kidney disease in HIV-positive patients

1. Moh’d Sharshir, MD
Nephrology Fellow

2.  Patients with HIV are at risk for both acute kidney injury (AKI)
and chronic kidney disease (CKD), secondary to:
 Medication nephrotoxicity.
 HIV-associated nephropathy (HIVAN).
 Immune complex kidney diseases.
 Thrombotic Microangiopathy (less commonly).

4.  Prior to the introduction of combination antiretroviral therapy
(ART), acute kidney injury (AKI) was commonly attributed to
septicemia, or volume depletion.

5.  The incidence of AKI in HIV-positive patients is higher than it is in
patients without HIV.
 The incidence of AKI in patients with HIV has also increased over
time.
Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality, Wyatt CM, Arons RR, 2006;20(4):561

6.  The risk factors for AKI among HIV-positive patients are similar to
risk factors for AKI in the general population:
 Older age.
 Diabetes mellitus.
 Chronic kidney disease (CKD).
 Acute or chronic liver disease.

7.  Risk factors are specific to HIV:
 Receiving ART.
 AIDS-defining illness.
 Co-infection with hepatitis C virus (HCV).
 Low CD4 count.
 High viral load.
Incidence and etiology of acute renal failure among ambulatory HIV-infected patients, Franceschini N, Napravnik S, Kidney Int. 2005;67(4):1526.

8.  As in the general population, the development of AKI increases
the risk of morbidity and mortality in HIV-positive patients
(Inpatient mortality and Long-term mortality).
Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality, Wyatt CM, Arons RR, 2006;20(4):561

9.  The most common types of AKI in patients with HIV infection,
similar to patients without HIV, are prerenal states and acute
tubular necrosis.

10. 1. Prerenal states:
2. Acute tubular necrosis:
3. Crystalluria with obstruction:
4. Interstitial nephritis:
Incidence and etiology of acute renal failure among ambulatory HIV-infected patients, Franceschini N, Kidney Int. 2005;67(4):1526.

11.  Patients with HIV infection are at risk for nephrotoxicity from ART,
as well as from medications used to treat opportunistic infections
or hepatitis virus co-infection.
 Medication nephrotoxicity may present with acute or chronic
kidney injury or with acid-base and electrolyte disturbances.

12.  Some of the more commonly agents include the following:
 Protease inhibitors :
 Indinavir and atazanavir are protease inhibitors that can cause
crystalluria and AKI.

13.  Tenofovir disoproxil fumarate (TDF) –
 Tenofovir is a nucleoside reverse transcriptase inhibitor, can
cause AKI, proximal tubular dysfunction, or both in combination.
According to expert guidelines, TDF should be avoided in patients
with an (eGFR) less than 60 mL/min/1.73 m2, and should be
discontinued in patients who experience a 25 percent or greater
decline to an eGFR less than 60 mL/min/1.73 m2.
The risk of kidney toxicity with TDF has varied across different
studies, with estimates ranging from 2-10 %.
The significance of antiretroviral-associated acute kidney injury in a cohort of ambulatory human immunodeficiency virus-infected patients, Wikman P, Nephrol Dial
Transplant. 2013;28(8):2073.

14.  Other antiviral agents – Acyclovir, foscarnet, and cidofovir are
drugs used to treat herpes simplex virus or cytomegalovirus
infection. Each of these agents can be associated with the
development of AKI.
 Anti-Pneumocystis drugs – Trimethoprim-sulfamethoxazole and,
less commonly, pentamidine are agents used to treat
Pneumocystis infection. Trimethoprim-sulfamethoxazole can
produce interstitial nephritis, while approximately 25 percent of
patients treated with pentamidine develop reversible AKI that is
likely due to nephrotoxic acute tubular necrosis.

15.  In addition, several antiretroviral agents can interfere with the
tubular secretion of creatinine, producing an increase in serum
creatinine (and decline in estimated glomerular filtration rate
[eGFR]) without a true decline in kidney function.
 These include the boosting agent, cobicistat, and the integrase
inhibitor, dolutegravir; the increase in serum creatinine with these
drugs occurs early and is typically in the range of 0.05 to 0.2
mg/dL.

16.  HIV-associated thrombotic microangiopathy can present with
significant AKI.
 Results of a large observational cohort study suggest that
systemic thrombotic microangiopathy is a rare complication of
HIV infection in the ART era.
HIV-associated thrombotic microangiopathy in the era of highly active antiretroviral therapy: an observational study, Becker S, Clin Infect Dis. 2004;39 Suppl 5:S267.

18.  The prevalence and incidence of HIV-related end-stage renal
disease (ESRD) are projected to increase as the prevalence of
HIV infection continues to rise.
Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease, Schwartz EJ, J Am Soc Nephrol. 2005;16(8):2412.

19.  Risk factors for incident or progressive CKD in HIV-positive
adults include hepatitis C virus (HCV) co-infection, low CD4 T cell
count, high HIV viral load, and traditional CKD risk factors such
as diabetes and hypertension.
 Treatment with tenofovir disoproxil fumarate (TDF) and boosted
protease inhibitors has also been associated with GFR decline or
decreased GFR in several studies, while ART in general appears
to slow the rate of renal function decline.

20.  The etiology of CKD in patients with HIV:
 HIV-independent disorders (such as hypertension, diabetes).
 Incomplete recovery from an episode of acute kidney injury.
 HIV-related disorders, including HIVAN.
 HIV immune complex kidney disease (HIVICK).
 In addition, many HIV-positive adults are also at risk for
glomerulonephritis secondary to HCV co-infection.

21.  The classic kidney disease of HIV infection, HIV-associated
nephropathy (HIVAN), was first described in 1984 in patients with
advanced HIV infection.
 HIVAN is a collapsing form of focal segmental glomerulosclerosis
(FSGS) with associated tubular microcysts and interstitial
inflammation.

22.  HIVAN classically presents with significant proteinuria and rapidly
progressive kidney disease in the setting of normal blood
pressure and normal to enlarged kidneys, although the
presentation may be less dramatic in the ART era.
 HIVAN is usually not seen in patients on ART who have a normal
CD4 T cell count and an undetectable HIV viral load.

23. Nearly 40% of HIV-positive patients with proteinuric kidney disease
and suspected HIVAN will have an alternative diagnosis on biopsy.
Renal pathology of human immunodeficiency virus infection, D'Agati V, Appel GB, Semin Nephrol. 1998;18(4):406.

24.  A number of immune complex kidney diseases have been
reported in patients with HIV infection, including:
 Membranous nephropathy.
 Membranoproliferative.
 Mesangial proliferative glomerulonephritis.
"lupus-like" proliferative glomerulonephritis.
 Though rare, IgA nephropathy has also been reported in the
setting of HIV infection.

25.  HCV co-infection has been associated with the development of
acute and chronic kidney disease.
 The classic clinical findings of cryoglobulinemia and
hypocomplementemia may be less common in co-infected
patients.

27.  Expert guidelines that recommend screening and early
identification of CKD in patients with HIV.
 HIV-positive individuals should have their GFR estimated at least
twice yearly and should have either a urinalysis or quantitative
assessment of urine protein excretion at least once yearly in order
to monitor for the development of kidney disease.
 Such patients whose eGFR has declined by 25 percent or more
to a level below 60 mL/min/1.73 m2, or who have protein
excretion greater than 300 mg/day, should be referred for
nephrology evaluation.

28.  Identification of CKD in a patient with HIV should prompt initiation
of ART (if not already started) and tight control of comorbid
diabetes and hypertension (if present).
 Medication doses should be adjusted for the calculated creatinine
clearance, with particular attention to nucleoside and nucleotide
reverse transcriptase inhibitors.

29.  Analyses of data from the US Renal Data System (USRDS) have
demonstrated similar outcomes in HIV-positive ESRD patients
treated with hemodialysis or peritoneal dialysis, as well as
significant improvements in survival in the ART era.