A large proportion of HIV-positive people diagnosed with chronic kidney disease go on to develop a serious illness or die within a few years, according to results from a large international study published in AIDS. Individuals were followed for an average of three years after diagnosis with chronic kidney disease and during this time approximately a quarter experienced a serious clinical event. The investigators found that several modifiable risk factors were associated with these illnesses and deaths, for example smoking, diabetes and a low CD4 cell count and detectable viral load.
“Several potentially modifiable risk factors predicted post-chronic kidney disease serious clinical events,” comment the authors. “Our findings suggest more intensified monitoring and interventions targeted towards these modifiable risk factors in those with chronic kidney disease is warranted.”
Chronic kidney disease is a well-recognised potential complication of infection with HIV. Its potential causes include a low CD4 cell count and ongoing HIV replication, co-infections, traditional risk factors such as diabetes and hypertension and the side effects of some medications.
However, relatively little is known about rates of serious illness and death following a diagnosis of chronic kidney disease among individuals with HIV. Nor is the association between these serious clinical events and modifiable risk factors well understood.
An international team of investigators led by Dr Lene Ryom of the University of Copenhagen therefore designed a prospective study involving 2467 HIV-positive people who had been diagnosed with chronic kidney disease. They were followed until early 2016 or until the development of end-stage kidney disease or another serious illness, such as cancer, cardiovascular disease, AIDS or death.
Chronic kidney disease was defined as confirmed eGFR of 60 ml/min per 1.733 or below or a 25% decline in eGFR. Data were obtained from the ongoing D:A:D study, a collaboration of cohorts in Europe, the United States and Australia, established to report on clinical events among HIV-positive individuals.
The majority of people with chronic kidney disease were white (51%), male (77%) and their median age was 60 years.
There was a high prevalence of potentially modifiable risk factors. A third of those diagnosed with chronic kidney disease were smokers, 16% were diabetic, a fifth had high blood pressure, 59% had high blood lipids and 30% had a CD4 cell count below 350 and/or a viral load above 10,000. Serious loss of kidney function (eGFR below 30ml/min per 1.73m3) was diagnosed in 6% of participants.
The median duration of follow-up was 2.7 years and during this time 24% of individuals experienced a serious clinical event. The most common was death (32 per 1000 person-years of follow-up), followed by diagnosis with a non-AIDS cancer (15 per 1000 person-years of follow-up), cardiovascular disease (15 per 1000 person-years of follow-up) and development of an AIDS-defining illness (13 per 1000 person-years of follow-up).
In the first year following diagnosis with chronic kidney disease an estimated 8% of individuals developed a serious clinical event, increasing to 29% after five years. The one- and five-year mortality rates were estimated at 4% and 15%, respectively. The most common causes of death were non-AIDS cancers (23%) and cardiovascular disease (20%). Fewer than 5% died of renal failure.
"Individuals with chronic kidney disease should receive regular follow-up and intensive efforts to address risk factors."
As regards modifiable risk factors and serious clinical outcomes, smoking was associated with all types of illnesses and also death. There was a strong association between diabetes and cardiovascular disease, non-AIDS cancers and also death. A low CD4 cell count and/or viral load above 10,000 was associated with the development of an AIDS-defining illness and death. Both these outcomes were also associated with a low BMI (below 18 kg/m2).
The investigators also looked at the proportion of serious clinical events attributable to modifiable risk factors. They calculated that 6 to 11% of all events would have been prevented had people not been smokers. Diabetes was estimated to be the cause of between 6% and 12% of cases of cardiovascular diseases and deaths. A third of AIDS diagnoses and 14% of AIDS-related deaths would have been prevented with optimal HIV control (a CD4 cell count of at least 350 and an undetectable viral load). Between 10% and 20% of cases of cardiovascular disease and deaths would have been prevented by reducing blood lipids.
Comparison of outcomes between HIV-positive individuals with and without chronic kidney disease showed that those with chronic kidney disease had an almost threefold increase in their risk of a serious clinical event or death. Individuals with chronic kidney disease had an especially high risk of developing end-stage renal disease (risk increased 65-fold) and of death (a fivefold increase in risk).
Rymon and colleagues believe their findings have immediate clinical significance. Individuals with chronic kidney disease should receive regular follow-up and intensive efforts should be taken to address risk factors that can contribute to the development of serious illnesses.
“In an era when many people living with HIV require less monitoring because of effective and well tolerated antiretroviral therapy, those living with even moderate chronic kidney disease have a high morbidity and mortality burden,” conclude the authors. “Our data further suggest that modifiable risk factors…play a central role for chronic kidney disease-related morbidity, and highlight the need of increasing monitoring, targeted interventions and focus on preventative measures for those living with HIV and chronic kidney disease.”
Ryom L et al. Serious clinical events in HIV-positive persons with chronic kidney disease. AIDS, online ahead of print, 2019.