Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

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.

Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir

“…We defined rapid eGFR decline using an average rate of decline over the period on ATV or LPV, based on the results of mixed-effects models and a minimum of 6-months exposure to these drugs. The definition of rapid progression proposed by D:A:D requires extensive (at least 3 year) follow-up and at least two creatinine measures per year, and was applied to individuals with eGFR at least 90 ml/min per 1.73 m 2 in the original study [ 29 ]. When these more stringent criteria were applied to our study population, only 140 individuals met the definition of rapid eGFR decline.…”

Monitoring of kidney function in HIV‐positive patients

“…Patients who progress to stage 3 CKD typically have CKD risk factors such as diabetes mellitus, hypertension, established cardiovascular disease or exposure to drugs with nephrotoxic potential . Other risk factors include older age, hepatitis C virus coinfection, low CD4 cell count, HIV viraemia, a history of AKI, the presence of mild renal dysfunction (eGFR < 70–75 mL/min/1.73 m 2 and/or albuminuria) , and rapid eGFR decline (≥ 5 mL/min/1.73 m 2 /year) . In those with normal renal function (eGFR > 90 mL/min/1.73 m 2 ), the incidence of stage 3 CKD is considerably lower (1.3 per 1000 person‐years) , and the average rate of annual eGFR decline small .…”

“…*Identify rapid eGFR decline (more than 5 mL/min/1.73 m 2 /year). [18,24,26,48], and rapid eGFR decline (≥ 5 mL/ min/1.73 m 2 /year) [49]. In those with normal renal function (eGFR > 90 mL/min/1.73 m 2 ), the incidence of stage 3 CKD is considerably lower (1.3 per 1000 person-years) [25,50], and the average rate of annual eGFR decline small [18,25,26,51].…”

Switching from tenofovir containing regimens to boosted protease inhibitor monotherapy: Impact on renal function

“…There is no consensus on the definition of rapid loss of renal function which makes it difficult to compare our results with other published series. 13 Patient's follow-up could have not be long enough to capture precisely CG-CrCl changes. To our knowledge this is the first study that has evaluated the effect of PI monotherapy in the reversibility of the decline in the CG-CrCl during TDF therapy.…”