Mortality and morbidity of dialysis patients are determined by many medical, social factors(non-technical) and the impact of technical advances in dialysis.

Quantification of dosage of dialysis The choice of membranes (high flux versus low flux), The choice between convection and diffusion, The chemical composition and biologic purity of dialysate, sodium and volume profiling, and intradialytic volume monitoring aiming at improving hemodynamic stability.

Dosage of dialysis Kt/Vurea and Online Quantification of Dialysis Dosage Duration and/or Frequency of Dialysis Is More Important than Kt/V

Kt/Vurea and Online Quantification of Dialysis Dosage single- pool Kt/Vurea (spKt/Vurea) index as a surrogate for removal of low molecular weight uremic retention solutes became widely applied after the report of the National Cooperative Dialysis Study (NCDS). >1.0 was adequate(1983) Kt/V represents adequacy of dialysis, expressed as the product of clearance per time multiplied by the duration and adjusted for body size by dividing this clearance by the distribution volume.

spKt/V overestimates equilibrated Kt/V with 0. 15 to 0 spKt/V overestimates equilibrated Kt/V with 0.15 to 0.20 because it fails to account for blood urea rebound after dialysis  1.2 Kt/V represents only the behavior of urea, a rough estimate of small-solute removal  Long term outcome? The Kt/V concept presumes that changing Kt/V by varying K or by varying t results in equal solute removals and outcomes

Industry developed devices that could estimate Kt/V online, mostly based on the principle of ionic dialysance(NaCl). Adjustments to correct intermethod differences may be necessary to ensure generalizability among ionic dialysance monitors in different dialysis machines.

HEMO study 1846 prevalent HD patients who were randomly assigned to a standard or high dosage of dialysis Standard-dosage goal was spKt/V of 1.25, and the high-dosage goal was spKt/V of 1.65 RR of 0.96 for high versus standard dosage; 95% confidence interval 0.84 to 1.10 19% lower risk for death than women in the standard-dosage group

N Engl J Med 2002;347:2010-9.

Women: RR 0.81 (p0.02) Men: no difference. Kidney International Vol. 65(2004) pp 1386-1394

DOPPS(Dialysis Outcomes and Practice Patterns Study) Estimated by urea reduction ratio This might suggest that current dialysis dosages are suboptimal for all but small women Neither Kt/V nor urea reduction ratio seem to have an effect on outcome.

American Journal of Kidney Diseases, Vol 43, No 6 (June), 2004: pp 1014-1023

American Journal of Kidney Diseases, Vol 43, No 6 (June), 2004: pp 1014-1023

Duration and /or Frequency of Dialysis Is More Important than Kt/V The factor time plays an even more important role in the removal of middle molecules or other solutes that are difficult to remove by standard HD, such as beta-2 microglobulin and phosphorus Mortality rate fell by 7% for each 30-min increase in session duration , independent of Kt/V (DOPPS)

Kidney International (2006) 69, 1222–1228

Kidney International (2006) 69, 1222–1228

Kidney International (2006) 69, 1222–1228

Nephrol Dial Transplant (2006) 21: 273–280

Only 10% of the patients on long-hour dialysis had high phosphate levels, whereas only 30% required phosphate binder prescriptions Extending treatment time comes for an economical price and that these modalities are affordable only when costs per treatment can be reduced.

One way to allow more flexibility in HD schemes, either by prolonging HD or by increasing its frequency, is to apply this strategy at home.

Membrane Flux: High Flux versus Low Flux Multilayer membranes, consisting of a very thin, semipermeable fleece and a much thicker supporting membrane. The concentration of Beta 2-microglobulin(B2M) decreases progressively when patients are treated on high-flux membranes

J Am Soc Nephrol 20: 645–654,2009 (MPO)

J Am Soc Nephrol 20: 645–654,2009

Membrane Permeability Outcome High-flux dialysis showed a significant survival benefit of 37%, after adjustment, of patients with a low serum albumin. Serum albumin>4g/dL=> no survival benefit.

HEMO study Low flux: B2Mclearance <10ml/min High flux: B2M clearance >14ml/hr/mmHg, with mean B2M >20ml/min

N Engl J Med, Vol. 347, No. 25 · December 19, 2002

N Engl J Med, Vol. 347, No. 25 · December 19, 2002

No significant survival difference There were significant reductions in the risk for death from cardiac causes and the combined outcome of first hospitalizations or death from a cardiac cause in the high-flux group. Patients who were enrolled in the study after >3.7 yr of maintenance dialysis: benefit on CVA and overall mortality.

Technical Innovations in Hardware and Software of Dialysis Monitors Online Monitoring Systems and Biofeedback Sodium Modeling Potassium Modeling Temperature Control Assessment of Fluid status and Body Composition

Sodium Modeling Sodium profiling with a high dialysate sodium concentration is an effective method to prevent intradialytic hypotension Expense of a positive sodium balance during the dialysis session Ultrafiltration rates can be reduced with better hemodynamic stability and without jeopardizing salt and water balances.

Potassium Modeling Patients presenting without sinus rhythm were 89% more likely to die and the risk for cardiovascular events and stroke increased by 75 and 16.4% Sudden shifts in plasma potassium induced during and after an HD session may be among the causes of death in arrhythmia-prone patient

Patients with frequent intradialytic premature ventricular complexes underwent dialysis using a dialysate with a fixed (2.5 mmol/L) potassium or one with an exponentially declining potassium (from 3.9 to 2.5 mmol/ L), the latter maintaining a constant blood-to-dialysate potassium gradient of 1.5 mmol/L throughout the procedure.

Kidney International, Vol. 50 (1996), Pp. 609—617

Temperature Control A positive thermal balance, as a result of either a warm dialysate or a hyperthermic response to volume depletion, may interfere with the adjustments in venous and arterial tone and cardiac response. Many studies have confirmed that when the dialysate temperature is adjusted to the range of 34 to 35.5°C

Adjusting Thermal Balance and Intradialytic Hypotension Nephrol Dial Transplant (2006) 21: 1883–1898

Adjusting Thermal Balance and dialysis Adequacy.

Assessment of Fluid Status and Body Composition The optimal postdialysis dry weight is in general clinically determined as the lowest body weight a patient can tolerate without intradialytic symptoms or hypotension. The clinical method is very simple and cheap, objective, noninvasive, and universally available and suffices in a large majority of cases

Inferior vena cava diameter, biochemical markers (e. g Inferior vena cava diameter, biochemical markers (e.g., atrial natriuretic peptide, brain natriuretic peptide [BNP], and its precursor NT-proBNP), BV monitoring (BVM), and bioimpedance can be applied for assessing various aspects of volume status. Inferior vena cava diameter and BNP: Correlates well with right atrial pressure but lacks sensitivity to assess dry weight, because it also largely depends on diastolic distensibility of the heart ProBNP is cleared by dialysis

BV : the most applied monitoring relies on the evolution of the hematocrit in the dialyzer inlet blood line Logics: If the parameter is within the desired values, the treatment continues unchanged.

Hypotension during dialysis (top) and symptoms during the inter-dialysis period (bottom). The frequency of dialysis hypotension is reported as a whole (left; *) and within each sequence. The latter also reports the frequency during the run-in period, here indicated as the first A period before each sequence. The analysis neglecting the sequence showed a statistically significant reduction in the hypotension event rate (P = 0.004). The average number of symptoms occurring during inter-dialysis is reported as early (**) when it occurred in the first 6 hours after the end of dialysis, or as late (‡) when occurring between this time and the start of the following dialysis session. All the values are statistically significant at 1 level (P < 0.001) Kidney Int 62: 1034– 1045, 2002

Patients in whom BVM remained stable, more fluid could be removed during a dialysis session than in patients with steep decrease of BV This study reflects only the clinical reality that some patients do and others do not tolerate ultrafiltration and that the latter tend to end up fluid overloaded. No study has evaluated whether these systems perform better than close observation of the patient by skilled nurses.

Bioimpedance analysis (BIA)

BIA Used for the assessment of fluid status for >30 yr. The multifrequency technique has allowed a more refined measurement of the extracellular and intracellular water

Nephrol Dial Transplant (2009) 24: 1574–1579

The translation of the results obtained with these nonclinical tools into hard clinical outcomes such as patient survival is difficult to demonstrate The best way to improve dialysis quality is to extend treatment time.

Purity of Dialysate and Dialysis Water

N Engl J Med 1998;338: 873-8.)

Purity of Dialysate and Dialysis Water HD patients are at risk for injury from chemical and microbiological contaminants in the dialysate, and the water and concentrates used to produce dialysate. Bacterial products such as endotoxins, fragments of endotoxin, peptidoglycans, and fragments of bacterial DNA, all potent inducers of cytokines and stimulators of the acute-phase response, are able to cross the pores into the bloodstream, leading to the stimulation of mononuclear cells and contributing to chronic inflammation.

Inflammatory state may be an important contributor to the long-term morbidity associated with HD

Ultrapure water. In the blood of HD patients who all had negative blood cultures. C-reactive protein serum and IL-6 levels were significantly higher in patients with than in those without these DNA fragments Difficult-to-detect germs are prone to generate proinflammatory agents other than intact endotoxin.

Hemofiltration and Hemodiafiltration Removal of large solutes is enhanced with therapies whereby some or all solute removal occurs by convection, such as hemodiafiltration (HDF) and hemofiltration (HF).

Kidney International (2006) 69, 2087–2093. doi:10. 1038/sj. ki Kidney International (2006) 69, 2087–2093. doi:10.1038/sj.ki.5000447; published online 26 April 2006

American Journal of Kidney Diseases, Vol 52, No 3 (September), 2008: pp 507-518

Conclusion Impressive technological innovations in the field of dialysis have been introduced in the past few decades; however, the translation of these technical achievements into hard clinical outcomes (patient survival) is more difficult to demonstrate. Even the best dialysis modality will not reverse the cardiovascular damage that has accumulated in the predialysis stage.

The only innovative strategy with some evidence of benefit on outcome for the time being is the application of high-flux membranes. Implementing new devices should never substitute sound clinical judgment or understanding of the basic physiology of dialysis.

High dosage Advantage for small women Duration (Treatment time) Advantage Na modeling/K modeling BVM/BIA Water purity Needs to be explored. High flux vs low flux Not convincing HDF Benefit

Thanks for your attention.