Abstract
BackgroundNo consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011.MethodsTwo definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years’ follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated.Results22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years’ follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years’ follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD.ConclusionsOur results suggest using three years’ follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals.
Highlights
No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, Rapid progression (RP))
The median number of estimated glomerular filtration rate (eGFR) measurements available per individual per year was 3 (IQR 2–3) years. The characteristics of those eligible for assessment for RP using the primary definition were similar to all included (Table 1), as for the other RP definitions based on varying follow-up periods and number of eGFR measurements/ year
Our results suggest a definition that would apply to individuals with normal baseline eGFR (≥90 ml/min/1.73 m2) with at least three years’ follow-up and at least two eGFR measurements per year, for the reasons described in subsequent paragraphs
Summary
No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). Developing a validated definition of an eGFR slope could guide future studies Studying those with initially normal renal function (defined by the Kidney Disease Improving Global Outcomes [KDIGO] as eGFR ≥90 ml/min/1.73 m2 [6]) who experience a rapid decline in their renal function is important, as it could potentially detect kidney impairment at an early stage, before manifest kidney disease has occurred [7,8]. A study from the Modification of Diet in Renal Disease (MDRD) study group, to determine baseline factors that predict the decline in GFR, made a case for rapid decline in renal function to be further investigated They reported that the mean rate of GFR decline was not significantly related to the baseline GFR, and this suggests an approximately linear mean eGFR decline as renal disease progresses [9]. Other definitions of RP have been used, including a >50% decrease in baseline eGFR value [19]
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