Abstract
Background: Albuminuria is a treatable medical condition linked to cardiovascular and kidney diseases. People living with HIV (PWH) are 1.5 to 2 times likely to develop cardiovascular disease when compared to the general population. However, knowledge of burden, trajectory and predictors of albuminuria among virally suppressed black PWH in sub-Saharan Africa is lacking. This PhD project compared two different cut-off points of albuminuria considered significant to warrant treatment (also known as clinically significant); estimated the prevalence of clinically significant albuminuria among PWH; examined the link between systemic inflammation (chemicals released by the body in response to chronic infection such as HIV) and albuminuria; and finally, assessed the evolution of albuminuria over time.Methods: Between January 2020 and March 2021, during COVID19 pandemic this PhD project used convenience sampling to enroll 1537 PWH treated at Princess Marina Hospital HIV clinic and satellite HIV clinics across the city of Gaborone, Botswana, into a cross-sectional study. Between January 2020 and March 2022, a sub-group of 867 participants from the main cross-sectional study (N=1537) were invited to participate in a 12-month prospective observational cohort study to assess albuminuria trajectory. Patients who reported activities or exposure to factors known to affect urine albumin levels were excluded. Study activities included obtaining a brief medical record, reviewing medical records, obtaining anthropometric measurements and providing a one-time morning blood and urine sample, for the cross-sectional studies and then month 0, 6 and 12 sampling for those participating in the prospective observational longitudinal study. Cohen’s kappa was used to assess agreement between sex-based and non-sex-based albumin-creatinine ratio (ACR) cut-off point to spot urine albumin (UA). The ACR cut-off point that categorized more participants as having albuminuria was used to estimate the prevalence of albuminuria. The association between systemic inflammation (exposure) and albuminuria was assessed using general additive models. Albuminuria longitudinal trajectory was assessed using growth mixture models, and then modified Poisson regression models for factors associated with albuminuria trajectory groups.
Results: Among the 1534 participants with complete data, their mean age was 48.5 (SD 10.3) years, they had been living with HIV for a median 14.3 (IQR 9.6-16.8) years and 764 (49.7%) were female. There was moderate agreement between nonsex based ACR cut-off point and UA, [Kappa static of 0.71 (95% CI 0.67, 0.76)]. The prevalence of albuminuria was 20.7% (318/1533) using sex-based ACR cut-off point. There was no association between systemic inflammation and albuminuria, p=0.82, p=0.26 and p=0.14 for IL1b, IL6 and sCD163 respectively. Participants were categorized into slow, 290/623 (46.5%) and fast, 333/623 (53.5%), increasing ACR trajectories, which translated into 4.7mg/g (IQR 3.1-7.3) and 11.5mg/g (IQR 2.6-31.9) increase in albuminuria respectively by the end of follow-up.
Conclusion: In a cohort of treated PWH in Botswana, one in five had clinically
significant albuminuria but HIV associated systemic inflammation was not linked to albuminuria. All participants in the prospective cohort experienced a rise in albuminuria. Larger longitudinal studies are required to establish frequency of screening for albuminuria among PWH. In addition, clinical trials are needed to study benefits of medical therapies for albuminuria among PWH.
| Date of Award | 11 Feb 2026 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Shabbar Jaffar (Supervisor), Duolao Wang (Supervisor) & Joseph N. Jarvis (Supervisor) |
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