12. “We believe to be able to keep patients
suffering from uremia and anuria alive so
long as blood vessels for punction are
available.”
Dr. Willem Kolff,Dr. Willem Kolff,
19441944
54. משפרת ()פריטוניאלית דיאליזהמשפרת ()פריטוניאלית דיאליזה
תפקודית דרגהתפקודית דרגה
Mehrotra et al. Kidney International 2006
Place of peritoneal dialysis in the management of treatment-resistant congestive heart failure
55. מורידה ()פריטוניאלית דיאליזהמורידה ()פריטוניאלית דיאליזה
אשפוזיםאשפוזים
Mehrotra et al. Kidney International 2006
Place of peritoneal dialysis in the management of treatment-resistant congestive heart failure
62. Erythropoeisis Stimulating Agents (ESA’s) &
hemodialysis
Anemia is very prevalent among hemodialysis patients
The major medical breakthrough that improved the well-
being of dialysis patients is Erythropoeitin or ESA’s
− Clinical use ~ 1990
− Improved anemia, cardiomegaly, exercise tolerance, appetite,
cognitive function, and replaced the uremic feel and look with a
sense of well-being and a healthy appearance
− Decreased transfusions and pretransplant sensitization
− Decreased morbidity and mortality
63. HOWEVER, it turned out that ESA’s can have
a negative impact on patients:
If Hb is raised to normal levels, there is
increased cardiovascular morbidity,
thromboembolic events & mortality.
65. ESA’s further negative impact:
Raise the cost of dialysis significantly:
− U.S. estimate for one year: $644,000,000 (Hynes
Dm et al. Am. J. Med.2002:112:169-75)
Use of ESA’s in oncology patients can
exacerbate outcomes and increase mortality
66. Realizing how significant Hgb levels are in the
rehabilitation of dialysis patients, we studied a
metal not usually measured in clinical medicine,
known to enhance erythropoeisis in
pharmacologic doses but also known to cause
side effects that lead to its discontinuation :
Cobalt
Jelkmann W. Intern Med.
2004 Aug;43(8):649-59
69. Correlation between
Hemoglobin & Cobalt:
R= 0.31 p<0.001
0
2
4
6
8
10
12
14
16
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5
Cobalt mcg/L
Hbg/dL
Correlation between
EPO dose & Cobalt:
R= -0.24 p=0.003
-
100.00
200.00
300.00
400.00
500.00
600.00
700.00
- 0.50 1.00 1.50 2.00 2.50 3.00 3.50
Cobalt mcg/L
EPOunits/kg/week
Despite our aim to treat all patients with ESA’s to a Hb goal
of 11-12, the Hb levels nevertheless correlated directly
with the Cobalt levels, and inversely with the ESA doses.
70. In summary:
• Anemia control is extremely important in dialysis patients, but
available treatments are imperfect
• Cobalt seems to be an important modulator of erythropoiesis in
hemodialysis patients:
•Levels are elevated in hemodialysis patients compared to normals
• " are elevated in patients who maintain elevated hb without
ESA’s compared to other patients
•Levels correlate directly with hb
• " correlate inversely with ESA doses
• Perhaps Cobalt has potential as a therapeutic agent and not only in
dialysis ???
75. המשך דמוגרפיים נתונים
•:ה פי על
•United State Renal Data System (USRDS(
•:1996
•7054גיל מעל חולים80.בדיאליזה טיפול החלו
•2003:
•13577גיל מעל חולים80בדיאליזה טיפול החלו
•של עליה57%תוך (האוכלוסיה לגידול (מתוקנת7
.שנים
Kurella, M, Covinsky, KE, Collins, AJ, Chertow, GM.
Octogenarians and nonagenarians starting dialysis in the
United States. Ann Intern Med 2007; 146:177.
80. דיאליזה בחולי ואיכותם החיים תוחלת
מבוגרים
•ה פי עלUSRDS:
•-מ למעלה בני לחולים65המטופלים שנה
.שנים ארבע של חיים תוחלת בדיאליזה
United States Renal Data System. Excerpts from the USRDS
2009 annual data report: Atlas of end-stage renal disease in
the United States. Am J Kidney Dis 2010; 55(Suppl 1):S1.
81. דיאליזה בחולי ואיכותם החיים תוחלת
מבוגרים
•:קנדי מחקר
•גיל מעל דיאליזה לחולי75:של שרידות
•אחת שנה-69%
•שנים שלוש-37%
•שנים חמש-20%
•התמותה על סופנית כליות ספיקת אי השפעת
.בגיל העליה עם יורדת
Letourneau, I, Ouimet, D, Dumont, M, et al. Renal
replacement in end-stage renal disease patients over 75
years old. Am J Nephrol 2003; 23:71.
Jassal, SV, Trpeski, L, Zhu, N, et al. Changes in survival
among elderly patients initiating dialysis from 1990 to 1999.
CMAJ 2007; 177:1033.
110. The rate of convective solute transport during dialysis depends on the sieving
coefficient of the solute for a given membrane(0-1; sieving coefficient of
β2microglobulin=0.6-1)) and the ultrafiltration rate, which depends on the
transmembrane pressure (TMP(.
Convective Therapies:
-High flux
-Hemofiltration
-Hemodiafiltration
111. New and Experimental Hemodialysis Techniques (1)
•Hemodiafiltration
•Wearable artificial kidney (WAK)
•Bioartificial kidney and bioengineered membranes
•Artificial nephron system (molecularly engineered
nanomembranes)
112. Convective therapies:
Hemofiltration:
Removal of large amounts pf fluid through increased tramsmebrane pressure
with parallel infusion or back diffusion of replacement fluid in the desired
amount.
Hemodiafiltration:
A combination of hemofiltration and hemodialysis
113. Improved clinical outcome with convective therapies:
•The convective process is associated with increased removal of larger
molecules;
•The use of high flux biocompatible membranes decreases cytokine
releases;
•The use of high quality dialysate (“ultrapure”) is associated with further
decrease in cytokine release and diminished exposure to other impurities.
114. Improved specific outcomes with hemodiafiltration:
•Hemodiafiltration with High Flux Polyphenylene Membrane (Phylther®). A
Much Cheaper Alternative to HCO Dialysis for Kappa Light Chain Cast
Nephropathy
(Desmeules et al, ASN, 2010)
•Reduced insulin resistance in diabetic hemodialysis patients.
•Improved quality of life (on short term follow up).
116. Canaud et al et al: Mortality risk for patients receiving hemodiafiltration vs.
hemodialysis: European results from the DOPPS. Kidney Int 69:2087, 2006.
117. New and Experimental Hemodialysis
Techniques (2(
•Hemodiafiltration
•Wearable artificial kidney (WAK)
•Bioartificial kidney and bioengineered membranes
•Artificial nephron system (molecularly engineered
nanomembranes)
118. Wearable Artificial Kidney (WAK )
A prototype of a wearable artificial kidney utilizing an adsorption
cartridge has been reported. It is worn as a belt, operated with
batteries, and weighs less than five pounds. A hollow fiber dialyzer is
used and dialysate is continuously regenerated by cartridges
containing sorbents. In preliminary studies in patients with end-stage
real disease, the device was worn for four to eight hours, resulting in
mean plasma urea and creatinine clearance rates of 23 and 21
mL/min, respectively. (Gura et al., CJASN, 2009)
121. New and Experimental Hemodialysis Techniques (3(
•Hemodiafiltration
•Wearable artificial kidney (WAK)
•Bioartificial kidney and bioengineered membranes
•Artificial nephron system (molecularly engineered nanomembranes)
122. The bioartificial kidney and bioengineered membranes
•A renal tubule assist device (RAD) that includes a conventional
hemodialysis filter and a bioreactor containing living renal proximal tubule
cells has been successfully engineered.
• Differentiated activity of these cells and survival advantages have been
demonstrated in large-animal models of sepsis and AKI.
•Data from phase I/II and phase II clinical studies have shown that the
addition of renal tubule cell therapy to conventional continuous renal
replacement therapy (CRRT) treatment resulted in a significant clinical
impact on survival, and that RAD treatment demonstrated an acceptable
safety profile.
The bioartificial kidney and bioengineered membranes in acute kidney injury. Ding
F, Humes HD. Nephron Exp Nephrol. 2008;109(4):e118-22
123. New and Experimental Hemodialysis Techniques (4(
•Hemodiafiltration
•Wearable artificial kidney (WAK)
•Bioartificial kidney and bioengineered membranes
•Artificial nephron system (molecularly engineered
nanomembranes)
126. In summary,
•The worldwide epidemic of chronic kidney disease shows
no signs of abating in the near future.
• Nephrology (hemodialysis) is at an exciting crossroad
with the application of innovative and novel technologies
that hold considerable promise for the near future.
)Niessensohn, Humes, Ronco and many others)
However,
“There is nothing better for the well being of the kidney
patient than a well functioning renal transplant”
Oscar Salvatierra MD, Transplant Surgeon
127. ''The main aim of our endeavours has always beenThe main aim of our endeavours has always been
to restore people to an enjoyable existence.to restore people to an enjoyable existence.
If it's not enjoyable, it should not be done.If it's not enjoyable, it should not be done.‘‘
Willem J. Kolff, 2003Willem J. Kolff, 2003
Belding Scribner,Belding Scribner,
1921-20031921-2003
Willem.J Kolff,Willem.J Kolff,
1910-20081910-2008