HIV infection remains incurable and indefinite ART is often limited by drug toxicity. Renal toxicity is a major cause for morbidity and mortality in HIV-infected patients. HIV infection is also a risk factor for CKD. Since kidney disease tends to be silent during the initial stages, therefore an accurate and reliable tool for measuring GFR in HIV-infected patients is urgently needed globally to properly monitor and manage HIV and ART-related renal diseases. A recent study showed high prevalence of CKD in HIV population [14
]. The exposure to ARV is a unique risk factor for HIV population. Certain ARVs have been shown to be nephrotoxic and can cause renal stone disease as well as chronic tubulointerstitial disease. The expansion of HIV population and the success of HIV treatment can extend the lives of the patients that over time, some of them may develop CKD and progress to ESRD which will ultimately impact all health care services. It is important to find a reliable tool to calculate/measure GFR so physicians can detect patients at risk for developing CKD. In addition, if this tool can accurately monitor the deterioration rate of the renal function so that doses of ART can be reduced, this will significantly help prevent the disease from occurring.
The re-expressed MDRD eGFR equation has been developed primarily for Caucasians and African-Americans with CKD [1
]. Recent studies have shown that the calculation of eGFR derived from a race without prior validation will result in inaccurate estimations of GFR unless a racial factor is added to the equation to provide a more precise estimation [5
]. Even though various eGFR equations have been studied in different races, the validation data have not been well studied in a large HIV population, especially in Asians. Our study has a large sample size (N=196) and is one of the first of its kind to compare various equations of estimated GFR against the radioisotope plasma clearance GFR in HIV-infected patients from Asia. The majority (95%) of the patients from the study’s cohort are on ART and their HIV RNA are well suppressed (VL<50 copies/mL). Some of the patients are overweight but many have abnormal body compositions due to ART-related lipodystrophy, resulting in low skeletal mass and high body fat mass.
We demonstrated that the expressed MDRD, CKD-EPI, re-expressed MDRD formula with Thai racial correction factor, Thai eGFR equation, cystatin C GFR, and 24-hr urine CrCl underestimated the reference GFR. The application of re-expressed MDRD and CKD-EPI equations derived from non HIV-CKD population had a bias of 18.9 mL/min/1.73m2
and 11.1 mL/min/ 1.73m2
respectively. The spread of the bias between the reference GFR and the eGFR by CKD-EPI was not evenly distributed (). When GFR was less than 110 mL/min/1.73m2
or more than 110 mL/min/ 1.73m2
, the eGFR from the CKD-EPI overestimated or underestimated the reference GFR, respectively. From all of the serum creatinine based eGFR equations, the reexpressed MDRD equation with Thai racial factor correction was the only equation that had the least bias of 6.2 mL/min/1.73m2
and an evenly distributed spread of bias. Therefore the re-expressed MDRD equation with Thai racial factor correction is more applicable to Thai HIV-CKD population. Our data agrees with Barraclough et al.’s [15
] data which showed that the MDRD formula was the most precise method for Caucasians infected with HIV.
The racial factor for each ethnicity is important. Recently, our group did a study in 350 HIV-uninfected patients with various CKD stages [16
]. We found that differences in ethnicity significantly affected the results of the MDRD-based eGFR equation and the racial factor for Thais was 1.129. When we used the adjusted MDRD equation with Thai racial factor on our HIV-infected population with an abnormal body composition but well-preserved kidney function compared to the uninfected population, GFR estimation was precise and accurate. This study showed that re-expressed MRDR equation with Thai racial factor can precisely and accurately be used in Thais with or without HIV infection.
The performance of the MDRD with Thai racial factor suggests that this equation is suitable for GFR estimation in our HIV-infected population. However, this formulation may not be applicable for all HIV-infected Asians because other studies conducted in Chinese [17
] and Japanese [19
] non-HIV-infected population have different racial factors of 1.23 and 0.88, respectively. This discrepancy within the Asian population makes it difficult to adopt a universal eGFR equation/racial corrected factor. It is unknown whether the body composition or the differences in determining the reference GFR method affected this disparity in eGFR equation and racial corrected factor for the MDRD-based GFR among Asians. The reference GFR from the Japanese study was obtained from using renal clearance of inulin whereas for the Chinese study, 99m
Tc DTPA was used. The techniques used in the Chinese study is similar to our group but we incorporated 10 time points within the 4 hours period instead of using only 2 time points as in the Chinese study. Furthermore, we performed all isotopic measurements at the same time during the day for all patients to avoid diurnal GFR variation.
Our data supports Bonjoch et al. [22
] who reported that cystatin C had the least bias compared to serum creatinine based eGFR equations in estimating isotopic GFR when used in 15 HIV-infected patients. The drawback of using cystatin C is that it is not standardized even though its use as a biomarker for renal function is increasing. It has been shown that there are systematic shifts in cystatin C levels [23
] and standardization is necessary before it can be systematically and routinely utilized in the clinical setting. Following cystatin C GFR, the second less biased technique is the use of CrCl by 24-hr urine collection. Unfortunately, 24-hr urine collection is the most impractical and difficult method to be used routinely in clinical practice; its precise collection of the urine has made this method unattractive.
The strength of this study is its large sample size as well as intensive measurements of isotopic GFR (10 time points). This data can also be applied to females as 43% of the patients in the study were females. Aside from that, the present study is representive for both HIV with and without lipodystrophy/abnormal body composition. The primary limitation of this study is that the results may not be generalizable to non-Thais and very few participants with impaired kidney function were included, therefore the comparison at lower levels of kidney function may be less reliable. In addition, most of the patients had high CD4 and undetectable VL or well-controlled HIV suppression so this data may not be applicable to patients with a more profound immunodeficiency or AIDS-related wasting.
In conclusion, we have proved that there is a need for the racial correction factor for the creatinine based eGFR equation for both non-HIV CKD and HIV population. Therefore, it is highly and strongly recommended that the existing creatinine based eGFR equations should be validated before using it in both non-HIV CKD and HIV population in epidemiologic studies and in the clinical setting.