INVITED ARTICLE HIV/AIDS

Kenneth H. Mayer, Section Editor

Kidney Disease in Patients with HIV Infection and AIDS

Jonathan Winston,1 Gilbert Deray,5 Trevor Hawkins,2 Lynda Szczech,3 Christina Wyatt,1 and Benjamin Young4
1
Mount Sinai School of Medicine, New York, New York; 2University of New Mexico, Southwest CARE Center, Santa Fe; 3Duke University Medical Center, Durham,
North Carolina; 4Rose Medical Center, Division of General Internal Medicine, University of Colorado at Denver and Health Sciences Center, Denver; and 5Department

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of Nephrology, Pitié–Salpêtrière Hospital, Paris, France

As patients infected with human immunodeficiency virus (HIV) live longer while receiving antiretroviral therapy, kidney
diseases have emerged as significant causes of morbidity and mortality. Black race, older age, hypertension, diabetes, low
CD4+ cell count, and high viral load remain important risk factors for kidney disease in this population. Chronic kidney
disease should be diagnosed in its early stages through routine screening and careful attention to changes in glomerular
filtration rate or creatinine clearance. Hypertension and diabetes must be aggressively treated. Antiretroviral regimens them-
selves have been implicated in acute or chronic kidney disease. The risk of kidney disease associated with the widely used
agent tenofovir continues to be studied, although its incidence in reported clinical trials and observational studies remains
quite low. Future studies about the relationship between black race and kidney disease, as well as strategies for early detection
and intervention of kidney disease, hold promise for meaningful reductions in morbidity and mortality associated with
kidney disease.

HISTORICAL PERSPECTIVE
The first reports of AIDS-related renal failure, published in the
mid-1980s, described cases of what we now recognize as HIV-
associated nephropathy (HIVAN) [1]. Before effective antiviral
therapy became available, HIVAN was so frequent and its clin-
ical features were so dramatic—heavy proteinuria and rapid
progression to end-stage renal disease (ESRD) in immunosup-
pressed black persons—that HIVAN became almost synony-
mous with HIV-associated chronic kidney disease (CKD). As
HIV spread through the black community, the ESRD incidence
increased substantially, and by the early 1990s, HIVAN became
the third leading cause of ESRD in black persons aged 20–64
years [2].
Since that time, the incidence and spectrum of kidney dis-
eases in HIV-infected patients have been altered by the wide-
spread use of HAART. The clinical course of kidney disease is
more indolent, the risk of ESRD has been reduced by 40%–
60%, the 1-year survival rate while undergoing dialysis has
increased from 25% to 75%, and kidney transplantation is a
Received 28 January 2008; accepted 13 August 2008; electronically published 23 October
2008.
Reprints or correspondence: Dr. Jonathan Winston, Mount Sinai School of Medicine, One
Gustave L. Levy Pl., Box 1243, New York, NY 10029 (jonathan.winston@mssm.edu).
Clinical Infectious Diseases 2008; 47:1449–57
 2008 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2008/4711-0014$15.00
DOI: 10.1086/593099
viable option [3–6]. Despite these improvements, risk factors
for kidney disease are highly prevalent among HIV-infected
patients, and kidney disease remains a significant cause of
morbidity and mortality, even among those patients receiving
HAART.
EPIDEMIOLOGY AND RISK FACTORS FOR CKD
IN HIV-INFECTED PATIENTS
CKD is defined as kidney damage or reduced kidney function
that persists for 13 months [7]. A useful indicator of kidney
damage is elevated urinary protein excretion, measured qual-
itatively with use of a urine dipstick or measured quantitatively
with use of a spot urine protein-to-creatinine ratio (or 24-h
urine collection). Kidney function can be reliably estimated
from the serum creatinine by calculating the creatinine clear-
ance or glomerular filtration rate (GFR) through use of the
Cockcroft-Gault or Modification of Diet in Renal Disease
(MDRD) equations, respectively. A GFR !60 mL/min meets
criteria for CKD, a cutoff supported by epidemiologic data
linking lower GFR to an increased frequency of hospitalization,
cardiovascular events, or death. Neither the Cockcroft-Gault
nor the MDRD equations has been specifically validated in the
HIV-infected population. The MDRD equation was derived
from patients with low GFR and therefore can yield variable
results in persons with normal renal function [8]. Nonetheless,
these estimates remain the most highly validated formulas avail-

HIV/AIDS • CID 2008:47 (1 December) • 1449

 Table 1. Antivirals and antibiotics with known nephrotoxicity.
Drug Reported nephrotoxicity
Acyclovir Crystal nephropathy
Adefovir Tubular toxicity
Aminoglycoside ARF
Amphotericin ARF, tubular toxicity
b-Lactams Interstitial nephritis
Cidofovir ARF, tubular toxicity
Foscarnet ARF, tubular toxicity
Gancyclovir ARF (rare)
Pentamidine Hyperkalemia, ARF
Sulfonamide Interstitial nephritis, crystal nephropathy
Trimethoprim Hyperkalemia, increased creatinine level
NOTE. Adapted from Berns and Kasbekar [27]. ARF, acute renal failure; CKD, chronic kidney disease.
able, and both equations are more sensitive than measurement
of serum creatinine alone.
Diabetes mellitus and hypertension are the 2 most frequent
causes of CKD in the general population. They increase the
CKD risk 10-fold and account for 71% of all ESRD cases [3,
9]. Diabetes and hypertension are increasingly common among
persons with HIV infection. The prevalence of diabetes was
14% in the Multicenter AIDS Cohort Study, 4-fold higher than
in seronegative control persons [10], and was associated with
cumulative exposure to nucleoside reverse-transcriptase inhib-
itors but not protease inhibitors (PIs) [11, 12]. Among those
included in the Multicenter AIDS Cohort Study, the prevalence
of hypertension is 3-fold higher than in age- and sex-matched
control persons (34.2% vs. 11.9%; P ! .001), and hypertensive
persons with HIV infection are more likely to have insulin
resistance and metabolic syndrome (64.3% vs. 16.9%; P !
.001) [13]. In a cross-sectional analysis of 129 HIV-infected
patients with CKD, the prevalence of documented hypertension
and the prevalence of diabetes mellitus were 55% and 20%,
respectively [14], which underscores the importance of opti-
mizing blood pressure and achieving glycemic control as a
means of minimizing the impact of CKD concomitant with
HIV infection.
Race is an important risk factor for CKD. Black persons
comprise 10% of the general population in the United States
but account for 130% of patients with ESRD [3]. Young, male
blacks have an 11-fold increased risk of CKD, compared with
their white counterparts [15]. Five new cases of ESRD develop
for every 100 cases of CKD in black persons, whereas only 1
new ESRD case develops for every 100 cases of CKD in whites
[16]. The burden of kidney disease in black persons with HIV
infection, compared with their HIV-infected white counter-
parts, is similarly disproportionate. Among persons with HIV
infection who receive dialysis, 91% are black [3]. Black race
increases the risk of microalbuminuria and proteinuria by at
least 2-fold [17, 18]. In a comparison between blacks and whites
1450 • CID 2008:47 (1 December) • HIV/AIDS
Risk factor(s)
Infusion, volume depletion
CKD
CKD, critical illness
CKD, critical illness, prolonged illness
b-Lactam allergy
CKD
CKD
…
CKD
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Sulfa allergy
CKD, volume depletion
in an analysis of 12 million patients who received care through
the Veterans Administration system, the multivariate hazard
ratio for ESRD in HIV-infected persons was 4.56 (95% CI,
3.44–6.05) [19]. The natural history of CKD is also considerably
more aggressive in HIV-infected blacks than in whites. Among
4259 patients observed in the Johns Hopkins HIV Clinical Co-
hort from 1990 through 2004, the risk for incident CKD was
2-fold higher among blacks (hazard ratio 1.9; 95% CI, 1.2–
2.8). After CKD diagnosis, however, the decrease in GFR was
6-fold more rapid among blacks, which dramatically increased
the likelihood of progression to ESRD (hazard ratio, 17.7; 95%
CI, 2.5–127) [20].
The aging of an HIV-infected population is another impor-
tant pathway by which the incidence of CKD can be expected
to continue to increase. GFR normally decreases with age. The
prevalence of CKD in the elderly population now approaches
50% [21]. Other risk factors for CKD in HIV-infected patients
are high viral load, low CD4+ lymphocyte count, and hepatitis
C virus coinfection [17]. The importance of recognizing CKD
is underscored by the strong correlation between CKD and both
morbidity and mortality. In the HIV Epidemiology Research
Study, proteinuria or an elevated serum creatinine level was
associated with an increased risk of hospitalization and mor-
tality [22, 23]. In the Women’s Interagency HIV Study, elevated
creatinine level and proteinuria were similarly predictive of an
increased risk of an AIDS-defining illness and mortality [24].
Acute renal failure (ARF) in HIV-infected persons. ARF is
highly prevalent among persons with HIV infection and, like
CKD, is linked to morbidity and mortality. Major risk factors
are the same as in the general population, including older age,
preexisting CKD, serious systemic illness or infection, and ex-
posure to nephrotoxic agents [25, 26]. Liver disease and low
CD4+ cell count also increase the risk of ARF among HIV-
infected persons. Table 1 lists antivirals and antibiotics with
nephrotoxic potential that are commonly used in treatment of
HIV-infected patients.
 Ten percent of patients in a large ambulatory clinic experi-
enced at least 1 episode of ARF over a 2-year period [25]. More
than one-half of these episodes were attributed to underlying
infections, 76% of which were AIDS-defining illnesses, and
almost three-quarters of them necessitated hospitalization.
Drug-related complications accounted for nearly one-third of
cases—the conventional nephrotoxin amphotericin was most
common—and liver disease accounted for 10% of cases. In an
analysis of administrative data from 12 million hospital dis-
charges in New York State, HIV infection was associated with
a 2.8-fold increase in documented ARF cases [26]. In-hospital
mortality was increased nearly 6-fold among HIV-infected pa-
tients with documented ARF.
IMPACT OF ANTIRETROVIRAL THERAPY (ART)
ON RENAL FUNCTION
Proper selection and dose-adjustment of antiretrovirals and
other commonly used drugs for patients with kidney disease
are important components of care for patients with HIV in-
fection. Tables 2 and 3 summarize the nephrotoxic potential
of antiretroviral agents and their recommended dose adjust-
ments for those with kidney disease. Isolated case reports of
nephrotoxicity have been reported with almost all agents, but
renal disease has been associated with indinavir and tenofovir
more often than with other drugs [27, 28].
Indinavir causes nephrolithiasis and chronic interstitial ne-
phritis in as many as 12% of patients who receive it. The
mainstay of prevention of this condition is adequate hydration,
with intake of at least 1.5 L of noncaffeinated fluid. One report
described 4 cases of renal colic and nephrolithiasis in patients
who received lopinavir-ritonavir treatment, but a causal effect
was not established [29]. Three cases of kidney stones con-
taining atazanavir have been reported, and a review of the US
Table 2. Antiretrovirals shown to be potentially nephrotoxic.
Drug Reported nephrotoxicity
Abacavir Acute renal failure, interstitial nephritis (rare)
Atazanavir Case reports of nephrolithiasis, interstitial
nephritis, reversible renal failure
Didanosine Tubular dysfunction (rare)
Efavirenz Single report of hypersensitivity reaction
Enfuvirtide Single report of glomerulonephritis
Indinavir Nephrolithiasis, crystalluria, dysuria, papil-
lary necrosis, acute renal failure
Lamivudine Tubular dysfunction (rare)
Ritonavir Reversible renal failure, but nephrotoxicity
not definitely established
Stavudine Tubular dysfunction (rare)
Tenofovir Tubular toxicity, Fanconi syndrome (rare),
decreased glomerular filtration rate
Food and Drug Administration adverse event reporting system
detected 12 additional confirmed cases [30–33]. Most cases
required hospitalization for pain relief and stent insertion, per-
cutaneous nephrostomy, lithotripsy, or endoscopic surgical ex-
traction. Predisposing factors are unknown, and the drug was
discontinued in most but not all cases.
The association of tenofovir with kidney disease has been an
area of interest since the drug underwent preclinical testing,
because of its structural similarity to adefovir and cidovir. These
acyclic nucleotide analogues are excreted by renal tubule cell
uptake and secretion [34]. Cidofovir at therapeutic doses can
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cause ARF, and a high incidence of ARF was noted when ad-
efovir was tested for treatment of HIV-1 infection at dosages
of 120 mg per day, which is 10-fold higher than the dosage for
treating hepatitis B virus infection. Both agents induce proximal
renal tubule cell damage, clinically characterized by phospha-
turia, a modest amount of proteinuria (“tubule” proteinuria),
and increases in serum creatinine [35, 36]. Consequently, con-
siderable attention has been paid to the incidence of ARF or
long-term reductions in GFR that are induced by tenofovir,
with use of data from phase II, III, and IV clinical trials; ex-
panded access programs before drug approval; and observa-
tional cohort studies. Case reports of tenofovir-induced ARF
do exist, sometimes associated with proteinuria, hypohospha-
temia, euglycemic glycosuria, hypouricemia, hypokalemia, or
metabolic acidosis. This is known as Fanconi syndrome when
most or all components are present.
In fact, tenofovir-associated renal dysfunction is a rare event
in prospective clinical trials, particularly among ART-naive pa-
tients. No significant change in GFR was demonstrated in a
comparison of tenofovir versus stavudine in combination with
lamivudine-efavirenz [37] or in a comparison of tenofovir-
emtricitabine versus fixed-dose zidovudine-lamivudine with
Risk factor(s)
…
Not established
…
…
…
Concomitant treatment with low-dose ritonavir; for nephrolithiasis, urine
pH 16, low lean body mass, treatment with trimethoprim-sulfamethoxa-
zole or acyclovir, chronic infection with hepatitis B or hepatitis C virus,
warm environmental temperature, high indinavir concentration
…
Concomitant treatment with nephrotoxic drugs, underlying renal pathology
…
Low body weight, impaired baseline renal function, concomitant treat-
ment with potentially nephrotoxic drugs
HIV/AIDS • CID 2008:47 (1 December) • 1451
Table 3. Nucleoside or nucleotide dosage adjustment for HIV-infected patients with reduced glomerular filtration rate.

Antiretrovirals Daily dosage Dosing in the case of renal insufficiency

Nucleoside reverse-transcriptase inhibitor

Abacavir 300 mg PO BID No need for dosage adjustment
Didanosine If 160 kg, 400 mg PO QD; if !60 kg, 250 mg QD For CrCl of 30–59 mL/min, 200 mg for weight 160 kg and 125 mg for weight !60 kg
For CrCl of 10–29 mL/min, 125 mg for weight 160 kg and 100 mg for weight !60 kg
For CrCl of !10 mL/min, 125 mg for weight 160 kg and 75 mg for weight !60 kg
For patients undergoing CAPD or HD, use same dose as for CrCl !10 mL/min
Emtricitabine 200 mg Oral capsule PO QD or 240 mg (24 mL) oral solution PO QD For CrCl of 30–49 mL/min, capsule of 200 mg every 48 h or solution of 120 mg every 24 h
For CrCl of 15–29 mL/min, capsule of 200 mg every 72 h or solution of 80 mg every 24 h
For CrCl of !15 mL/min, capsule of 200 mg every 96 h orsolution of 60 mg every 24 h or HD*
Lamivudine 300 mg PO QD or 150 mg PO BID For CrCl of 30–49 mL/min, 150 mg QD
For CrCl of 15–29 mL/min, 150 mg 1 time, then 100 mg QD
For CrCl of 5–14 mL/min, 150 mg 1 time, then 50 mg QD
For CrCl of !5 mL/min, 50 mg 1 time, then 25 mg QD or HD*

Stavudine If 160 kg, 40 mg PO BID; if !60 kg, 30 mg PO BID For CrCl of 26–50 mL/min, 20 mg every 12 h for weight 160 kg and 15 mg every 12 h for weight !60 kg
For CrCl of 10–25 mL/min, 20 mg every 24 h for weight 160 kg and 15 mg every 24 h or HD*
Tenofovir 300 mg PO QD For CrCl of 30–49 mL/min, 300 mg every 48 h
For CrCl of 10–29 kg, 300 mg twice weekly
for ESRD, 300 mg every 7 days or HD*
Tenofovir plus emtricitabine 1 Tablet PO QD For CrCl of 30–49 mL/min, tablet every 48 h
For CrCl !30 kg, not recommended
Zidovudine 300 mg PO BID For “severe” renal impairment or HD*, 100 mg TID or 300 mg QD
Nonnucleoside reverse-transcriptase inhibitor
Delavirdine 400 mg PO TID No dosage adjustment necessary
Efavirenz 600 mg PO QD, 1 tablet PO QD No dosage adjustment necessary; Atripla not recommended if CrCl !50 mL/min
Efavirenz-tenofovir-emtricitabine 600 mg PO QD, 1 tablet PO QD Atripla not recommended if CrCl !50 mL/min
Nevirapine 200 mg PO BID No dosage adjustment necessary
Protease inhibitor
Atazanavir 400 mg PO QD No dosage adjustment necessary for patients not requiring HD
Darunavir 600 mg Plus 100 mg ritonavir PO BID No dosage adjustment necessary
Fosamprenavir 1400 mg PO BID No dosage adjustment necessary
Indinavir 800 mg PO every 8 h No dosage adjustment necessary
Lopinavir-ritonavir 400–100 mg PO BID or 800–200 mg PO QD (QD for treatment-naive patients only) No dosage adjustment necessary
Nelfinavir 1250 mg PO BID No dosage adjustment necessary
Ritonavir 600 mg PO BID No dosage adjustment necessary
Saquinavir soft gel cap 1200 mg TID No dosage adjustment necessary
Tipranavir 500 mg PO BID; with ritonavir, 200 mg PO BID No dosage adjustment necessary
Entry inhibitor
Enfuvirtide 90 mg Subcutaneously every 12 h No dosage adjustment necessary
Maraviroc The recommended dose differs on the basis of concomitant medications No dosage recommendation; use with caution; patients with CrCL !50 mL/min should receive
because of drug interactions: 150 mg, 300 mg, or 600 mg BID maraviroc and CYP3A inhibitor only if potential benefit outweighs the risk
Integrase inhibitor
Raltegravir 400 mg BID QD No dosage adjustment

NOTE. Adapted from US Department of Health and Human Services guidelines for the use of antiretroviral agents in HIV-1–infected adults and adolescents [61]. Atripla, efavirenz-emtricitabine-tenofovir;
BID, twice per day; CAPD, continuous ambulatory peritoneal dialysis; CrCL, creatinine clearance level; ESRD, end-stage renal disease; HD, hemodialysis; HD*, dose after HD; PO, orally; QD, every day; TID, 3
times per day.

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efavirenz in ART-naive patients during 144 weeks of treatment
[38]. Adverse renal events did not develop in a subgroup anal-
ysis of blacks in these 2 trials [39]. In the Development of
Antiviral Therapy trial, which exclusively comprised patients
from Uganda and Zimbabwe, 2469 (74%) of the 3316 enrolled
patients received first-line ART with tenofovir and zidovudine-
lamivudine. The overall incidence of severe reduction in GFR
was low (1.6%), and no difference in renal safety endpoints
was detected between the regimens [40].
Decreases in GFR in tenofovir-treated patients have been
reported. In the Johns Hopkins Cohort, GFR decreased to a
greater extent in tenofovir-treated patients than in non–ten-
fovir-treated patients (19 vs. 11 mL/min), an effect restricted
to treatment-experienced patients [41]. Treatment-experienced
patients could be more sensitive to adverse effects of tenofovir,
more likely to experience adverse drug interactions, or more
likely to develop kidney disease because of advanced HIV dis-
ease and its attendant comorbidities. The HIV Outpatient Study
compared the renal outcomes of 593 tenofovir-treated subjects
and 521 HAART-treated subjects who did not receive tenofovir.
Tenofovir was associated with a small but statistically significant
decrease in GFR, but only 1.1% of tenofovir-treated patients
discontinued the drug because of adverse renal events [42].
Area under the curve for tenofovir is increased when it is
combined with ritonavir-boosted PIs. One explanation has been
that boosted PIs increase tenofovir’s nephrotoxic potential by
competing for the same renal transporters, thus impairing its
tubule secretion, but recent studies do not support such a
mechanism [43]. In 1 study involving ∼140 subjects, a teno-
fovir-boosted PI regimen was associated with a 7–10 mL/min
greater decrease in GFR over 48 weeks, compared with a te-
nofovir–nonnucleoside reverse-transcriptase inhibitor or non–
tenofovir-containing regimen [44]. A higher proportion of te-
nofovir-treated patients in that report were treatment experi-
enced, which perhaps contributed to those observations. In
another study, 53 patients treated with tenofovir and boosted
atazanavir after multiple prior treatment failures experienced
a 7.8 mL/min decrease in GFR over 48 weeks [45], but control
individuals were not studied. In an observational study of 445
tenofovir-treated patients observed for a mean of 13 months,
GFR decreased a mean of 7 mL/min, and 2% of patients ex-
perienced a decrease in GFR to !60 mL/min. Concurrent use
of didanosine or amprenavir increased the risk of a decrease
in GFR [46]. Again, the change in GFR in non–tenofovir-con-
taining regimens was not reported.
Several reports support the renal safety of tenofovir-boosted
PI regimens. When tenofovir was coadministered with either
atazanavir-ritonavir or lopinavir-ritonavir in heavily treatment-
experienced patients, the rate of drug discontinuation attrib-
utable to renal disease was 1.3% [47]. A similar rate of drug
discontinuation (1%–2%) was observed when lopinavir (800
mg) plus ritonavir (200 mg) once per day was compared with
400 mg/100 mg twice per day and when fosamprenavir-rito-
navir was compared with atazanavir-ritonavir, all in combi-
nation with tenofovir-emtricitabine [48, 49]. In the CASTLE
Study—which compared atazanavir-ritonavir at 300 mg/100
mg once per day with lopinavir-ritonavir at 400 mg/100 mg
twice per day, both with fixed-dose tenofovir-emtricitabine—
the rate of adverse event–related drug discontinuations was low
(2% and 3%, respectively) [50]. The impact of a potential in-
teraction between boosted PIs and tenofovir was specifically
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analyzed in the HIV Outpatient Study cohort by comparing
renal function in 300 tenofovir-treated patients who received
either nonnucleoside reverse-transcriptase inhibitors or boosted
PIs (atazanavir or lopinavir). The 12-month intrapatient change
in rate of creatinine clearance was not different between groups
[51].
Data on the safety of tenofovir among patients with CKD
is very limited. A small historical case series of 13 persons
with CKD (median creatinine level, 1.7 mg/dL; median cre-
atinine clearance, 56 mL/min; median GFR, 49 mL/min/1.73
m2) who received tenofovir for a median of 13 months showed
a confirmed increase in National Kidney Foundation stage in
2 persons [52]. Eleven of 13 patients received an inappropriately
high daily dosage of tenofovir, but limited median 12-month
changes in creatinine clearance level or GFR were observed
(+2.9 mL/min and +3.7 mL/min/1.73m2, respectively). Several
patients had significant improvement in measured renal
function.
All of these data show low absolute rates of drug discontin-
uation caused by renal dysfunction (0%–2%) or no differences
in severe renal adverse events when tenofovir-containing reg-
imens are compared with regimens not containing tenofovir
[53–55]. GFR can decrease 7–10 mL/min over the course of 1
year in tenofovir-treated patients, but in most studies, the in-
crease in serum creatinine level was too small to be identified
as clinically significant (∼0.05 mg/dL), GFR remained in the
normal range, and the rate of drug discontinuation was not
greater for patients who received tenofovir. If the decrease in
GFR were to continue for many years, it would have serious
clinical implications, but no such trend has been reported.
These data underscore the importance of carefully screening
patients for preexisting renal disease, of following recommen-
dations for appropriate dosage adjustments in patients with
renal impairment, and of closely monitoring patients for
changes in renal function. From the renal safety perspective, it
would be prudent to seek an alternative and equally effective
agent for patients who initiate ART with impaired kidney func-
tion (GFR, !60 mL/min), although other safety issues must
also be considered.
HIV/AIDS • CID 2008:47 (1 December) • 1453
TREATING HIV-INFECTED PATIENTS WITH CKD
Kidney function should be assessed according to existing In-
fectious Diseases Society of America guidelines [28]. All patients
should have a screening urinalysis and a calculated estimate of
GFR. Those at high risk for kidney disease (i.e., those with
black race, CD4+ count !200 cells/mm3, HIV RNA levels 14000
copies/mL, diabetes, hypertension, or coinfection) should be
screened annually to detect subtle changes over time. The stan-
dard urinary dipstick is a sufficient screen for proteinuria, but
diabetic patients must be tested for microalbuminuria, defined
as urinary albumin excretion of 30–300 mg/mg creatinine, a
range not detected using conventional dipsticks [56]. Microal-
buminuria in diabetic patients predicts subsequent decreases
in GFR, and treatment with angiotensin-converting enzyme
inhibitors or angiotensin-receptor blockers is indicated [57].
Microalbuminuria in nondiabetic patients has been linked to
future cardiovascular events [58], a risk that may be modified
by angiotensin-converting enzyme inhibitors or angiotensin-
receptor blockers [59]. Several issues warrant further study
when considering routine testing for microalbuminuria in non-
diabetic patients with HIV infection: the reproducibility of the
measurements, their proper timing (before or after initiation
of ART), and proven benefits of long-term treatment with an-
giotensin-converting enzyme inhibitors or receptor blockers.
The general approach to diagnosing the cause of kidney dis-
ease is to seek reversible causes. Information obtained through
the patient history and physical examination should be sup-
plemented by a urinalysis to quantify protein excretion and to
test for urinary cells and casts, as well as a renal sonogram to
assess kidney size and structure. Additional testing should be
individualized (figure 1). A kidney biopsy should be strongly
Figure 1. A simplified algorithm for diagnosing and treating chronic kidney disease (CKD)
1454 • CID 2008:47 (1 December) • HIV/AIDS
considered for patients with unexplained kidney disease, es-
pecially those with heavy proteinuria or reduced GFR, because
they are at the greatest risk of ESRD. It is difficult to predict
which disease may be affecting the kidneys on clinical grounds
alone, although in 1 center, HIVAN was considerably more
common when viral load was 1400 copies/mL, whereas diseases
such as hypertension, diabetes, or classic focal segmental glom-
erulosclerosis were more common when viral load was !400
copies/mL [60]. A special circumstance for a kidney biopsy
exists when seeking the diagnosis of HIVAN in a HAART-naive
patient with kidney disease, particularly when ART would not
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otherwise be warranted because of a CD4+ T cell count 1350
cells/mm3. Ongoing viral replication is directly responsible for
the renal disease in HIVAN, and ART is recommended, irre-
spective of CD4+ T cell count, because it preserves kidney func-
tion and improves survival [5, 61, 62].
For most patients, the most effective approach to CKD treat-
ment is effective medical management of diabetes and hyper-
tension. Blood pressure should be monitored at each office visit,
and antihypertensive treatment should be targeted to a blood
pressure !130/80 mm Hg [63]. Angiotensin-converting enzyme
inhibitors or angiotensin-receptor blockers are the drugs of first
choice, because they reduce urinary protein excretion [57] and
slow the progression to ESRD (figure 2). Beta-blockers or non-
dihydropyridine calcium channel blockers are alternatives, but
their metabolism can be blocked by PIs. Most patients with
hypertension and diabetes will require at least 2 antihyperten-
sive medications to achieve optimal control of blood pressure
[64].
Glycemic control is critically important in delaying the pro-
gression of diabetic nephropathy. The American Diabetes As-

Figure 2. Relationship between achieved blood pressure controls and
decreases in glomerular filtration rate (GFR) in clinical trials of diabetic
and nondiabetic renal disease. HTN, hypertension; MAP, mean arterial
blood pressure. Reprinted from Bakris et al. [64] with permission.
sociation recommends that adults with diabetes strive to main-
tain a glycated hemoglobin A1C level of !7.0%, preprandial
plasma glucose level of 90–130 mg/dL (5.0–7.2 mmol/L), and
peak postprandial plasma glucose level of !180 mg/dL (!10.0
mmol/L). Components of a successful glycemic control plan
include blood glucose self-monitoring, hemoglobin A1C testing
at least 2 times each year for patients who meet treatment goals
and quarterly for patients who have not met their goals, and
individualized medical nutrition therapy.
Kidney disease tends to be asymptomatic and is usually not
the primary focus of a visit to an HIV clinic [28]. The presence
of kidney disease should be anticipated, and screening and
proper interpretation of the relationship between serum cre-
atinine level and GFR are recommended. Just as optimal control
of HIV replication is achievable for most patients, so too is
control of hypertension and diabetes. The future holds enor-
mous opportunities for research in new markers for early de-
tection of kidney disease, prevention strategies, novel thera-
peutics, and a better understanding of the interaction between
black race and kidney disease.
Acknowledgments
We acknowledge Healthmatters Communications for receiving payments
from the commercial supporter for research and editorial assistance.
Financial support. This article is derived from a content-development
meeting, Renal Considerations in HIV Management (2007). An indepen-
dent educational grant for this program, including a Continuing Medical
Education–certified Web cast, was provided by Gilead Sciences Medical
Affairs.
Potential conflicts of interest. J.W. has received consulting and lecture
fees from Gilead Sciences. T.H. has received consulting and/or speaker fees
from Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Sciences,
Merck, Monogram Bioscience, Pfizer, and Tibotech. L.S. has received con-
sulting fees from Ortho Biotech Clinical Affairs, Nabi Pharmaceuticals,
Gilead, Fresenius Medical Care, Kureha, Affymax, and Acologix; lecture
fees from Nabi Biopharmaceuticals, Fresenius Medical Care, Glaxo-
SmithKline, Gilead, Genzyme, Abbott, Amgen, and Ortho Biotech; and
grant support from Ortho Biotech Clinical Affairs, GlaxoSmithKline, Pfizer,
and Genzyme. C.W. has received grant support from the Gilead Foundation
and lecture fees from Gilead Sciences and Roche. B.Y. has been a consultant
to Bristol-Myers Squibb, Cerner Corporation, Gilead Sciences, Glaxo-
SmithKline, Hoffman-LaRoche, Merck, Monogram Bioscience, Pfizer, and
Vertex Pharmaceuticals; has served on the speakers’ bureau for Glaxo-
SmithKline, Merck, and Monogram Bioscience; and has received grant and/
or research funding from Bristol-Myers Squibb, Cerner, Gilead Sciences,
GlaxoSmithKline, Hoffman-LaRoche, and Merck. G.D.; no conflicts.
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