Impact of lean mass and bone density on glomerular filtration...
Transcript of Impact of lean mass and bone density on glomerular filtration...
IMPACT OF LEAN AND BONE MASS ON
GLOMERULAR FILTRATION RATE ESTIMATION IN PEOPLE LIVING WITH HIV/AIDS
Corinne Isnard Bagnis
and Laurence Pieroni, Rachida Inaoui, Philippe Maksud,
Stéphanie Lallauret, Marc-Antoine Valantin, Roland Tubiana, Christine Katlama, Gilbert Deray, Marie Courbebaisse, JérômeTourret and Sophie Tezenas du Montcel
[email protected] Pitié Salpetrière Hospital, Paris, France
BACKGROUND AND AIM OF THE STUDY
5 to 8% patients living with HIV/AIDS (PLWHA) exhibit Chronic
kidney disease (stage 3 : GFR below 30/ml/min/1.73m 2)
The optimal way to estimate GFR in PLWHA patients is not
known although MDRD and CKD EPI formulae are validated in
general population
Moreover, the impact of muscle mass on creatinine blood
level and therefore on GFR estimation is unknown in these
patients
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METHODS
• 44 HIV-1 patients were included in a transversal monocentric comparative
study evaluating the accuracy of the different diagnostic tests available
compared to the gold standard measurement of GFR
• Adult, male, caucasian patients with an estimated GFR between 60 and 30
ml/min/1.73 m2 were included. Serum creatinine and cystatin C were
measured
• GFR was estimated using Cockcroft, MDRD, aMDRD, CKD EPI, CKD EPIcyst,
CKD EPIcyst/creat formulae, and measured using isotopic Chrome51 EDTA
clearance
• Bone and muscle mass were measured by DEXA scan (dual Xray
absorbtiometry)
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Table 1A: Demographic data and treatment details at inclusion
Mean
or frequency
SD or %
Age 62 (10)
Age >50 (n=44) 36 (82%)
Delay since HIV infection diagnosis (years) (n=43) 19 (7)
Diabetes mellitus 13 (30%)
Hypertension (n=36) 17 (47%)
HAART (Highly active antiretroviral therapy) 42 (95%)
Tenofovir 20 (45%)
Atazanavir 15 (34%)
CD4 count (cells/mm3) (n=38) 446 (191)
CD4 count (cells/mm3) < 350 (n=38) 13 (34%)
Viral load (n=40)
≤40
among which ≤20
36 (90%)
28 (70%)
72 1 (2.5%)
120 1 (2.5%)
160 1 (2.5%)
56 402 1 (2.5%)
VHB infection 10 (23%)
VHC infection 4 (9%)
VHC VHB co infection 1 (2%)
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Table 1B: Biological data (mGFR: measured glomerular filtration rate)
Normal values Mean or frequency
SD or % mGFR (ml/min/1.73m2) 63.4 (16.5)
Blood
Enzymatic plasma creatinine (µmol/L) According to age and sex 139.9 (51.5)
Urea (mmol/L) According to age and sex 8.8 (3.1)
Albumin (g/L) 37-48 44.4 (3.7)
CRP (mg/L) < 5 7.1 (8.1)
CRP>10 mg/L 6 (14%)
Cystatin C (mg/L) < 1.2 1.6 (0.5)
Urines
Creatinine (mmol/L) ND 9.0 (5.2)
Cystatine C (mg/L) ND 1.0 (4.7) Proteinuria (g/L) <0.10 0.5 (0.7)
WHICH FORMULAE PERFORMS BEST ?
• Mean measured isotopic GFR was 63.4±13.5 ml/min/1.73m2
• All formulae under-estimated GFR
• Best performance was provided by CKD EPI with
• the best accuracy 30%
• a good precision
• a low bias
• and highest correlation coefficient
• CKD EPI Cyst and CKD EPI Cyst/creat performed worse than the
CKD EPI and sMDRD formula
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BODY COMPOSITION (BMI = BODY MASS
INDEX, BMC = BONE MINERAL CONTENT) 7
8BODY COMPOSITION (BMI = BODY MASS INDEX, BMC = BONE MINERAL CONTENT)
Patients characteristics
and GFR estimation
according to lean mass
(All GFR expressed as
ml/min/1.73m²)
Median (IQR) or frequency (%) in each lean mass category: N (%)
<70% (n=10)
70-85% (n=28)
>85% (n=6)
p-value†
Lean Mass 57961 (52716-60841)
55052 (47658-58638)
51475 (44325-61990)
-
Serum Creatinine (enzymatic)
124 (118-143) 127 (119-154) 121 (114-131) 0.7425
Age>50 years 9 (90%) 23 (82%) 4 (67%) 0.6271
Weight (kg) 86 (79-94) 70 (61-73) 59 (51-72) 0.0024
BMI (kg/m2) 30 (25-31) 23 (21-24) 21 (18-21) 0.0005
BMI > 25 kg/m2 6 (60%) 5 (18%) 0 0.0132
Low T-score (<-1) 1 (10%) 19 (68%) 5 (83%) 0.0017
Delay since HIV diagnosis
years
19 (16-20) 22 (16-24) 21 (18-23)
0.4588
CD4 < 350/mm3 3 (33%) 8 (35%) 2 (33%) 1
Tenofovir 2 (20%) 14 (50%) 4 (67%) 0.1637
Atazanavir 3 (30%) 11 (39%) 1 (17%) 0.6586
GFR measured 57 (53-72) 66 (53.5-70.5) 64.5 (50-74) 0.8653
Cockcroft Enzymatic 68 (53-75) 53 (40-58.5) 58 (34-59) 0.0488
Cockcroft Enzymatic/SC 81 (56-87) 54 (39.5-64) 55.2 (32-65) 0.0310
MDRD Enzymatic 51 (43- 54) 50.5 (39.5-54) 53.5 (48-59) 0.6856
CKD EPI 51.5 (44-57) 51.5 (40-56.5) 57 (49-65) 0.5805
CKD EPI-Cyst 46.5 (39-55) 50 (33.5-56) 51.5 (32-60) 0.9462
CKD EPI-creat-cyst 50 (42-54) 51.5 (33-58) 54 (40-64) 0.8605
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GFR ESTIMATION ACCORDING TO LEAN MASS
Patients with higher weights
and BMI had lower lean mass
values and lower T scores
GFR estimation according to bone mineralization (All GFR expressed as ml/min/1.73m²)
N (Median (IQR) or N(%) in each T-score category
< -1 (n=25)
³ -1 (n=19)
p-value †
Age>50 years 20 (80%) 16 (84%) 1
Weight (kg) 68 (57-72) 79 (70-90) 0.0012
BMI (kg/m2) 21 (21-23) 25 (22-30) 0.0010
BMI > 25 kg/m2 2 (8%) 9 (47%) 0.0045
Measured GFR 66 (53-71) 59 (53-72) 0.8682
Delay since HIV diagnosis (years) 20 (14-24) 20 (17-23) 0.9608
Cd4 count < 350/mm3 7 (33%) 6 (35%) 1
Tenofovir 11 (44%) 9 (47%) 1
Atazanavir 11 (44%) 4 (21%) 0.1985
Cockcroft Enzymatic 52 (35-59) 60 (51-73) 0.0380
Cockcroft Enzymatic/body
surface area 49 (37.5-61) 68 (50-84) 0.0310
MDRD Enzymatic 50 (47-54) 51 (41-55) 0.8309
CKD EPI 52 (48-60) 54 (44-57) 0.8775
CKD EPI-Cyst 48 (35-53) 51 (36-60) 0.3933
CKD EPI-Combined 49 (40-60) 52 (39-59) 0.6019
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Only weight and BMI
influenced T-scores
values
DISCUSSION
Our study is underpowered because of an inferior number
of included patients (n=44) than what was estimated
(n=60)
Our study does not allow to draw any conclusions for
women or patients from African descent because, due to
expected number of patients to include, we deliberately
chose to restrain our study to Caucasian men
Normal muscle mass in the HIV population is not known
We used dexa scan to measure lean mass but few studies
document the best method
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MAIN MESSAGES
• All formulae under-estimated GFR
• Best performance was provided by CKD EPI with the best accuracy 30%, a
good precision, a low bias and highest correlation coefficient
• Cockcroft formula estimated GFR was significantly correlated with lean mass
values and bone mineralization (T-scores)
• Cockcroft bias was significantly lower in patients with low bone mineralization than in
the other two groups, indicating less over estimation of GFR
• No significant difference was observed using other estimations based on lean
mass or T-score categorization
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• 16 out of 44 patients exhibited abnormal muscular mass (< 70%)
• had the lower values for T-score (often below -1)
• had higher BMI and measured weights
• Using total body BMD T score, 24 patients (56%) exhibited values below -
1 SD
• Low bone mass (estimated by T-scores below 1 SD) was significantly correlated
to increased lean mass
• No other factor than BMI impacted significantly on T-scores
• The different treatment received (vitamin D, calcium, bisphosphonates) had no
significant impact on bone mass
• In our study, tenofovir did not exhibit any significant effect on lean mass nor
bone mass but significantly influenced absolute bias (p<0.05)
MAIN MESSAGES13