High levels of net endogenous acid production (NEAP), which is determined in part by diet, is associated with a greater risk of including end-stage renal disease (ESRD) or doubling of serum creatinine in African Americans.
Chart Explanation: There were 229 renal events [including ESRD or doubling of serum creatinine from baseline] over a follow-up of 12 months after randomization. Among those with proteinuria, where proteinuria is defined by urine protein-to-creatinine ratio (UPCR) > 0.22, there are 128 renal events compared with 101 renal events amongst without proteinuria (UPCR< 0.22). In the overall model, none of the quartiles of NEAP were associated with any significant risk of composite ESRD or doubling of serum creatinine (p-value<0.05). When NEAP was treated as a continuous predictor, the risk was still not significant (p-value=0.17). The adjusted association between quartiles of NEAP and composite renal events stratified by categories of UPCR were not statistically significant. However, among those with UPCR<0.22, higher NEAP was associated with 22% more composite renal events (p-value=0.05).
The African American Study of Kidney Disease and Hypertension (AASK) is a randomized, double-blind, controlled study in nondiabetic African Americans with hypertensive renal disease. Participants were assigned to two levels of target blood pressure and also randomized to receive one of three antihypertensive drugs. The study aim was to determine the effects of blood pressure control level and specific antihypertensive drugs with the primary outcome of progression of hypertensive kidney disease as measured by change in GFR. The trial phase of the study was from 1995-2001 with a cohort follow-up phase from 2002-2007. Participants participated in 24-hour urine collections every 6 months during the trial and annually as part of the cohort study.
Analyses for this measure were limited to 632 AASK Study patients with usable iothalamate GFR and 24-hour urine collection data. The composite outcome of progression to ESRD or doubling of serum creatinine was measured with mixed models and adjusted Cox proportional-hazards models.
Net endogenous acid production (NEAP) was estimated from the intakes of protein and potassium as defined in the equation: net endogenous acid production (mEq/day)= - 10.2+ 54.5 (protein intake (g/day) /potassium intake (mEq/day)). Models were stratified by categories of proteinuria (urine protein-to-creatinine ratio (UPCR) <0.22 vs. >=0.22). The cut-point for proteinuria was prespecified and has been used as a standard threshold for all AASK analyses.
|Description of Measure||Risk of ESRD or Doubling of Serum Creatinine Associated with NEAP|
|Data Source||AASK Multi-center prospective longitudinal cohort study|
|Type of Data Source||Public|
|Data Set||AASK summarized data|
|Health Care System Data||No|
|Regional or National?||National|
|Demographic Group||Self-identified African Americans with hypertension, no diabetes, and aged between 18 to 70 years with a GFR of 20 -65 mL/min per 1.73 m2|
|Numerator||Composite outcome of ESRD or doubling of serum creatinine|
|Denominator||AASK participants with 24-hour urine collections |
|Definition of CKD||GFR of 20 - 65 mL/min per 1.73 m2 (for entry into study)|
|Glomerular filtration rate||Estimated, MDRD Study equation|
|Primary Data Source Indicator||Serum creatinine level or incident ESRD|
|Primary Indicator Method of Measurement||Serum creatinine via blood test; ESRD as indicated by dialysis or transplant|
|Secondary (1) Variable||Net endogenous acid production|
|Secondary (1) Indicator Method of Measurement||24-hour urea nitrogen and potassium levels|
|Frequency of Measurement (Primary)||Baseline and every 6 months of the study|
|U.S. Region Covered by Primary Variable||11 clinical centers throughout the United States (Cleveland, Ohio; Nashville, Tennessee; Dallas, Texas; Baltimore, Maryland; Washington, D.C.; Atlanta, Georgia; Los Angeles, California)|
|Period Currently Available||2007|
|Additional Data Items of Interest||Adjusted variables (age, gender, European ancestry percentage, baseline GFR)|
|Limitations of Indicator||Study population is very specific, diet was measured only through urinalysis|
|Analytical Considerations||As with all cohort studies, selection bias and possible confounding|