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

D:A:D study Group

doi:10.1186/1471-2369-15-51

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

D:A:D study Group

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	51
Journal	BMC Nephrology
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/1471-2369-15-51
Publication status	Published - 25 Mar 2014

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10.1186/1471-2369-15-51

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@article{eb44202bb70b4373a20d22fa747ebeb1,

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 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 = "Chronic kidney disease, Estimated glomerular filtration rate, HIV, Kidney disease, Rapid progression",

author = "Kamara, {D. A.} and L. Ryom and Michael Ross and O. Kirk and Peter Reiss and P. Morlat and O. Moranne and Fux, {C. A.} and A. Mocroft and C. Sabin and Lundgren, {J. D.} and Smith, {Colette J.} and B. Powderly and N. Shortman and C. Moecklinghoff and G. Reilly and X. Franquet and L. Ryom and C. Sabin and D. Kamara and C. Smith and A. Phillips and A. Mocroft and J. Tverland and M. Mansfeld and J. Nielsen and D. Raben and Lundgren, {J. D.} and {Salb{\o}l Brandt}, R. and M. Rickenbach and I. Fanti and E. Krum and M. Hillebregt and S. Geffard and A. Sundstr{\"o}m and M. Delforge and E. Fontas and F. Torres and H. McManus and S. Wright and J. Kj{\ae}r and A. Sj{\o}l and P. Meidahl and J. Helweg-Larsen and {Schmidt Iversen}, J. and L. Ryom and A. Mocroft and O. Kirk and P. Reiss and M. Ross and Fux, {C. A.} and P. Morlat and O. Moranne and Kesselring, {A. M.} and Kamara, {D. A.} and C. Smith and Lundgren, {J. D.} and C. Smith and L. Ryom and A. Phillips and R. Weber and P. Morlat and C. Pradier and P. Reiss and N. Friis-M{\o}ller and J. Kowalska and Lundgren, {J. D.} and C. Sabin and M. Law and {D'Arminio Monforte}, A. and F. Dabis and M. Bruyand and P. Reiss and C. Smith and Kamara, {D. A.} and M. Bower and G. F{\"a}tkenheuer and A. Donald and A. Grulich and L. Ryom and Lundgren, {J. D.} and P. Reiss and S. Zaheri and M. Hillebregt and L. Gras and Prins, {J. M.} and Kuijpers, {T. W.} and Scherpbier, {H. J.} and {Van Der Meer}, {J. T.M.} and Wit, {F. W.M.N.} and Godfried, {M. H.} and P. Reiss and {Van Der Poll}, T. and Nellen, {F. J.B.} and Lange, {J. M.A.} and Geerlings, {S. E.} and {Van Vugt}, M. and D. Pajkrt and Bos, {J. C.} and {Van Der Valk}, M. and Grijsen, {M. L.} and Wiersinga, {W. J.} and A. Goorhuis and Hovius, {J. W.R.} and S. Lowe and {Oude Lashof}, A. and D. Posthouwer and Pronk, {M. J.H.} and Ammerlaan, {H. S.M.} and {Van Der Ende}, {M. E.} and {De Vries-Sluijs}, {T. E.M.S.} and Schurink, {C. A.M.} and Nouwen, {J. L.} and A. Verbon and Rijnders, {B. J.A.} and {Van Gorp}, {E. C.M.} and {Van Der Feltz}, M. and Driessen, {G. J.A.} and {Van Rossum}, {A. M.C.} and J. Branger and Schippers, {E. F.} and {Van Nieuwkoop}, C. and {Van Elzakker}, {E. P.} and Groeneveld, {P. H.P.} and Bouwhuis, {J. W.} and R. Soetekouw and {Ten Kate}, {R. W.} and Kroon, {F. P.} and {Van Dissel}, {J. T.} and Arend, {S. M.} and {De Boer}, {M. G.J.} and H. Jolink and {Ter Vollaard}, {H. J.M.} and Bauer, {M. P.} and {Den Hollander}, {J. G.} and K. Pogany and {Van Twillert}, G. and W. Kortmann and {Cohen Stuart}, {J. W.T.} and Diederen, {B. M.W.} and Leyten, {E. M.S.} and Gelinck, {L. B.S.} and Kootstra, {G. J.} and Delsing, {C. E.} and K. Brinkman and Blok, {W. L.} and Frissen, {P. H.J.} and Schouten, {W. E.M.} and {Van Den Berk}, {G. E.L.} and {Van Kasteren}, {M. E.E.} and Brouwer, {A. E.} and J. Veenstra and Lettinga, {K. D.} and Mulder, {J. W.} and Vrouenraets, {S. M.E.} and Lauw, {F. N.} and {Van Eeden}, A. and Verhagen, {D. 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Fontas and C. Caissotti and P. Dellamonica and E. Bernard and E. Cua and {De Salvador-Guillouet}, F. and J. Durant and S. Ferrando and V. Mondain-Miton and A. Naqvi and I. Perbost and B. Prouvost-Keller and S. Pillet and P. Pugliese and V. Rahelinirina and Roger, {P. M.} and K. Dollet and V. Aubert and J. Barth and M. Battegay and E. Bernasconi and J. B{\"o}ni and Bucher, {H. C.} and C. Burton-Jeangros and A. Calmy and M. Cavassini and M. Egger and L. Elzi and J. Fehr and J. Fellay and H. Furrer and Fux, {C. A.} and M. Gorgievski and H. G{\"u}nthard and D. Haerry and B. Hasse and Hirsch, {H. H.} and I. H{\"o}sli and C. Kahlert and L. Kaiser and O. Keiser and T. Klimkait and H. Kovari and B. Ledergerber and G. Martinetti and {Martinez De Tejada}, B. and K. Metzner and N. M{\"u}ller and D. Nadal and G. Pantaleo and A. Rauch and A. Regenass and M. Rickenbach and C. Rudin and P. Schmid and D. Schultze and F. Sch{\"o}ni-Affolter and J. Sch{\"u}pbach and R. Speck and P. Taff{\'e} and P. Tarr and A. Telenti and A. Trkola and P. Vernazza and R. Weber and S. Yerly and {D:A:D study Group}",

year = "2014",

month = mar,

day = "25",

doi = "10.1186/1471-2369-15-51",

language = "English",

volume = "15",

journal = "BMC Nephrology",

issn = "1471-2369",

publisher = "BioMed Central",

number = "1",

}

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, D. A.

AU - Ryom, L.

AU - Ross, Michael

AU - Kirk, O.

AU - Reiss, Peter

AU - Morlat, P.

AU - Moranne, O.

AU - Fux, C. A.

AU - Mocroft, A.

AU - Sabin, C.

AU - Lundgren, J. D.

AU - Smith, Colette J.

AU - Powderly, B.

AU - Shortman, N.

AU - Moecklinghoff, C.

AU - Reilly, G.

AU - Franquet, X.

AU - Ryom, L.

AU - Sabin, C.

AU - Kamara, D.

AU - Smith, C.

AU - Phillips, A.

AU - Mocroft, A.

AU - Tverland, J.

AU - Mansfeld, M.

AU - Nielsen, J.

AU - Raben, D.

AU - Lundgren, J. D.

AU - Salbøl Brandt, R.

AU - Rickenbach, M.

AU - Fanti, I.

AU - Krum, E.

AU - Hillebregt, M.

AU - Geffard, S.

AU - Sundström, A.

AU - Delforge, M.

AU - Fontas, E.

AU - Torres, F.

AU - McManus, H.

AU - Wright, S.

AU - Kjær, J.

AU - Sjøl, A.

AU - Meidahl, P.

AU - Helweg-Larsen, J.

AU - Schmidt Iversen, J.

AU - Ryom, L.

AU - Mocroft, A.

AU - Kirk, O.

AU - Reiss, P.

AU - Ross, M.

AU - Fux, C. A.

AU - Morlat, P.

AU - Moranne, O.

AU - Kesselring, A. M.

AU - Kamara, D. A.

AU - Smith, C.

AU - Lundgren, J. D.

AU - Smith, C.

AU - Ryom, L.

AU - Phillips, A.

AU - Weber, R.

AU - Morlat, P.

AU - Pradier, C.

AU - Reiss, P.

AU - Friis-Møller, N.

AU - Kowalska, J.

AU - Lundgren, J. D.

AU - Sabin, C.

AU - Law, M.

AU - D'Arminio Monforte, A.

AU - Dabis, F.

AU - Bruyand, M.

AU - Reiss, P.

AU - Smith, C.

AU - Kamara, D. A.

AU - Bower, M.

AU - Fätkenheuer, G.

AU - Donald, A.

AU - Grulich, A.

AU - Ryom, L.

AU - Lundgren, J. D.

AU - Reiss, P.

AU - Zaheri, S.

AU - Hillebregt, M.

AU - Gras, L.

AU - Prins, J. M.

AU - Kuijpers, T. W.

AU - Scherpbier, H. J.

AU - Van Der Meer, J. T.M.

AU - Wit, F. W.M.N.

AU - Godfried, M. H.

AU - Reiss, P.

AU - Van Der Poll, T.

AU - Nellen, F. J.B.

AU - Lange, J. M.A.

AU - Geerlings, S. E.

AU - Van Vugt, M.

AU - Pajkrt, D.

AU - Bos, J. C.

AU - Van Der Valk, M.

AU - Grijsen, M. L.

AU - Wiersinga, W. J.

AU - Goorhuis, A.

AU - Hovius, J. W.R.

AU - Lowe, S.

AU - Oude Lashof, A.

AU - Posthouwer, D.

AU - Pronk, M. J.H.

AU - Ammerlaan, H. S.M.

AU - Van Der Ende, M. E.

AU - De Vries-Sluijs, T. E.M.S.

AU - Schurink, C. A.M.

AU - Nouwen, J. L.

AU - Verbon, A.

AU - Rijnders, B. J.A.

AU - Van Gorp, E. C.M.

AU - Van Der Feltz, M.

AU - Driessen, G. J.A.

AU - Van Rossum, A. M.C.

AU - Branger, J.

AU - Schippers, E. F.

AU - Van Nieuwkoop, C.

AU - Van Elzakker, E. P.

AU - Groeneveld, P. H.P.

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AU - Weber, R.

AU - Yerly, S.

AU - D:A:D study Group

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 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.

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 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.

KW - Chronic kidney disease

KW - Estimated glomerular filtration rate

KW - HIV

KW - Kidney disease

KW - Rapid progression

UR - http://www.scopus.com/inward/record.url?scp=84898407890&partnerID=8YFLogxK

U2 - 10.1186/1471-2369-15-51

DO - 10.1186/1471-2369-15-51

M3 - Article

C2 - 24666792

AN - SCOPUS:84898407890

VL - 15

JO - BMC Nephrology

JF - BMC Nephrology

SN - 1471-2369

IS - 1

M1 - 51

ER -

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

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