Kidney Disease in HIV
Infection:
Beyond HIVAN
Christina M. Wyatt, MD
Assistant Professor of Medicine
Mount Sinai School of Medicine
New York, New York
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #2
Disclosures
Gilead Sciences/ Gilead Foundation
– Support for investigator-initiated research
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #3
Clinical Case
56yo AA women with nausea/ vomiting x 2 weeks
PMH:
– HIV/ AIDS, last CD4 ~300
– HCV cirrhosis
Meds:
– Tenofovir/ FTC
– Lopinavir/ ritonavir
– Ibuprofen x 1 week
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #4
Clinical Case
139 109 78
3.9 15.2 21 (baseline 1.4)
Urinalysis: + protein, ketones, glucose
Plain film: normal bowel gas pattern
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #5
Acute Kidney Injury in HIV
More common in HIV patients
Risk factors
– Chronic kidney disease
– Advanced HIV
– Hepatitis C co-infection
Associated with adverse outcomes
– ESRD, cardiovascular disease, & death
Franceschini et al. KI 2005
Wyatt et al. AIDS 2006
Roe et al. CID 2008
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Choi et al. KI 2010
Slide #6
Clinical Case
HIV-HCV & cirrhosis, c/o N/V x 2 weeks
– Meds: TDF/ FTC, LPV/r, ibuprofen
139 109 78 79
3.9 15.2 21
Phos 5.2
Urinalysis: + protein, ketones, glucose
Urine Na 60
Unremarkable renal US
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #7
Tenofovir Toxicity
Classic presentation: proximal tubulopathy
~2% of patients develop significant toxicity
– More frequent sub-clinical abnormalities
– Stable decrease in eGFR in cohort studies
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #8
Tenofovir Toxicity
Risk factors remain controversial
– Unrecognized low GFR
– Genetic predisposition
– Concomitant medications
ddi, boosted PI, NSAID
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #9
Tenofovir Toxicity: On the Horizon
Investigational fixed-dose pill
– TDF/ FTC/ Elvitegravir/ GS-9350
– in estimated GFR (eGFR) vs TDF/ FTC/EFV
GS-9350 (cobicistat)
– Rapid & reversible in eGFR, no ∆ measured GFR
Likely interferes with creatinine secretion
– Also reported to boost atazanavir
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
CROI/ ICAAC 2010
Slide #10
Clinical Case #2
43 yo AA women with chronic kidney disease
PMH:
– HIV-HCV, nadir CD4 > 200
– Hypertension x 20 years
– Type 2 diabetes x 8 years
Meds:
– AZT/ 3TC
– Amlodipine, lisinopril
– Insulin
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #11
Clinical Case
BP 156/98
BMI 31
139 109 55 208
4.9 18.2 6.2
Phos 6.4
Urinalysis 3+ protein, 1+ glucose
Urine protein:creatinine 3.2g
CD4 598
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #12
HIV-Associated Nephropathy
Wyatt, Klotman, & D’Agati. Seminars in Nephrology 2008
Advanced HIV disease
Strong racial disparity
DHHS guidelines: indication for ART
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #13
HIV & Chronic Kidney Disease (CKD)
HIVAN
Immune Complex
Membranous/MPGN
Diabetes/ HTN
AIN
Other
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Szczech et al. Kidney Int 2004
Slide #14
HIV & CKD in the ART Era
Spectrum of CKD is changing
– Less classic HIVAN
– More comorbid kidney disease
Kidney biopsy is underutilized for diagnosis
– No increase in risk compared to HIV-negative
HCV co-infection associated with higher risk
Szczech et al. Kidney Int 2004
Berliner et al. Am J Nephrol 2008
From CM Wyatt, MD, at 14th
Tabatai et al. CJASN 2009
Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #15
CKD Screening in HIV
Screen all patients at diagnosis
– Creatinine-based GFR estimate
– Urine protein
Annual screening in high-risk patients
– Black race
– HCV co-infection
– Advanced HIV disease
– Diabetes or hypertension
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
IDSA Guidelines: Gupta et al. CID 2005
Slide #16
Clinical Case
HIV-HCV, DM, HTN, and Stage 5 CKD
Kidney biopsy: advanced diabetic
nephropathy, hypertensive vascular changes
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #17
Managing Comorbid CKD
Tight blood pressure & glycemic control are
standard of care for CKD
CKD is strongly associated with increased
cardiovascular risk
– Limited data on the effect of CV risk modification
Drug regimen & dosing should be reviewed
Gupta et al. CID 2005
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Choi et al. Circulation 2010
Slide #18
HIV & End-Stage Renal Disease
Only accounts for ESRD attributed to HIVAN
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
USRDS Annual Data Report 2010
Slide #19
Which of the following should be
discussed with this patient?
Hemodialysis
Peritoneal dialysis
Kidney transplant
None of the above
All of the above
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #20
Management of ESRD in HIV
Similar survival with HD vs PD
– Early referral may avoid catheter use
ARV regimen & drug dosing should be
reviewed carefully
Ahuja et al. AJKD 2003
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA Choi et al. CID 2007
Slide #21
HIV & Kidney Transplant
Poor outcomes prior to ART
Promising observational data in the ART era
– USRDS & UNOS, including “paired kidneys”
– Similar outcomes adjusted for age, comorbidity
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Slide #22
HIV & Kidney Transplant
Prospective, multi-center study
– 150 kidney transplant recipients, 2003-2009
Undetectable VL, CD4 > 200, stable ART
– Acceptable graft & patient survival
– No increase in opportunistic infections
5 ADIs
7 non-AIDS cancers
2 biopsy-proven HIVAN
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Stock et al. NEJM 2010
Slide #23
HIV & Kidney Transplant
Prospective, multi-center study
– High incidence of acute rejection
– Drug interactions
PI calcineurin inhibitor levels
NNRTI calcineurin inhibitor levels
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA
Stock et al. NEJM 2010
Slide #24
Kidney Disease in HIV
AKI is common & linked to poor outcomes
Antiretroviral toxicity may be difficult to
distinguish from other causes of AKI or CKD
Comorbid CKD is increasingly prevalent
HIV patients are candidates for HD or PD, and
stable patients may be candidates for kidney
transplant
From CM Wyatt, MD, at 14th Annual Ryan White HIV/AIDS Program Clinical Conference, IAS–USA