case presentation: kidney disease - virology...
TRANSCRIPT
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Slide #1
Case Presentation: Kidney Disease
Christina Wyatt, MDMount Sinai, New York
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Slide #2
Disclosures
Investigator-initiated research support Gilead Sciences
Honoraria for internal education Bristol Myers Squibb
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Slide #3
Kidney Disease is Common in HIV
Both acute & chronic kidney disease are more common in HIV-infected adults
Wyatt et al. AIDS 2008Choi et al. JASN 2007Medapalli et al. JAIDS 2012
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Slide #4
Acute Kidney Injury is Associated with Adverse Outcomes in HIV
Choi et al. KI 2010
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Slide #5
Chronic Kidney Disease (CKD) is Associated with Adverse Outcomes
Wyatt et al. JAIDS 2010Choi et al. Circ 2010*
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Slide #6
Case Presentation
46 year old HIV-HCV+ black man referred for rising creatinine
Baseline 0.9 mg/dL 1.3 four months ago 1.5(80 mmol/L 133)
eGFR 118 64 mL/min/1.73m2
CrCl (70kg man) 102 61 mL/min
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Slide #7
Case Presentation
HIV-HCV diagnosed 2010– Risk factor MSM, no history of IDU– Nadir CD4 > 200; on ARVs since diagnosis– CD4 > 500; HIV-RNA undetectable
No other medical history Family history of DM and HTN, no CKD Current meds: FTC/TDF, dolutegravir
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Slide #8
Case Presentation
Thin, well-groomed manBP 112/64Weight 57 kg
eGFR 118 76 64 mL/min/1.73m2
CrCl 83 57 50 mL/min
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Slide #9
GFR Estimates are Just That
Serum creatinine is not an ideal marker – Influenced by muscle mass– Both filtered and secreted
Estimates perform ‘OK’ in stable HIV– Studies have included few ART-naïve patients
Inker et al. JAIDS 2012Gagneux-Brunon et al. AIDS 2013
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Slide #10
Best Choice of GFR Estimate Varies
FDA dosing guidelines are based on CrCl CKD-EPI is usually the most accurate Near dosing thresholds, clinical judgment
is essential. For example:– 3TC has a wider therapeutic window– Ask about diet/ supplements– Consider meds that inhibit creatinine
secretion Inker et al. JAIDS 2012Vrouenraets et al. Clin Nephrol 2012
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Slide #11
Drugs used in HIV Interfere with Creatinine Secretion
Blood Urine
OCT2
Creatinine
MATE1 X CobicistatRitonavir
Dolutegravir XRilpivirine
MATE2 X Trimethoprim
Lepist et al, Kidney Int 2014Moss et al, Antimicrob Agents Chemother 2013
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Slide #12
ART & Low GFR: Role of RTV?
Mocroft et al. AIDS 2010*Sherzer et al. AIDS 2012Ryom et al. JID 2013
EUROSIDA (CrCl<60)
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Slide #13
Cystatin C-based GFR estimates?
Potential advantages in unique settings:– Extremes of muscle mass– Drugs that interfere with creatinine secretion
Stronger association with mortality in HIV– May reflect systemic inflammation
Choi et al, AJKD 2010Lucas et al, HIV Med 2014
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Slide #14
Cystatin C-based GFR estimates?
Lower accuracy & higher bias in HIV
Inker et al. JAIDS 2012May still be useful if normal/ low
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Slide #15
Back to Our Case
46 year old HIV-HCV+ black man referred for rising creatinine
Baseline 0.9 mg/dL 1.3 four months ago 1.5
Creatine/ high protein diet
Darunavir/r Dolutegravir(FTC/TDF continued)
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Slide #16
Case Presentation
Creatinine 0.9 mg/dL 1.3 1.5 1.3 mg/dL
Cystatin C 0.77 mg/L (normal range 0.5-1.0)Urinalysis: no protein, no glucose; UPCR 0.09
Off creatine/ diet
eGFR (Cr): 76 mL/min/1.73m2
eGFR (CysC): 113 mL/min/1.73m2
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Slide #17
Our Case: Alternate Ending
46 year old HIV-HCV+ black man referred for rising creatinine
Baseline 0.9 mg/dL 1.3 four months ago 1.5
No changes in diet/ meds
Urinalysis: 2+ protein, no glucose, no cells
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Slide #18
Case Presentation: Ending 2
46 year old HIV-HCV+ black man with rising creatinine and proteinuria– HIV-related disease?– HCV-related disease?– Comorbid disease?– Medication nephrotoxicity?
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Slide #19
HIV-Associated Nephropathy?
Berliner et al. Am J Nephrol 2008
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Slide #20
Case Presentation: Ending 2
46 year old HIV-HCV+ black man with rising creatinine and proteinuria– HIV-related disease: probably not– HCV-related disease?– Comorbid disease?– Medication nephrotoxicity?
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Slide #21
Case Presentation: Critics’ Choice
Urine protein: creatinine 1.1 UA: 1+ protein, otherwise negative Serum complements normal Serum cryoglobulin negative Rheumatoid factor slightly elevated Serum bicarbonate, phosphorus & uric acid wnl
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Slide #22
Kidney Biopsy Can Provide a Definitive Diagnosis
Courtesy of Glen Markowitz & Vivette D’Agati
Unclear diagnosisLimited alternativesHBV co-infection
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Slide #23
Potential for Nephrotoxicity with Tenofovir Alafenamide?
0 12 24-30
-20
-10
0
10
20 E/C/F/TAF
STB
Time (Weeks)
Med
ian
(Q1,
Q3)
cha
nge
from
bas
elin
eeG
FR C
ockr
oft-G
ault
(mL/
min
)
Zolopa et al. CROI 2013*Sax et al. Lancet 2014
Cobicistat effect
Tenofovir effect
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Slide #24
Potential for Toxicity with TAF: Switch Studies
Phase 3 trial of full-dose E/C/F/TAF in stable patients with GFR 30-69 (80 with GFR < 50)
No significant change in eGFR with switch Reduction in proteinuria/ albuminuria Rapid decline in RBP & β2-microglobulin?
Fordyce et al. CROI 2015
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Slide #25
Our Case: The Hollywood Ending
Increased risk for TDF toxicity, particularly with planned HCV therapy?– Low body weight, uncertain GFR estimates– Regimen already switched to avoid PI/r
A candidate for TAF when approved?
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Slide #26
Our Case: Alternate Ending
Safety of re-challenge with TAF in patients with known or suspected TDF toxicity is unknown