HIV and Renal Health
Dr. Patrice Junod
Clinique médicale l’Actuel
This activity is supported by
an educational grant from:
Program Development
Principle Content Development
Anita Rachlis
Ali Zahirieh
David Fletcher
Content Contributors
Gord Arbess
Brian Conway
Marianne Harris
Patrice Junod
Graham Smith
Alice Tseng
Consultant
Linda Robinson
Jean-Guy Baril
Chris Fraser
Christine Hughes
Marek Smieja
Rachel Therrien
Sharon Walmsley
Mélanie Hamel
Conflict of Interest Declaration
This program was developed with consultants through an
educational grant from Janssen Inc. The faculty members
received financial compensation for developing &
presenting this program.
Faculty Disclosures
•
•
•
•
•
Abbvie
Gilead
Janssen
Merck
ViiV
Objectives
• Discuss factors that can impact renal health in HIV patients
• List which renal lab tests are the most clinically relevant and how
often they should be performed
• Present a practical tool for the management of declining renal
function
• Apply these learnings using interactive patient case examples
Background: HIV and the Kydney
Renal Disease in HIV Positive Patients
• Kidney disease is an important complication of HIV infection in
the era of antiretroviral therapy1
• In a retrospective study of 487 consecutive HIV positive patients
with normal renal function, the initial prevalence of CKD was 2%2
– After 5 years of follow-up, 6% had progressed to CKD
– Older age was a multivariate predictor of CKD for this cohort
1
2
Gupta SK, et al. Clinical Infectious Disease 2005;40:1559-1585.
Gupta SK, et al. Clinical Nephrology 2004;61:1-6.
Kidney Disease in HIV Positive Patients
• The spectrum of kidney disease in HIV includes:
– HIV-associated nephropathy
– Immune complex kidney disease
– Medication nephrotoxicity
– Kidney disease related to co-morbid conditions
• Diabetes, hypertension, and hepatitis virus co-infection
Wyatt CM. AJM 2007;120:488-49.
Risk Factors for Kidney Disease in the
HIV Positive Population
Ethnicity
Family
History
Age
HIV
= Modifiable
= Nonmodifiable
CKD
Risk
Nephrotoxic
medication
Hypertension
Diabetes
Hepatitis C
Gupta SK, et al. Clinical Infectious Disease 2005;40:1559-1585.
Chronic Kidney Disease in HIV
• Prevalence 3-15%
• Race and other genetic factors
• Hypertension
• Diabetes mellitus
• Hepatitis C virus infection
• Decreased CD4 cell count
• Increased viral load
• Nephrotoxic Drugs
Medications and Renal Disease
Prerenal
ACE-I
ARBs
Direct Renin
Inhibitors
Amphotericin
NSAIDS
Cyclosporine
Diuretics
Interferon
Tubular Injury
Cidofovir
Adefovir
Tenofovir
Didanosine
Lamivudine
Stavudine
Aminoglycosides
Amphotericin
Cocaine
Foscarnet
Pentamidine
Ketamin
Allergic
Interstitial
Nephritis
Abacavir
Indinavir
Ritonavir
Atazanavir
Acyclovir
Cephalosporins
Penicillins
Ciprofloxacin
TMP/SMX
Rifampin
NSAIDs
Proton Pump
Inhibitors
Thrombotic
Microangiopathy
Indinavir
Cocaine
Cyclosporine
Valacyclovir
TMP/SMX: trimethoprim and sulfamethoxazole
Adapted from: Guo X, Nzerue C. Cleve Clin J Med 2002;69:289-312.
Obstructive
Indinavir
Atazanavir
Acyclovir
Foscarnet
Sulfadiazine
TMP/SMX
HIV & The Kidney: Summary
• Acute Kidney Injury (AKI) is more common in
individuals with HIV infection
• Chronic Kidney Disease (CKD) is more common in
individuals with HIV infection
• Proteinuria is more common in individuals with HIV
infection
• Proximal tubular dysfunction is more common in
individuals with HIV infection
Classification of CKD
Stage
Description
GFR
(mL/min/1.73m2)
I
Urinary and/or Structural
Abnormality
> 89
II
Urinary and/or Structural
Abnormality
60 - 89
IIIa
Mild GFR decline
45 - 59
IIIb
Moderate GFR decline
30 - 44
IV
Severe GFR decline
15 - 29
V
Kidney Failure
< 15
ESRD
Requiring Renal Replacement
Therapy
Levey A. KI 2010;80: 17.
Three Important Measures
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
Three Important Measures
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
How Do We Measure GFR?
• Gold standard:
– inulin clearance
– iothalamate clearance
– Iohexol
• “Practical”
– serum creatinine
– 24-hr urine collection for creatinine clearance (cumbersome!)
– equations, equations, equations
Renal Function Measurement
• Serum creatinine
– Metabolism of creatine in skeletal muscle and from dietary meat
intake
– Production tied to muscle mass
• Age, weight, sex, amputations, corticosteroid use
– Modestly influenced by diet
– Filtered by glomerulus and secreted by proximal tubule
• Proportionally increased secretion with reduced GFR
– Creatinine may not increase until up to 50% of GFR is lost
• Secretion inhibited by drugs including cimetidine, trimethoprim,
dapsone, cobicistat
– Large intra-person and intra-laboratory variation
• Intra-person variation 7−20%
• Poor intra-laboratory calibration particularly affecting higher GFRs
Krop JS, et al. Arch Intern Med 1999;159:1777-1783.
Coresh J, et al. Am J Kidney Dis 2002;39:920-929.
Serum Creatinine 110 μmol/L
Serum Creatinine 110 μmol/L
40 ml/min
140 ml/min
The same serum creatinine represents very different
GFRs in these two individuals
Cockcroft-Gault Equation
CrCl = weight x (140 – age) / (serum Cr x 49)*
•Estimates CrCl (not GFR)
•Derived from a study of 249 white Canadian hospitalized veterans
who had 2 similar 24-hr urine CrCl measurements
•Validated for renal dosing of drugs
* X 0.8 if female
MDRD Equation
•
MDRD GFR (mL/min/1.73m2) = 175 x [serum
creatinine(µmol/L)/88.4]-1.154 x (Age) -0.203 x (0.742 if female) x (1.21
if African American)
•
Estimates Glomerular Filtration Rate
•
Derived from 1070 individuals with advanced chronic kidney
disease
•
60% male, 88% white, 6% DM
CKD-EPI
• Newest Equation of the three
• Non-linear based equation
• More accurate in estimating GFR in those with mild CKD
Levey et al. Ann Intern Med 2009;150: 604-612.
Three Important Measures
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
Quantifying Proteinuria
• Normal
– < 150 mg/day of proteinuria
– < 30 mg/day of albuminuria
• Quantification strategies:
– Dipstick
• Measure ONLY albumin at a CONCENTRATION > 300 mg/L
– 24-hr urine collection
• Helpful if patient performs a ‘complete’ collection
– Spot urine albumin:creatinine (or protein:creatinine)
• Can increase sensitivity for detecting proteinuria in a convenient
fashion
Practical Point
• A typical man produces roughly
15 mmol of creatinine/day
• A typical woman produces roughly
10 mmol of creatinine/day
• The protein:creatinine (PCR) or albumin:creatinine (ACR) tell
you how much protein/albumin is present in the urine per mmol
of Cr
• Thus multiplying the ACR by 10 in woman and by 15 in men will
give you an estimate of that individual’s 24hr excretion of
albumin (the exact same applies to PCR)
Implications of Proteinuria
• A marker of increased risk of CV events
• Increased risk of CKD progression
– (notably when > 1g/day protein or 200mg/day albumin)
Three Important Measures
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
Tubular Functions
• “Reabsorption”
– Water
– Electrolytes
– Bicarbonate
– Glucose
– Filtered proteins
• Secretion
– Organic Anions/Cations
– Drugs
– Metabolic Byproducts
• Creatinine
Ernst M, Moser M. N Engl J Med 2009;361:2153-2164.
Proximal Tubular
Function
• Protein Reabsorption
• Phosphate Reabsorption
• Glucose Reabsorption
• Amino Acid Reabsorption
• Creatinine Secretion
• Bicarbonate
“reabsorption”
Ernst M, Moser M. N Engl J Med 2009;361:2153-2164.
“What Are You Looking For?”
• Some Evidence of Proximal Tubular Injury
– Urine:
• glucosuria in absence of diabetes
• Non-albumin based proteinuria
– measure both albuminuria & proteinuria
– high urinary β2-microglobulin excretion
• Evidence of ATN (hemegranular casts)
– Serum:
• non-anion gap metabolic acidosis, creatinine rise
• Hypophosphatemia & high urinary phosphate excretion
– Calculate the Fractional Excretion of Phosphate*
– (Urinary PO4/Ur Cr) / (Serum PO4/Serum Cr)
– Abnomal = greater than 10% in setting of hypophosphatemia
Increased risk of abnormal proximal renal
tubular function with HIV infection and
antiretroviral therapy
• Aquitaine Cohort
• 399 patients in a cross sectional analysis
• Overall prevalence of PRTD was high at 6.5 %
• 29.6 % stage 1 or 2 kidney disease
• 5.3 % stage 3 to 5 kidney disease
F-A Dauchy et al. Kidney International 2011;80:302-309.
Increased risk of abnormal proximal renal
tubular function with HIV infection and
antiretroviral therapy
• Multivariate Analysis showed significant independent
associations
• Age (OR 1.28 per 5 year increase)
• TDF (OR 1.23 per year)
• ATZ (OR 1.28)
• Primary tubular abnormalities can be missed even when severe
and can lead to decline in GFR
• Early screening is necessary to avoid them
F-A Dauchy et al. Kidney International 2011;80:302-309.
Guidelines
IDSA Guidelines:
Evaluating and Monitoring CKD in HIV
• All patients at the time of HIV diagnosis should be assessed for existing
kidney disease
– Calculated estimate of renal function and
– Screening for proteinuria
• Dipstick, protein/creat ratio or albumin/creat ratio?
• If there is no evidence of kidney disease at initial evaluation, patients at
high risk for the development of proteinuric renal disease should
undergo annual screening
– African American persons
– CD4+ cell counts <200 mL or HIV RNA levels >4000 copies/mL
– Diabetes mellitus
– Hypertension
– Hepatitis C virus coinfection
• Patients without risk factors for kidney disease should be followed
clinically and reassessed based on the occurrence of signs and
symptoms or as clinical events dictate
Gupta SK et al. Clin Infect Dis 2005;40:1559-1585.
IDSA Initial Evaluation Recommendations
• Obtain baseline GFR:
– All patients at the time of HIV diagnosis should be assessed for
existing kidney disease with a screening urinalysis for proteinuria
and a calculated estimate of renal function
• Annual screening:
– If there is no evidence of proteinuria at initial evaluation, patients
at high risk for the development of proteinuric renal disease should
undergo annual screening
– Renal function should be estimated on a yearly basis to assess for
changes over time
• When to consider a nephrology consult:
– Additional evaluations and referral to a nephrologist are
recommended for patients with proteinuria of grade ≥1+ by
dipstick analysis or GFR<60 mL/min per 1.73m2
Gupta SK, et al. Clinical Infectious Disease 2005;40:1559-1585.
DHHS Recommendations
Table 3. Laboratory Monitoring Schedule for Patients Before and After Initiation of Antiretroviral Therapy
Entry info
care
Follow-up
before ART
ART
Initiation or
modification
Follow-up 2-8
weeks postART
initiation or
modification
Every 3-6
months
ALT, AST, T
bilirubin


Every 6-12
months




CBC with
differential


Every 3-6
months


If on ZDV


Fasting lipid
profile


If normal
annually


Consider 4-8
weeks after
starting new
ART regimen
that affects
lipids
Fasting
glucose or
hemoglobin
A1C


If normal
annually

Urinalysis

Pregnancy
test


If startting
EFV
Every 6
months

If abnormal at
last
measurement

If abnormal at
last
measurement
Every 12
months

If abnormal
at last
measurem
ent

If abnormal at
last
measurement

If on TDF
Treatme
nt failure
Clinically
indicated





Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
Department of Health and Human Services.
Available at http://aidsinfo.nih.gov/ContentFiles/Adultand
Emerging Evidence
• Kidney Stones
• Chronic Kidney Disease (CKD)
Renal Stones
• Renal stones are risk factor for chronic kidney disease (CKD)
• Urolithiasis well-known side effect of indinavir
– Considered to be drug crystallization in urine
• Urolithiasis also associated with atazanavir
– Probably similar etiology
Hamada et al. Clin Infect Dis, 2012
ATV & Renal Stones: Hamada et al.
• Cohort analysis of 1240 patients
– ATV/r (n=465) or other protease inhibitors (n=775)
• Renal stones developed in 31 patients on ATV/r (6.7%) and 4
patients (0.52%) on other PIs
– Risk was 10 times higher in ATV/r group
• Patients on ATV/r had lower eGFR
– Lower eGFR associated with renal stones
Hamada et al. Clin Infect Dis, 2012
ATV & Renal Stones: Rockwood et al.
ATV
(n = 1,206)
EFV / DRV / LPV
combined cohort
(n=4,449)
24
24
Prevalence of kidney stones
per 1,000 patients (95% CI)
20
(13 - 30)
5.4
(3.2 – 7.6)
< 0.001
Event rate per 1,000 pt-yrs of
exposure, n (95% CI)
7.3
(4.7 - 10.8)
1.9
(1.2 - 2.8)
< 0.001
No. of patients with
kidney stones
p value
• Event rate remained significantly higher in the ATV cohort after adjusting for prior ATV and
IDV exposure
• ATV/r patients who developed renal stones had significantly higher bilirubin levels vs. ATV/r
patients who did not develop stones
• At study baseline, 42% of ATV/r patients who developed renal stones had chronic renal
impairment vs. 4.5% of ATV/r patients who did not develop stones
Rockwood N, et al. 17e conférence annuelle de la BHIVA,
Bournemouth, 2011, résumé O4.
Renal Impairment PI’s vs EFV
Hazard ratio*
(95% CI)
p value
LPV/r
1.69
(1.1 - 2.6)
0.017
ATV/r
1.52
(1.14 - 2.03)
0.004
DRV/r
1.31
(0.94 à 1.81)
0.108
EFV
1.00
*Adjusted for gender, age at start of HAART, ethnicity, baseline eGFR, baseline CD4 cell count, baseline
viral load, HBsAg, prior exposure to TDF and IDV and total duration of TDF exposure
Au cours des 12 premiers mois, 49 % des sujets ayant développé une insuffisance rénale
s’étaient rétablis (TFGe > 60 ml/min/1,73 m2).
Rockwood et al., J Antivir Antiretrovir
2012,N,
4:2et al. J Antivir Antiretrovir 2012;4: 21-25.
Rockwood
ACTG 5202: Creatinine Clearance
Median Change in Calculated Creatinine from Baseline
(mL/min)
10
Median Creatinine Clearance: ATV/r vs. EFV
8
6
**
* p = 0,001 p/r at ATV/r
** p < 0,001 p/r at ATV/r
*
4
Week 4848
Week
Week 9696
Week
2
ATV/r
0
EFV
ATV/r
EFV
-2
+ABC/3TC
-4
n
338 287
377 330
+TDF/FTC
360 327
Daar et al. Ann Intern Med, 2011
394 352
Chronic Kidney Disease & ARV Exposure
Incidence of CKD with Each Additional Year of Exposure
Annual Increased
Risk
Medication
Atazanavir + Tenofovir
41 %
Atazanavir
22 %
Tenofovir
16 %
Indinavir
11 %
Lopinavir/r
8%
Mean follow up was 3.7 years
N = 6,843
Adapté de Mocroft et al. AIDS, 2010
ARVs & Renal Impairment: The D:A:D
Cohort
•
Cohort of 49,734
•
First analysis to focus on patients with normal
renal function at baseline (n=22,603)
– eGFR > 90 ml/min/1.73m2
•
Followed to confirmed:
– eGFR < 70 ml/min/1.73m2
– Or eGFR < 60 ml/min/1.73m2
– Or last available eGFR
Ryom et al. Présentation d’affiche, CROI, 2012
D:A:D Cohort: Results
•
N=22,603
•
4.5 year follow up
•
468 (2.1%) patients progressed to eGFR < 70
–
•
131 (0.6%) patients progressed to CKD
–
•
incidence rate 4.78/1000 patient years
incidence rate 1.33/1000 patient years
Equals an annual decline of at least 4-5 ml/min
CKD=Chronic Kidney Disease
Ryom et al. Présentation d’affiche, CROI, 2012
ARVs Exposure Rates of ceGFR <70 from
eGFR > 90 (adjusted analysis)
Ryom et al. Poster presentation, CROI, 2012
Canadian Observational Cohort
(CANOC) Collaboration
Time to Impaired eGFR
Medication
Adjusted Hazard
Ratio (95% CI)
P Value
Non PI
1.00
Tenofovir
1.16
0.177
Lopinavir
1.32
0.024
Atazanavir
1.46
< 0.001
N = 965
Adapté de Hosein et al. Présentation d’affiche, IAS, 2011
EuroSIDA Study: Risk for Chronic Kidney Disease
• Analysis of patients with ≥ 3 creatinine measurements + body weight
– 6,842 patients with 21,482 person-years of follow-up
• Definition of CKD (eGFR by Cockcroft-Gault)
– If baseline eGFR ≥60 mL/min/1.73 m2, fall to <60
– If baseline eGFR <60 mL/min/1.73 m2, fall by 25%
• 225 (3.3%) progressed to CKD
Cumulative Exposure to ARVs and Risk of CKD
Univariable
Multivariable
IRR/year
95% CI
P-value
IRR/year
95% CI
P-value
Tenofovir
1.32
1.21-1.41
<0.0001
1.16
1.06-1.25
<0.0001
Indinavir
1.18
1.13-1.24
<0.0001
1.12
1.06-1.18
<0.0001
Atazanavir
1.48
1.35-1.62
<0.0001
1.21
1.09-1.34
0.0003
Lopinavir/r
1.15
1.07-1.23
<0.0001
1.08
1.01-1.16
0.030
Risk factors for CKD on TDF: age, HTN, HCV, lower eGFR, lower CD4+ count
Kirk O, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 107LB.
EuroSIDA STUDY: Crude Incidence Rate of CKD and
Increasing Exposure to ARVs
Incidence per 100 PYFU (95% CI)
N with CKD
10
86 21 34 29 55
Tenofovir
67 31 35 25 67
Indinavir
127 20 19 11 48
Atazanavir
143 23 20 18 21
Lopinavir/r
1
.01
Not 0-1 1-2 2-3
started
>3
Not 0-1 1-2 2-3
started
>3
Not 0-1 1-2 2-3
started
>3
Not 0-1 1-2 2-3
started
>3
Years of Exposure to ARV
CKD, confirmed (persisting for >3 months) decrease in eGFR ≤60 mL/min/1.73m2 if eGFR at baseline
>60 mL/min/1.73m2 or confirmed 25% decrease in eGFR if baseline eGFR≤60 mL/min/1.73m2
Kirk, CROI 2010; 107LB.
Algorithm
1- Algorithm Nephropathy
Advisory Committee on the clinical management of people living with
HIV
2- HIV and Renal Health – Management tool
National Development Committee – Supported by Janssen
PERIODIC HEALTH EXAMINATION OF
ADULTS LIVING WITH HIV (HUMAN
IMMUNODEFICIENCY VIRUS)
− Nephropathy −
Advisory Committee on the Clinical Management of Persons Living with HIV
Screening for Kidney Problems
Advisory Committee on the Clinical Management of Persons Living with HIV
Screening schedule based on risk factors for kidney disease (EACS 2011)
Untreated HIV+
patients
Assessment of risk
factors for CKD*
Urinalysis or urine
dipstick
eGFR
Phosphorus
Treated HIV+ patients
Without TDF
With TDF
Annual
Annual
6–12 months
Annual
Annual
6 months if
GFR < 60
3-6 months
6-12 months
3-6 months
3-6 months
As needed
As needed
Optional
3-6 months
* Risk factors for CKD:
Diabetes, hypertension, CVD, viral hepatitis, concomitant
nephrotoxic drugs, family history of CKD, black African ethnicity
GFR using CKD-EPI or
MDRD
> 60 and < 90 cc/min
< 60 cc/min*
Increase in
Cr > 20%
for > 3
months**
Repeat
CKD-EPI or
MDRD
calculation
< 30 cc/min*
Glucose+
Protein+
HypoPO4
ACR and
MAU
CaPO4
Renal
ultrasound
Refer to
algorithms
(next pages)
GFR < 90
GFR > 90
Follow up
every
3 months
Regular
follow-up
Refer to
proteinuria
algorithm
(next
page)
Referral to
nephrologist
or internist
* If GFR < 50 cc/min: consider adjusting the dose of certain
ARV and concomitant medications
** Test for tubulopathy if GFR declines
> 10 cc/min while on tenofovir
GFR using CKD-EPI or
MDRD
> 60 and < 90 cc/min
< 60 cc/min*
Increase in
Cr > 20%
for > 3
months**
Repeat
CKD-EPI or
MDRD
calculation
< 30 cc/min*
Glucose+
Protein+
HypoPO4
ACR and
MAU
CaPO4
Renal
ultrasound
Refer to
algorithms
(next pages)
GFR < 90
GFR > 90
Follow up
every
3 months
Regular
follow-up
Refer to
proteinuria
algorithm
(next
page)
Referral to
nephrologist
or internist
* If GFR < 50 cc/min: consider adjusting the dose of certain
ARV and concomitant medications
** Test for tubulopathy if GFR declines
> 10 cc/min while on tenofovir
> 60 and < 90 cc/min
Increase in Cr
> 20%
for > 3
months**
Glucose+
Protein+
HypoPO4
Repeat CKD-EPI
or MDRD
Refer to
algorithms
(next pages)
calculation
GFR using CKD-EPI or
MDRD
* If GFR < 50 cc/min: consider
adjusting the dose of certain
ARV and concomitant
medications
GFR < 90
GFR > 90
** Test for tubulopathy if GFR
declines
> 10 cc/min while on tenofovir
Follow up
every
3 months
Regular
follow-up
GFR using CKD-EPI or
MDRD
> 60 and < 90 cc/min
< 60 cc/min*
Increase in
Cr > 20%
for > 3
months**
Repeat
CKD-EPI or
MDRD
calculation
< 30 cc/min*
Glucose+
Protein+
HypoPO4
ACR and
MAU
CaPO4
Renal
ultrasound
Refer to
algorithms
(next pages)
GFR < 90
GFR > 90
Follow up
every
3 months
Regular
follow-up
Refer to
proteinuria
algorithm
(next
page)
Referral to
nephrologist
or internist
* If GFR < 50 cc/min: consider adjusting the dose of certain
ARV and concomitant medications
** Test for tubulopathy if GFR declines
> 10 cc/min while on tenofovir
GFR using CKD-EPI or MDRD
< 60 cc/min*
ACR and MAU
Refer to
proteinuria
algorithm
(next page)
< 30 cc/min*
CaPO4
Renal
ultrasound
Referral to
nephrologist or
internist
* If GFR < 50
cc/min:
consider
adjusting the
dose of certain
ARV and
concomitant
medications
** Test for
tubulopathy if
GFR declines
> 10 cc/min
while on
tenofovir
Urinalysis or urine dipstick
Glucose > 0
Protein ≥ 1 + or 0.25
g/L
Fasting glucose
+
Rule out diabetes
Repeat at next appt.
Glycosuri
a
DB +
Glycosuri
a
DB –
Protein ≥
1+ or 0.25
g/L
Protein <
1+ or 0.25
g/L
DB
follow-up
Repeat 1x
ACR and
MAU
Normal
Glycosuri
a
DB –
Referral to
nephrologist
or internist
ACR > 0.05 g/mmol
or
MAU > 2.1 mg/mmol
or
hematuria (> 2
RBC/HPF)
- Renal ultrasound
- Ascertain the risk
factors
- Referral to nephrologist
or internist, or to urologist
for isolated hematuria
ACR ≤ 0.05 g/mmol
and MAU <
2.1 mg/mmol
Normal
Urinalysis or urine dipstick
Glucose > 0
Protein ≥ 1 + or 0.25
g/L
Fasting glucose
+
Rule out diabetes
Repeat at next appt.
Glycosuri
a
DB +
Glycosuri
a
DB –
Protein ≥
1+ or 0.25
g/L
Protein <
1+ or 0.25
g/L
DB
follow-up
Repeat 1x
ACR and
MAU
Normal
Glycosuri
a
DB –
Referral to
nephrologist
or internist
ACR > 0.05 g/mmol
or
MAU > 2.1 mg/mmol
or
hematuria (> 2
RBC/HPF)
- Renal ultrasound
- Ascertain the risk
factors
- Referral to nephrologist
or internist, or to urologist
for isolated hematuria
ACR ≤ 0.05 g/mmol
and MAU <
2.1 mg/mmol
Normal
Urinalysis or urine dipstick
Glucose > 0
Fasting glucose
+
Rule out diabetes
Glycosuri
a
DB +
Glycosuri
a
DB –
DB
follow-up
Repeat 1x
Glycosuri
a
DB –
Referral to
nephrologist
or internist
Urinalysis or urine dipstick
Glucose > 0
Protein ≥ 1 + or 0.25
g/L
Fasting glucose
+
Rule out diabetes
Repeat at next appt.
Glycosuri
a
DB +
Glycosuri
a
DB –
Protein ≥
1+ or 0.25
g/L
Protein <
1+ or 0.25
g/L
DB
follow-up
Repeat 1x
ACR and
MAU
Normal
Glycosuri
a
DB –
Referral to
nephrologist
or internist
ACR > 0.05 g/mmol
or
MAU > 2.1 mg/mmol
or
hematuria (> 2
RBC/HPF)
- Renal ultrasound
- Ascertain the risk
factors
- Referral to nephrologist
or internist, or to urologist
for isolated hematuria
ACR ≤ 0.05 g/mmol
and MAU <
2.1 mg/mmol
Normal
Urinalysis or urine dipstick
Protein ≥ 1 + or 0.25
g/L
Repeat at next appt.
Protein ≥
1+ or 0.25
g/L
Protein <
1+ or 0.25
g/L
ACR and
MAU
Normal
ACR > 0.05 g/mmol
or
MAU > 2.1 mg/mmol
or
hematuria (> 2
RBC/HPF)
- Renal ultrasound
- Ascertain the risk
factors
- Referral to nephrologist
or internist, or to urologist
for isolated hematuria
ACR ≤ 0.05 g/mmol
and MAU <
2.1 mg/mmol
Normal
Serum
phosphorus
0.65 – normal
level
Repeat in 3
months
0.32 – 0.65
mmol/L
Repeat in 1 month
< 0.32 mmol/L
< normal levels
Treat immediately
Referral to
nephrologist
Repeat and if <
normal levels
25-OH Vit D
< 50:
deficiency
< 75:
insufficiency
Vit D Rx
> 75
Normal
PTH assay
Abnorma
l
Referral to
nephrologist
or internist
Normal
Urinary fractional excretion
of phosphorus if available
(if > 20% or > 10% and
hypophosphatemia: referral
to a specialist
Albumincorrected Ca
Abnorma
l
Referral to
nephrologist
or internist
Normal
Serum
phosphorus
0.65 – normal
level
Repeat in 3
months
0.32 – 0.65
mmol/L
Repeat in 1 month
< 0.32 mmol/L
< normal levels
Treat immediately
Referral to
nephrologist
Repeat and if <
normal levels
25-OH Vit D
< 50:
deficiency
< 75:
insufficiency
Vit D Rx
> 75
Normal
PTH assay
Abnorma
l
Referral to
nephrologist
or internist
Normal
Urinary fractional excretion
of phosphorus if available
(if > 20% or > 10% and
hypophosphatemia: referral
to a specialist
Albumincorrected Ca
Abnorma
l
Referral to
nephrologist
or internist
Normal
Serum
phosphorus
0.65 – normal
level
Repeat in 3
months
0.32 – 0.65
mmol/L
Repeat in 1 month
< 0.32 mmol/L
Treat immediately
Referral to
nephrologist
< normal levels
Repeat and if <
normal levels
Urinary fractional excretion
of phosphorus if available
(if > 20% or > 10% and
hypophosphatemia: referral
to a specialist
Serum
phosphorus
0.65 – normal
level
Repeat in 3
months
0.32 – 0.65
mmol/L
Repeat in 1 month
< 0.32 mmol/L
< normal levels
Treat immediately
Referral to
nephrologist
Repeat and if <
normal levels
25-OH Vit D
< 50:
deficiency
< 75:
insufficiency
Vit D Rx
> 75
Normal
PTH assay
Abnorma
l
Referral to
nephrologist
or internist
Normal
Urinary fractional excretion
of phosphorus if available
(if > 20% or > 10% and
hypophosphatemia: referral
to a specialist
Albumincorrected Ca
Abnorma
l
Referral to
nephrologist
or internist
Normal
Serum
phosphorus
< normal levels
Repeat and if <
normal levels
25-OH Vit D
< 50:
deficiency
< 75:
insufficiency
Vit D Rx
> 75
Normal
PTH assay
Abnorma
l
Referral to
nephrologist
or internist
Normal
Urinary fractional excretion
of phosphorus if available
(if > 20% or > 10% and
hypophosphatemia: referral
to a specialist
Albumincorrected Ca
Abnorma
l
Referral to
nephrologist
or internist
Normal
Algorithm
Algorithm
Algorithm
Algorithm
Algorithm
Case Study
Aging Woman with longstanding HIV and
multiple comorbidities
Dr. Gord Arbess
Background Information
• 62 year old woman
• From Jamaica
• HIV + since 1996, heterosexual transmission
• Nadir CD4 108, VL > 500,000
• Intermittent adherence
• Multiple ARV Regimens due to intolerance/resistance (AZT, 3TC,
ddI, d4T, Nelfinavir, Amprenavir, LPV, EFV, Indinavir, Tenofovir,
RTV)
• Hx ABC/3TC HSR
Multiple Co-Morbidities
• Obese
• Hypertension
• NIDDM (Gastroparesis-intermittent vomiting)
• Sleep Apnea-CPAP
• Angina?
• Severe Osteoarthritis Knees
• Hypothyroid
• Hyperlipidemia
• Major Depression
HIV Medications
Present HIV Regimen started June 2012
• Darunavir 800 mg/d
• Ritonavir 100 mg/d
• Raltegravir 400 mg bid
• Etravirine 400 mg/d
Other Medications
• Lisinopril
• Atorvastatin
• Ibuprofen
• Metformin
• Cipralex
• Zofran
• Eltroxin
Routine Bloodwork
You notice Serum Cr is 158 (eGFR 48) on routine BW in
August 2012
What Would You Do?
GFR using CKD-EPI or MDRD
< 60 cc/min*
ACR and MAU
Refer to
proteinuria
algorithm
(next page)
< 30 cc/min*
CaPO4
Renal
ultrasound
Referral to
nephrologist or
internist
* If GFR < 50
cc/min:
consider
adjusting the
dose of certain
ARV and
concomitant
medications
** Test for
tubulopathy if
GFR declines
> 10 cc/min
while on
tenofovir
Algorithm
Investigations to assess Renal Function
• Urinalysis
• ACR
• Serum Cr (eGFR)
• Electrolytes, Bicarb, albumin
• Urine for Protein, Cr
• Renal Ultrasound
• Other?
• Biopsy?
Results
•
•
•
•
•
•
•
•
•
•
VL < 40 CD 4 843
Hgb 108
BS 7.3
Hga1c 0.061
ACR 1.1
Trace Protein, no blood, no glucose, 10-15 White cells/hpf, occ
red cells/hpf, hyaline casts with some cells
Spot urine 0.1 g/L protein, 7.8 mmol/L Cr
Cr 118-160 range (eGFR 48-54 range) over number of years
Normal electrolytes, normal albumin, normal Bicarb
Normal renal Ultrasound (small-sized kidneys)
What Would You Do?
Urinalysis or urine dipstick
Glucose > 0
Protein ≥ 1 + or 0.25
g/L
Fasting glucose
+
Rule out diabetes
Repeat at next appt.
Glycosuri
a
DB +
Glycosuri
a
DB –
Protein ≥
1+ or 0.25
g/L
Protein <
1+ or 0.25
g/L
DB
follow-up
Repeat 1x
ACR and
MAU
Normal
Glycosuri
a
DB –
Referral to
nephrologist
or internist
ACR > 0.05 g/mmol
or
MAU > 2.1 mg/mmol
or
hematuria (> 2
RBC/HPF)
- Renal ultrasound
- Ascertain the risk
factors
- Referral to nephrologist
or internist, or to urologist
for isolated hematuria
ACR ≤ 0.05 g/mmol
and MAU <
2.1 mg/mmol
Normal
Algorithm
What do you think could be accounting for
Cr elevation?
Etiology
• HIVAN?
• IgA Nephropathy?
• Medication-related?
• Hypertension?
• NIDDM?
• Pre-renal component/volume contraction?
• Other?
How would you manage this patient?
Management Options?
• Do you d/c metformin?
• Do you d/c NSAIDs?
• Do you d/c statin?
• Do you Need to dose Adjust ARVs?
• Should you Change ARVs?
• Do you Hold Ace Inhibitor?
• Do you ensure BP/BS well controlled?
• Do Nothing?
Follow Up
• BP well controlled
• Hga1c 0.062, therefore Metformin stopped
• Asked not to take any NSAIDS
• ARV regimen continued at same doses
• Continued same dose of statin, ACEi
• Cr monitored closely in range of 118-130 (eGFR 55-60 range)