Preliminary
Results of the NIED Study
Although NIED Study is only halfway through, some clinically
relevant findings based on the analyses of the data from the first 12 to 30
months of the study have led to following publications and reports:
(A) Protein Intake and Outcome in High Kt/V [1]: In 122 MHD patients with a delivered
Kt/Vsp>1.20,
independent of their residual renal function, the nPNA and Kt/Vsp
did not correlate significantly (r=0.09) except when analysis was limited to
Kt/V values <1.5 (r=0.54). Both nPNA
and serum albumin predicted prospective hospitalization and mortality in MHD
patients with Kt/V > 1.20.
(B) Erythropoietin Hypo-responsiveness [2]: Elements of MICS including a high
MIS value and increased serum levels of inflammatory markers (CRP, IL-6, and
TNF-α), and decreased serum levels of nutritional values (total
cholesterol, prealbumin and TIBC) correlated with EPO hypo-responsiveness in
MHD patients of NIED Study.
(C)
Significance of Appetite in MHD Patients [3]: Anorexia was found to be associated
with increased levels of pro-inflammatory cytokines, a worse MIS score,
refractory anemia, and poor clinical outcome including a 4-fold increase in mortality, higher hospitalization rates, and
a poor QoL in MHD patients.
(D) Reverse Epidemiology of
Homocysteine [4]: The associations between total
homocysteine (thcys) level and markers of MICS and
12-month prospective hospitalization and mortality in 367 MHD patients of the
NIED cohort was examined; 94% of MHD patients had hyperhomocysteinemia
(thcys>13.5 µmol/L). Thcys
had statistically significant correlations with some markers of nutrition but
not with serum CRP, IL-6 or TNF-α. Mortality and hospitalization rates
were significantly higher in patients with lower
thcys levels. The lowest thcys
quartile conferred a 2-fold increase in risk of death independent of
hypoalbuminemia.
(E) Comparing Outcome-Predictability
of Markers of MICS [5]: The association of 10 markers of MICS with
prospective mortality and hospitalization in 378 MHD patients of the NIED Study
cohort was examined. The magnitude of relative risk of death and
hospitalization was greatest for MIS, CRP and IL-6. In extended multivariate
models that included all 10 MICS markers and 11 additional covariates simultaneously,
CRP and MIS were the only consistent predictors of mortality and
hospitalization, and their outcome-predictability was superior to serum
albumin. Among case-mix covariates, Charlson comorbidity
index was the only statistically significant outcome-predictor in all
models.
(F) Reverse Epidemiology of Serum
Iron: [6]: In a large cohort of 1,283 MHD
patients from 10 DaVita dialysis facilities, mortality was significantly
greater in the lowest serum iron quartile. Multivariate Poisson and Cox models
adjusted for relevant covariates including administered EPO and iron doses
showed that both serum iron level and iron saturation ratio had significant but
inverse associations with prospective mortality and hospitalization. This
reverse association remained significant in a sub-cohort of 322 MHD patients of
the NIED Study after additional adjustments for comorbid conditions and serum
CRP to reflect inflammation.
(G) Outcome-Predictability of
Peripheral Lymphocyte Percentage [7]: The associations of the baseline white blood cell
count (WBC) and lymphocyte percentage (LYM%) with 12-month mortality and three
measures of hospitalization in a cohort of 1,283 MHD patients from 10
outpatient DaVita dialysis clinics in Los Angeles County, as well as in a
sub-cohort of 372 MHD patients (NIED Study) with additional measures of
inflammation, nutrition and comorbidity. A high WBC and a low LYM% were
associated with significant increase in mortality and hospitalization in MHD
patients.
(E) Reverse
Epidemiology of LDL Cholesterol [8]: An inverse J-shaped association has been found between
serum LDL and prospective mortality in 629 MHD patients, even after controlling
for CRP and other pertinent factors. Over a 2.5 year follow-up, lowest
quartiles of LDL and total cholesterol had the highest all-cause and
cardiovascular mortality (p<0.05). This paradoxical association may have
significant clinical implications for the management of dyslipidemia
in MHD patients.
(F) Serum
Myeloperoxidase [9]: In 128 MHD patients serum
myeloperoxidase (MPO) is correlated with serum IL1-β, ferritin and
albumin. Serum MPO appears to be associated with some but not all markers of
MICS.
(G) Markers of Lipoprotein Oxidation
and Inflammation [10]: HDL inflammatory/anti-inflammatory
properties (HIAP) was measured in sera of 188 MHD patients. Higher prevalence
of pro-inflammatory HDL was observed in obese MHD patients, which may suggest
that adipose tissue promote inflammation in obese MHD patients. Moreover, serum
paraoxonase (PON), an esterase that inhibits the
“oxidization of low-density lipoprotein” (LDLOX), was measured in 189 MHD
patients, including 150 patients in whom PON was also measured simultaneously.
PON was significantly but inversely correlated with serum CRP and serum IL-1
β. Similarly, LDLOX was significantly associated with CRP.
(H) Coronary Artery Calcification and
MICS [11]: A higher serum ferritin,
HDL-cholesterol and TNF-α and a worse anemia were associated with an
increased risk of higher CAC scores in 85 MHD patients of the NIED Sub-study.
(I) Body Composition
Assessment Comparison [12]: In 90 MHD patients who agreed to
undergo tests of body composition in the NIED Sub-study, the BIA and TSF tend
to overestimate while NIR tends to underestimate the body fat percentage when
compared to DEXA as the reference standard. Both BIA and NIR had superior
correlations with DEXA (r>0.85) compared to TSF based method. We concluded
that both NIR and BIA are acceptable body composition tests. However, the NIR
is a more patient- and evaluator-friendly method for outpatient dialysis units.
Reference:
1. Kalantar-Zadeh K, Supasyndh
O, Lehn RS, McAllister CJ, Kopple
JD: Normalized protein nitrogen appearance is correlated with hospitalization
and mortality in hemodialysis patients with Kt/V greater than 1.20. J Ren Nutr 13:15-25, 2003
2. Kalantar-Zadeh
K, McAllister CJ, Lehn RS, Lee GH, Nissenson AR, Kopple JD: Effect of
malnutrition-inflammation complex syndrome on EPO hyporesponsiveness
in maintenance hemodialysis patients. Am J Kidney Dis 42:761-773, 2003
3. Kalantar-Zadeh
K, Block G, McAllister CJ, Humphreys MH, Kopple JD: Appetite and inflammation,
nutrition, anemia and clinical outcome in hemodialysis patients. Am J Clin Nutr, 2004 Aug [in-press]
4. Kalantar-Zadeh
K, Block G, Humphreys MH, McAllister CJ, Kopple JD: A
low, rather than a high, total plasma homocysteine is an indicator of poor
outcome in hemodialysis patients. J Am
Soc Nephrol 15:442-453, 2004
5. Kalantar-Zadeh
K, Kopple JD, Humphreys MH, Block G: Comparing outcome
predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients. Nephrol Dial Transplant 19:1507-1519, 2004
6. Kalantar-Zadeh
K, McAllister CJ, Lehn RS, Liu E, Kopple
JD: A low serum iron level is a predictor of poor outcome in hemodialysis
patients. Am J Kidney Dis
43:671-684, 2004
7. Kuwae
N, Kopple J, Kalantar-Zadeh K: A low lymphocyte count
is a predictor of mortality and hospitalization in hemodialysis patients. Clin Nephrology, 2004 [submitted]
8. Kalantar-Zadeh
K, Horwich TB, Fonarow GC, Anker SD, Kopple JD: A Low, rather
than a high, serum LDL cholesterol is associated with increased mortality in
hemodialysis patients even after controlling for inflammation. 37th annual conference of the American
Society of Nephrology; J Am Soc Neph, Nov 2004
[in-press]
9. Kalantar-Zadeh
K, Brennan ML: Serum myeloperoxidase measurement and its correlates in
maintenance hemodialysis patients. 37th
annual conference of the American Society of Nephrology; J Am Soc Neph, Nov 2004 [in-press]
10. Kalantar-Zadeh
K, Kamranpour N, Kopple JD: Association between novel HDL
inflammatory/anti-inflammatory properties
with body mass index in hemodialysis patients. 37th annual conference of the American Society of Nephrology; J Am Soc Neph, Nov 2004 [in-press]
11. Kalantar-Zadeh
K, Bross R, Takasu J, Budoff MJ: Associations between markers of
malnutrition-inflammation complex syndrome and anemia and coronary artery
calcification in hemodialysis patients. 37th
annual conference of the American Society of Nephrology; J Am Soc Neph, Nov 2004 [in-press]
12. Kalantar-Zadeh
K, Bross R, Zitterkoph J,
Colman S, Gjertson DW, Kopple
JD: Comparing four body composition assessment methods for body fat measurement
in dialysis patients. 37th annual
conference of the American Society of Nephrology; J Am Soc Neph,
Nov 2004 [in-press]
Contact:
Kamyar Kalantar-Zadeh, MD, PhD, MPH,
FAAP, FACP
Assistant Professor of Medicine and Pediatrics
Director of Off-Campus Dialysis Expansion Program and Epidemiology
UCLA David Geffen School of Medicine
Harbor-UCLA Medical Center
1124 W. Carson St., C-1 Annex, Box 406
Torrance, CA 90502-2064
Tel: (310) 222-3891
Fax: (310) 782-1837
Cell: (310) 686-7908
Pager: (310) 501-2692
Email Address: kamkal@ucla.edu
http://www.nephrology.rei.edu/kkalantar.htm
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