Presentation in UNM's HIV focused project ECHO regarding kidney issues in individuals living with HIV.

1. Project ECHO® - UNM
HIV TeleECHO Clinic
Kidney Disease in HIV
February 21st 2023
Division Chief, Nephrology, University of New Mexico HSC
Christos Argyropoulos MD PhD FASN

2. Conflict of Interest Disclosure Statement
Consultant fees: Bayer, Otsuka, Quanta, Integrity CME
Research Support: Astra Zeneca
This presentation was reviewed by UNMHSC and
SCAETC faculty to ensure it meets Continuing
Education guidelines.
This program is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and
Human Services (HHS) as part of an award totaling $3,132,205, with 0% financed with non-governmental sources. The views
expressed do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of
trade names, commercial practices, or organizations imply endorsement by the U.S. Government. Any trade/brand names for
products mentioned during this presentation are for training and identification purposes only.

3. Learning Objectives
1. Describe the spectrum of kidney diseases in patients
living with HIV and antiretroviral therapies
2. Recognize the presence of kidney disease and its
clinicolaboratory manifestations
3. Identify candidates for novel therapies for
management of CKD & renal replacement therapies

4. Spectrum of Kidney Disease in HIV
Acute Kidney Injury
• Risk factors
(nonspecific) similar to
those in the general
population
• Risk factors specific to
the HIV population
Chronic Kidney Disease
• HIV-associated
Nephropathy
• Immune Complex
mediated kidney disease
• Glomerulonephritis due to
HCV coinfection
• Complications of
antiretroviral therapy
• Diabetic/non-diabetic
CKD seen in the general
population
Reference 14 font

5. Acute Kidney Injury in HIV
Diagnosis rests on the
KDIGO staging system
AIDS 29(9):p 1061-1066, June 1, 2015. Kidney Int. 2010 Sep;78(5):478-85
HIV Medicine(2019),20, 77--87)
HIV-dependent factors HIV-independent factors Nephrotoxic drugs
CD4 < 200 cells/μL
Viraemia > 10 000
copies/mL
History of ART
exposure
AIDS-defining illness
Advanced age
Male gender
Black race
Diabetes
CKD
Hypertension
HCV coinfection
Liver disease
Low serum albumin
Low body mass index
Hypomagnesaemia
Clinical severity
systems (e.g.
APACHE) in
hospitalized patients
HIV-related
Nucleoside reverse
transcriptase
inhibitors (abacavir,
tenofovir)
Protease inhibitors
(indinavir, ritonavir,
atazanavir)
Nonnucleoside
reverse transcriptase
inhibitors
(nevirapine)
Non-HIV-related
Antibiotics
Antivirals
Antifungals
NSAIDs
Contrast
Class/stage eGFR/Creatinine Urine Output
Risk/1 ↑ SCr ≥ 26.5 μmol/L
(≥ 0.3 mg/dL) or ↑
SCr ≥ 150–200% (1.5–
2×)
< 0.5 mL/kg/h (> 6 h)
Injury/2 ↑ SCr > 200–300%
(> 2–3X)
< 0.5 mL/kg/h (> 12 h)
Failure/3 ↑ SCr > 300% (> 3×)
or ↑SCr to
≥ 353.6 μmol/L
(≥ 4 mg/dL) or
initiation of renal
replacement therapy
< 0.3 mL/kg/h (24 h)
or anuria (12 h)
AKI outcomes: ↑ OR (2.64) for acute mortality
Persistently ↑ risk over the long term (> 90 days)

6. Chronic Kidney Disease Syndromes: HIVAN
Focal Segmental
Glomerulosclerosis pattern
Requires expression of HIV genes
(Nef/Vpr) in the kidney
Progressive, proteinuric kidney
disease leading to dialysis : very
common in the pre-ART era
APOL1 Risk variant (common in
African Americans) elevates risk of
HIVAN & progressive CKD even in
virologically controlled patients
No specific therapy
Am J Kidney Dis. 68(2):e13-e14.
J Am Soc Nephrol 2017 Nov;28(11):3142-3154.

7. Chronic Kidney Disease: Immune Complex
Kidney Disease
• HIV infection is associated with numerous
glomerulonephritides , e.g. HIV-associated
immune complex kidney disease (HIVICD),
and other glomerulonephritides
• Hepatitis C can be associated with a specific
form of glomerulonephritis (MPGN) usually in
the context of mixed cryoglobulinemia
• Renal biopsy is the only way to differentiate
among the various kidney pathologies
• The development of HIVICD is the result of
the complex interplay between host–
pathogen interactions, genetic susceptibility,
and environmental factors
• Data regarding the optimal treatment
strategy for patients with HIVICD are limited
• Treatment is based on the primary histologic
lesion
https://www.nature.com/articles/nrneph.2015.216

8. Chronic Kidney Disease Syndromes:
Drug considerations
J Am Soc Nephrol 2017 Nov;28(11):3142-3154.
Generic Name
Associated Kidney
Diseases
TDF Proximal tubulopathy
Low molecular weight
proteinuria
AKI
Nephrogenic diabetes
insipidus
CKD
TAF
a
Safer alternative to TDF
Atazanavir Crystalluria
Urolithiasis
Tubulointerstitial
nephritis
CKD
Lopinavir Albuminuria
Low molecular weight
proteinuria
CKD
Not all creatinine elevations are due to
nephrotoxicity !!!

9. Not all tenofovirs are created equal when it
comes to kidney safety
J Am Soc Nephrol 2017 Nov;28(11):3142-3154. AIDS 2019.33(9):p 1455-1465
J Infect Dis 2020 Jul 23;222(4):637-64 AIDS 2020 Dec 1;34(15):2259-2268
• TAF is more kidney friendly version of TDF
• Pooled meta-analysis of registrational
trials show substantially less tubulopathy
and discontinuation rate due to kidney
specific adverse events
• In patients with evidence of kidney
damage (proteinuria) or impaired eGFR
switching may improve both parameters

10. Chronic Kidney Disease in HIV: Diabetes as
an accelerant
J Acquir Immune Defic Syndr 2012 Aug 1;60(4):393-9

11. Screening for CKD in those living
with HIV
General
considerations
PrEP Considerations
eGFR at least x2 annually
Screening for proteinuria:
Urinalysis
Urine protein/creatinine
ratio OR
Urine albumin to creatinine
ration
Refer to nephro for
↓eGFr by 25%, eGFR < 60,
or UACR > 300mg/g
creatinine
Optional for < 30 o w/o
comorbidities
Screen within 3 mo in others
Q 6-12 in those > 50 or
anyone with a ClCr < 90
Kidney International (2018) 93, 545–559 Lancet HIV 2022; 9: e242–53
https://www.who.int/publications/i/item/9789240031593

12. Criteria for kidney biopsy and nephrology referral
in the era of Diabetic Kidney Disease
Kidney International (2018) 93, 545–559
 Atypical presentation of diabetes
with kidney disease (no different than
the general population)
 Absence of retinopathy (T1D)
 Albuminuria developing <5 or >25 the
onset of disease (T1D)
 Immunological markers or active
urinary sediment
 Acute/sudden onset
macroalbuminuria or the nephrotic
syndrome
 Nephritic syndrome
 Hematuria
 Rapid decline in renal function
 Significant reduction in eGFR (>30%)
after initiation Renal Angiotensin
System inhibition
 Acute Kidney Injury
J Clin Med. 2015 May; 4(5): 998–1009
Kidney Biopsy Suggested Algorithm in the KDIGO Guidelines

13. Various forms of kidney pathologies are
found in kidney biopsy studies
Kidney International (2020) 97, 1006–101

14. Various forms of kidney pathologies are
found in kidney biopsy studies
Kidney International (2020) 97, 1006–101
Diabetic Kidney Disease & HIVAN are
the dominant kidney pathologies in
HIV/HCV co-infection

15. https://www.ajkd.org/article/S0272-6386(21)00924-0/fulltext

16. Effects of SGLT2i on diabetic and non
diabetic forms of kidney disease
Lancet 2022;400:1788-1801

17. Treatment Considerations of CKD in the 21st
century: caveats
Reference 14 font
Most clinical studies of therapies in diabetic and non-
diabetic forms of CKD exclude patients with HIV
Even traditional therapies in this space e.g. ACE
inhibitors should be formally considered off label for
patients with HIV
Same concept applies to the current standard of
therapy in CKD (sodium glucose co-transported two
inhibitors, SGLT2i, “flozins”) for diabetic and non
diabetic kidney disease and the non-steroidal
mineralocorticoid antagonists (MRAs, finerenone for
diabetic kidney disease)

18. Dialysis in patients living with HIV
Historically (pre-ART era) dialysis was associated
with very poor outcomes in patients with HIV
In the ART era, dialysis is a valid treatment option
for patients living with HIV
Options driven predominantly by patient
preference, personal values and local availability :
1. In center , thrice weekly hemodialysis
2. Home (peritoneal) dialysis: higher rate of catheter
infections and peritonitis in patients with poorly
controlled HIV
3. Home (hemo) dialysis
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-017-
0466-0

19. Kidney Transplantation is a valid
option for renal replacement therapy
in patients living with HIV
N Engl J Med 2010 Nov 18;363(21):2004-14
Meets Standard Transplant Criteria Plus the
Following
Effective HIV suppression for ≥6 mo before
transplantation
HIV-1 RNA <50 copies per 1 ml
CD4+ cell count >200 cells per 1 mm
3
No active opportunistic infections
No prior history of
Progressive multifocal leukoencephalopathy
Primary central nervous system lymphoma
Pulmonary aspergillosis
Visceral Kaposi sarcoma
Coccidiomycosis
Chronic intestinal cryptosporidiosis >1 mo
Hepatology evaluation for patients coinfected
with hepatitis B or hepatitis C virus

20. Optimization of ART may be required prior
to kidney transplantation
Drug Drug Interactions must be considered before
transplantation
NNRTIs may lead to higher doses of
immunosuppressive medications
Protease inhibitors lead to significantly lower doses
PIs may lead to higher risk of allograft loss and
death compared to non PI regimens
INSTIs and maraviroc are rather “clean” agents from
DDI
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026768
https://www.tandfonline.com/doi/full/10.1080/14656566.2019.161

21. Resources
ASN DKD education
module
https://epc.asn-
online.org/learning_course/manage
ment-of-chronic-kidney-disease-in-
people-with-diabetes/
Educational module about
the holistic management of
(Diabetic) Kidney Disease
HIV and Kidney Disease
https://hivinfo.nih.gov/understanding-
hiv/fact-sheets/hiv-and-kidney-disease.
National Kidney Foundation:
https://www.kidney.org/atoz/conten
t/about-chronic-kidney-disease
HIV and Chronic Kidney Disease:
What You Need to Know | National
Kidney Foundation
Patient facing educational materials
about CKD in the general population
and HIV
IAPAC factsheet about CKD in
HIV
https://www.iapac.org/fact-
sheet/hiv-and-kidney-disease/