Longitudinal estimated GFR trajectories in patients with and without type 2 diabetes and nephropathy

Journal article

Background

In clinical practice and in clinical trials changes in serum creatinine are used to evaluate changes in kidney function. It has been assumed that these changes follow a linear pattern when serum creatinine is converted to estimated glomerular filtration rate (eGFR). However, the paradigm that kidney function declines linearly over time has been questioned by studies showing either linear or nonlinear patterns. To verify how this impact on kidney end points in intervention trials, we analyzed eGFR trajectories in multiple clinical trials of patients with and without diabetes.

Study Design

Longitudinal observational study

Setting and participants

Six clinical trials with repeated measurements of serum creatinine

Predictor or Factor

Patient demographic and clinical parameters

Outcomes

Probability of nonlinear eGFR function trajectory calculated for each patient from a Bayesian model of individual eGFR trajectories

Results

The median probability of a nonlinear eGFR decline in all trials was 0.26 [0.13 – 0.48]. The median probability was 0.28 in diabetes vs. 0.09 in non-diabetes trials (p<0.01). The percentage of patients with a >50% probability of nonlinear eGFR decline was generally low, ranging from 19.3 to 31.7% in the diabetes and from 15.1 to 21.2% in the non-diabetic trials. In the pooled dataset, a multivariable linear regression showed that higher baseline eGFR, male gender, diabetes status, steeper eGFR slope, and non-renin-angiotensin-aldosterone-system antihypertensives, were independently associated with a greater probability of a nonlinear eGFR trajectory.

Limitations

Relatively short follow-up and no measured GFR

Conclusion

In both diabetes and non-diabetes trials the majority of patients show a more or less linear eGFR decline. These data support the paradigm that in diabetic and non-diabetic kidney disease eGFR decline progresses linearly over time during a clinical trial period. However, in diabetes one should take the nonlinearity proportion into account in the design of a clinical trial.

Authors: Weldegiorgis, M; de Zeeuw, D; Li, L; Parving, H; Hou, F

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: American Journal of Kidney Diseases
• Volume: 71
• Issue: 1
• Pages: 91-101
• Publication date: 2017-11-16
• Acceptance date: 2017-09-03
• DOI: 10.1053/j.ajkd.2017.08.010
• EISSN: 1523-6838
• ISSN: 0272-6386
• Pmid: 29153995
• Language: English
• Keywords: nephropathy; chronic kidney disease (CKD); estimated glomerular filtration rate (eGFR); renal end point; diabetic nephropathy; nonlinear eGFR slope; renal function trajectory; GFR slope; disease progression; serum creatinine