Uraemia Progression in Chronic Kidney Disease Stages 3–5 Is Not Constant

Abstract

Introduction: Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m²/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimated GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating. Methods: 1,441 patients attending a nephrology clinic over a 21-year period, with an initial eGFR <60 ml/min/1.73 m² and an observation period ≧2 years, were included. eGFR was calculated from all creatinine measurements. 420 patients developed end-stage renal disease (ESRD). First- and second-order polynomial regression analysis of eGFR against time was performed for each patient individually. Patients had accelerating uraemia progression if the second-order term coefficient was negative. Results: The initial eGFR was 30.8 ±15.1 ml/min/1.73 m². The second-order coefficient was median –0.15 ml/min/1.73 m²/year² (interquartile range –0.92, +0.34). Significantly more patients had an accelerating loss (62%, p < 0.001). Acceleration was mainly seen when eGFR was <30 ml/min. ΔGFR was mean 1.47 ± 4.5 ml/min/1.73 m²/year (male 1.67, female 1.22). ESRD patients lost 5.4 ± 5.4 ml/min/year/1.73 m² during the last year before ESRD. Accelerating loss was seen for all diagnoses except polycystic disease. Diagnoses with higher ΔGFR were polycystic renal disease (3.3 ml/min/1.73 m²/year), hypertensive nephropathy (2.1 ml/min/1.73 m²/year) and diabetic nephropathy (2.6 ml/min/ 1.73 m²/year). There was no evidence of improvement in overall uraemia progression during the period of observation. Conclusions: Uraemia progression in CKD stages 3–5 is not linear, but shows an accelerating trend. This suggests that hyperfiltration mechanisms play a role in CKD progression. ESRD cannot thus be predicted from previous ΔGFR alone.

Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis

“…In these studies, the reported annual eGFR decline for the whole CKD population ranged between 1.5 and 2.1 mL/min/1.73 m 2 , and for patients who initiated dialysis, it ranged between 3.9 and 7.3 mL/min/1.73 m 2 . 15 , 17 , 18 Previous literature is in line with our finding that the mean annual rates of kidney function decline in CKD 3–5 cohorts are much lower than in dialysis-based studies.…”

Defining new surrogate markers for CKD progression

“…The progression of CKD to ESRD often describes an inexorable path from nephron loss to ESRD, where the rate of loss of function is at first linear over time [15] and then accelerates beginning in late stage III CKD [16, 17]. Further, the slope and uniformity of progression rate may vary greatly for individual patients [18].…”

Comparison of Clinical Trajectories before Initiation of Renal Replacement Therapy between Diabetic Nephropathy and Nephrosclerosis on the KDIGO Guidelines Heat Map

“…Declines in eGFR, such as a 30% reduction over 2 years, were reported to be strongly and consistently associated with the risks for ESKD and mortality and have been considered an alternative endpoint for CKD progression [ 9 ]. Although the traditional view of kidney function decline in CKD is a steady linear decline (or slope), albeit at different rates among individuals, recent studies have evaluated the trajectories of decline and have shown they are often not linear [ 10 – 12 ]. The average overall rate of decline reported in 1441 adult individuals with stage 3–5 CKD was 1.47 mL/min/1.73 m 2 ; however, the rate was faster in individuals with eGFR < 30 mL/min/1.73 m 2 and accelerated in the year before the development of ESKD [ 10 ].…”

“…Although the traditional view of kidney function decline in CKD is a steady linear decline (or slope), albeit at different rates among individuals, recent studies have evaluated the trajectories of decline and have shown they are often not linear [ 10 – 12 ]. The average overall rate of decline reported in 1441 adult individuals with stage 3–5 CKD was 1.47 mL/min/1.73 m 2 ; however, the rate was faster in individuals with eGFR < 30 mL/min/1.73 m 2 and accelerated in the year before the development of ESKD [ 10 ]. Individuals with steeper trajectories were more likely to have been hospitalized and to receive a diagnosis of AKI during hospitalization [ 12 ].…”