Open Access Highly Accessed Research article

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

David A Kamara18*, Lene Ryom29*, Michael Ross3, Ole Kirk2, Peter Reiss4, Philippe Morlat5, Olivier Moranne6, Christoph A Fux7, Amanda Mocroft1, Caroline Sabin1, Jens D Lundgren2, Colette J Smith1 and the D:A:D study Group

Author Affiliations

1 Research Dept. of Infection and Population Health, University College London, London, United Kingdom

2 Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, CHIP, Section 2100, Finsencentret, Copenhagen, Denmark

3 Division of Nephrology, Mount Sinai School of Medicine, New York, USA

4 Academic Medical Center, Div. of Infectious Diseases and Dept. of Global Health, University of Amsterdam, Amsterdam, The Netherlands

5 Service de médecine interne et maladies infectieuses, Hôpital Saint-André, CHU de Bordeaux, France

6 Nephrology department, Public Health department, CHU Nice, France

7 Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Switzerland

8 Research Department of Infection and Population Health, UCL, Royal Free Campus,Rowland Hill Street, London NW3 2PF, UK

9 Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, CHIP, Section 2100, Finsencentret, Blegdamsvej 9 2100, Copenhagen Ø, Denmark

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BMC Nephrology 2014, 15:51  doi:10.1186/1471-2369-15-51

Published: 25 March 2014

Abstract

Background

No 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.

Methods

Two 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.

Results

22,603 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.

Conclusions

Our 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.

Keywords:
HIV; Kidney disease; Rapid progression; Estimated glomerular filtration rate; Chronic kidney disease