Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD). Methods A collaborative meta-analysis of general population cohorts was undertaken to pool standardized data for all-cause and cardiovascular mortality. The two kidney measures and potential confounders from 14 studies (105,872 participants; 730,577 person-years) with urine albumin-to-creatinine ratio (ACR) measurements and seven studies (1,128,310 participants; 4,732,110 person-years) with urine protein dipstick measurements were modeled. Findings In ACR studies, mortality risk was unrelated to eGFR between 75-105 ml/min/1·73 m2 and increased at lower eGFR. Adjusted hazard ratios (HRs) for all-cause mortality at eGFR 60, 45, and 15 (versus 95) ml/min/1·73 m2 were 1·18 (95% CI: 1·05-1·32), 1·57 (1·39-1·78), and 3·14 (2·39-4·13), respectively. ACR was associated with mortality risk linearly on the log-log scale without threshold effects. Adjusted HRs for all-cause mortality at ACR 10, 30, and 300 (versus 5) mg/g were 1·20 (1·15-1·26), 1·63 (1·50-1·77), and 2·22 (1·97-2·51). eGFR and ACR were multiplicatively associated with mortality without evidence of interaction. Similar findings were observed for cardiovascular mortality and in dipstick studies. Interpretation Lower eGFR (<60 ml/min/1·73 m2) and higher albuminuria (ACR ≥10 mg/g) were independent predictors of mortality risk in the general population. This study provides quantitative data for using both kidney measures for risk evaluation and CKD definition and staging.

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A B S T R A C T Micropuncture studies were performed in the dog to examine the relationship between sodium and phosphate transport in the proximal tubule. In hydropenic, thyroparathyroidectomized animals, administration of parathyroid extract, saline, or acetazolamide resulted in a fall in proximal tubule fluid-to-plasma (TF/P) inulin ratio as well as a rise in tubule fluid-toplasma ultrafilterable (TF/UF) phosphate ratio. A correlation was found between the changes in fractional reabsorption of sodium and phosphate but the phosphate changes were generally greater than those of sodium. Also, a high distal phosphate delivery in the face of low fractional excretion of phosphate in the urine in thyroparathyroidectomized dogs suggests significant phosphate reabsorption in the distal nephron. On the other hand, calcium chloride infusion to saline-loaded, normal dogs to suppress endogenous parathyroid hormone reduced proximal TF/UF phosphate without change in TF/P inulin, while both parameters remained unchanged in saline-loaded, thyroparathyroidectomized dogs after calcium infusion. An increase in proximal TF/UF phosphate associated with unchanged TF/P inulin was also demonstrated by administration of highly purified parathyroid hormone to saline-loaded, thyroparathyroidectomized dogs. It was concluded that although proximal tubule phosphate transport is generally closely related to that of sodium, the two can dissociate under certain experimental conditions, especially under the influence of parathyroid hormone. These observations also indicate that the effect of parathyroid hormone on proximal tubule phosphate transport is not solely dependent upon its effect on sodium transport.