Older age and baseline kidney function, not ARV choice, are key risk factors for chronic kidney disease in people with HIV in Australian cohort

Older age and lower baseline kidney function are the only significant risk factors for the development of chronic kidney disease (CKD) in HIV-positive adults, investigators from Australia report in AIDS. No antiretroviral (ARV) drug was associated with a decline in estimated glomerular filtration rate (eGFR) – a key marker of kidney function – below the key 60 ml/min threshold.

“Our study was not designed to address ARV treatment decisions; however, in demonstrating increased CKD risk associated with an eGFR of 60-89 ml/min, we have highlighted a subgroup in which earlier tailoring of ART [antiretroviral therapy] may be appropriate,” comment the authors. “Our finding that neither current, nor cumulative TDF [tenofovir disoproxil fumarate] exposure increased the risk of CKD was not in keeping with the wider literature and international guidelines would suggest avoidance of TDF in individuals with a high risk of CKD.”

There is a well-established association between HIV infection and an increased risk of CKD. Reasons include damage caused by the virus, a high prevalence of traditional risk factors such as diabetes and hypertension, and the side-effects of some antiretroviral drugs. Of note, older age is also an acknowledged risk factor for CKD.

Glossary

hypertension

Raised blood pressure.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

glucose

A simple form of sugar found in the bloodstream. All sugars and starches are converted into glucose before they are absorbed. Cells use glucose as a source of energy. People with a constant high glucose level might have a disease called diabetes.

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

With this in mind, investigators in Melbourne, Australia, designed a retrospective study involving 748 adult HIV-positive people who received care between 2009 and 2016. All had normal kidney function at baseline (eGFR above 60ml/min). The study’s aims were to identify risk factors associated with the development of CKD and also to see if two widely used risk scores (short D:A:D and Scherzer) were able to accurately predict which people had the highest risk of developing CKD (two consecutive eGFR results less than 60 ml/min).

Study participants were predominately male (91%) and had a median age of 46 years. Data on blood pressure were available for two-thirds of people and 26% of these individuals had hypertension (blood pressure of at least 140/90 mmHg). Medium serum glucose was within the normal range, though 5% of people were classified as diabetic. Most of the participants (93%) were taking ART. Median CD4 cell count was 483 cells/mm3 and two-thirds were virologically suppressed.

Baseline median eGFR was 106ml/min and declined by a median of 0.53min/ml per year. Only a third of people underwent urinary analysis, with 7% of these individuals having proteinuria.

During a median of 4.7 years of follow-up, CKD developed in 5% of people.

Individuals who went on to develop CKD had a lower median baseline eGFR compared to those who retained good kidney function (75m/min vs 107 ml/min). They were older (median 55 years vs 46 years).

In initial analysis, older age, diabetes, proteinuria, higher baseline creatinine, lower baseline eGFR, longer duration of HIV infection and lower nadir CD4 cell count were all risk factors for the development of CKD.

In the multivariate analysis that controlled for potential confounders, the only significant factors were older age (OR = 3.03; 95% CI, 1.20-7.65, p = 0.02) and lower baseline eGFR (OR = 10.39; 95% CI, 4.73-22.83, p < 0.001).

“ARV use at baseline was not found to be associated with subsequent development of CKD,” comment the authors. “Neither current, nor cumulative TDF exposure was associated with the development of CKD.”

Both risk scores predicted CKD, with results favouring the short D:A:D score. The Scherzer risk score includes age, blood glucose, triglycerides, hypertension, CD4 cell count and proteinuria. The D:A:D risk score takes into account age, sex, injecting drug use, hepatitis C virus co-infection, eGFR and nadir (lowest ever) CD4 cell count.

Limitations of the study include its retrospective, observational, single-centre design. Data were also lacking for many people for key markers or risk factors for CKD, such as hypertension and proteinuria.

 “Our results confirm that ageing significantly increases the risk of CKD, which has important implications with respect to the increasing life expectancy of HIV-positive individuals,” write the researchers. “A lower baseline eGFR of 60-89 ml/min was associated with subsequent risk of CKD.”

“Risk prediction tools can assist clinicians to stratify those at highest risk, with most to gain from increased monitoring, judicious ARV selection and aggressive management of risk factors,” they conclude.

References

Woolnough EL et al. Predictors of chronic kidney disease and utility of risk prediction scores in HIV-positive individuals. AIDS, 32: 1829-35, 2018.

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