Kidney function can improve in patients with hypertensive CKD

Abstract

The typical assumption is that patients with CKD will have progressive nephropathy. Methodological issues, such as measurement error and regression to the mean, have made it difficult to document whether kidney function might improve in some patients. Here, we used data from 12 years of follow-up in the African American Study of Kidney Disease and Hypertension to determine whether some patients with CKD can experience a sustained improvement in GFR. We calculated estimated GFR (eGFR) based on serum creatinine measurements during both the trial and cohort phases. We defined clearly improved patients as those with positive eGFR slopes that we could not explain by random measurement variation under Bayesian mixed-effects models. Of 949 patients with at least three follow-up eGFR measurements, 31 (3.3%) demonstrated clearly positive eGFR slopes. The mean slope among these patients was +1.06 (0.12) ml/min per 1.73 m(2) per yr, compared with -2.45 (0.07) ml/min per 1.73 m(2) per yr among the remaining patients. During the trial phase, 24 (77%) of these 31 patients also had clearly positive slopes of (125)I-iothalamate-measured GFR during the trial phase. Low levels of proteinuria at baseline and randomization to the lower BP goal (mean arterial pressure ≤92 mmHg) associated with improved eGFR. In conclusion, the extended follow-up from this study provides strong evidence that kidney function can improve in some patients with hypertensive CKD.

Figure 1.

Distribution of estimated eGFR slopes (least-squares versus Bayesian) of study participants. This graph shows the histograms that compare the distribution of the least-squares eGFR slopes obtained by applying linear regression to individual participant with the Bayesian estimates obtained from the Bayesian linear mixed models.

Figure 2.

Probabilities of having a positive slope (being an improver). This graph shows the histogram of probabilities of having a positive slope (being an improver) for all participants. The height of each vertical bar represents the number of participants in that category. There are 31 patients with P≥0.95, and 94 patients with P≥0.5.

Figure 3.

Estimated GFR (eGFR) trajectories of the 31 improvers. (A–C) eGFR trajectories of the 31 improvers are shown. (D) The solid straight line shows the mean progression pattern of the improvers, whereas the dashed straight line represents the mean progression pattern of the nonimprovers. Gray regions represent the confidence bands.

Figure 4.

Distribution of urinary protein by improvers and nonimprovers. The solid line is the density curve of urinary protein for nonimprovers, whereas the dashed line is for improvers. Density curves are obtained using kernel-based smoothing method.