Michele Provenzano1, Paolo Chiodini2, Roberto Minutolo1, Carmine Zoccali3, Vincenzo Bellizzi4, Giuseppe Conte1, Francesco Locatelli5, Giovanni Tripepi3, Lucia Del Vecchio5, Francesca Mallamaci3, Lucia Di Micco6, Domenico Russo7, Hiddo J L Heerspink8, Luca De Nicola1. 1. Nephrology Unit, University of Campania Luigi Vanvitelli, Naples, Italy. 2. Medical Statistics Unit, University of Campania Luigi Vanvitelli, Naples, Italy. 3. Nephrology Center of National Research Institute of Biomedicine and Molecular Immunology, Reggio Calabria, Italy. 4. Division of Nephrology, Dialysis and Transplantation, Salerno Medical School, University Hospital San Giovanni di Dio e Ruggi d'Aragona Unit-University, Salerno, Italy. 5. Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy. 6. Division of Nephrology, A. Landolfi Hospital, Solofra, Avellino, Italy. 7. Department of Public Health, University of Naples Federico II, Naples, Italy. 8. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
BACKGROUND: In non-dialysis chronic kidney disease (CKD), absolute proteinuria (Uprot) depends on the extent of kidney damage and residual glomerular filtration rate (GFR). We therefore evaluated, as compared with Uprot, the strength of association of proteinuria indexed to estimated GFR (eGFR) with end-stage renal disease (ESRD) risk. METHODS: In a multi-cohort prospective study in 3957 CKD patients of Stages G3-G5 referred to nephrology clinics, we tested two multivariable Cox models for ESRD risk, with either Uprot (g/24 h) or filtration-adjusted proteinuria (F-Uprot) calculated as Uprot/eGFR ×100. RESULTS: Mean ± SD age was 67 ± 14 years, males 60%, diabetics 29%, cardiovascular disease (CVD) 34%, eGFR 32 ± 13 mL/min/1.73 m2, median (interquartile range) Uprot 0.41 (0.12-1.29) g/24 h and F-Uprot 1.41 (0.36-4.93) g/24 h per 100 mL/min/1.73 m2 eGFR. Over a median follow-up of 44 months, 862 patients reached ESRD. At competing risk analysis, ESRD risk progressively increased when F-Uprot was 1.0-4.9 and ≥5.0 versus <1.0 g/24 h per 100 mL/min/1.73 m2 eGFR in Stages G3a-G4 (P < 0.001) and Stage G5 (P = 0.002). Multivariable Cox analysis showed that Uprot predicts ESRD in Stages G3a-G4 while in G5 the effect was not significant; conversely, F-Uprot significantly predicted ESRD at all stages. The F-Uprot model allowed a significantly better prediction versus the Uprot model according to Akaike information criterion. Net reclassification improvement was 12.2% (95% confidence interval 4.2-21.1), with higher reclassification in elderly, diabetes and CVD, as well as in diabetic nephropathy and glomerulonephritis, and in CKD Stages G4 and G5. CONCLUSIONS: In patients referred to nephrology clinics, F-Uprot predicts ESRD at all stages of overt CKD and improves, as compared with Uprot, reclassification of patients for renal risk, especially in more advanced and complicated disease.
BACKGROUND: In non-dialysis chronic kidney disease (CKD), absolute proteinuria (Uprot) depends on the extent of kidney damage and residual glomerular filtration rate (GFR). We therefore evaluated, as compared with Uprot, the strength of association of proteinuria indexed to estimated GFR (eGFR) with end-stage renal disease (ESRD) risk. METHODS: In a multi-cohort prospective study in 3957 CKDpatients of Stages G3-G5 referred to nephrology clinics, we tested two multivariable Cox models for ESRD risk, with either Uprot (g/24 h) or filtration-adjusted proteinuria (F-Uprot) calculated as Uprot/eGFR ×100. RESULTS: Mean ± SD age was 67 ± 14 years, males 60%, diabetics 29%, cardiovascular disease (CVD) 34%, eGFR 32 ± 13 mL/min/1.73 m2, median (interquartile range) Uprot 0.41 (0.12-1.29) g/24 h and F-Uprot 1.41 (0.36-4.93) g/24 h per 100 mL/min/1.73 m2 eGFR. Over a median follow-up of 44 months, 862 patients reached ESRD. At competing risk analysis, ESRD risk progressively increased when F-Uprot was 1.0-4.9 and ≥5.0 versus <1.0 g/24 h per 100 mL/min/1.73 m2 eGFR in Stages G3a-G4 (P < 0.001) and Stage G5 (P = 0.002). Multivariable Cox analysis showed that Uprot predicts ESRD in Stages G3a-G4 while in G5 the effect was not significant; conversely, F-Uprot significantly predicted ESRD at all stages. The F-Uprot model allowed a significantly better prediction versus the Uprot model according to Akaike information criterion. Net reclassification improvement was 12.2% (95% confidence interval 4.2-21.1), with higher reclassification in elderly, diabetes and CVD, as well as in diabetic nephropathy and glomerulonephritis, and in CKD Stages G4 and G5. CONCLUSIONS: In patients referred to nephrology clinics, F-Uprot predicts ESRD at all stages of overt CKD and improves, as compared with Uprot, reclassification of patients for renal risk, especially in more advanced and complicated disease.
Authors: Nora A Khreba; Mostafa Abdelsalam; A M Wahab; Mohammed Sanad; Rania Elhelaly; Mohammed Adel; Ghada El-Kannishy Journal: Int J Nephrol Date: 2019-03-12
Authors: Carlo Garofalo; Silvio Borrelli; Toni De Stefano; Luca De Nicola; Carlo Vita; Nicola Peruzzu; Antonella Netti; Giuseppe Conte; Michele Provenzano; Roberto Minutolo Journal: Int Urol Nephrol Date: 2021-07-12 Impact factor: 2.370