Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Chronic kidney disease in the global adult HIV-infected population: A systematic review and meta-analysis

  • Udeme E. Ekrikpo ,

    Contributed equally to this work with: Udeme E. Ekrikpo, Andre P. Kengne

    Roles Conceptualization, Formal analysis, Writing – original draft, Writing – review & editing

    Affiliations Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa, Renal Unit, Department of Medicine, University of Uyo, Uyo, Nigeria, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa

  • Andre P. Kengne ,

    Contributed equally to this work with: Udeme E. Ekrikpo, Andre P. Kengne

    Roles Conceptualization, Formal analysis, Supervision, Writing – original draft, Writing – review & editing

    Affiliation Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, Cape Town, South Africa

  • Aminu K. Bello ,

    Roles Conceptualization, Supervision, Writing – original draft, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation Division of Nephrology and Immunology, Department of Medicine, University of Alberta, Edmonton, Canada

  • Emmanuel E. Effa ,

    Roles Conceptualization, Writing – original draft, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation Renal Unit, Department of Medicine, University of Calabar, Calabar, Nigeria

  • Jean Jacques Noubiap ,

    Roles Conceptualization, Formal analysis, Writing – original draft, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa

  • Babatunde L. Salako ,

    Roles Conceptualization, Writing – original draft, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria

  • Brian L. Rayner ,

    Roles Conceptualization, Writing – original draft, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliations Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa, Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa

  • Giuseppe Remuzzi ,

    Roles Conceptualization, Supervision, Writing – original draft, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Bergamo, Italy

  • Ikechi G. Okpechi

    Roles Conceptualization, Formal analysis, Supervision, Writing – original draft, Writing – review & editing

    Ikechi.Okpechi@uct.ac.za

    Affiliations Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa, Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa

Abstract

Introduction

The widespread use of antiretroviral therapies (ART) has increased life expectancy in HIV patients, predisposing them to chronic non-communicable diseases including Chronic Kidney Disease (CKD). We performed a systematic review and meta-analysis (PROSPERO registration number CRD42016036246) to determine the global and regional prevalence of CKD in HIV patients.

Methods

We searched PubMed, Web of Science, EBSCO and AJOL for articles published between January 1982 and May 2016. CKD was defined as estimated glomerular filtration rate (eGFR) <60ml/min using the MDRD, Cockcroft-Gault or CKD-EPI equations. Random effects model was used to combine prevalence estimates from across studies after variance stabilization via Freeman–Tukey transformation.

Result

Sixty-one eligible articles (n = 209,078 HIV patients) in 60 countries were selected. The overall CKD prevalence was 6.4% (95%CI 5.2–7.7%) with MDRD, 4.8% (95%CI 2.9–7.1%) with CKD-EPI and 12.3% (95%CI 8.4–16.7%) with Cockcroft–Gault; p = 0.003 for difference across estimators. Sub-group analysis identified differences in prevalence by WHO region with Africa having the highest MDRD-based prevalence at 7.9% (95%CI 5.2–11.1%). Within Africa, the pooled MDRD-based prevalence was highest in West Africa [14.6% (95%CI 9.9–20.0%)] and lowest in Southern Africa (3.2%, 95%CI 3.0–3.4%). The heterogeneity observed could be explained by WHO region, comorbid hypertension and diabetes mellitus, but not by gender, hepatitis B or C coinfection, CD4 count or antiretroviral status.

Conclusion

CKD is common in HIV-infected people, particularly in Africa. HIV treatment programs need to intensify screening for CKD with added need to introduce global guidelines for CKD identification and treatment in HIV positive patients.

Introduction

Chronic Kidney Disease (CKD) is a worldwide public health problem; moving from 27th to the 18th most important global cause of death within the last 2 decades [1]. This degree of shift was second only to HIV/AIDS [1], suggesting a significant relationship between HIV and CKD as an important intersection between chronic non-communicable diseases (NCDs) and communicable diseases.

With the roll-out of antiretroviral therapies (ARTs), individuals with HIV are now living longer. As a consequence, the spectrum of kidney diseases in HIV patients has broadened, ranging from asymptomatic changes in renal function like proteinuria, [2, 3] electrolyte losses [4] and acute kidney injury [5] occurring from diarrheal illnesses to various degrees of CKD occurring as a result of renal damage from chronic non-communicable diseases or HIV-associated nephropathy (HIVAN). Furthermore, the use of certain medications included in some ART regimens such as tenofovir and ritonavir, has been shown to increase the risk of CKD[6]. Among incident end-stage renal disease (ESRD) patients, HIV has been implicated as the etiologic factor in 0.4%–0.7% of patients in France [7, 8]; 0.5%–1.1% in Spain [9, 10]; 6.6% in Cameroon [11]; and 28.5% in South Africa [12]. One large study has shown that as much as 3.3% of HIV positive patients with normal baseline estimated glomerular filtration rate (eGFR) developed CKD over a relatively short follow up period of 3.7 years, highlighting the burden of kidney disease in HIV patients [13]. The prevalence of CKD in HIV-infected individuals varies widely between geographic regions and depends on the reporting methods and the definition of CKD used, ranging from 2% to 38% [14, 15]. Although there is an increasing number of individual reports on the prevalence of CKD in the HIV population, the data have not been appropriately synthesized to date.

In this analysis, we synthesized available data on CKD prevalence in the adult HIV population at both regional and global levels. The overarching goal was to provide an essential basis to guide contextualized effective prevention and control strategies to tackle the burden of CKD in this population.

Methods

Selection of studies for inclusion in the review

The Preferred Reporting Items for Systematic Reviews and Meta–Analysis (PRISMA) 2009 guidelines [16] served as the template for reporting the present review (S1 Table, Fig 1). The study protocol was published at the International Prospective Register of systematic reviews, (PROSPERO registration number CRD42016036246). All observational studies and clinical trials reporting on the prevalence of CKD in HIV-infected adults (≥ 18 years) or providing enough data to compute it, using established creatinine-based equations [Modification of Diet in Renal Disease (MDRD) [17], Cockcroft–Gault (CG) [18], Chronic Kidney Disease Epidemiology (CKD-EPI) [19]] to estimate GFR were included. CKD was defined as eGFR <60ml/min/1.73m2 irrespective of proteinuria status. Studies that reported CKD as eGFR <60ml/min/1.73m2 and/or persistent proteinuria were only included if we could compute the frequency of those with eGFR <60 ml/min/1.73m2 from available data in the article. We also included studies that reported CKD prevalence using a single estimated eGFR in order to accommodate studies from low-income countries where repeated serum creatinine measurement might not have been performed. A comparison of the pooled prevalence from studies with a single eGFR estimate and that with multiple estimates was also undertaken. We excluded studies with small sample size (<100 participants) and those including both adult and pediatric populations in which it was not possible to disaggregate data for adults. For studies published in more than one report (duplicates), the most comprehensive reporting the largest sample size was considered.

Identification of studies

We searched PubMed/MEDLINE, EBSCO, Web of Science and African Journals Online to identify all relevant articles reporting data on the prevalence of CKD in HIV-infected adults published from January 1, 1982 (when the HIV epidemic started) to September 30, 2016. We conceived and applied a search strategy based on the combination of relevant terms relating to HIV and CKD. The search strategy for Pubmed, web of science, EBSCO and AJOL is shown in S2 Table. No language restrictions were applied. References of all relevant research articles and reviews were also scrutinized to identify additional potential data sources.

Assessment of methodological quality of included articles

The methodological quality of included studies was evaluated using the 9-point rating system developed by Stanifer et al [20] and modified for the purposes of this study. The scoring criteria for quality of studies is shown in S3 Table while S4 Table shows the methodological quality of the included articles. The scoring criteria assessed factors related to representativeness of the study participants, sampling, sample size and assessment of possible confounders to the relationship between HIV and CKD. Studies were rated as having a high, medium or low methodological quality when they were assigned a score higher than 6, 5 and 6; or 4 and below respectively.

Study selection and data extraction

Two investigators (UEE and IGO) independently screened the titles and abstracts of articles retrieved from literature search, and the full-texts of articles found potentially eligible were obtained and further assessed for final inclusion (Fig 1). Disagreements were resolved by consensus or consultation of a third investigator (APK). For clinical trials, we used baseline data. A World Health Organization (WHO) region [21] was assigned to each study depending on the country of recruitment. All studies from Africa were subsequently seperated from the rest and further sub-divided into the different African Union (AU) sub-regions [22] for the purpose of statistical comparisons. Two investigators (UEE and EEE) independently extracted data; discrepancies between investigators were resolved through discussion until consensus was achieved. In one instance [23], an author was contacted for clarification where data was uncertain. Data extracted included first author name, year of publication, country of study origin, WHO region, African sub-region (if study was from Africa), gender proportions in the study population, median age, Body mass index (BMI), CD4 count and viral load of the study population, prevalence of hepatitis B, C co-infection; and the prevalence of hypertension and diabetes mellitus in the study population.

Statistical analyses

A meta-analysis was used to summarize prevalence data. We pooled the study-specific estimates using a random-effects meta-analysis model (DerSimonian-Laird) to obtain an overall summary estimate of the prevalence of CKD according to the different eGFR equations across studies [24], after stabilizing the variance of individual studies with the use of the Freeman-Tukey double arcsine transformation to minimize the effect of extreme prevalence on the overall estimate [25]. Heterogeneity was assessed using the χ2 test on Cochrane’s Q statistic [26] and quantified by calculating the I2 (with values of 25%, 50% and 75% representing low, medium and high heterogeneity respectively)[27]. Subgroups analysis was also performed using the Q-test based on ANOVA. We assessed the presence of publication bias using funnel plots and the Egger’s test [28]. We assessed inter-rater agreement for study inclusion and data extraction using Cohen’s kappa (κ) coefficient [29]. A p-value <0.05 was considered indicative of statistically significant difference between subgroups. Data was analyzed using the statistical software Open Meta Analyst [30] and the metaprop [31] package in STATA version 14.0 for Windows (Stata Corp. 2015. Stata Statistical Software: Release 14. College Station, Tx: Stata Corp USA).

Results

The initial literature search retrieved 1220 articles of which 99 were selected after title and abstract screening for full-text review. Finally, 61 articles [23, 3291] were eligible and included in this systematic review (Fig 1). There was a high agreement between investigators for study inclusion (κ = 0.81).

Included studies reported on 209,078 HIV-infected adults from 60 countries. There were 46,295 participants (26 studies) from Africa; 52,785 (9 studies) from Europe; 52,305 (11 studies) from North America; 3,661 (4 studies) from South America; 49,147 (9 studies) from Western Pacific and 248 (1 study) from the Eastern Mediterranean. One study [76] from multiple countries in more than two continents had 4,637 HIV–infected adults. MDRD, CG and CKD-EPI equations were used to estimate GFR in 45 studies (n = 167,011 participants), 19 studies (n = 59,414 participants) and 14 studies (n = 41,791 participants) respectively. Thirty-one studies (n = 111,415 participants) used MDRD [3235, 3745, 48, 5154, 57, 59, 62, 6569, 82, 84, 85, 89] equation only; 7 (n = 16,756 participants) used CKD–EPI [7680, 83, 86] and 9 (n = 24,622 participants) used CG only [23, 7075, 81]. Seven articles (n = 31,268 participants) applied MDRD and CG [36, 50, 55, 56, 60, 64, 87]; 4 (n = 20,742 participants) applied MDRD and CKD-EPI [46, 47, 49, 58] while 3 (n = 4,275 participants) applied all 3 equations [61, 63, 88]. Most of the articles were cross-sectional (75.4%); followed by cohort studies (18.0%); then case-control 2 (3.3%); clinical trials 2 (3.3%).

The component studies had a sample size range of 163 [58] to 41,862 [89] participants with the proportion of women ranging from 0% [79] to 100% [88]. The mean age of participants ranged from 31.4 [86] to 48.7 [39] years, and median CD4 count from 147 cells/ul [70] to 651 cells/ul [76]. Some studies [23, 34, 35, 42, 55, 59, 7377, 80, 89] consisted exclusively of ART–naïve individuals while the rest had varying proportions on ARTs. The prevalence of hepatitis B and C co-infection ranged from 1.6% [33] to 15.1% [70] and from 3.3% [69] to 50.3% [47] respectively. Most of the studies had medium methodological quality (63.9%, n = 39) (S4 Table); 11 studies (18.0%) were of high quality, including 2 (7.7%) studies from Africa, 3 (33.3%) from Europe and 3 (27.3%) from North America. Table 1 provides a summary of data extracted.

thumbnail
Table 1. Summary of extracted data from all included studies.

https://doi.org/10.1371/journal.pone.0195443.t001

The overall prevalence of CKD was 6.4% (95%CI 5.2–7.7%, N = 45 studies, 167,011 participants, I2 = 98.9%, heterogeneity-p<0.001) using the MDRD equation, 4.8% (95%CI 2.9–7.1%, N = 14 studies, 41,791 participants, I2 = 98.7%; p<0.001) with CKD-EPI and 12.3% (95%CI 8.4–16.7%; N = 19 studies, 59,414 participants, I2 = 99.4%, p<0.001) with the CG equation (p = 0.003 for difference across GFR estimators) (Fig 2). There was no evidence of publication bias (Fig 3) all p≥0.147 for the Egger test).

thumbnail
Fig 2. Forest plot showing the overall CKD prevalence in the HIV-infected using the MDRD, CKD-EPI and CG equations.

For each study the black box represents the study estimate (prevalence of CKD) and the horizontal bar represents the 95% confidence intervals (95%CI). The yellow diamond at the lower tail for each equation is the pooled effect estimates from random effects models.

https://doi.org/10.1371/journal.pone.0195443.g002

thumbnail
Fig 3. Funnel plots for included studies across different serum creatinine-based GFR equations.

For each estimation equation, the arcsine transformed proportion of participants with CKD (relative to the total sample) for each relevant study (horizontal axis) is plotted against its standard error (vertical axis), and represented by the dots. When the dots distribute symmetrically in a funnel shape, this implies an absence of bias. All p-values were >0.05 (Egger test) indicating no evidence of significant publication bias.

https://doi.org/10.1371/journal.pone.0195443.g003

Using the MDRD equation, the African region had the highest prevalence estimate at 7.9% (95%CI 5.2%-11.2%) while the European region had the lowest estimate at 3.7% (95%CI 2.5–5.1%); p = 0.004 for difference across regions. Summaries of pooled prevalence by region and GFR estimators are presented in Fig 4 and Table 2; summary statistics from meta-analyses of prevalence studies on CKD in people with HIV using random effects model and arcsine transformations are shown in S5 Table.

thumbnail
Table 2. Summary statistics from meta-analyses of prevalence studies on CKD in people with HIV using random effects model and arcsine transformations.

https://doi.org/10.1371/journal.pone.0195443.t002

thumbnail
Fig 4. Summary of pooled prevalence of CKD in HIV populations across WHO regions.

https://doi.org/10.1371/journal.pone.0195443.g004

CKD prevalence was also high in Africa using the CKD-EPI equation: 7.0% (95%CI 2.8–12.9%). Studies using CG equation were mostly from Africa (84% of the studies), precluding sound regional analysis. The pooled prevalence of CKD in Africa from CG estimator was 13.7% (95%CI 9.1–19.0%); Table 2.

Of the studies performed in Africa, studies originating from West Africa had the highest pooled prevalence estimate using the MDRD equation: 14.6% (95%CI 9.9–20.0%) while the estimates from Southern Africa (3.2%, 95%CI 3.0–3.4%) were the lowest; p<0.001 for difference across African sub-regions, (Fig 5, Table 2). With the CG equation, West Africa still had the highest estimate, 22.0% (95%CI 11.8–34.3%); East Africa’s estimate was 20.2% (95% CI 12.0–29.9) while Southern Africa had 7.5% (95%CI 5.4–9.9%) (Table 1); p<0.001 for difference across the regions.

thumbnail
Fig 5. Summary of pooled prevalence of CKD in HIV populations of the African sub-regions.

https://doi.org/10.1371/journal.pone.0195443.g005

One study [88] reported CKD prevalence for only women and another [79] for only men; the pooled prevalence for men compared to women (MDRD) was 4.9% (95%CI 3.1–7.0%) versus 4.5% (95%CI 3.3–5.8%), p = 0.93 for difference by gender. The pooled prevalence (CG equation) for men was 8.3% (95%CI 1.1–20.8%) while that for women was 15.2% (95%CI 4.9–29.7%); p-value = 0.41 for difference by gender, (S5 Table).

Older (≥median age 38.5 years) compared with younger participants (<38.5 years) had lower but non-significant difference in CKD prevalence: MDRD: 6.1% (95%CI 4.6–7.9%) vs. 6.9% (95%CI 5.2–8.8%), p = 0.54; CKD-EPI: 4.8% (95%CI 2.6–7.5%) vs. 4.8% (95%CI 2.3–8.2%), p = 0.98; CG: 8.5% (95%CI 4.5–13.6%) vs. 14.2% (95%CI 7.9–21.9%), p = 0.17. Substantial heterogeneity was apparent within age-groups regardless of the criteria (all p-heterogeneity <0.001). The CKD prevalence rates for patients with co-infection with hepatitis B and C, by level of CD4 count, by ART status and for those with comorbid systemic hypertension and diabetes mellitus are summarized in S5 Table. Importantly, we found that co-infection with hepatitis B or C, level of CD4 count and use of ART did not have a significant effect on CKD prevalence. However, CKD prevalence was significantly increased with comorbid hypertension (MDRD: 20.7% [95%CI 14.3–27.8%] vs 5.4% [95%CI 3.4–7.9%]; p<0.001) or diabetes mellitus (MDRD: 19.4% [95%CI 13.5–26.0%] vs 8.4% [95%CI 5.5–11.8%]; p<0.001) (S5 Table).

Twenty-one studies [3538, 41, 42, 45, 47, 52, 54, 60, 64, 65, 68, 69, 72, 77, 81, 85, 90, 91] had serum creatinine measured at least twice (four from sub-Saharan Africa [SSA]), a minimum of three months apart. The pooled prevalence for MDRD equation-based studies was 4.7% (95%CI 3.7–5.9%); CKD-EPI 2.6% (95%CI 2.3–3.0%) and CG 5.1% (95%CI 2.8–8.0%), with a significant difference across estimators (p<0.001). The forest plot showing the pooled prevalence of CKD in HIV populations for studies with at least two eGFR estimates using MDRD, CKD-EPI and CG equations is given in S1 Fig. There was no evidence of publication bias as shown in the funnel plots for studies with two or more eGFR values (S2 Fig), p-value = 0.07 for the Egger test).

Using the MDRD equation, the pooled prevalence of CKD reported from African studies that used two eGFR measurements was 4.2% (95%CI 1.4–8.3%) versus 8.9% (95%CI 5.3–13.3) (p-value 0.09) for those that used one eGFR measurement. For studies from North America, the pooled CKD prevalence for studies with at least 2 eGFR measures was 6.1% (95%CI 4.5–7.9%) compared to the pooled prevalence of studies with one eGFR measure of 7.6% (95%CI 5.2–10.4%), p = 0.34. The forest plot showing pooled prevalence for studies with two or more MDRD-based eGFR estimates across the WHO regions is shown in S3 Fig.

Discussion

To our knowledge, this is the first attempt to provide prevalence estimates for CKD in HIV populations across various WHO regions. Prevalence was highest in Africa and lowest in Europe although the data shows substantial heterogeneity. Despite this, sociodemographic and clinical factors such as gender, age, coinfections with HBV and HCV did not significantly affect the estimates while coincident hypertension and diabetes mellitus had significant effect on the estimates. Paradoxically, our analysis did not reveal significant contribution to CKD prevalence of HIV related factors such as CD4 counts and ART status.

The overall prevalence of CKD in HIV populations is high, regardless of estimator used. This is more so in Africa where the prevalence of CKD in the general population is already high [20]. The high CKD prevalence in HIV patients presents an enormous challenge to health care systems in low to middle income countries (LMICs) with high prevalence of HIV and where access to CKD care is significantly lacking [92]. The clinical and economic implication of a high CKD burden has effects on the functioning of health systems. In higher income countries, high CKD burden may represent remarkable increase in healthcare costs for managing HIV related CKD whereas in LMICs, it may mean enormous pressure on an already weakened and poorly funded health system. The interplay between HIV and CKD also presents an opportunity for integration of chronic non-communicable disease care with communicable disease treatment as this may enhance more effective use of health resources and improve long term outcomes for HIV patients. It is important to determine if there is a higher CKD prevalence among HIV populations than the general population. In Africa, the prevalence of individuals with eGFR less than 60ml/min/1.73m2 in the general population is not clear but Stanifer et al[20] reported a pooled prevalence of 13.9% using both eGFR and proteinuria in the definition of CKD. Studies in Sub-saharan Africa have reported a prevalence of eGFR less than 60ml/min/1.73m2 of 1.6%[93] to 8.0%[94] using the MDRD formula. In this analysis, the pooled prevalence (using MDRD) was 7.9% for Sub-Saharan Africa. However, studies undertaking head-to-head comparison of CKD prevalence in the HIV–infected population and the general population [95, 96] in climes with better data collection suggest higher CKD prevalence in the HIV population than the general population.

Consistently, there was significant difference in the prevalence reported across the three estimators. Prevalence estimates obtained using the CG equation were generally higher than those obtained from MDRD and CKD-EPI with CKD-EPI being the most conservative of the three. In the general population, the CKD-EPI equation appears to outperform the MDRD and CG equations [9799]; however, the best equation for GFR estimation and cut-off for definition of CKD in HIV patients remains controversial [100]. Some authors have suggested that existing equations do not take into account the lean muscle mass of malnourished HIV patients and the lipodystrophy associated with ART use [101]. One study report suggests that the CKD-EPI equation may underestimate CKD prevalence in the HIV population in Africans [102]. Whether this is also applicable to European or North American HIV populations, is uncertain. Other studies have supported the idea that eGFR values obtained from CG do not have clinically significant difference from those obtained from CKD-EPI equation in HIV patients and so could be used interchangeably [103], while MDRD is thought to be less sensitive to moderate GFR reductions and thus not useful in HIV patients with early CKD [64]. Noteworthy is the observation that most of the studies from Africa (where patients present with advanced HIV disease) used the Cockroft-Gault equation to estimate GFR either alone or in combination with other creatinine-based formulae. This may be responsible for the relatively higher CKD prevalence obtained from the Cockroft-Gault equation. There have been attempts at validating these creatinine-based estimators in the HIV population [104106] but there is yet no consensus on the best creatinine-based GFR estimator in this special population.

Although not statistically significant in most of the comparisons, there was clearly a trend towards lower CKD prevalence estimates in the studies with more than one GFR estimate compared with those with only one estimate. This validates the KDIGO position of demonstration of GFR <60ml/min/1.73m2 for at least 3 months [107] before a firm diagnosis of CKD is made. This may provide evidence of significant risk of overestimation of CKD prevalence in single eGFR studies because of the possibility of undiagnosed acute kidney injury (AKI) especially in patients with HIV who tend to have higher risk of AKI than the general population [108].

Hypertension and diabetes mellitus remains significant risk factors for CKD in the HIV population as seen in this analysis when head-to-head comparison was performed between HIV only cohorts and HIV/hypertension or DM co-morbidities. Both hypertension and diabetes mellitus are age-related conditions and with the increasing age of HIV patients, a higher prevalence of CKD might be predicted in future in HIV positive patients. Both conditions, however, did not appear to explain some of the heterogeneities in CKD prevalence estimates, when comparison was made based on median hypertension or DM prevalence (S5 Table). This may not be unconnected with the lack of uniformity in the definition or method of assessment of these factors among the constituent studies. For example, one study [38] defined hypertension as blood pressure of at least 160/90mmHg while others [33, 43] used a cut-off of 140/90mmHg. Also, some studies [35, 44, 85] did not provide definition of hypertension while others [36] used patient-reported history of hypertension. Similarly diabetes mellitus had varying definitions ranging from self-reported history of diabetes mellitus [36] to a combination of fasting plasma glucose, random plasma glucose, related symptoms and current use of antidiabetic medication [37, 90] or inadequate information about criteria for diagnosis [82]. However, multivariate regression in some of the component studies [38, 82, 109] identified significant association between diabetes and hypertension with CKD in HIV patients.

The effect of hepatitis B and/or hepatitis C on CKD occurrence in HIV patients has not been consistent. In this study, we found no significant difference in the pooled prevalence of studies with high hepatitis B or C co-infection compared with those with low prevalence of these viral co-infections. Some observational studies have found a higher risk of CKD [35, 90, 110] among hepatitis B or C co-infected HIV patients while others found no significant effect with hepatitis B or C co-infection [36, 37]. A meta-analysis investigating the effect of hepatitis C co-infection on CKD occurrence and progression in HIV patients [111] found significantly increased risk of CKD, proteinuria and AKI in co-infected individuals compared to those with only HIV infection. We are unaware of any published meta-analysis comparing CKD prevalence or progression in HIV-hepatitis B co-infected individuals with HIV only patients though observational studies [110, 112] suggest increased CKD risk with hepatitis B co-infection. Aggregation of data from high-income countries (high HCV co-infection and relatively low CKD prevalence) with LMIC (low HCV co-infection and high CKD-HIV prevalence) may have led to a loss of significant difference in CKD prevalence in the HIV-HCV co-infected compared to those without the co-infection.

One possible reason for the relatively high prevalence of CKD in African patients is late presentation to HIV care clinics at advanced stages of disease. This is evidenced by the significantly lower CD4 counts in African patients compared to the other regions. This may be compounded by late initiation of anti-retroviral medications giving adequate time for HIV–induced or related damage to the kidneys. In North America, ARTs are given to all HIV–infected individuals regardless of CD4 count to reduce morbidity and mortality associated with HIV infection [113]. This is has not been the case in most SSA countries where cut-offs of CD4 counts were used for initiation of ART [South Africa (2013), < 350cells/μl [114]; South Africa (2015), <500 cells/μl [115]; Nigeria (2007), <200/μl [116]; Nigeria (2010), <350 cells/μl [117]]. It was only in 2016 that ART initiation was done regardless of CD4 count in some SSA countries. The effect of this policy change on CKD prevalence among HIV patients may only become apparent in the future. Early initiation of ARTs, especially in blacks, has been proposed as one of the measures for preventing CKD progression among HIV patients [118]. As more patients in SSA access ARTs it is possible that the incidence of CKD may not be too different between individuals of SSA origin compared with Caucasians [81]. There is also the problem of poor and inadequate facilities for long term monitoring of HIV patients on ARTs in Africa which makes early diagnosis of CKD difficult.

Furthermore, CKD in HIV patients may occur because of repeated episodes of undocumented AKI. AKI is common among HIV patients and is an important cause of morbidity and mortality in this patient group with sepsis and hypovolemia from diarrhea being the commonest causes [119121]. AKI has also been documented as an independent risk factor for future ESRD with increasing ESRD risk associated with worsening AKI stage in HIV patients [109, 122].

The higher prevalence of HIV–related kidney disease in African Americans compared to Caucasian Americans [52] and very high CKD prevalence among HIV patients in West Africa suggests a possible genetic role in the increased CKD prevalence in SSA. This hypothesis is further strengthened by the observation that most African Americans are of West African origin and this study has shown the highest prevalence of CKD in HIV among West Africans. APOL1 and MYH9 polymorphisms have been implicated in conferring possible increased risk of CKD in Africans [123127] but there may be more, yet to be identified, genetic risk factors. There also may be confounding environmental factors in Africa contributing to the increased CKD risk among HIV patients.

The global HIV population is quite heterogeneous; male preponderance in North America and Europe whereas females constitute 60–70% of the HIV patients in the African studies reviewed. The influence, if any, of gender difference on the CKD prevalence remains unclear. The prevalence of traditional risk factors for CKD like hypertension, diabetes mellitus and Hepatitis C is also higher in North America and Europe than in Africa. The high prevalence of these modifiable CKD risk factors present a window of opportunity for sustaining therapies that may ultimately slow down CKD progression. The experience garnered from chronic care management of HIV could be leveraged as a platform for integration of non-communicable disease services into HIV populations. The different dimensions of HIV care–prevention, diagnosis, enrollment into care, disease management and palliative care—could also be useful for NCDs. The integrated care model appears to have achieved good results in parts of SSA [128] and emphasis on CKD preventive services among the HIV population may reduce the burden of CKD in LMICs.

There is still inadequate information about the best creatinine–based eGFR formula for Africa in general [93] and the HIV population specifically and as our study has not been able to address this, it is a limitation. Some have suggested that non-inclusion of race to the MDRD equation may improve eGFR estimation in Africans [129] but this has not been validated in the HIV population. The use of Cystatin C is not yet widespread in Africa and may not be sustainable in Africa because of the cost. It is important to determine the best measure of CKD in this special population. We did not include individuals with eGFR greater than 60mls/min/1.73m2 and persistent proteinuria in this study. If the definition of CKD was made to include persistent proteinuria, then the prevalence of CKD among HIV patients may be much higher than reported in this study. The lack of information on specific antiretroviral drugs and their potential contribution to the burden of CKD in this work is a limitation.

The burden of CKD in HIV positive patients is high globally, particularly in African patients. HIV treatment programs need to intensify routine screening for CKD at baseline and ART follow up clinics using relatively cheap and simple test for urinary proteins. There is now a great need to produce global guidelines for CKD identification and treatment in HIV patients and integrate treatment for chronic non-communicable disease with HIV patient care.

Supporting information

S2 Table. Search strategy for Pubmed, web of science, EBSCO host and AJOL.

https://doi.org/10.1371/journal.pone.0195443.s002

(DOCX)

S3 Table. Scoring criteria for quality of studies.

https://doi.org/10.1371/journal.pone.0195443.s003

(DOCX)

S4 Table. Assessment of methodological quality of included articles.

https://doi.org/10.1371/journal.pone.0195443.s004

(DOCX)

S5 Table. Summary statistics from meta-analyses of prevalence studies on CKD in people with HIV random effects model and arcsine transformations (subgroup analyses of gender, ARV status, CD4 count levels, Age groups, and co-morbid hypertension, diabetes mellitus, hepatitis B and C infection).

https://doi.org/10.1371/journal.pone.0195443.s005

(DOCX)

S1 Fig. Forest plot showing the pooled prevalence of CKD in HIV populations for studies with at least two eGFR estimates using MDRD, CKD-EPI and CG equations.

https://doi.org/10.1371/journal.pone.0195443.s006

(TIF)

S2 Fig. Funnel plots for studies with two or more eGFR values.

https://doi.org/10.1371/journal.pone.0195443.s007

(TIF)

S3 Fig. Forest plot showing pooled prevalence for studies with two or more MDRD-based eGFR estimates across the WHO regions.

https://doi.org/10.1371/journal.pone.0195443.s008

(TIF)

References

  1. 1. Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. The Lancet. 2015;385(9981):1975–82.
  2. 2. Han TM, Naicker S, Ramdial PK, Assounga AG. A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa. Kidney international. 2006;69(12):2243–50. pmid:16672914
  3. 3. Szczech LA, Menezes P, Byrd Quinlivan E, van der Horst C, Bartlett JA, Svetkey LP. Microalbuminuria predicts overt proteinuria among patients with HIV infection. HIV medicine. 2010;11(7):419–26. pmid:20059571
  4. 4. Musso CG, Belloso WH, Glassock RJ. Water, electrolytes, and acid-base alterations in human immunodeficiency virus infected patients. World journal of nephrology. 2016;5(1):33–42. pmid:26788462
  5. 5. Li Y, Shlipak MG, Grunfeld C, Choi AI. Incidence and risk factors for acute kidney injury in HIV Infection. American journal of nephrology. 2012;35(4):327–34. pmid:22456100
  6. 6. Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, et al. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. The lancet HIV. 2016;3(1):e23–32. pmid:26762990
  7. 7. Poignet JL, Desassis JF, Chanton N, Litchinko MB, Zins B, Kolko A, et al. [Prevalence of HIV infection in dialysis patients: results of a national multicenter study]. Nephrologie. 1999;20(3):159–63. pmid:10418006
  8. 8. Vigneau C, Guiard-Schmid JB, Tourret J, Flahault A, Rozenbaum W, Pialoux G, et al. The clinical characteristics of HIV-infected patients receiving dialysis in France between 1997 and 2002. Kidney international. 2005;67(4):1509–14. pmid:15780104
  9. 9. Barril G, Trullas JC, Gonzalez-Parra E, Moreno A, Bergada E, Jofre R, et al. [Prevalence of HIV-1-infection in dialysis units in Spain and potential candidates for renal transplantation: results of a Spanish survey]. Enfermedades infecciosas y microbiologia clinica. 2005;23(6):335–9.
  10. 10. Trullas JC, Barril G, Cofan F, Moreno A, Cases A, Fernandez-Lucas M, et al. Prevalence and clinical characteristics of HIV type 1-infected patients receiving dialysis in Spain: results of a Spanish survey in 2006: GESIDA 48/05 study. AIDS research and human retroviruses. 2008;24(10):1229–35. pmid:18834322
  11. 11. Halle MP, Takongue C, Kengne AP, Kaze FF, Ngu KB. Epidemiological profile of patients with end stage renal disease in a referral hospital in Cameroon. BMC nephrology. 2015;16:59. pmid:25896605
  12. 12. Madala ND, Thusi GP, Assounga AG, Naicker S. Characteristics of South African patients presenting with kidney disease in rural KwaZulu-Natal: a cross sectional study. BMC nephrology. 2014;15:61. pmid:24731300
  13. 13. Mocroft A, Kirk O, Reiss P, De Wit S, Sedlacek D, Beniowski M, et al. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. AIDS (London, England). 2010;24(11):1667–78.
  14. 14. Rosenberg AZ, Naicker S, Winkler CA, Kopp JB. HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment. Nature Reviews Nephrology. 2015;11(3):150–60. pmid:25686569
  15. 15. Winston JA. HIV and CKD epidemiology. Advances in chronic kidney disease. 2010;17(1):19–25. pmid:20005485
  16. 16. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS med. 2009;6(7):e1000097. pmid:19621072
  17. 17. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Annals of internal medicine. 1999;130(6):461–70. pmid:10075613
  18. 18. Cockcroft DW, Gault H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. pmid:1244564
  19. 19. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Annals of internal medicine. 2009;150(9):604–12. pmid:19414839
  20. 20. Stanifer JW, Jing B, Tolan S, Helmke N, Mukerjee R, Naicker S, et al. The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis. The Lancet Global health. 2014;2(3):e174–81. pmid:25102850
  21. 21. WHO. WHO Regional Offices Geneva: World Health Organization; 2017 [http://www.who.int/about/regions/en/.
  22. 22. AU. Strengthening popular participation in the African Union—a guide to AU structures and processes. South Africa: Open Society Initiative for Southern Africa; 2009. p. 11, 62–3.
  23. 23. Sakajiki AM, Adamu B, Arogundade FA, Abdu A, Atanda AT, Garba BI. Prevalence, risk factors, and histological pattern of kidney disease in patients with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome at Aminu Kano Teaching Hospital: A clinicopathologic study. Annals of Nigerian Medicine. 2014;8(2):69–75.
  24. 24. Higgins J, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses [journal article as teaching resource, deposited by John Flynn]. British medical journal. 2003;327:557–60. pmid:12958120
  25. 25. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. Journal of epidemiology and community health. 2013;67(11):974–8. pmid:23963506
  26. 26. Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10(1):101–29.
  27. 27. Higgins J, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics in medicine. 2002;21(11):1539–58. pmid:12111919
  28. 28. Egger M, Smith GD, Minder C. Bias in meta-analysis detected by a simple, graphical test. British Medical Journal. 1998;316(7129):470–1.
  29. 29. Viera AJ, Garrett JM. Understanding interobserver agreement: the kappa statistic. Fam Med. 2005;37(5):360–3. pmid:15883903
  30. 30. Wallace BC, Schmid CH, Lau J, Trikalinos TA. Meta-Analyst: software for meta-analysis of binary, continuous and diagnostic data. BMC medical research methodology. 2009;9(1):80.
  31. 31. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Archives of public health = Archives belges de sante publique. 2014;72(1):39. pmid:25810908
  32. 32. Adedeji TA, Adedeji NO, Adebisi SA, Idowu AA, Fawale MB, Jimoh KA. Prevalence and Pattern of Chronic Kidney Disease in Antiretroviral-Naive Patients with HIV/AIDS. Journal of the International Association of Providers of AIDS Care. 2015;14(5):434–40. pmid:26013249
  33. 33. Al-Sheikh H, Al-Sunaid M, Alrajhi AA. HIV-associated nephropathy in Saudi Arabia. Annals of Saudi Medicine. 2013;33(4):347–50. pmid:24060712
  34. 34. Anyabolu EN, Chukwuonye II, Arodiwe E, Ijoma CK, Ulasi I. Prevalence and predictors of chronic kidney disease in newly diagnosed human immunodeficiency virus patients in Owerri, Nigeria. Indian Journal of Nephrology. 2016;26(1):10–5. pmid:26937072
  35. 35. Cao Y, Gong MC, Han Y, Xie J, Li XM, Zhang LX, et al. Prevalence and risk factors for chronic kidney disease among HIV-infected antiretroviral therapy-naive patients in Mainland China: A multicenter cross-sectional study. Nephrology. 2013;18(4):307–12. pmid:23311442
  36. 36. Cailhol J, Nkurunziza B, Izzedine H, Nindagiye E, Munyana L, Baramperanye E, et al. Prevalence of chronic kidney disease among people living with HIV/AIDS in Burundi: a cross-sectional study. BMC nephrology. 2011;12.
  37. 37. Calza L, Vanino E, Magistrelli E, Salvadori C, Cascavilla A, Colangeli V, et al. Prevalence of renal disease within an urban HIV-infected cohort in northern Italy. Clinical and experimental nephrology. 2014;18(1):104–12. pmid:23712539
  38. 38. Campbell LJ, Ibrahim F, Fisher M, Holt SG, Hendry BM, Post FA. Spectrum of chronic kidney disease in HIV-infected patients. HIV medicine. 2009;10(6):329–36. pmid:19226409
  39. 39. Choi AI, Rodriguez RA, Bacchetti P, Volberding PA, Havlir D, Bertenthal D, et al. Low rates of antiretroviral therapy among HIV-infected patients with chronic kidney disease. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2007;45(12):1633–9.
  40. 40. Crum-Cianflone N, Ganesan A, Teneza-Mora N, Riddle M, Medina S, Barahona I, et al. Prevalence and factors associated with renal dysfunction among HIV-infected patients. AIDS patient care and STDs. 2010;24(6):353–60. pmid:20515419
  41. 41. Colson AW, Florence E, Augustijn H, Verpooten GA, Lynen L, Gheuens E. Prevalence of chronic renal failure stage 3 or more in HIV-infected patients in Antwerp: an observational study. Acta clinica Belgica. 2010;65(6):392–8. pmid:21268952
  42. 42. Ekat MH, Courpotin C, Diafouka M, Akolbout M, Mahambou-Nsonde D, Bitsindou PR, et al. [Prevalence and factors associated with renal disease among patients with newly diagnoses of HIV in Brazzaville, Republic of Congo]. Medecine et sante tropicales. 2013;23(2):176–80. pmid:23787222
  43. 43. Fernando SK, Finkelstein FO, Moore BA, Weissman S. Prevalence of chronic kidney disease in an urban HIV infected population. American Journal of the Medical Sciences. 2008;335(2):89–94.
  44. 44. Fischer MJ, Wyatt CM, Gordon K, Gibert CL, Brown ST, Rimland D, et al. Hepatitis C and the risk of kidney disease and mortality in veterans with HIV. Journal of acquired immune deficiency syndromes (1999). 2010;53(2):222–6.
  45. 45. Flandre P, Pugliese P, Cuzin L, Bagnis CI, Tack I, Cabie A, et al. Risk Factors of Chronic Kidney Disease in HIV-infected Patients. Clinical Journal of the American Society of Nephrology. 2011;6(7):1700–7. pmid:21566114
  46. 46. George E, Lucas GM, Nadkarni GN, Fine DM, Moore R, Atta MG. Kidney function and the risk of cardiovascular events in HIV-1-infected patients. AIDS (London, England). 2010;24(3):387–94.
  47. 47. Gonzalez-Lopez A, Chocarro-Martinez A, Alvarez-Navia F, Alvarez-Tundidor S, Andres-Martin B, Nava-Rebollo A, et al. Prevalence of chronic kidney disease in patients infected by the human immunodeficiency virus. Nefrologia. 2014;34(1):126–9.
  48. 48. Gracey D, Chan D, Bailey M, Richards D, Dalton B. Screening and management of renal disease in human immunodeficiency virus-infected patients in Australia. Internal medicine journal. 2013;43(4):410–6. pmid:22931386
  49. 49. Ibrahim F, Hamzah L, Jones R, Nitsch D, Sabin C, Post FA. Comparison of CKD-EPI and MDRD to estimate baseline renal function in HIV-positive patients. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association. 2012;27(6):2291–7.
  50. 50. Longo AL, Lepira FB, Sumaili EK, Makulo JRR, Mukumbi H, Bukabau JB, et al. Prevalence of Low Estimated Glomerular Filtration Rate, Proteinuria, and Associated Risk Factors Among HIV-Infected Black Patients Using Cockroft-Gault and Modification of Diet in Renal Disease Study Equations. Jaids-Journal of Acquired Immune Deficiency Syndromes. 2012;59(1):59–64.
  51. 51. Lucas GM, Clarke W, Kagaayi J, Atta MG, Fine DM, Laeyendecker O, et al. Decreased Kidney Function in a Community-based Cohort of HIV-Infected and HIV-Negative Individuals in Rakai, Uganda. Jaids-Journal of Acquired Immune Deficiency Syndromes. 2010;55(4):491–4.
  52. 52. Lucas GM, Lau B, Atta MG, Fine DM, Keruly J, Moore RD. Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-Infected individuals: A tale of two races. Journal of Infectious Diseases. 2008;197(11):1548–57. pmid:18422458
  53. 53. Mayor AM, Dworkin M, Quesada L, Rios-Olivares E, Hunter-Mellado RF. The morbidity and mortality associated with kidney disease in an HIV-infected cohort in Puerto Rico. Ethnicity & disease. 2010;20(1 Suppl 1):S1-163-7.
  54. 54. Menezes AM, Torelly J, Real L, Bay M, Poeta J, Sprinz E. Prevalence and Risk Factors Associated to Chronic Kidney Disease in HIV-Infected Patients on HAART and Undetectable Viral Load in Brazil. Plos One. 2011;6(10).
  55. 55. Msango L, Downs JA, Kalluvya SE, Kidenya BR, Kabangila R, Johnson WD, et al. Renal dysfunction among HIV-infected patients starting antiretroviral therapy. AIDS (London, England). 2011;25(11):1421–5.
  56. 56. Mulenga LB, Kruse G, Lakhi S, Cantrell RA, Reid SE, Zulu I, et al. Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. AIDS (London, England). 2008;22(14):1821–7.
  57. 57. Nakamura Y, Shibuya A, Suzuki H, Ando M. [Prevalence of chronic kidney disease (CKD) and significant contributors to CKD in HIV-infected patients]. Nihon Jinzo Gakkai shi. 2008;50(4):499–505. pmid:18546881
  58. 58. Obirikorang C, Osakunor DNM, Ntaadu B, Adarkwa OK. Renal Function in Ghanaian HIV-Infected Patients on Highly Active Antiretroviral Therapy: A Case-Control Study. Plos One. 2014;9(6).
  59. 59. Okafor UH, Unuigbe EI, Wokoma FS. Spectrum of Clinical Presentations in Human Immunodeficiency Virus (HIV) Infected Patients with Renal Disease. African journal of infectious diseases. 2011;5(2):28–32. pmid:23878704
  60. 60. Overton ET, Nurutdinova D, Freeman J, Seyfried W, Mondy KE. Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy. HIV medicine. 2009;10(6):343–50. pmid:19490182
  61. 61. Owiredu WK, Quaye L, Amidu N, Addai-Mensah O. Renal insufficiency in Ghanaian HIV infected patients: need for dose adjustment. African health sciences. 2013;13(1):101–11. pmid:23658575
  62. 62. Peck RN, Shedafa R, Kalluvya S, Downs JA, Todd J, Suthanthiran M, et al. Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study. Bmc Medicine. 2014;12.
  63. 63. Sarfo FS, Keegan R, Appiah L, Shakoor S, Phillips R, Norman B, et al. High prevalence of renal dysfunction and association with risk of death amongst HIV-infected Ghanaians. Journal of Infection. 2013;67(1):43–50. pmid:23542785
  64. 64. Stohr W, Walker AS, Munderi P, Tugume S, Gilks CF, Darbyshire JH, et al. Estimating glomerular filtration rate in HIV-infected adults in Africa: comparison of Cockcroft-Gault and Modification of Diet in Renal Disease formulae. Antiviral therapy. 2008;13(6):761–70. pmid:18839777
  65. 65. Sorli ML, Guelar A, Montero M, Gonzalez A, Rodriguez E, Knobel H. Chronic kidney disease prevalence and risk factors among HIV-infected patients. Jaids-Journal of Acquired Immune Deficiency Syndromes. 2008;48(4):506–8.
  66. 66. Umeizudike T, Mabayoje M, Okany C, Adeyomoye A, Okubadejo N. Prevalence of chronic kidney disease in HIV positive patients in Lagos, south-west Nigeria. Nephrology Rev. 2012;4:22–6.
  67. 67. Wyatt CM, Winston JA, Malvestutto CD, Fishbein DA, Barash I, Cohen AJ, et al. Chronic kidney disease in HIV infection: an urban epidemic. AIDS (London, England). 2007;21(15):2101–3.
  68. 68. Yanagisawa N, Ando M, Suganuma A, Akifumi I, Ajisawa A. [Prevalence of kidney disease in HIV-infected patients in Japan—A single center study]. Kansenshogaku zasshi The Journal of the Japanese Association for Infectious Diseases. 2010;84(1):28–32. pmid:20170011
  69. 69. Yanagisawa N, Ando M, Ajisawa A, Imamura A, Suganuma A, Tsuchiya K, et al. Clinical characteristics of kidney disease in Japanese HIV-infected patients. Nephron Clinical practice. 2011;118(3):c285–91. pmid:21212692
  70. 70. Agbaji OO, Onu A, Agaba PE, Muazu MA, Falang KD, Idoko JA. Predictors of impaired renal function among HIV infected patients commencing highly active antiretroviral therapy in Jos, Nigeria. Nigerian medical journal: journal of the Nigeria Medical Association. 2011;52(3):182–5.
  71. 71. Brennan A, Evans D, Maskew M, Naicker S, Ive P, Sanne I, et al. Relationship between renal dysfunction, nephrotoxicity and death among HIV adults on tenofovir. AIDS (London, England). 2011;25(13):1603–9.
  72. 72. Kamkuemah M, Kaplan R, Bekker LG, Little F, Myer L. Renal impairment in HIV-infected patients initiating tenofovir-containing antiretroviral therapy regimens in a Primary Healthcare Setting in South Africa. Tropical medicine & international health: TM & IH. 2015;20(4):518–26.
  73. 73. Onodugo OD, Chukwuka C, Onyedum C, Ejim E, Mbah A, Nkwo P, et al. Baseline Renal Function among Antiretroviral Therapy-Naive, HIV-Infected Patients in South East Nigeria. Journal of the International Association of Providers of AIDS Care. 2013.
  74. 74. Reid A, Stohr W, Walker AS, Williams IG, Kityo C, Hughes P, et al. Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2008;46(8):1271–81.
  75. 75. Struik GM, den Exter RA, Munthali C, Chipeta D, van Oosterhout JJ, Nouwen JL, et al. The prevalence of renal impairment among adults with early HIV disease in Blantyre, Malawi. International journal of STD & AIDS. 2011;22(8):457–62.
  76. 76. Achhra AC, Mocroft A, Ross MJ, Ryom L, Lucas GM, Furrer H, et al. Kidney disease in antiretroviral-naive HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV medicine. 2015;16:55–63. pmid:25711324
  77. 77. Bandera A, Gori A, Sabbatini F, Madeddu G, Bonora S, Libertone R, et al. Evaluation of the Prognostic Value of Impaired Renal Function on Clinical Progression in a Large Cohort of HIV-Infected People Seen for Care in Italy. PLoS One. 2015;10(5):e0124252. pmid:25933346
  78. 78. Bonjoch A, Juega J, Puig J, Perez-Alvarez N, Aiestaran A, Echeverria P, et al. High prevalence of signs of renal damage despite normal renal function in a cohort of HIV-infected patients: evaluation of associated factors. AIDS patient care and STDs. 2014;28(10):524–9. pmid:25238104
  79. 79. Estrella MM, Parekh RS, Astor BC, Bolan R, Evans RW, Palella FJ Jr., et al. Chronic kidney disease and estimates of kidney function in HIV infection: a cross-sectional study in the multicenter AIDS cohort study. Journal of acquired immune deficiency syndromes (1999). 2011;57(5):380–6.
  80. 80. Zachor H, Machekano R, Estrella MM, Veldkamp PJ, Zeier MD, Uthman OA, et al. Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens. AIDS (London, England). 2016;30(8):1221–8.
  81. 81. Schoffelen AF, Smit C, van Lelyveld SFL, Vogt L, Bauer MP, Reiss P, et al. Diminished Impact of Ethnicity as a Risk Factor for Chronic Kidney Disease in the Current HIV Treatment Era. Journal of Infectious Diseases. 2015;212(2):264–74. pmid:25601941
  82. 82. Fulop T, Olivier J, Meador RS, Hall J, Islam N, Mena L, et al. Screening for chronic kidney disease in the ambulatory HIV population. Clinical Nephrology. 2010;73(3):190–6. pmid:20178717
  83. 83. Santiago P, Grinsztejn B, Friedman RK, Cunha CB, Coelho LE, Luz PM, et al. Screening for decreased glomerular filtration rate and associated risk factors in a cohort of HIV-infected patients in a middle-income country. PLoS One. 2014;9(4):e93748. pmid:24699873
  84. 84. Muramatsu T, Yanagisawa N, Chikasawa Y, Seita I, Yotsumoto M, Otaki M, et al. [Prevalence of chronic kidney disease among HIV-infected individuals in Japan—a report from two tertiary hospitals]. Kansenshogaku zasshi The Journal of the Japanese Association for Infectious Diseases. 2013;87(1):14–21. pmid:23484373
  85. 85. Cheung CY, Wong KM, Lee MP, Liu YL, Kwok H, Chung R, et al. Prevalence of chronic kidney disease in Chinese HIV-infected patients. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association. 2007;22(11):3186–90.
  86. 86. Odongo P, Wanyama R, Obol JH, Apiyo P, Byakika-Kibwika P. Impaired renal function and associated risk factors in newly diagnosed HIV-infected adults in Gulu Hospital, Northern Uganda. BMC nephrology. 2015;16:43. pmid:25881003
  87. 87. Wools-Kaloustian K, Gupta SK, Muloma E, Owino-Ong’or W, Sidle J, Aubrey RW, et al. Renal disease in an antiretroviral-naive HIV-infected outpatient population in Western Kenya. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association. 2007;22(8):2208–12.
  88. 88. Wyatt CM, Shi Q, Novak JE, Hoover DR, Szczech L, Mugabo JS, et al. Prevalence of kidney disease in HIV-infected and uninfected Rwandan women. PLoS One. 2011;6(3):e18352. pmid:21464937
  89. 89. Zhao Y, Zhang M, Shi CX, Zhang Y, Cai W, Zhao Q, et al. Renal Function in Chinese HIV-Positive Individuals following Initiation of Antiretroviral Therapy. PLoS One. 2015;10(8):e0135462. pmid:26317657
  90. 90. Hsieh M-H, Lu P-L, Kuo M-C, Lin W-R, Lin C-Y, Lai C-C, et al. Prevalence of and associated factors with chronic kidney disease in human immunodeficiency virus-infected patients in Taiwan. Journal of Microbiology, Immunology and Infection. 2015;48(3):256–62.
  91. 91. Mizushima D, Tanuma J, Kanaya F, Nishijima T, Gatanaga H, Lam NT, et al. WHO antiretroviral therapy guidelines 2010 and impact of tenofovir on chronic kidney disease in Vietnamese HIV-infected patients. PloS one. 2013;8(11):e79885. pmid:24223203
  92. 92. Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. Lancet. 2015;385(9981):1975–82. pmid:25777665
  93. 93. Eastwood JB, Kerry SM, Plange-Rhule J, Micah FB, Antwi S, Boa FG, et al. Assessment of GFR by four methods in adults in Ashanti, Ghana: the need for an eGFR equation for lean African populations. Nephrology Dialysis Transplantation. 2010;25(7):2178–87.
  94. 94. Sumaili EK, Krzesinski JM, Zinga CV, Cohen EP, Delanaye P, Munyanga SM, et al. Prevalence of chronic kidney disease in Kinshasa: results of a pilot study from the Democratic Republic of Congo. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association. 2009;24(1):117–22.
  95. 95. Goulet JL, Fultz SL, Rimland D, Butt A, Gibert C, Rodriguez-Barradas M, et al. Do patterns of comorbidity vary by HIV status, age, and HIV severity? Clinical Infectious Diseases. 2007;45(12):1593–601. pmid:18190322
  96. 96. Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clinical Infectious Diseases. 2011;53(11):1120–6. pmid:21998278
  97. 97. Mulay AV, Gokhale SM. Comparison of serum creatinine-based estimating equations with gates protocol for predicting glomerular filtration rate in indian population. Indian J Nephrol. 2017;27(2):124–8. pmid:28356664
  98. 98. Xie P, Huang JM, Lin HY, Wu WJ, Pan LP. CDK-EPI equation may be the most proper formula based on creatinine in determining glomerular filtration rate in Chinese patients with chronic kidney disease. Int Urol Nephrol. 2013;45(4):1057–64. pmid:23136033
  99. 99. Al-Wakeel JS. Accuracy and precision of the CKD-EPI and MDRD predictive equations compared with glomerular filtration rate measured by inulin clearance in a Saudi population. Ann Saudi Med. 2016;36(2):128–34. pmid:27018810
  100. 100. Mocroft A. The difficulties of classifying renal disease in HIV-infected patients. HIV medicine. 2011;12(1):1–3. pmid:21129144
  101. 101. Barraclough K, Er L, Ng F, Harris M, Montaner J, Levin A. A Comparison of the Predictive Performance of Different Methods of Kidney Function Estimation in a Well-Characterized HIV-Infected Population. Nephron Clinical Practice. 2009;111(1):c39–c48. pmid:19052469
  102. 102. Glaser N, Deckert A, Phiri S, Rothenbacher D, Neuhann F. Comparison of Various Equations for Estimating GFR in Malawi: How to Determine Renal Function in Resource Limited Settings? PLoS ONE. 2015;10(6):e0130453. pmid:26083345
  103. 103. Mocroft A, Ryom L, Reiss P, Furrer H, D’Arminio Monforte A, Gatell J, et al. A comparison of estimated glomerular filtration rates using Cockcroft–Gault and the Chronic Kidney Disease Epidemiology Collaboration estimating equations in HIV infection. HIV medicine. 2014;15(3):144–52. pmid:24118916
  104. 104. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C. New England Journal of Medicine. 2012;367(1):20–9. pmid:22762315
  105. 105. Bhasin B, Lau B, Atta MG, Fine DM, Estrella MM, Schwartz GJ, et al. HIV viremia and T-cell activation differentially affect the performance of glomerular filtration rate equations based on creatinine and cystatin C. PLoS One. 2013;8(12):e82028. pmid:24376511
  106. 106. Wyatt CM, Schwartz GJ, Owino Ong’or W, Abuya J, Abraham AG, Mboku C, et al. Estimating kidney function in HIV-infected adults in Kenya: comparison to a direct measure of glomerular filtration rate by iohexol clearance. PLoS One. 2013;8(8):e69601. pmid:23950899
  107. 107. Levey AS, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney international. 2011;80(1):17–28. pmid:21150873
  108. 108. Evans RDR, Hemmilä U, Craik A, Mtekateka M, Hamilton F, Kawale Z, et al. Incidence, aetiology and outcome of community-acquired acute kidney injury in medical admissions in Malawi. BMC nephrology. 2017;18(1):21. pmid:28088183
  109. 109. Choi AI, Li Y, Parikh C, Volberding PA, Shlipak MG. Long-term clinical consequences of acute kidney injury in the HIV-infected. Kidney international. 2010;78(5):478–85. pmid:20520594
  110. 110. Mocroft A, Neuhaus J, Peters L, Ryom L, Bickel M, Grint D, et al. Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults. PLoS One. 2012;7(7):e40245. pmid:22911697
  111. 111. Wyatt CM, Malvestutto C, Coca SG, Klotman PE, Parikh CR. The Impact of Hepatitis C Virus Co-infection on HIV-Related Kidney Disease: A Systematic Review and Meta-analysis. AIDS (London, England). 2008;22(14):1799–807.
  112. 112. Ganesan A, Krantz EM, Huppler Hullsiek K, Riddle MS, Weintrob AC, Lalani T, et al. Determinants of incident chronic kidney disease and progression in a cohort of HIV-infected persons with unrestricted access to health care. HIV medicine. 2013;14(2):65–76. pmid:22808988
  113. 113. AIDSinfo. Guidelines for the use of Antiretroviral Agents in HIV-1 infected Adults and Adolescents2016 16th November 2016 https://aidsinfo.nih.gov/contentfiles/lvguidelines/AA_Recommendations.pdf.
  114. 114. Department of Health RoSA. The South African Antiretroviral treatment guidelines 20132013 17th November 2016]. http://www.sahivsoc.org/Files/2013%20ART%20Treatment%20Guidelines%20Final%2025%20March%202013%20corrected.pdf.
  115. 115. Health NDo. National Consolidated Guidelines for the Prevention of Mother-to-child transmission of HIV (PMTCT) and the Management of HIV in Children, adolesecnts and adults2015. http://www.sahivsoc.org/Files/ART%20Guidelines%2015052015.pdf.
  116. 116. Nigeria FMoH. National Guidelines for HIV and AIDS treatment and care in adolescents and adults2007 17th November 2016]. http://www.who.int/hiv/amds/Nigeria_adult_2007.pdf.
  117. 117. Nigeria FMoH. 2010 17th November 2016 17th November 2016]. https://aidsfree.usaid.gov/sites/default/files/tx_nigeria_adults_ado_2010.pdf.
  118. 118. Schwartz EJ, Szczech LA, Ross MJ, Klotman ME, Winston JA, Klotman PE. Highly Active Antiretroviral Therapy and the Epidemic of HIV+ End-Stage Renal Disease. Journal of the American Society of Nephrology. 2005;16(8):2412–20. pmid:15987747
  119. 119. Prakash J, Gupta T, Prakash S, Rathore SS, Usha , Sunder S. Acute kidney injury in patients with human immunodeficiency virus infection. Indian J Nephrol. 2015;25(2):86–90. pmid:25838645
  120. 120. Vachiat AI, Musenge E, Wadee S, Naicker S. Renal failure in HIV-positive patients-a South African experience. Clinical kidney journal. 2013;6(6):584–9. pmid:26069826
  121. 121. Naicker S, Aboud O, Gharbi MB. Epidemiology of acute kidney injury in Africa. Seminars in nephrology. 2008;28(4):348–53. pmid:18620957
  122. 122. Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute Kidney Injury and Chronic Kidney Disease as Interconnected Syndromes. New England Journal of Medicine. 2014;371(1):58–66. pmid:24988558
  123. 123. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans. Science. 2010;329(5993):841–5. pmid:20647424
  124. 124. Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, et al. APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy. Journal of the American Society of Nephrology. 2011;22(11):2129–37. pmid:21997394
  125. 125. Papeta N, Kiryluk K, Patel A, Sterken R, Kacak N, Snyder HJ, et al. APOL1 Variants Increase Risk for FSGS and HIVAN but Not IgA Nephropathy. Journal of the American Society of Nephrology. 2011;22(11):1991–6. pmid:21997397
  126. 126. Tayo BO, Kramer H, Salako BL, Gottesman O, McKenzie CA, Ogunniyi A, et al. Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians. International Urology and Nephrology. 2013;45(2):485–94. pmid:22956460
  127. 127. Ulasi II, Tzur S, Wasser WG, Shemer R, Kruzel E, Feigin E, et al. High Population Frequencies of APOL1 Risk Variants Are Associated with Increased Prevalence of Non-Diabetic Chronic Kidney Disease in the Igbo People from South-Eastern Nigeria. Nephron Clinical Practice. 2013;123(1–2):123–8. pmid:23860441
  128. 128. Edwards JK, Bygrave H, Van den Bergh R, Kizito W, Cheti E, Kosgei RJ, et al. HIV with non-communicable diseases in primary care in Kibera, Nairobi, Kenya: characteristics and outcomes 2010–2013. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2015;109(7):440–6. pmid:25997923
  129. 129. Madala ND, Nkwanyana N, Dubula T, Naiker IP. Predictive performance of eGFR equations in South Africans of African and Indian ancestry compared with (9)(9)mTc-DTPA imaging. Int Urol Nephrol. 2012;44(3):847–55. pmid:21373844