Proteinuria or Albuminuria as Markers of Kidney and Cardiovascular Disease Risk : An Individual Patient-Level Meta-analysis

Hiddo J L Heerspink¹, Morgan E Grams², Yingying Sang³, Shoshana H Ballew³, Josef Coresh³, Aditya Surapaneni², Natalia Alencar de Pinho⁴, Nigel J Brunskill⁵, Alexander R Chang⁶, Elizabeth Ciemins⁷, Laura M Dember⁸, Keiko Kabasawa⁹, Lindsey Kornowske¹⁰, Adeera Levin¹¹, Rupert Major¹², Patrick B Mark¹³, Eric McArthur¹⁴, James Medcalf⁵, Marie Metzger¹⁵, Girish N Nadkarni¹⁶, David M J Naimark¹⁷, Cassianne Robinson-Cohen¹⁸, Keiichi Sumida¹⁹, Robin W M Vernooij²⁰, Ron T Gansevoort²¹, Bengt Fellström²², Steven Chadban²³; CKD Prognosis Consortium

Collaborators, Affiliations

Collaborators

CKD Prognosis Consortium:
Elvis Akwo, Natalia Alencar de Pinho, Radica Alicic, Shoshana H Ballew, Erwin P Bottinger, Nigel J Brunskill, Juan-Jesus Carrero, Steven Chadban, Alexander R Chang, Jing Chen, Elizabeth Ciemins, Christian Combe, Josef Coresh, Kenn Daratha, Laura M Dember, Ognjenka Djurdjev, Stephen B Ellis, Carina Flaherty, Martin Flamant, Luc Frimat, Ron T Gansevoort, Amit X Garg, Morgan E Grams, Jamie Green, Jean-Philippe Haymann, Jing He, Pascal Houillier, Yumi Ito, Cami Jones, Keiko Kabasawa, H Lester Kirchner, Lindsey Kornowske, Csaba P Kovesdy, Jennifer S Lees, Andrew S Levey, Adeera Levin, Ruth J F Loos, Rupert Major, Patrick B Mark, Kunihiro Matsushita, Eric McArthur, James Medcalf, Marie Metzger, Jeff Mohl, Girish N Nadkarni, David M J Naimark, Ichiei Narita, Dorothea Nitsch, Kevan Polkinghorne, Cassianne Robinson-Cohen, Yingying Sang, David Shepherd, Michael G Shlipak, Prabin Shrestha, Gurmukteshwar Singh, James Sondheimer, Bénédicte Stengel, Michael K Sullivan, Keiichi Sumida, Aditya Surapaneni, Junta Tanaka, Mila Tang, Navdeep Tangri, Jamie P Traynor, Katherine Tuttle, Robin W M Vernooij, Angela Yee-Moon Wang, Matt Weir, Waleed Zafar

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands (H.J.L.H.).
² Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, New York (M.E.G., A.S.).
³ Optimal Aging Institute, New York University Grossman School of Medicine, New York, New York (Y.S., S.H.B., J.C.).
⁴ Centre for Research in Epidemiology and Population Health, Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France (N.A.de P.).
⁵ Department of Cardiovascular Sciences, University of Leicester, and John Walls Renal Unit, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (N.J.B., J.M.).
⁶ Department of Nephrology, Geisinger, Danville, Pennsylvania (A.R.C.).
⁷ American Medical Group Association, Alexandria, Virginia (E.C.).
⁸ Renal-Electrolyte and Hypertension Division, Department of Medicine, and Department of Biostatistics, Epidemiology and Informatics, and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (L.M.D.).
⁹ Department of Health Promotion Medicine and Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (K.K.).
¹⁰ Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington (L.K.).
¹¹ Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada (A.L.).
¹² School of Medical Sciences, Public Health and Epidemiology Division, College of Life Sciences, University of Leicester; University of Hospitals of Leicester NHS Trust; and Leicester, Leicestershire and Rutland Integrated Care Board, Leicester, United Kingdom (R.M.).
¹³ School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom (P.B.M.).
¹⁴ ICES and London Health Sciences Centre Research Institute, London, Ontario, Canada (E.M.).
¹⁵ Clinical Epidemiology Team, Paris-Saclay University, Paris-Sud University, Université de Versailles Saint-Quentin-en-Yvelines, Centre for Research in Epidemiology and Population Health, Inserm U1018, Villejuif, France (M.M.).
¹⁶ Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (G.N.N.).
¹⁷ Department of Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada (D.M.J.N.).
¹⁸ Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (C.R.-C.).
¹⁹ Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.S.).
²⁰ Department of Nephrology and Hypertension and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (R.W.M.V.).
²¹ Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (R.T.G.).
²² Division of Renal Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden (B.F.).
²³ Department of Renal Medicine, Royal Prince Alfred Hospital, and Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia (S.C.).

PMID: 41183334
DOI: 10.7326/ANNALS-25-02117

Proteinuria or Albuminuria as Markers of Kidney and Cardiovascular Disease Risk : An Individual Patient-Level Meta-analysis

Hiddo J L Heerspink et al. Ann Intern Med. 2025.

. 2025 Nov 4.

doi: 10.7326/ANNALS-25-02117. Online ahead of print.

Authors

Collaborators

CKD Prognosis Consortium:
Elvis Akwo, Natalia Alencar de Pinho, Radica Alicic, Shoshana H Ballew, Erwin P Bottinger, Nigel J Brunskill, Juan-Jesus Carrero, Steven Chadban, Alexander R Chang, Jing Chen, Elizabeth Ciemins, Christian Combe, Josef Coresh, Kenn Daratha, Laura M Dember, Ognjenka Djurdjev, Stephen B Ellis, Carina Flaherty, Martin Flamant, Luc Frimat, Ron T Gansevoort, Amit X Garg, Morgan E Grams, Jamie Green, Jean-Philippe Haymann, Jing He, Pascal Houillier, Yumi Ito, Cami Jones, Keiko Kabasawa, H Lester Kirchner, Lindsey Kornowske, Csaba P Kovesdy, Jennifer S Lees, Andrew S Levey, Adeera Levin, Ruth J F Loos, Rupert Major, Patrick B Mark, Kunihiro Matsushita, Eric McArthur, James Medcalf, Marie Metzger, Jeff Mohl, Girish N Nadkarni, David M J Naimark, Ichiei Narita, Dorothea Nitsch, Kevan Polkinghorne, Cassianne Robinson-Cohen, Yingying Sang, David Shepherd, Michael G Shlipak, Prabin Shrestha, Gurmukteshwar Singh, James Sondheimer, Bénédicte Stengel, Michael K Sullivan, Keiichi Sumida, Aditya Surapaneni, Junta Tanaka, Mila Tang, Navdeep Tangri, Jamie P Traynor, Katherine Tuttle, Robin W M Vernooij, Angela Yee-Moon Wang, Matt Weir, Waleed Zafar

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands (H.J.L.H.).
² Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, New York (M.E.G., A.S.).
³ Optimal Aging Institute, New York University Grossman School of Medicine, New York, New York (Y.S., S.H.B., J.C.).
⁴ Centre for Research in Epidemiology and Population Health, Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France (N.A.de P.).
⁵ Department of Cardiovascular Sciences, University of Leicester, and John Walls Renal Unit, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (N.J.B., J.M.).
⁶ Department of Nephrology, Geisinger, Danville, Pennsylvania (A.R.C.).
⁷ American Medical Group Association, Alexandria, Virginia (E.C.).
⁸ Renal-Electrolyte and Hypertension Division, Department of Medicine, and Department of Biostatistics, Epidemiology and Informatics, and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (L.M.D.).
⁹ Department of Health Promotion Medicine and Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (K.K.).
¹⁰ Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington (L.K.).
¹¹ Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada (A.L.).
¹² School of Medical Sciences, Public Health and Epidemiology Division, College of Life Sciences, University of Leicester; University of Hospitals of Leicester NHS Trust; and Leicester, Leicestershire and Rutland Integrated Care Board, Leicester, United Kingdom (R.M.).
¹³ School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom (P.B.M.).
¹⁴ ICES and London Health Sciences Centre Research Institute, London, Ontario, Canada (E.M.).
¹⁵ Clinical Epidemiology Team, Paris-Saclay University, Paris-Sud University, Université de Versailles Saint-Quentin-en-Yvelines, Centre for Research in Epidemiology and Population Health, Inserm U1018, Villejuif, France (M.M.).
¹⁶ Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (G.N.N.).
¹⁷ Department of Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada (D.M.J.N.).
¹⁸ Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (C.R.-C.).
¹⁹ Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.S.).
²⁰ Department of Nephrology and Hypertension and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (R.W.M.V.).
²¹ Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (R.T.G.).
²² Division of Renal Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden (B.F.).
²³ Department of Renal Medicine, Royal Prince Alfred Hospital, and Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia (S.C.).

PMID: 41183334
DOI: 10.7326/ANNALS-25-02117

Abstract

Background: Urinary albumin-creatinine ratio (UACR) and urinary protein-creatinine ratio (UPCR) are both used in clinical practice to diagnose and monitor chronic kidney disease (CKD). Which measure exhibits stronger associations with clinical outcomes and whether this varies by patient characteristics are unknown.

Objective: To assess and compare the performance of UACR and UPCR across CKD-related clinical outcomes.

Design: Individual patient-level meta-analysis.

Setting: 38 research and clinical cohorts.

Participants: 148 994 participants with same-day measurements of UACR and UPCR.

Measurements: We quantified the associations of UACR and UPCR with subsequent clinical outcomes, including kidney failure and cardiovascular events, using Cox proportional hazards regression. Analyses were done in each cohort, followed by random-effects meta-analysis. Subgroups included those based on severity of proteinuria, type 2 diabetes, estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m², and glomerular disease.

Results: There were 148 994 participants and 9773 kidney failure events during a median of 3.8 years of follow-up. Higher UACR and UPCR both had a log-linear association with increased risk for kidney failure. The association with kidney failure was somewhat stronger for UACR (adjusted hazard ratio [HR] per SD increment, 2.55 [95% CI, 2.36 to 2.74]) than UPCR (HR, 2.40 [CI, 2.28 to 2.53]; P for comparison<0.001). Results were consistent to slightly stronger in subgroups with UACR greater than 30 mg/g, UPCR greater than 500 mg/g, eGFR less than 60 mL/min/1.73 m², diabetes, and glomerular disease. Associations between UACR and UPCR were generally similar for cardiovascular outcomes but favored UACR in subgroups with moderately to severely elevated UACR.

Limitation: Assessment of UACR and UPCR in spot urine samples.

Conclusion: Overall, UACR was more strongly associated with kidney failure than UPCR (particularly in subgroups with higher UACR), supporting the use of UACR rather than UPCR to diagnose and risk-stratify patients.

Primary funding source: National Kidney Foundation and National Institute of Diabetes and Digestive and Kidney Diseases.

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Disclosures: Disclosure forms are available with the article online.

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Proteinuria or Albuminuria as Markers of Kidney and Cardiovascular Disease Risk : An Individual Patient-Level Meta-analysis

Collaborators

Affiliations

Proteinuria or Albuminuria as Markers of Kidney and Cardiovascular Disease Risk : An Individual Patient-Level Meta-analysis

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous