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.

Limited data are available on the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end stage renal disease (ESRD) among individuals with chronic kidney disease (CKD). We conducted a collaborative meta-analysis of 21,688 participants selected for CKD from 13 cohorts. After adjustment for potential confounders and albuminuria, a 15 mL/min/1.73 m2 lower eGFR below 45 mL/min/1.73 m2 was significantly associated with mortality (pooled hazard ratio [HR] 1.47 [95% CI: 1.22–1.79]), and ESRD (pooled HR 6.24 [95% CI: 4.84–8.05]). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eight-fold higher albumin:creatinine ratio (ACR) or protein:creatinine ratio (PCR) was significantly associated with mortality (pooled HR 1.40 [95% CI: 1.27–1.55]), without evidence of significant heterogeneity. An eight-fold higher ACR or PCR was also strongly associated with ESRD (pooled HR 3.04 [95% CI: 2.27–4.08]), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD. The associations are stronger for ESRD than for mortality. The observed associations are consistent with CKD classification based on eGFR stages, and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Background A comprehensive assessment of the association of patients’ renal replacement therapy (RRT) modality on their participation in life activities (physical function, travel, recreation, freedom, work) is needed. Study Design Systematic review of peer-reviewed published studies. Setting & Population Adults undergoing RRT (hemodialysis, peritoneal dialysis, or transplantation). Selection Criteria for Studies We searched PubMed, Cochrane Library, and EMBASE from January 1980 through April 2012 for English-language articles that compared participation in life activities among patients receiving 1) hemodialysis compared with peritoneal dialysis, 2) hemodialysis compared with kidney transplantation, or 3) peritoneal dialysis compared with kidney transplantation. Predictor RRT modality. Outcomes Reported rates of physical function, travel, recreation, freedom, and work-related activities by RRT modality. Results A total of 46 studies (6 prospective cohort, 38 cross-sectional, and 2 pre-post transplantation) provided relevant comparisons of life participation activities among patients treated with hemodialysis, peritoneal dialysis, and kidney transplantation. Studies were conducted from 1985 to 2011 among diverse patient populations in 16 distinct locations. A majority of studies reported greater life participation rates among patients with kidney transplants compared to patients receiving either hemodialysis or peritoneal dialysis. In contrast, a majority of studies reported no differences in outcomes between patients receiving hemodialysis and patients receiving peritoneal dialysis. These results were consistent throughout the study period, across diverse populations, and among the subset of studies that performed appropriate adjustments for potential confounding factors. Limitations Many studies included in the review had significant design weaknesses. Conclusions Evidence suggests patients with kidney transplants may experience better rates of life participation compared to patients receiving dialysis, while patients receiving hemodialysis and patients receiving peritoneal dialysis may experience similar rates of life participation. Rigorously performed studies are needed to better inform patients about the association of RRT on these important patient reported outcomes.

Summary The Haemophilia Quality of Life Questionnaire for Adults (Haem‐A‐QoL) measures health‐related quality of life (HRQoL) in adults with haemophilia; however, change score thresholds for identifying individuals experiencing a HRQoL benefit have not been appropriately investigated. The objective of this analysis was to derive appropriate HRQoL responder definitions (RDs) for two Haem‐A‐QoL domains that reflect key impairments, ‘Physical Health’ and ‘Sports & Leisure,’ and the Haem‐A‐QoL ‘Total Score’ using anchor‐ and distribution‐based methods. In this analysis, data from adults in A‐LONG and B‐LONG, two Phase 3 clinical studies of rFVIIIFc in haemophilia A and rFIXFc in haemophilia B, respectively, were used. The anchor‐based approach identified Haem‐A‐QoL changes corresponding to EQ‐5D item improvements between baseline and 6 months; the distribution‐based methods examined the magnitude at baseline of one‐half standard deviation and the standard error of measurement. Through triangulation, the most appropriate RDs were derived. Of the 133 A‐LONG and 73 B‐LONG subjects with baseline Haem‐A‐QoL scores, 67 and 51 subjects, respectively, completed the Haem‐A‐QoL questionnaire at both baseline and 6 months follow‐up. Triangulation of anchor‐ and distribution‐based estimates with the observed Haem‐A‐QoL change scores identified a 10‐point reduction in the ‘Physical Health’ and ‘Sports & Leisure’ domains, and a 7‐point reduction in ‘Total Score’ as the RD thresholds most indicative of HRQoL benefit. These empirically derived RDs for two key Haem‐A‐QoL domains and ‘Total Score’ are reasonable and practical thresholds for identifying subjects with notable improvements in HRQoL, and provides HRQoL RDs that can be used for further analysis and interpretation of data from haemophilia clinical trials.

Changes in Haem-A-QoL key domains and 'Total Score' suggest that prophylaxis with long-acting rFVIIIFc or rFIXFc resulted in meaningful HRQoL improvements.