In this cross-sectional study, we evaluated the clinical utility of Cystatin C based eGFR in assessing renal function among patients with HIV/AIDS on ART at Mildmay Uganda. We used the Cockcroft-Gault formula as the reference for eGFR estimates. The prevalence of kidney disease in our study population was 10.2%. The sensitivity of Cystatin C based eGFR was (15.1%) and specificity of (99.3%) with the Positive and negative predictive values of 70% and 91.16% respectively. The positive and negative likelihood ratios are 21 and 0.8 respectively. The diagnostic efficiency of Cystatin C based eGFR at different levels with area under curve was (AUC = 0.77, 95% CI = 0.72–0.82).
Our study had strengths and limitations. A major strength being we analyzed serum Cystatin C-based eGFR in a laboratory equipped with a state-of-the-art chemistry analyzer and our adherence to strict good clinical laboratory practice (GCLP) helped minimize systematic error. However, due to technical requirements and safety considerations, we were unable to measure GFR using gold standard methods such as exogenous markers like Inexhol or inulin. Additionally, the absence of published likelihood ratios limited our ability to compare our findings with those from other studies. The study was done in a routine clinical setup that mimics the general situation in many resources limited settings. However, this study was carried out in a clinical center of excellence where most of the services like drug supply, laboratory supplies, expert physicians and consultants are quite reliable which may be different from what is available in majority of the health facilities offering similar services countywide.
Similarly, large bodies of research [31, 32] have documented prevalence of kidney diseases in HIV-infected persons. Jones et al. and Wools-Kaloustian and colleagues reported prevalence of GFR less than 60 mL/min/1.73 m2 between 11.5% and 15.2%, respectively [10, 33]. Contrary to our findings, Kalyesubula et al. (2015) reported a prevalence of 14.8% in kidney disease in Uganda [34, 35].
The sensitivity of Cystatin C based eGFR based eGFR was 15.1% and specificity of 99.3% with the positive and negative predictive values of 70% and 91.16% respectively for Cystatin C based eGFR formula at a cut off 60 mL/min/1.73m2. The high specificity of Cystatin C based eGFR means the test correctly identifies disease free individuals 99.3% of the times. This result suggests that we can use this test as a confirmatory test for kidney disease. However, the low sensitivity of Cystatin C based eGFR which limits its ability to be used as screening test could have been influenced by choice of the reference method. The high negative predictive value means 91% of patients who have a negative (normal GFR as defined by Cystatin C based eGFR) do not have kidney disease. However, the low positive predictive values 70% in our study could be attributed to the low prevalence of kidney disease among the study participants. Contrary to our findings, a study by Chantrel et al. 2000, reported a sensitivity of Cystatin C based eGFR of 75% [36]. However, this variation could be attributed to the selection of the reference standard, which could have influenced the sensitivity of Cystatin C-based eGFR. Nevertheless, when compared to creatinine, Cystatin C-based eGFR demonstrated a performance more closely aligned with the GFR reference examination. Furthermore, assays for cystatin C using the immunonephelometric procedure showed a stronger correlation. Therefore, reclassifying patients based on Cystatin-based eGFR could offer advantages for both patient care and healthcare systems.
Our finding showed a high positive likelihood ratio of 21(95% CI = 8.1, 55). Converting the likelihood ratios to odds using Bayes’ theorem gave posttest odds of 2.4 with posterior probability 70%, (95% CI 48—86%) given a positive test. This result implies given a positive test (reduced GFR as determined by Cystatin C based eGFR) increases the probability of having renal disease to 70%. The negative likelihood ratio of 0.8, (95% CI = 0.8–0.9) with the posterior probability 9% (95% CI = 8% -10%) and odds of (0.1). This means the chances of having a negative test (normal GFR) as determined by Cystatin C based eGFR in a subject with renal disease is only 9%. These results further imply that Cystatin C based eGFR will correctly identify 91% of individuals without renal disease. Thus, in conjunction with other renal tests we can use Cystatin C based eGFR as a confirmatory test to rule out kidney disease.
In this study we report a reasonable accuracy of Cystatin C based eGFR based formula in classifying kidney dysfunction as indicated by the Area under Curve (AUC) of 0.768, (95% CI = 0.71, 0.821) on the receiver operating characteristics curve (Fig. 1). This result means Cystatin C based eGFR will correctly identify 76.8% have kidney disease (reduced GFR as determined by Cystatin C based eGFR). These findings are in agreement with the study conducted by [37], in assessment of serum Cystatin C based eGFR as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function, the study reported that serum Cystatin C based eGFR is a reliable marker in patients with mildly to moderately impaired kidney function and has a fair diagnostic accuracy than serum Creatinine.
Our study implies that the appropriate use of ART may attenuate the growing epidemic of HIV-1-associated nephropathy. These findings are similar to studies conducted by [38], HIV-1-associated nephropathy and response to highly-active antiretroviral therapy that indicated a substantial reduction in human immunodeficiency virus-1-associated nephropathy incidence chronic kidney disease among patients on ART. Other studies indicated that ART improves renal function by reduction in HIV associated nephropathy and HIV immune complex disease which are directly attributed to HIV infection [39,40,41,42,43]. We found no significant difference in kidney function in HIV positive adults treated with TDF or non-TDF NNRTI based ART regimen (p = 0.87) and well as duration on HAART (p = 0.93). In line with our study [44], We found that Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen.
Nonetheless, our study offers valuable insights into the potential benefits of using Cystatin C-based eGFR in diagnosing and managing renal disease in HIV-positive individuals, particularly highlighting the high precision of Cystatin C-based eGFR formulas. This precision enables easy comparison of eGFR estimates between different laboratories and time points, regardless of the specific formula used.
In resource-limited settings, where access to advanced diagnostics may be limited, using Cystatin C-based eGFR as a confirmatory test could be a practical approach. This could help reduce the need for more expensive or invasive tests and facilitate timely diagnosis and management of kidney disease in HIV/AIDS patients on HAART.
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- Source: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03581-3