Infections are a major contributor to morbidity and mortality in end-stage renal disease (ESRD)
patients. A better understanding of the interplay between infectious processes and ESRD may
eventually lead to the development of targeted treatment strategies aimed at lowering overall disease
morbidity and mortality. Monogenic causes are a major contributor to the development of adult
chronic kidney disease (CKD). Recent studies identified a genetic cause in 10% to 20% of adults with
CKD. With the introduction of whole-exome sequencing (WES) into clinical mainstay, this
proportion is expected to increase in the future. Once patients develop CKD/ESRD due to a genetic
cause, secondary changes, such as a compromised immune status, affect overall disease progression
and clinical outcomes. Stratification according to genotype may enable us to study its effects on
secondary disease outcomes, such as infectious risk. Moreover, this knowledge will enable us to better
understand the molecular interplay between primary disease and secondary disease outcomes.
Sources of information:
We conducted a literature review using search engines such as PubMed, PubMed central, and
Medline, as well as cumulative knowledge from our respective areas of expertise.
Methods:
This is a transdisciplinary perspective on infectious complications in ESRD due to monogenic causes,
such as autosomal dominant polycystic kidney disease (ADPKD), combining expertise in genomics
and immunology.
Key findings:
In ADPKD, infection is a frequent complication manifesting primarily as lower urinary tract infection
and less frequently as renal infection. Infectious episodes may be a direct consequence of a specific underlying structural abnormality, for example the characteristic cysts, among others. However,
evidence suggests that infectious disease risk is also increased in ESRD due to secondary not-wellunderstood
disease mechanisms. These disease mechanisms may vary depending on the underlying
nature of the primary disease. While the infectious disease risk is well documented in ADPKD, there
are currently insufficient data on the risk in other monogenic causes of ESRD. WES in combination
with novel technologies, such as RNA sequencing and single-cell RNA sequencing, can provide
insight into the molecular mechanisms of disease progression in different monogenic causes of
CKD/ESRD and may lead to the development of novel risk-stratification profiles in the future.
Limitations:
This is not a systematic review of the literature and the proposed perspective is tainted by the authors’
point of view on the topic.
Implications:
WES in combination with novel technologies such as RNA sequencing may enable us to fully unravel
underlying disease mechanisms and secondary disease outcomes in monogenic causes of CKD and
better characterize individual risk profiles. This understanding will hopefully facilitate the
development of novel targeted therapies.
Keywords: End-Stage Renal Disease, infection, immune system, polycystic kidney
disease, monogenic kidney disease, whole-exome sequencing, RNA sequencing
Publication date: 25/09/2021
https://ijbpas.com/pdf/2021/September/MS_IJBPAS_2021_SEPT_SPCL_1020.pdf
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https://doi.org/10.31032/IJBPAS/2021/10.9.1020
