Novel Therapies in APOL1-Mediated Kidney Disease: From Molecular Pathways to Therapeutic Options

Vasquez-Rios, George; De Cos, Marina; Campbell, Kirk N.

doi:10.1016/j.ekir.2023.08.028

Cited by 7 publications

(6 citation statements)

References 78 publications

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“…The possible explanation could be differences in the study populations; in our study we enrolled patients with early CKD (CKD stages 1-3) unlike other studies that enrolled patients in CKD stage 4, also in this study only black patients were enrolled unlike in other studies. Studies have reported individuals with advanced CKD stages and African ancestry have a faster rate of CKD progression (45,46).…”

Section: Discussionmentioning

confidence: 99%

Progression of chronic kidney disease among adults attending tertiary hospitals in Dodoma, Tanzania

Katatwire,

Meremo

2024

Preprint

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Background Chronic kidney disease (CKD) in resource constrained settings can silently and rapidly progress to end stage kidney disease (ESKD). Thus, it is important to identify patients at risk of CKD progression for appropriate and timely interventions. Methods A prospective longitudinal study was conducted among adults with CKD attending nephrology and medical outpatient (MOPD) clinics of two tertiary hospitals in Dodoma, Tanzania between November 2020 to March 2022. Demographic and clinical data were extracted from patient files, as well as measurements of vital signs and face to face interviews conducted at baseline and at follow up. Patients provided urine and blood samples for laboratory investigations at study entry (0) and at 12 months. Descriptive and inferential statistics were performed using SPSS software version 26, and multivariable logistic regression analysis was used to identify factors associated with CKD progression. Results A total of 352 participants with median age of 54 (47–59) years were enrolled, the prevalence of CKD progression by a sustained decline in eGFR > 4 ml/min/1.73m2 per year was 28.0% (97/346). For CKD progressors; the baseline median eGFR was 43 (41–49) mL/min/1.73 m2, urine protein creatinine ratio (uPCR) was 0.099 (0.025–0.158) g/g and haemoglobin were 11.7 (9.7–12.6) g/dl. Of the patients with CKD progression, 73(75.3%) patients had diabetes mellitus, 70 (72.2%) of the patients had hypertension, 57 (58.8%) had significant proteinuria and 57 (58.8%) had anaemia. Variables associated with CKD progression after multivariate logistic regression analysis were; diabetes mellitus (OR = 7.02, 95% CI 3.01–16.39, P = 0.001), use of local herbs (OR = 27.98, 95% CI 11.08–70.70, P = 0.001), anaemia (OR = 2.49, 95% CI 1.32–4.68, P = 0.005), proteinuria (OR = 7.51, 95% CI 3.49–16.19 P = 0.001). Half (52.5%) of the patients with CKD progression were found to have left ventricular hypertrophy (LVH) and a total of 14 (11.9%) patients died during the study period. Conclusion The prevalence of CKD progression is high in our settings. Diabetes mellitus, proteinuria, anaemia and use of local herbal medicines were significant risk factors for CKD progression. More than half of the patients who had CKD progression were found to have LVH and few patients died.

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Section: Discussionmentioning

confidence: 99%

Progression of chronic kidney disease among adults attending tertiary hospitals in Dodoma, Tanzania

Katatwire,

Meremo

2024

Preprint

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“…135,136 Further mediators of excess ApoL1 are postulated, including Stimulator of interferon genes, RIG-1, JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathways, and NF-κβ in the setting of HIV. 136,137 Insight has been gained into the pathogenic mechanisms inciting podocyte injury, but the clinical application of genetic testing outside a research setting remains to be determined. Despite a lower prevalence of HIVAN following cART initiated at HIV diagnosis, APOL1 G1, and G2 alleles remain a contributor to worsening renal function.…”

Section: Apol1 Risk Alleles Contribute To Hiv-associated Renal Diseasementioning

confidence: 99%

“…135 Human studies using antisense oligonucleotides are awaiting results. 137 Inaxaplin, an APOL1 small molecule inhibitor, has been shown to reduce proteinuria successfully in phase II clinical trials. 140 With ongoing clinical trials, JAK/STAT pathway inhibitors are promising therapies targeting APOL1-mediated inflammatory pathways.…”

Section: Apol1 Risk Alleles Contribute To Hiv-associated Renal Diseasementioning

confidence: 99%

Section: Renal Comorbidities In People Living With Hivmentioning

confidence: 99%

“…Despite a lower prevalence of HIVAN following cART initiated at HIV diagnosis, APOL1 G1, and G2 alleles remain a contributor to worsening renal function. 137 In one study, 2 renal risk variants were associated with higher level HIV viraemia (odds ratio, 2.37 [95% CI, 1.0–5.63]; P =0.05). However, compliance with cART could not be confirmed.…”

Section: Renal Comorbidities In People Living With Hivmentioning

confidence: 99%

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Cardiac and Renal Comorbidities in Aging People Living With HIV

McCutcheon,

Nqebelele,

Murray

et al. 2024

Circulation Research

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Contemporary World Health Organization data indicates that ≈39 million people are living with the human immunodeficiency virus. Of these, 24 million have been reported to have successfully accessed combination antiretroviral therapy. In 1996, the World Health Organization endorsed the widespread use of combination antiretroviral therapy, transforming human immunodeficiency virus infection from being a life-threatening disease to a chronic illness characterized by multiple comorbidities. The increased access to combination antiretroviral therapy has translated to people living with human immunodeficiency virus (PLWH) no longer having a reduced life expectancy. Although aging as a biological process increases exposure to oxidative stress and subsequent systemic inflammation, this effect is likely enhanced in PLWH as they age. This narrative review engages the intricate interplay between human immunodeficiency virus associated chronic inflammation, combination antiretroviral therapy, and cardiac and renal comorbidities development in aging PLWH. We examine the evolving demographic profile of PLWH, emphasizing the increasing prevalence of aging individuals within this population. A central focus of the review discusses the pathophysiological mechanisms that underpin the heightened susceptibility of PLWH to renal and cardiac diseases as they age.

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Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2

Sula Karreci,

Jacas,

Donovan

et al. 2024

Kidney International

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Novel Therapies in APOL1-Mediated Kidney Disease: From Molecular Pathways to Therapeutic Options

Cited by 7 publications

References 78 publications

Progression of chronic kidney disease among adults attending tertiary hospitals in Dodoma, Tanzania

Progression of chronic kidney disease among adults attending tertiary hospitals in Dodoma, Tanzania

Cardiac and Renal Comorbidities in Aging People Living With HIV

Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2

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