Predictive power of sequential measures of albuminuria for progression to ESRD or death in Pima Indians with type 2 diabetes

Abstract

Background: To determine whether historic albuminuria measurements provide additional predictive value for diabetic end-stage renal disease (ESRD) and natural mortality over the most recent measurement, ie, whether "regression" from high albuminuria has a different prognosis than stability at the lower level.

Study design: Observational longitudinal study.

Setting & participants: Pima Indians 15 years or older with type 2 diabetes and at least 2 consecutive measurements of urinary albumin-creatinine ratio (ACR) within 6 years.

Predictors: Sequential measurements of urinary ACR.

Outcomes & measurements: Proportional hazards analyses were used to estimate the risk of ESRD and natural death associated with the first and second ACR measurement. The ability of these highly correlated variables to predict outcome was compared with receiver operating characteristic curves calculated by means of the generalized c statistic.

Results: In 983 subjects, 136 developed ESRD and 180 died of natural causes during a maximum follow-up of 12.6 years. Each doubling in the second ACR was associated with a 1.71-fold greater incidence of ESRD (95% confidence interval, 1.54 to 1.89) and 1.16-fold greater natural mortality (95% confidence interval, 1.07 to 1.27) adjusted for age, sex, diabetes duration, and antihypertensive medication. The addition of the first ACR measurement to the model did not add to the predictive value for ESRD or mortality. In pairwise comparisons of c statistics, the second ACR was a significantly better predictor of ESRD than the first ACR.

Limitations: The predictive value of ACR measurements is decreased to the extent that its precision is based on a single measure.

Conclusion: The predictive power of the latest ACR for ESRD and natural mortality in patients with diabetes is not enhanced by knowledge of the preceding ACR. Therefore, ACR changes over time, ie, regression or progression, add minimal predictive value beyond the latest measurement in the series.

Figure 1

Unadjusted incidence rate ratio for diabetic end-stage renal disease (ESRD; N = 89 cases) relative to persistently normal albumin-creatinine ratio (ACR). The table below the figure comparatively shows hazard ratios for diabetic ESRD according to change in ACR with 95% confidence intervals adjusted for age, sex, diabetes duration, and antihypertensive medication. Macroalbuminuria (Macro) was truncated at less than 3,000 mg/g. Sample size for each category is listed in Table 2. Abbreviations: Normal, normal ACR; Micro, microalbuminuria; ACR₋₁, first ACR measurement; ACR₀, second ACR measurement. *P < 0.05 compared with the group with persistently normal ACR.

Figure 2

Unadjusted death rate ratio for natural mortality (N = 144 deaths) relative to persistently normal albumin-creatinine ratio (ACR). The table below the figure comparatively shows hazard ratios for natural death according to change in ACR with 95% confidence intervals adjusted for age, sex, diabetes duration, and antihypertensive medication. Macroalbuminuria (Macro) was truncated at less than 3,000 mg/g. Sample size for each category is listed in Table 2. Abbreviations: Normal, normal ACR; Micro, microalbuminuria; ACR₋₁, first ACR measurement; ACR₀, second ACR measurement. *P < 0.05 compared with the group with persistently normal ACR.