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

David A. Kamara, Lene Ryom, Michael J. Ross, Ole Kirk, Peter Reiss, Philippe Morlat, Olivier Moranne, Christoph A. Fux, Amanda Mocroft, Caroline Sabin, Jens D. Lundgren, Colette J. Smith

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 m 2/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.

Original languageEnglish (US)
Article number51
JournalBMC Nephrology
Volume15
Issue number1
DOIs
StatePublished - Mar 25 2014
Externally publishedYes

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Glomerular Filtration Rate
HIV
Kidney
Anti-HIV Agents
Chronic Renal Insufficiency
Sensitivity and Specificity

Keywords

  • Chronic kidney disease
  • Estimated glomerular filtration rate
  • HIV
  • Kidney disease
  • Rapid progression

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons : The D:A:D study. / Kamara, David A.; Ryom, Lene; Ross, Michael J.; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A.; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D.; Smith, Colette J.

In: BMC Nephrology, Vol. 15, No. 1, 51, 25.03.2014.

Research output: Contribution to journalArticle

Kamara, DA, Ryom, L, Ross, MJ, Kirk, O, Reiss, P, Morlat, P, Moranne, O, Fux, CA, Mocroft, A, Sabin, C, Lundgren, JD & Smith, CJ 2014, 'Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: The D:A:D study', BMC Nephrology, vol. 15, no. 1, 51. https://doi.org/10.1186/1471-2369-15-51
Kamara, David A. ; Ryom, Lene ; Ross, Michael J. ; Kirk, Ole ; Reiss, Peter ; Morlat, Philippe ; Moranne, Olivier ; Fux, Christoph A. ; Mocroft, Amanda ; Sabin, Caroline ; Lundgren, Jens D. ; Smith, Colette J. / Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons : The D:A:D study. In: BMC Nephrology. 2014 ; Vol. 15, No. 1.
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title = "Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: The D:A:D study",
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 m 2/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 = "Chronic kidney disease, Estimated glomerular filtration rate, HIV, Kidney disease, Rapid progression",
author = "Kamara, {David A.} and Lene Ryom and Ross, {Michael J.} and Ole Kirk and Peter Reiss and Philippe Morlat and Olivier Moranne and Fux, {Christoph A.} and Amanda Mocroft and Caroline Sabin and Lundgren, {Jens D.} and Smith, {Colette J.}",
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TY - JOUR

T1 - Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons

T2 - The D:A:D study

AU - Kamara, David A.

AU - Ryom, Lene

AU - Ross, Michael J.

AU - Kirk, Ole

AU - Reiss, Peter

AU - Morlat, Philippe

AU - Moranne, Olivier

AU - Fux, Christoph A.

AU - Mocroft, Amanda

AU - Sabin, Caroline

AU - Lundgren, Jens D.

AU - Smith, Colette J.

PY - 2014/3/25

Y1 - 2014/3/25

N2 - 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 m 2/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.

AB - 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 m 2/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.

KW - Chronic kidney disease

KW - Estimated glomerular filtration rate

KW - HIV

KW - Kidney disease

KW - Rapid progression

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