HIV and Renal Health

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)

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.

Classification of CKD

• Glomerular Filtration Rate (GFR)

• Proteinuria

• Proximal Tubular Function

Three Important Measures


• Proteinuria



• 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.


• 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

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


• Proteinuria



• “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 fro

m B

asel

ine

(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 toolNational 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+ patientsWithout 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 HIVScreening 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


ACR and MAU


(next page)






for > 3 months**

Repeat CKD-EPI or

MDRD calculation


GFR < 90


GFR > 90

Regular follow-up

Follow up every

3 months






Increase in Cr > 20%for > 3

months**

Repeat CKD-EPI or MDRD

calculation


GFR < 90


GFR > 90

Regular follow-up

Follow up every

3 months



ACR and MAU


(next page)






for > 3 months**

Repeat CKD-EPI or

MDRD calculation


GFR < 90


GFR > 90

Regular follow-up

Follow up every

3 months




ACR and MAU


(next page)

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 –


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)


Glucose > 0

Glycosuria

DB +

Glycosuria

DB –

DB follow-up

Fasting glucose+

Rule out diabetes

Repeat 1x

Glycosuria

DB –



2.1 mg/mmol

Normal




hematuria




g/L


g/L

NormalACR and

MAU

ACR > 0.05 g/mmolor

MAU > 2.1 mg/mmolor



Glucose > 0

Glycosuria

DB +

Glycosuria

DB –

DB follow-up

Fasting glucose+

Rule out diabetes

Repeat 1x

Glycosuria

DB –



Glucose > 0

Glycosuria

DB +

Glycosuria

DB –

DB follow-up

Fasting glucose+

Rule out diabetes

Repeat 1x

Glycosuria

DB –



2.1 mg/mmol

Normal




hematuria




g/L


g/L

NormalACR and

MAU

ACR > 0.05 g/mmolor

MAU > 2.1 mg/mmolor




2.1 mg/mmol

Normal




hematuria




g/L


g/L

NormalACR and

MAU

ACR > 0.05 g/mmolor

MAU > 2.1 mg/mmolor


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


Urinary fractional excretion of phosphorus if available (if > 20% or > 10% and hypophosphatemia: referral to a specialist

Abnormal Normal


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




> 75

Vit D Rx Normal

Abnormal Normal



Abnormal Normal



0.32 – 0.65 mmol/L

< 0.32 mmol/L

Repeat in 3 months

Repeat in 1 month


nephrologist

Serum phosphorus

< normal levels




0.32 – 0.65 mmol/L

< 0.32 mmol/L

Repeat in 3 months

Repeat in 1 month


nephrologist

Serum phosphorus

< normal levels




> 75

Vit D Rx Normal

Abnormal Normal



Abnormal Normal



0.32 – 0.65 mmol/L

< 0.32 mmol/L

Repeat in 3 months

Repeat in 1 month


nephrologist

Serum phosphorus

< normal levels




> 75

Vit D Rx Normal

Abnormal Normal



Abnormal Normal


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?


ACR and MAU


(next page)

Referral to nephrologist or

internist





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?


Glucose > 0

Glycosuria

DB +

Glycosuria

DB –

DB follow-up

Fasting glucose+

Rule out diabetes

Repeat 1x

Glycosuria

DB –



2.1 mg/mmol

Normal




hematuria




g/L


g/L

NormalACR and

MAU

ACR > 0.05 g/mmolor

MAU > 2.1 mg/mmolor


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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HIV and Renal Health

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