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Page 2 of 15 Original Research

inhibitor (NtRTI), tenofovir disoproxil fumarate (TDF), guidelines recommend therefore that the Counahan-Barratt
the nucleoside reverse transcriptase inhibitors (NRTIs) equation be used to measure the eGFR of youths aged 10–16
emtricitabine (FTC) or lamivudine (3TC) and the non- years and the Modifications of Diet in Renal Disease (MDRD)
nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz equation be used for adolescents and adults 16 years of age
6
(EFV). This is first-line ART. Current SA national ART and older. 9
guidelines indicate that the integrase strand transfer inhibitor
(INSTI), dolutegravir (DTG), has replaced efavirenz for all The Cockcroft-Gault (CG) equation incorporates the serum
except women of child-bearing age who may fall pregnant or creatinine level and the variables of weight, age and sex in
those initiating ART in the first trimester of pregnancy. 9,10 the measurement of the eGFR. 21 The equation has
Tenofovir however remains the standard NRTI-backbone of limitations: in pregnancy, at the extremes of weight, and in
all first-line ART in southern Africa. those on dialysis for acute renal failure. Its principal use is
in drug dosing and pharmacokinetic studies. The MDRD
20
equation adds a fourth variable: race. 22 This ethnicity
TDF is an acyclic nucleoside phosphate prodrug. Its long adjustment-factor is based on African Americans and
half-life permits once-daily dosing. Although the drug is tends to overestimate the GFR in sub-Saharan (African)
extensively filtered by the kidneys, 20% – 30% is actively populations. 23 The CKD–Epidemiology Collaboration
11
reabsorbed at the proximal tubule. TDF is an occasional (EPI) equation is recommended by the KDIGO guidelines
cause of renal injury viz. a proximal renal tubulopathy and a group and has been validated in participants with and
salt-wasting syndrome (Fanconi Syndrome and renal tubular without impaired renal function with eGFR < 90 mL/
acidosis), drug-induced acute kidney injury and a slower, min/1.73 min². 17,24 The SA National Health Laboratory
general decline in glomerular filtration, diabetes insipidus, Service (SA-NHLS) currently reports both the MDRD and
and a dysregulation of the kidney’s calcium and phosphorus CKD-EPI eGFR without ethnic adjustment. The adoption
metabolism. 11,12 Impaired renal function may also result from of the CKD-EPI equation in SA has been delayed due to
the use of other drugs, such as aminoglycosides, limited local data.
sulphonamides, and amphotericin B, the presence of HIV-
associated nephropathy (HIVAN), blood-borne infection, for Routine laboratory serum creatinine measurements are
example tuberculosis, bacteraemia and fungaemia, HIV- analysed on Jaffe and enzymatic assays. These methods
associated immune-complex kidney disease and common should be traceable to isotope dilution mass spectrometry
comorbidities such as hypertension and diabetes mellitus. 13,14 (IDMS) method and the Standard Reference Material for
Pre-existing mild renal dysfunction may increase creatinine in serum (SRM 967). NHLS laboratories in SA
susceptibility to the toxicity of TDF. Kidney function must generally use the modified kinetic Jaffe method, as opposed
be evaluated before starting ART: the use of TDF is to the enzymatic assay, as it is more affordable. The World
contraindicated if the estimated glomerular filtration rate Health Organization’s (WHO) guidelines indicate that at
(eGFR) is < 50 mL/min. Patients on TDF have serum room temperature, creatinine is stable for 2–3 days. 25
creatinine measured at 3 and 6 months following the initiation However, a report from Shepherd et al. noted a significant
26
of ART and biannually thereafter. In high-risk patients, for increase in creatinine levels measured on the kinetic Jaffe
example with coexistent hypertension or diabetes, the method when processing occurred later than 24 h. This
26
creatinine is measured more frequently. 9 impacted the study’s eGFR results and had caused the renal
misclassification of patients. A turnaround time for serum
26
The measurement of the GFR confirms and stages the degree creatinine measurements from local clinics in Gauteng of
of renal impairment and provides a platform for the ongoing 12–72 h has been observed at NHLS laboratories, as reported
monitoring of kidney function. Although the urinary in the internal TAT reports. This delay increases with the
clearance of inulin is the gold standard of GFR measurement, remoteness of clinics due to the poor transport networks,
15
the method is time-consuming, expensive and impractical in the restricted working hours at referral laboratories, and the
most clinical settings. Endogenous substances such as serum greater workload of regional laboratories. The aim of this
creatinine and cystatin C are cheaper, provide more rapid study was to determine, in HIV-positive black South
16
results and are widely available. Although the National Africans not on ART, the stability limit (SL), that is, the time
Institute for Health and Care Excellence (NICE) and the at room temperature, when the serum creatinine results are
Kidney Disease Improving Global Outcomes (KDIGO) still within the maximum permissible instability (MPI)
groups both base their eGFR assessment (equations) on range. 27
cystatin C, its cost and lack of standardisation excludes its
general use. 17,18 Creatinine is produced at a constant rate, is Methods
present in all body fluids, and is filtered by the glomerulus. Study population
Its serum level is influenced by several biological factors,
such as active secretion by the renal tubules in the presence Twenty-two (n = 22) newly diagnosed and treatment-naïve
of declining renal function, diet, extremes of muscle mass, people living with HIV between the ages of 18 and 70 years
age, gender, drugs and the use of creatine supplements. 19 were randomly recruited from the Alexandra Health
Several equations control for some of these variables. The Community Centre in Alexandra, Johannesburg, SA. The
20
SA National Department of Health (SANDOH) 2019 minimum number of participants required for testing

http://www.sajhivmed.org.za 188 Open Access