The association of chronic kidney disease complications by albuminuria and glomerular filtration rate: a cross-sectional analysis

Abstract

Background: Albuminuria is strongly associated with future risk for cardiovascular and kidney outcomes, and has been proposed to be included in the classification of chronic kidney disease (CKD) along with glomerular filtration rate (GFR). Few data are available on whether albuminuria is associated with concurrent complications of CKD. Methods: A cross-sectional analysis of 1,665 participants screened for the Modification of Diet in Renal Disease (MDRD) study was performed to examine the association between albuminuria (determined using urine albumin-creatinine ratio (ACR)) and measured GFR (determined using urinary clearance of iothalamate) with anemia, acidosis, hyperphosphatemia, and hypertension. Results: Mean GFR (± SD) was 39 ml/min/1.73 m2 (± 21) and the median (25 – 75th percentile) ACR was 161 (38 – 680) mg/g. In multivariable models adjusted for age, sex, race, kidney disease etiology, and GFR, higher ACR levels were not associated with any complication. For example, comparing ACR > 300 mg/g vs. < 30 mg/g, the prevalence ratio (95% CI) for anemia was 0.98 (0.81 – 1.20), acidosis 1.13 (0.86 – 1.48), hyperphosphatemia 1.69 (0.91 – 3.17), and hypertension 1.04 (0.97 – 1.12). Lower levels of GFR were associated with all complications. For example, GFR levels < 30 ml/min/1.73 m2 vs. GFR levels 60 – 89 ml/min/1.73 m2 were associated with prevalence ratios (95% CI) of anemia 4.35 (3.18 – 5.96), acidosis 5.31 (3.41 – 8.29), hyperphosphatemia 23.8 (7.71 – 73.6), and hypertension 1.21 (1.10 – 1.32). Conclusions: Albuminuria is not associated with complications after controlling for GFR in patients younger than 70 years of age with non-diabetic CKD and GFR less than 90 ml/min/1.73 m2 and thus would not affect clinical action plans for decisions regarding evaluation and treatment of complications in similar populations.

Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium

“…In the Modification of Diet in Renal Disease (MDRD) Study, lower levels of eGFR, but not higher levels of urine protein, were strongly associated with anemia, hypoalbuminemia, acidosis, and hyperphosphatemia and hypertension. 11 Similarly, in the National Health and Nutrition Examination Survey (NHANES), a representative population cohort in the United States, lower eGFR was strongly associated with anemia, hypoalbuminemia, acidosis, hypertension, and hyperparathyroidism, but there was minimal association between higher levels of albuminuria and all of these abnormalities. 10 In our study, we expanded upon these studies by using both continuous values of the laboratory tests and categorical assessments of the abnormalities, and demonstration of the consistency of the risk associations across CKD and general population/high risk cohort, geographic regions, and participant characteristics including diabetes, age, sex, race, and a proxy for menopausal status.…”

“…Prior studies in general population and CKD cohorts have documented the risk of abnormalities with the level of eGFR or albuminuria, [6][7][8][9] but few have looked comprehensively and concomitantly across the new CKD staging system, which classifies the severity of CKD by eGFR (G) and albuminuria (A) stage. 10,11 In addition, the consistency of risk associations across diverse global cohorts along a wide range of eGFR, albuminuria, age, and diabetes has not been determined.…”

Prevalence and complications of chronic kidney disease in a representative elderly population in Iceland

“…These complications are important in clinical care decisions, and new medications are available to treat some of them. The strong association of concomitant metabolic complications of CKD with lower estimated glomerular filtration rate (eGFR) has been established previously [9][10][11][12][13][14][15][16]. However, few studies evaluating associations with metabolic complications have focused on the elderly [10,13,14] or have incorporated both eGFR and albuminuria when defining CKD [9,10,15].…”

“…The strong association of concomitant metabolic complications of CKD with lower estimated glomerular filtration rate (eGFR) has been established previously [9][10][11][12][13][14][15][16]. However, few studies evaluating associations with metabolic complications have focused on the elderly [10,13,14] or have incorporated both eGFR and albuminuria when defining CKD [9,10,15]. Prior studies were also limited by estimation of GFR only from serum creatinine [13,14,[17][18][19][20], which may be biased by non-GFR determinants in the elderly.…”

“…There was substantial variability in eGFR [mean (SD) 64 (18) mL/min/1.73 m 2 ] and ACR [median (interquartile range) 8 (5,17) mg/g]. The prevalence (95% confidence interval) of reduced eGFR (<60 mL/min/1.73 m 2 ), albuminuria (ACR >30 mg/g) and CKD (either reduced eGFR or albuminuria) was 40% (38-41), 14% (12)(13)(14)(15) and 45% (43-47), respectively. The prevalence of complications was higher among those with versus without CKD: hyperparathyroidism (38 versus 15%), anemia (26 versus 14%), hypoalbuminemia (19 versus 13%), increased anion gap (9 versus 5%), acidosis (5 versus 1%); (P ≤ 0.02 for all), except hyperphosphatemia (1 versus 1%) and hyperkalemia (0% overall).…”