New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study
Authors: Minutolo Roberto , Provenzano Michele , Chiodini Paolo , Borrelli Silvio , Garofalo Carlo , Andreucci Michele , Liberti Maria Elena , Bellizzi Vincenzo , Conte Giuseppe , De Nicola Luca ,   The Collaborative Study Group on the Conservative Treatment of CKD of the Italian Society of Nephrology, De Nicola L , Minutolo R , Zamboli P , Iodice F C , Borrelli S , Chiodini P , Signoriello S , Gallo C , Conte G , Cianciaruso B , Pota A , Nappi F , Avella F , Di Iorio B R , Bellizzi V , Cestaro R , Martignetti V , Morrone L , Lupo A , Abaterusso C , Donadio C , Bonomini M , Sirolli V , Casino F , Lopez T , Detomaso F , Giannattasio M , Virgilio M , Tarantino G , Cristofano C , Tuccillo S , Chimienti S , Petrarulo F , Giancaspro V , Strippoli M , Laraia E , Gallucci M , Gigante B , Lodeserto C , Santese D , Montanaro A , Giordano R , Caglioti A , Fuiano G , Zoccali C , Caridi G , Postorino M , Savica V , Monardo P , Bellinghieri G , Santoro D , Castellino P , Rapisarda F , Fatuzzo P , Messina A , Dal Canton A , Esposito V , Formica M , Segoloni G , Gallieni M , Locatelli F , Tarchini R , Meneghel G , Oldrizzi L , Cossu M , Di Giulio S , Malaguti M , Pizzarelli F , Quintaliani G , Cianciaruso B , Pisani A , Conte G , De Nicola L , Minutolo R , Bonofiglio R , Fuiano G , Grandaliano G , Bellinghieri G , Santoro D , Cianciaruso B , Russo D , Pota A , Di Micco L , Torraca S , Sabbatini M , Pisani A , Bellizzi V 
Published: January 2022

Background

Anemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known.

Methods

We performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR &lt;60 mL/min/1.73 m2 regularly followed in renal clinics. We estimated the incidence of mild anemia (hemoglobin 11–12 g/dL in women and 11–13 g/dL in men) and severe anemia (hemoglobin &lt;11 g/dL or use of erythropoiesis-stimulating agents) during a 3-year follow-up period. Thereafter we estimated the risk of end-stage kidney disease (ESKD) and all-cause death associated with new-onset mild and severe anemia.

Results

The mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1–1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR &lt;30 mL/min/1.73 m2 and proteinuria &gt;0.50 g/day. Male sex, moderate CKD (eGFR 30–44 mL/min/1.73 m2) and moderate proteinuria (0.15–0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02–1.98]} and all-cause death [HR 1.55 (95% CI 1.04–2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20–2.51)] and death [HR 1.83 (95% CI 1.05–3.19)].

Conclusions

New-onset anemia is frequent, particularly in patients with more severe renal damage and in those with diabetes mellitus. The occurrence of anemia, even of a mild degree, is associated with mortality risk and faster progression towards ESKD.