Supporting renal health in PLHIV
This article has been commissioned and funded by ViiV Healthcare
Authors: Dr Marta Boffito, Chelsea and Westminster Hospital, London and Prof Bruce Hendry, King's College London
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Monitoring and maintenance of renal function should be an important part of the clinical management of PLHIV. Renal function should be monitored on a regular basis, along with ongoing assessment of risk factors for renal injury.
Careful consideration of combination antiretroviral therapy (cART) is also necessary. In patients with existing renal impairment and those at risk, regimens containing tenofovir (as tenofovir disoproxil fumarate, TDF) and/or protease inhibitors (PIs) should be used with caution, and avoided where possible. A two-drug regimen consisting of Tivicay® (dolutegravir) plus lamivudine has been shown to be non-inferior to a three-drug regimen in achieving an undetectable viral load, and may be an option for patients in whom renal function is a concern.2
|Renal biomarker||Adjusted mean change from baseline||P value|
|DTG plus 3TC (two-drug regimen)||DTG/FTC/TDF (three-drug regimen)|
|GFR from creatinine,
CKD-EPI (mL/min/1.73 m2)
|Cystatin C (mg/L)||-0.1||0.0||<0.0001|
|GFR from cystatin C,
CKD-EPI (mL/min/1.73 m2)
These data suggest that a two-drug regimen consisting of DTG plus 3TC allows PLHIV to achieve and maintain undetectability, while simultaneously reducing the number of antiretrovirals (versus standard three-drug cART) and supporting renal function.
Age: 54 years old
Body mass index: 29.1 kg/m2
- Type 2 diabetes (T2D) since 2009, on metformin + sitagliptin
- HbA1c 8.1% [reference (non-diabetic) value <6.0%23]
- History of recurrent urinary tract infection: pyelonephritis in 2005
- Diagnosed with HIV in 2013 following visit to Sierra Leone
- Started cART immediately, with TDF/FTC/EFV (efavirenz)
- HIV viral load undetectable at 3 months, but severe dizziness and insomnia were experienced due to EFV
- Subsequently switched to, and still maintained on, darunavir/ritonavir (DRV/r) + FTC/TDF
- Her eGFR (Cockcroft-Gault) is 65 mL/min and she has a urinary protein-creatinine ratio (uPCR) of 55 mg/mmol (values >15 mg/mmol are abnormal)
- Current medication: cART, antidiabetics, ibuprofen as needed for back pain
What would you do to support her renal function?
- Refer her to a diabetologist or endocrinologist?
- Refer to a nephrologist?
- Change her anti-HIV or pain medication?
- Watch and wait: continue with routine follow-up, including monitoring of renal function?
- PIs and TDF should be used with caution in patients with, or at risk of, renal impairment. In particular, the use of a boosting agent (in this case, ritonavir) in combination with TDF should be avoided in this setting
- Consequently, L.S. was switched to DTG plus 3TC, to eliminate both TDF and the boosted PI from her regimen
- Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are potentially nephrotoxic; she was therefore switched to paracetamol
- Additionally, her HbA1c and uPCR suggested suboptimal diabetic control and diabetic nephropathy, respectively; she was referred to an endocrinologist for review
- DTG increases metformin concentrations,21 so this was highlighted in the referral letter
- L.S. was advised to monitor her glucose levels more closely than normal for several weeks and asked to take her readings with her to her endocrinology appointment
- At 3 months, L.S. maintained her undetectable viral load and reported no side effects from treatment
- Her eGFR was stable at 65 mL/min, and her HbA1c was now 7.5%; no changes to her metformin dosage had been made
Ask the nephrologist
Prof Bruce Hendry
- What should I be doing to optimise renal health in PLHIV?
- Assess renal status at baseline and on follow-up using a creatinine-based measure of eGFR, usually CKD-EPI, and by quantifying proteinuria [either urinary albumin-creatinine ratio (uACR) or uPCR]. Repeat measurements at least annually, and more frequently if there are adverse results or trends
- Recognise important co-morbidities as relevant to renal risk, particularly cardiovascular disease, diabetes and hypertension
- Guard against over-the-counter use of potentially nephrotoxic agents, such as NSAIDs
- Ensure diabetes and hypertension are detected and well-managed, in collaboration with the full multidisciplinary team. Investigate suspected cardiovascular disease
- Where renal issues or risk are identified, choose renal-friendly antiretrovirals and avoid TDF and boosted PIs
- Diets high in protein and creatine are unlikely to be a risk for healthy kidneys, but I would advise against them in PLHIV with, or at high risk of, CKD. These diets may slightly increase serum creatinine
- What advice/information should I give PLHIV around renal function, whether or not they have evidence of renal impairment?
- Always stay well hydrated before routine blood tests
- Your care team will regularly assess your kidney function, taking into account other factors that might affect how well they are working
- They will tell you what you can do to help maintain the health of your kidneys and will take steps to ensure your HIV treatment does not cause harm
- Be sure to discuss all your medications and therapies with your care team so that they can help you make choices that will support your overall health
- Keeping your heart healthy is important for your kidney health and vice versa. Always report any symptoms like shortness of breath, chest pain or swollen ankles to your healthcare team
- When should I refer to a nephrologist?
- Always refer to a nephrologist if the eGFR is <30 mL/min, or if proteinuria is grade A3 (e.g. uACR >30 mg/mmol or uPCR >50 mg/mmol)
- When eGFR is 30-60 mL/min or proteinuria is grade A2, a referral may be appropriate if there is no renal diagnosis or if trends are negative and treatment choices are unclear
- Haematuria should always be investigated to establish the cause
- Unexplained abnormalities of renal imaging (e.g. multiple cysts) or of biochemistry (e.g. hyperkalaemia) should be investigated and referred as appropriate, sometimes to nephrology
About the authors
Dr Marta Boffito, MD, PhD, FRCP, is Consultant Physician, HIV Service Lead and Clinical Research Lead at the Chelsea and Westminster Hospital in London, and is a Reader at Imperial College London. In addition to her clinical duties, Dr Boffito is the lead investigator on a number of major HIV clinical trials and has a special interest in antiretroviral pharmacology.
Prof Bruce Hendry, MD, PhD, FRCP, is Emeritus Professor of Renal Medicine at King’s College London and Chair of the South-West Thames Institute for Renal Research (SWTIRR). He has over 25 years’ experience as a clinical nephrologist and has a special interest in the kidney health of PLHIV.
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PM-GB-DLM-WCNT-190002 | October 2019