HIV and Renal HealthDr. Patrice Junod
Clinique médicale l’Actuel
This activity is supported byan educational grant from:
Content Contributors
Principle Content Development
Gord Arbess Jean-Guy Baril Mélanie HamelBrian Conway Chris FraserMarianne Harris Christine HughesPatrice Junod Marek SmiejaGraham Smith Rachel TherrienAlice Tseng Sharon Walmsley
ConsultantLinda Robinson
Anita Rachlis Ali Zahirieh David Fletcher
Program Development
This program was developed with consultants through an educational grant from Janssen Inc. The faculty members received financial compensation for developing & presenting this program.
Conflict of Interest Declaration
Faculty Disclosures
• Abbvie• Gilead• Janssen• Merck• ViiV
• 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
Objectives
Background: HIV and the Kydney
• 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 Gupta SK, et al. Clinical Infectious Disease 2005;40:1559-1585.2 Gupta SK, et al. Clinical Nephrology 2004;61:1-6.
Renal 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.
Kidney Disease in HIV Positive Patients
Age FamilyHistory
Nephrotoxicmedication Diabetes
HIV Hyper-tension
Hepatitis C
Ethnicity
CKDRisk
= Modifiable= Nonmodifiable
Gupta SK, et al. Clinical Infectious Disease 2005;40:1559-1585.
Risk Factors for Kidney Disease in the HIV Positive Population
• Prevalence 3-15%
• Race and other genetic factors
• Hypertension
• Diabetes mellitus
• Hepatitis C virus infection
• Decreased CD4 cell count
• Increased viral load
• Nephrotoxic Drugs
Chronic Kidney Disease in HIV
Adapted from: Guo X, Nzerue C. Cleve Clin J Med 2002;69:289-312.
TMP/SMX: trimethoprim and sulfamethoxazole
Prerenal Tubular InjuryAllergic
Interstitial Nephritis
Thrombotic Microangiopathy Obstructive
ACE-IARBsDirect Renin
InhibitorsAmphotericinNSAIDSCyclosporineDiureticsInterferon
CidofovirAdefovirTenofovirDidanosineLamivudineStavudineAminoglycosidesAmphotericinCocaineFoscarnetPentamidineKetamin
AbacavirIndinavirRitonavirAtazanavirAcyclovirCephalosporinsPenicillinsCiprofloxacinTMP/SMXRifampinNSAIDsProton Pump
Inhibitors
IndinavirCocaineCyclosporineValacyclovir
IndinavirAtazanavirAcyclovirFoscarnetSulfadiazineTMP/SMX
Medications and Renal Disease
• 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
HIV & The Kidney: Summary
Stage Description GFR(mL/min/1.73m2)
IUrinary and/or Structural
Abnormality> 89
IIUrinary and/or Structural
Abnormality60 - 89
IIIa Mild GFR decline 45 - 59
IIIb Moderate GFR decline 30 - 44
IV Severe GFR decline 15 - 29
V Kidney Failure < 15
ESRDRequiring Renal Replacement
Therapy
Levey A. KI 2010;80: 17.
Classification of CKD
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
Three Important Measures
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
Three Important Measures
• Gold standard:– inulin clearance– iothalamate clearance– Iohexol
• “Practical”– serum creatinine– 24-hr urine collection for creatinine clearance (cumbersome!)– equations, equations, equations
How Do We Measure GFR?
• 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.
Renal Function Measurement
Serum Creatinine 110 μmol/L
The same serum creatinine represents very different GFRs in these two individuals
40 ml/min 140 ml/min
Serum Creatinine 110 μmol/L
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
Cockcroft-Gault 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
MDRD Equation
• Newest Equation of the three• Non-linear based equation• More accurate in estimating GFR in those with mild CKD
CKD-EPI
Levey et al. Ann Intern Med 2009;150: 604-612.
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
Three Important Measures
• 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
Quantifying Proteinuria
• 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)
Practical Point
• A marker of increased risk of CV events
• Increased risk of CKD progression – (notably when > 1g/day protein or 200mg/day albumin)
Implications of Proteinuria
• Glomerular Filtration Rate (GFR)
• Proteinuria
• Proximal Tubular Function
Three Important Measures
• “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.
Tubular Functions
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”
• 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
“What Are You Looking For?”
• 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
Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy
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
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
Entry info care
Follow-up before ART
ART Initiation or modificatio
n
Follow-up 2-8 weeks post-
ART initiation or modification
Every 3-6 months
Every 6 months
Every 12 months
Treatment failure
Clinically indicated
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
If abnormal at
last measurement
If abnormal
at last measurem
ent
Fasting glucose or
hemoglobin A1C
If normal annually
If abnormal at
last measurement
If abnormal at
last measurement
Urinalysis If on TDF
Pregnancy test
If startting
EFV
Table 3. Laboratory Monitoring Schedule for Patients Before and After Initiation of Antiretroviral Therapy
• Kidney Stones
• Chronic Kidney Disease (CKD)
Emerging Evidence
• 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
Renal Stones
• 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: Hamada et al.
• 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
ATV(n = 1,206)
EFV / DRV / LPV combined cohort
(n=4,449)p value
No. of patients with kidney stones
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
Rockwood N, et al. 17e conférence annuelle de la BHIVA,Bournemouth, 2011, résumé O4.
ATV & Renal Stones: Rockwood et al.
*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
Rockwood N, et al. J Antivir Antiretrovir 2012;4: 21-25.
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
Au cours des 12 premiers mois, 49 % des sujets ayant développé une insuffisance rénales’étaient rétablis (TFGe > 60 ml/min/1,73 m2).
Rockwood et al., J Antivir Antiretrovir 2012, 4:2
Renal Impairment PI’s vs EFV
Daar et al. Ann Intern Med, 2011
n 338 287 377 330 360 327 394 352 Med
ian
Cha
nge
in C
alcu
late
d C
reat
inin
e fr
om B
ase
line
(mL/
min
)
***
ATV/rEFV EFV
ATV/r
+ABC/3TC +TDF/FTC
Median Creatinine Clearance: ATV/r vs. EFV
* p = 0,001 p/r at ATV/r** p < 0,001 p/r at ATV/r
Week 48
Week 96
ACTG 5202: Creatinine Clearance
Medication Annual Increased Risk
Atazanavir + Tenofovir 41 %
Atazanavir 22 %
Tenofovir 16 %
Indinavir 11 %
Lopinavir/r 8 %
Adapté de Mocroft et al. AIDS, 2010
N = 6,843
Mean follow up was 3.7 years
Incidence of CKD with Each Additional Year of Exposure
Chronic Kidney Disease & ARV Exposure
• 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
ARVs & Renal Impairment: The D:A:D Cohort
• N=22,603
• 4.5 year follow up
• 468 (2.1%) patients progressed to eGFR < 70 – incidence rate 4.78/1000 patient years
• 131 (0.6%) patients progressed to CKD– incidence rate 1.33/1000 patient years
• Equals an annual decline of at least 4-5 ml/min
Ryom et al. Présentation d’affiche, CROI, 2012
CKD=Chronic Kidney Disease
D:A:D Cohort: Results
Ryom et al. Poster presentation, CROI, 2012
ARVs Exposure Rates of ceGFR <70 from eGFR > 90 (adjusted analysis)
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
Adapté de Hosein et al. Présentation d’affiche, IAS, 2011
N = 965
Time to Impaired eGFR
Canadian Observational Cohort(CANOC) Collaboration
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
Risk factors for CKD on TDF: age, HTN, HCV, lower eGFR, lower CD4+ count
Cumulative Exposure to ARVs and Risk of CKD
Kirk O, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 107LB.
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
EuroSIDA STUDY: Crude Incidence Rate of CKD and Increasing Exposure to ARVs
Kirk, CROI 2010; 107LB.
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
Inci
denc
e pe
r 100
PYF
U (9
5% C
I)
Years of Exposure to ARV
N with CKD
Not 0-1 1-2 2-3 >3started
Not 0-1 1-2 2-3 >3
86 21 34 29 55 67 31 35 25 67
Not 0-1 1-2 2-3 >3
127 20 19 11 48
Not 0-1 1-2 2-3 >3
143 23 20 18 21
started started started
Tenofovir Indinavir Atazanavir Lopinavir/r10
1
.01
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
Algorithm
− Nephropathy −
Advisory Committee on the Clinical Management of Persons Living with HIV
PERIODIC HEALTH EXAMINATION OF ADULTS LIVING WITH HIV (HUMAN
IMMUNODEFICIENCY VIRUS)
Screening schedule based on risk factors for kidney disease (EACS 2011)
Untreated HIV+ patients
Treated HIV+ patients
Without TDF With TDF
Assessment of risk factors for CKD* Annual Annual 6–12 months
Urinalysis or urine dipstick Annual
Annual6 months if GFR < 60
3-6 months
eGFR 6-12 months 3-6 months 3-6 months
Phosphorus As needed As needed Optional3-6 months
* Risk factors for CKD:Diabetes, hypertension, CVD, viral hepatitis, concomitant nephrotoxic drugs, family history of CKD, black African ethnicity
Advisory Committee on the Clinical Management of Persons Living with HIV
Screening for Kidney Problems
GFR using CKD-EPI or MDRD
ACR and MAU
Refer to proteinuria algorithm
(next page)
Referral to nephrologist or internist
< 60 cc/min* < 30 cc/min*
CaPO4 Renal
ultrasound
> 60 and < 90 cc/min
Increase in Cr > 20%
for > 3 months**
Repeat CKD-EPI or
MDRD calculation
Refer to algorithms (next pages)
GFR < 90
Glucose+Protein+HypoPO4
GFR > 90
Regular follow-up
Follow up every
3 months
* 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
ACR and MAU
Refer to proteinuria algorithm
(next page)
Referral to nephrologist or internist
< 60 cc/min* < 30 cc/min*
CaPO4 Renal
ultrasound
> 60 and < 90 cc/min
Increase in Cr > 20%
for > 3 months**
Repeat CKD-EPI or
MDRD calculation
Refer to algorithms (next pages)
GFR < 90
Glucose+Protein+HypoPO4
GFR > 90
Regular follow-up
Follow up every
3 months
* 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
* 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**
Repeat CKD-EPI or MDRD
calculation
Refer to algorithms (next pages)
GFR < 90
Glucose+Protein+HypoPO4
GFR > 90
Regular follow-up
Follow up every
3 months
GFR using CKD-EPI or MDRD
GFR using CKD-EPI or MDRD
ACR and MAU
Refer to proteinuria algorithm
(next page)
Referral to nephrologist or internist
< 60 cc/min* < 30 cc/min*
CaPO4 Renal
ultrasound
> 60 and < 90 cc/min
Increase in Cr > 20%
for > 3 months**
Repeat CKD-EPI or
MDRD calculation
Refer to algorithms (next pages)
GFR < 90
Glucose+Protein+HypoPO4
GFR > 90
Regular follow-up
Follow up every
3 months
* 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
ACR and MAU
Refer to proteinuria algorithm
(next page)
Referral to nephrologist or
internist
< 60 cc/min* < 30 cc/min*
CaPO4 Renal ultrasound
* 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
Glycosuria
DB +
Glycosuria
DB –
DB follow-up
Fasting glucose+
Rule out diabetes
Repeat 1x
Glycosuria
DB –
Referral to nephrologist or internist
ACR ≤ 0.05 g/mmol and MAU <
2.1 mg/mmol
Normal
- Renal ultrasound- Ascertain the risk
factors- Referral to nephrologist
or internist, or to urologist for isolated
hematuria
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
NormalACR and
MAU
ACR > 0.05 g/mmolor
MAU > 2.1 mg/mmolor
hematuria (> 2 RBC/HPF)
Urinalysis or urine dipstick
Glucose > 0
Glycosuria
DB +
Glycosuria
DB –
DB follow-up
Fasting glucose+
Rule out diabetes
Repeat 1x
Glycosuria
DB –
Referral to nephrologist or internist
ACR ≤ 0.05 g/mmol and MAU <
2.1 mg/mmol
Normal
- Renal ultrasound- Ascertain the risk
factors- Referral to nephrologist
or internist, or to urologist for isolated
hematuria
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
NormalACR and
MAU
ACR > 0.05 g/mmolor
MAU > 2.1 mg/mmolor
hematuria (> 2 RBC/HPF)
Urinalysis or urine dipstick
Glucose > 0
Glycosuria
DB +
Glycosuria
DB –
DB follow-up
Fasting glucose+
Rule out diabetes
Repeat 1x
Glycosuria
DB –
Referral to nephrologist or internist
Urinalysis or urine dipstick
Glucose > 0
Glycosuria
DB +
Glycosuria
DB –
DB follow-up
Fasting glucose+
Rule out diabetes
Repeat 1x
Glycosuria
DB –
Referral to nephrologist or internist
ACR ≤ 0.05 g/mmol and MAU <
2.1 mg/mmol
Normal
- Renal ultrasound- Ascertain the risk
factors- Referral to nephrologist
or internist, or to urologist for isolated
hematuria
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
NormalACR and
MAU
ACR > 0.05 g/mmolor
MAU > 2.1 mg/mmolor
hematuria (> 2 RBC/HPF)
Urinalysis or urine dipstick
ACR ≤ 0.05 g/mmol and MAU <
2.1 mg/mmol
Normal
- Renal ultrasound- Ascertain the risk
factors- Referral to nephrologist
or internist, or to urologist for isolated
hematuria
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
NormalACR and
MAU
ACR > 0.05 g/mmolor
MAU > 2.1 mg/mmolor
hematuria (> 2 RBC/HPF)
Serum phosphorus
< normal levels
Repeat and if < normal levels
PTH assay25-OH Vit D Albumin-corrected Ca
< 50: deficiency< 75: insufficiency
> 75
Vit D Rx Normal
Abnormal Normal
Referral to nephrologist or internist
Urinary fractional excretion of phosphorus if available (if > 20% or > 10% and hypophosphatemia: referral to a specialist
Abnormal Normal
Referral to nephrologist or internist
0.65 – normal level
0.32 – 0.65 mmol/L
< 0.32 mmol/L
Repeat in 3 months
Repeat in 1 month
Treat immediatelyReferral to
nephrologist
Serum phosphorus
< normal levels
Repeat and if < normal levels
PTH assay25-OH Vit D Albumin-corrected Ca
< 50: deficiency< 75: insufficiency
> 75
Vit D Rx Normal
Abnormal Normal
Referral to nephrologist or internist
Urinary fractional excretion of phosphorus if available (if > 20% or > 10% and hypophosphatemia: referral to a specialist
Abnormal Normal
Referral to nephrologist or internist
0.65 – normal level
0.32 – 0.65 mmol/L
< 0.32 mmol/L
Repeat in 3 months
Repeat in 1 month
Treat immediatelyReferral to
nephrologist
Serum phosphorus
< normal levels
Repeat and if < normal levels
Urinary fractional excretion of phosphorus if available (if > 20% or > 10% and hypophosphatemia: referral to a specialist
0.65 – normal level
0.32 – 0.65 mmol/L
< 0.32 mmol/L
Repeat in 3 months
Repeat in 1 month
Treat immediatelyReferral to
nephrologist
Serum phosphorus
< normal levels
Repeat and if < normal levels
PTH assay25-OH Vit D Albumin-corrected Ca
< 50: deficiency< 75: insufficiency
> 75
Vit D Rx Normal
Abnormal Normal
Referral to nephrologist or internist
Urinary fractional excretion of phosphorus if available (if > 20% or > 10% and hypophosphatemia: referral to a specialist
Abnormal Normal
Referral to nephrologist or internist
0.65 – normal level
0.32 – 0.65 mmol/L
< 0.32 mmol/L
Repeat in 3 months
Repeat in 1 month
Treat immediatelyReferral to
nephrologist
Serum phosphorus
< normal levels
Repeat and if < normal levels
PTH assay25-OH Vit D Albumin-corrected Ca
< 50: deficiency< 75: insufficiency
> 75
Vit D Rx Normal
Abnormal Normal
Referral to nephrologist or internist
Urinary fractional excretion of phosphorus if available (if > 20% or > 10% and hypophosphatemia: referral to a specialist
Abnormal Normal
Referral to nephrologist or internist
Algorithm
Algorithm
Algorithm
Algorithm
Algorithm
Case Study
Aging Woman with longstanding HIV and multiple comorbidities
Dr. Gord Arbess
• 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
Background Information
• Obese
• Hypertension
• NIDDM (Gastroparesis-intermittent vomiting)
• Sleep Apnea-CPAP
• Angina?
• Severe Osteoarthritis Knees
• Hypothyroid
• Hyperlipidemia
• Major Depression
Multiple Co-Morbidities
Present HIV Regimen started June 2012
• Darunavir 800 mg/d
• Ritonavir 100 mg/d
• Raltegravir 400 mg bid
• Etravirine 400 mg/d
HIV Medications
• Lisinopril
• Atorvastatin
• Ibuprofen
• Metformin
• Cipralex
• Zofran
• Eltroxin
Other Medications
You notice Serum Cr is 158 (eGFR 48) on routine BW in August 2012
Routine Bloodwork
What Would You Do?
GFR using CKD-EPI or MDRD
ACR and MAU
Refer to proteinuria algorithm
(next page)
Referral to nephrologist or
internist
< 60 cc/min* < 30 cc/min*
CaPO4 Renal ultrasound
* 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
• Urinalysis
• ACR
• Serum Cr (eGFR)
• Electrolytes, Bicarb, albumin
• Urine for Protein, Cr
• Renal Ultrasound
• Other?
• Biopsy?
Investigations to assess Renal Function
• 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)
Results
What Would You Do?
Urinalysis or urine dipstick
Glucose > 0
Glycosuria
DB +
Glycosuria
DB –
DB follow-up
Fasting glucose+
Rule out diabetes
Repeat 1x
Glycosuria
DB –
Referral to nephrologist or internist
ACR ≤ 0.05 g/mmol and MAU <
2.1 mg/mmol
Normal
- Renal ultrasound- Ascertain the risk
factors- Referral to nephrologist
or internist, or to urologist for isolated
hematuria
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
NormalACR and
MAU
ACR > 0.05 g/mmolor
MAU > 2.1 mg/mmolor
hematuria (> 2 RBC/HPF)
Algorithm
What do you think could be accounting forCr elevation?
• HIVAN?
• IgA Nephropathy?
• Medication-related?
• Hypertension?
• NIDDM?
• Pre-renal component/volume contraction?
• Other?
Etiology
How would you manage this patient?
• 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?
Management Options?
• 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)
Follow Up
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