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Introduction Data on renal impairment in sub-Saharan Africa (SSA) remains scarce, determination of renal function is not part of routine assessments. We evaluated renal function and blood pressure in a cohort of people living with HIV (PLWH) on antiretroviral treatment (ART) in the Renal Care Zambia project (ReCaZa). Methods Using routine data from an HIV outpatient clinic from 2011-2013, we retrospectively estimated the glomerular filtration rate (eGFR, CKD-Epi formula) of PLWH on ART in Lusaka, Zambia. Data were included if adults had had at least one serum creatinine recorded and had been on ART for a minimum of three months. We investigated the differences in eGFR between ART subgroups with and without tenofovir disproxil fumarate (TDF), and applied multivariable linear models to associate ART and eGFR, adjusted for eGFR before ART initiation. Results and discussion Among 1118 PLWH (63,3% female, mean age 41.8 years, 83% ever on TDF; median duration 1461 [range 98 to 4342] days) on ART, 28.3% had an eGFR <90 ml/min, and 5.5% <60 ml/min at their last measurement. Information on other conditions associated with renal impairment was not systematically documented. Fourteen per cent of the PLWH who later switched to TDF-free ART had an initial eGFR lower 60ml/min. Nineteen percent had first-time hypertensive readings at their last visit. The multivariable models suggest that physicians acted according to guidelines and replaced TDF-containing ART if patients developed moderate/severe renal impairment. Conclusions Assessment of renal function in SSA remains a challenge. The vast majority of PLWH benefit from long-term ART, including improved renal function. However, approximately 5% of PLWH on ART may have clinically relevant decreased eGFR, and 27% hypertension. While a routine renal assessment might not be feasible, strategies to identify patients at risk are warranted. Targeted monitoring prior and during ART is recommended, however, should not delay ART access.
The study protocol received ethical clearance from the ethical committee of Heidelberg University (approval number S-024/2014) and Chreso University (approval number 2013-Sept-001). Written informed consent from patients was not required since this retrospective research only used routinely collected data. Since 2004, CM contributes considerably to the provision of HIV services in Lusaka Central and Southern provinces of Zambia. It serves more than 40,000 clients in care, with 15,000 receiving ART. Chreso Ministries in Lusaka (Chreso Lusaka, CL) see the largest number of PLWH. CL is located in a densely populated, low-income area of Lusaka, with estimated 44,000 inhabitants. Patients usually register after voluntary counselling and testing or through maternal and child health services. Following an equitable access approach, persons eligible for ART are 1) PLWH tested positive with a CD4 count <500 cells/ml, 2) HIV+ pregnant or breastfeeding women, 3) partners of these women, 4) individuals with HIV/TB co-infection, and 5) children less than 15 years. After registration, body weight and vital signs (e.g. blood pressure) are recorded. Haemoglobin (Hbg), AST and ALT, serum creatinine and CD4-counts are routinely assessed at enrolment. More specific diagnostic procedures e.g. for diabetes or viral hepatitis are not part of the routine assessment. Starting with the first patient file that came into the data management unit on a clinic day, and as many of the consecutive files as possible were entered into a separate study database. Data were included in the analysis if the persons were 18 years or older at HIV diagnosis, had at least one creatinine determination between January 1, 2011 and December 31, 2013, and if they had received ART for at least 90 days at their last creatinine measurement. If ART was initiated before HIV diagnosis (persons transferred in), their HIV diagnosis date was set to the initiation of ART. Data were processed, transferred and analysed in a pseudonymized form. Samples were obtained onsite by trained lab technicians as part of a routine evaluation. Plasma creatinine concentrations were determined by photometric assay (Jaffe reaction, Roche). Reference values were 62–106 μmol/l for men and 44–80 for women. Standardized control samples were analysed every day. Repetitive control measurements with standard samples in the normal and pathological range resulted in inter-assay coefficients of variation of 5.5% and 3.7%, respectively. Complete blood count including hemoglobin concentration (ABX Micros 60, Axonlab, Switzerland), CD4 count (BD Facscount, USA), and alanine transaminase (ALT) and aspartate transaminase (AST) analysis (Cobras c111, Roche, Germany) were performed. We estimated the eGFR according to the CKD-EPI equation [18]: (κ = 0.7 for women, κ = 0.9 for men; α = -0.329 for women, α = -0.411 for men). Persons were classified in eGFR categories 1 to 5, according to the Kidney Disease Improving Global Outcomes (KDIGO). Persons with an eGFR equal to or above category 3a (< 60ml/min) were categorized as having a renal impairment requiring immediate attention. Blood pressure (BP) was taken twice using manual syphingo-manometers, with the patients seated with their arm resting on a desk. Persons were grouped into systolic BP <120, 120–139, and ≥140 mm HG categories. Mean arterial pressure (MAP = diastolic+1/3[systolic-diastolic]) was calculated. Data were retrieved for 1) date of first laboratory test after HIV diagnosis, and 2) date of last creatinine determination between 2011 and 2013. Statistical comparison was done by means of Wilcoxon signed rank test. Univariate analyses at time of last creatinine determination were used to investigate differences between persons continuously receiving TDF-free ART (ARTTDF free), continuously receiving TDF-containing ART (ARTTDF), and persons whose TDF-containing ART was switched to a TDF-free ART (ARTswtiched) over the course of time. A multivariable linear regression model was applied to the subgroup of patients with an additional creatinine reading available after HIV diagnosis but before ART initiation (N = 565) to investigate associations of eGFR and ART categories at their last measurement, adjusted for initial eGFR, age and sex. After confounder assessment, systolic blood pressure and length of HIV duration were included. ART time period was highly correlated with HIV duration time (Pearson correlation coefficient 0.92), thus excluded from the model. Additionally, two sensitivity analyses at the last point of measurement were performed (N = 1118) to account for possible selection bias in the subgroup, and to investigate differences in single ART regimens. Treatment interruptions and crossovers could not be determined. All modelling was done in SAS version 9.3. Linear relations of all continuous covariates to the outcome were confirmed by the multivariate fractional polynomials approach in Stata version 14 [19].
