HIV and Kidney Disease. Sean Kelly, MD Assistant Professor of Medicine Vanderbilt Division of Infectious Diseases

HIV and Kidney Disease

Sean Kelly, MD

Assistant Professor of Medicine Vanderbilt Division of Infectious Diseases

Case 1

45-year-old man with a history of hypertension presented to the ED with shortness of breath and chest pain. He was found to have BP 220/95 and serum creatinine of 8.1 mg/dL. Lymphadenopathy was present on exam. HIV screen was positive,

Case 1

What is this man likely experiencing?

A.  Hypertensive nephropathy

B.  HIV Immune Complex Disease

C.  HIV-Associated Nephropathy

D.  Diabetic Nephropathy

What is chronic kidney disease?

•  Persistent (>3 months) abnormalities in kidney

structure or function

▫  Proteinuria/albuminuria

▫  Tubular disorders causing electrolyte

abnormalities

▫  GFR <60 mL/minute/1.73 m2 

Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease Work Group KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease, Kidney Int Suppl, 2013, vol. 3(pg. 1-150)

From: Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Clin Infect Dis. 2014;59(9):e96-e138. doi:10.1093/cid/ciu617

Clin Infect Dis | © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CKD

•  The US prevalence of CKD (any stage) is 14% •  Most have underlying diabetes and/or

cardiovascular disease

•  CKD is associated with higher mortality •  117.9/1,000, vs 47.5/1,000 for those

without CKD

•  Cardiovascular disease accounts for about half of deaths among those with End-Stage Renal Disease (ESRD)

CKD and HIV

•  Occurs 2 to 5-fold higher than among HIV-

•  Prevalence of 5-10% among PLWH in North

America and Europe

A5322

•  A5322 - HAILO: Long-Term Follow-up of Older

HIV-infected Adults: Addressing Issues of Aging, HIV Infection and Inflammation

▫  Ongoing study of 1,035 PLWH (age ≥40 years)

▫  Evaluates the long-term effects of treated HIV on

chronic inflammation and incidence of non-AIDS clinical events among older PLWH

A5322

•  10% had CKD at enrollment

•  Among 936 participants with no CKD at

enrollment, there were 14 incident cases within ~3 years of follow-up

▫  Rate per 100 person-years: 0.48 (CI 95%

Types of Kidney Disease Associated

with HIV

•  Secondary to HIV itself

▫  HIV-Associated Nephropathy

▫  HIV Immune Complex Disease

•  Secondary to other infections/sources of inflammation ▫  HBV/HCV co-infection •  Secondary to medications .

HIV-Associated Nephropathy (HIVAN)

•  The most common cause of kidney disease

among PLWH

•  Usually when CD4 <200 cells/uL

•  Rapid progression to ESRD

•  90% are of African descent

▫  Associations with polymorphisms of APOL1 gene,

which may confer resistance to trypanosomiasis

Wyatt CM. Kidney Disease and HIV Infection. Top Antivir Med. 2017 Feb/Mar;25(1):13-16. Rao TK, et al. N Engl J Med. 1984;310:669-673. 294.

HIV-Associated Nephropathy (HIVAN)

•  Distinct histology

▫  Collapsing form of focal segmental

glomerulosclerosis (FSGS)

•  Pathogenesis

▫  Direct infection of tubular and glomerular

epithelial cells by HIV

•  Treatment:

▫  ART, limited role for adjunctive therapies

(ACE-inhibitors, corticosteroids)

Wyatt CM. Kidney Disease and HIV Infection. Top Antivir Med. 2017 Feb/Mar;25(1):13-16. Rao TK, et al. N Engl J Med. 1984;310:669-673. 294.

HIV Immune Complex Disease

(HIV-ICD)

•  Spectrum of immune-complex deposition

diseases in HIV infection, multiple mechanisms

▫  IgA nephropathy

▫  Membranoproliferative glomerulonephritis

▫  Lupus-like glomerulonephritis

▫  Membranous nephropathy

•  Treatment is not well-characterized (this disease

is not well-characterized)

Nobakht E, et al. HIV-associated immune complex kidney disease. Nat Rev Nephrol. 2016 May;12(5):291-300. doi: 10.1038/nrneph.2015.216. Epub 2016 Jan 19.

HIV-ICD

•  A very common occurrence in HIV

▫  Cause of 25% CKD cases ▫  Associations: –  Older age –  Black race –  Hepatitis C coinfection –  lower CD4 count

Naicker S, Rahmanian S, Kopp JB. HIV and chronic kidney disease. Clinic Nephrol. 2015;83(7 Suppl 1):32-8.

HIV and Kidney Disease

•  HCV co-infection

▫  Associated with progression to CKD, regardless of

HCV viremia level

▫  Spectrum of immune-complex diseases

–  Majority of HIV-ICD patients have HCV co-infection

Mocroft A, et al. Hepatitis B and C coinfection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults. PLoS One. 2012;7 (7):e40245.

Peters L, et al. Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients. AIDS. 2012;26(15):1917-1926.

Lucas G, et al. Hepatitis C co-infection and the risk of chronic kidney disease in HIV+ individuals: Does hepatitis C Viremia matter? [Abstract 718]. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013; Atlanta, Georgia.

HIV and Kidney Disease

•  Acute Kidney Injury

▫  More frequent in PLWH than the general

population

▫  Infections, including AIDS-defining infections and

sepsis, are the leading cause in hospitalized patients

▫  Higher proportion of traditional CKD risk factors

in HIV-infected population

–  Diabetes, hypertension, HCV-coinfection

Franceschini N, et al. Incidence and etiology of acute renal failure among ambulatory HIV infected patients. Kidney Int. 2005;67(4):1526-1531. Wyatt CM. Kidney Disease and HIV Infection. Top Antivir Med. 2017 Feb/Mar;25(1):13-16.

•  Other causes of acute and chronic kidney disease

▫  Chronic obstructive uropathy

–  Indinavir, atazanavir

–  Chemotherapy for lymphoma

▫  Rhabdomyolysis

▫  Thrombotic thrombocytopenic purpura

▫  Medication-related

Case 2

•  57yoM with well-controlled HIV on STRIBILD®

(undetectable, CD4 count 848), chronic hepatitis B, well-controlled diabetes on metformin (most recent Hgb A1c 6.3), hypertension controlled with lisinopril 10mg and amlodipine 5mg (BP 129/85mmHg), also taking aspirin 81 and

atorvastatin 40mg daily. His eGFR is 55, down from 59 six months prior. Which medication would you adjust?

Case 2

A.  Increase lisinopril to 20mg

B.  Switch STRIBILD® to Genvoya®

C.  Switch STRIBILD® to Triumeq®

D.  Add insulin

Case 2

•  STRIBILD®

▫  tenofovir disoproxil fumarate (TDF)

▫  emtricitabine

▫  elvitegravir/c

•  Genvoya®

▫  tenofovir alafenamide (TAF)

▫  emtricitabine ▫  elvitegravir/c •  Triumeq® ▫  abacavir ▫  lamivudine ▫  dolutegravir

Nephrotoxic medications

•  Medication-related

▫  Tenofovir disoproxil fumarate (TDF)

–  Proximal tubule dysfunction – Fanconi Syndome

–  Hypophosphatemia, glycosuria, proteinuria

–  Decreased GFR

–  Likely due to mitochondrial toxicity of proximal tubule

Beatriz Fernandez-Fernandez, et al. Tenofovir Nephrotoxicity: 2011 Update. AIDS Res Treat. 2011; 2011: 354908. Wyatt CM. Kidney Disease and HIV Infection. Top Antivir Med. 2017 Feb/Mar;25(1):13-16.

Nephrotoxic medications

•  Other ART

▫  Cumulative exposure to indinavir, lopinavir,

atazanavir

▫  Atazanavir is associated with recurrent nephrolithiasis

▫  Dolutegravir can increase creatinine without affecting

GFR •  TMP/SMX (Bactrim) •  Pentamidine •  Sulfadiazine •  Amphotericin •  Foscarnet

CKD and cardiovascular disease

•  CKD is an independent risk factor for

cardiovascular events

•  Among US veterans, PLWH with GFR <30 AND

presence of albuminuria had 6-fold higher risk of cardiovascular event compared with PLWH with normal GFR and no albuminuria

Choi AI,  Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons, Circulation, 2010, vol. 121 (pg. 651-8)

Screening for CKD

•  Creatinine/eGFR

▫  At ART initiation or change

▫  Twice annually

•  Urinalysis or measure of urine albumin/protein

▫  When ART is initiated or changed

▫  Annually

•  Renal ultrasound if decline in GFR

Treatment of CKD

•  ART!

•  ACE inhibitors

•  Blood pressure control

▫  <140/90mmHg

▫  <130/80mmHg if moderate-severe albuminuria

•  Optimal diabetes management

•  Cardiovascular disease primary prevention

(aspirin, statin)

Treatment of CKD

•  If HCV co-infection, consider HCV treatment

•  If taking tenofovir disoproxil fumarate (TDF),

consider switch to tenofovir alafenamide or another NRTI backbone

Treatment of ESRD

•  Renal replacement therapy

▫  Hemodialysis

▫  Peritoneal dialysis

▫  Average 5-year survival: 35.8%

•  Kidney transplantation

▫  Average 5-year survival: 85.5%

▫  HIV+ donors to HIV+ recipients is a promising

strategy to increase donor pool, more data are needed to evaluate survival

NIDDK, 2017

Kidney Transplantation

•  1988 – National Organ Transplant Act made it

illegal for PLWH to donate organs

•  2010 – South Africa; Stock et al, demonstrated

equivalent outcomes in HIV+ and HIV- organ recipients

•  2013 – HIV Organ Policy Equity (HOPE) Act passed

with bipartisan support

▫  Allows PLWH to donate organs

•  2016 – the first HIV+ to HIV+ kidney transplants

performed at Johns Hopkins

▫  Benefits not only HIV+ recipients, but all awaiting