Cardiovascular Journal of Africa: Vol 31 No 2 (March/April 2020)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 2, March/April 2020 AFRICA 91
Impact of metabolic and inflammatory changes on
glomerular function beyond conventional risk factors in
an urban South Africa community with prevalent obesity
Glenda Norman, Angela J Woodiwiss, Vernice Peterson, Monica Gomes, Pinhas Sareli, Gavin R Norton
Abstract
Objectives: To determine the extent to which metabolic and
inflammatory changes are associated with renal damage
beyond conventional risk factors in a community sample with
a high prevalence of obesity in urban South Africa.
Methods: This was a cross-sectional, community-based study
in 1 010 (n = 872 without diabetes mellitus, DM) randomly
selected participants over 16 years of age in an urban, devel-
oping community (Soweto, Johannesburg) with a high preva-
lence of obesity (41.8%). We assessed estimated glomerular
filtration rate (eGFR), conventional risk factors including
adiposity indices, and metabolic changes and plasma resis-
tin concentrations (ELISA) and the homeostasis model of
insulin resistance (HOMA-IR). Relationships independent
of haemodynamic loads were confirmed using ambulatory
blood pressure and central arterial haemodynamics.
Results: In multivariate regression models conducted in
those without DM, HOMA-IR (standardised β-coefficient
= –0.13 ± 0.03, p < 0.0001) and plasma resistin concentra-
tions (β-coefficient = –0.10 ± 0.02, p < 0.0001) were second
only to age, and at least as strong as systolic blood pressure
( β-coefficient = –0.04 ± 0.03, p = 0.19) in the impact on eGFR,
while alternative conventional risk factors including adipos-
ity indices and the metabolic syndrome features contributed
little to eGFR. Similar results were obtained in relationships
with chronic kidney disease (CKD) and in the whole group
including those with DM. Adjustments for ambulatory blood
pressure or central arterial loads did not influence these rela-
tionships.
Conclusions: The impact on glomerular function of insulin
resistance and inflammatory changes is well beyond modi-
fiable conventional risk factors, including the metabolic
syndrome. Targeting conventional risk factors alone is likely
to result in a marked residual risk of renal damage produced
by insulin resistance and inflammation.
Keywords: chronic kidney disease, resistin, insulin resistance
Submitted 7/2/19, accepted 2/10/19
Published online
Cardiovasc J Afr 2020; 31: 91–102
DOI: 10.5830/CVJA-2019-057
Chronic kidney disease (CKD), as defined by reductions in
estimated glomerular filtration rate (eGFR), is in most countries
a major public health problem.1,2 CKD not only progresses to
end-stage renal disease, but also predicts cardiovascular events
beyond conventional risk factors.3-8 Although poor control of
hypertension and diabetes mellitus accounts for a substantial
portion of reductions in eGFR, decreases in eGFR may be
attributed to obesity.9-11 Importantly, several studies have
demonstrated relationships between the obesity-associated
metabolic change, insulin resistance, 12-15 or increased circulating
concentrations of pro-inflammatory adipokines16-29 and renal
dysfunction independent of diabetes mellitus or conventional
blood pressure (BP). These effects may be through direct actions
on the kidney,30-32and as a consequence, the adverse effects of these
metabolic and inflammatory changes may not be amenable to
preventative strategies by targeting conventional risk factors alone.
Obesity-associated insulin resistance or adipocytokine
changes may nevertheless also contribute to the development
of type 2 diabetes mellitus or hypertension.30 Hence the impact
of these changes on renal function may not be distinct from
these conventional risk factors.30 Targeting conventional
risk factors may therefore have major benefits to preventing
metabolic or inflammatory effects on CKD. However, the
extent to which insulin resistance and adipocytokine changes
compared to modifiable conventional cardiovascular risk factors
determine eGFR or CKD is unclear. Therefore, in a large
sample of a community with prevalent obesity, we assessed
the relative impact on eGFR and CKD of insulin resistance
and inflammatory changes compared to that of modifiable
conventional risk factors including metabolic syndrome features.
To avoid the statistical limitation of performing multiple
comparisons with several biomarkers, in this study we focused
on the pro-inflammatory adipokine resistin, as of all the
adipokines, resistin has demonstrated the most consistent and
robust relationships with renal dysfunction.16,18-26,28,29
Methods
This study was conducted according to the principles outlined
in the Helsinki Declaration. The Committee for Research
on Human Subjects of the University of the Witwatersrand
approved the protocol (approval numbers: M02-04-72 renewed
as M07-04-69, M12-04-108 and M17-04-01). Participants gave
informed, written consent.
Cardiovascular Pathophysiology and Genomics Research
Unit, School of Physiology, Faculty of Health Sciences,
University of the Witwatersrand, Johannesburg, South Africa
Glenda Norman, PhD
Angela J Woodiwiss, PhD,
Vernice Peterson, PhD
Monica Gomes, MS
Pinhas Sareli, MD, FRCP
Gavin R Norton, MD, PhD,