Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis

Abstract

Background Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease (CKD). It is unknown, however, whether the association of the CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status. Methods We performed a meta-analysis of 45 cohorts (25 general population, 7 high-risk and 13 CKD cohorts), including 1,127,656 participants (364,344 with hypertension). Adjusted hazard ratios (HRs) for all-cause mortality (84,078 deaths from 40 cohorts) and ESRD (7,587 events from 21 cohorts) by hypertensive status were obtained for each study and pooled using random-effects models. Findings Low eGFR and high albuminuria were associated with mortality in both non-hypertensive and hypertensive individuals in the general population and high-risk cohorts. Mortality risk was higher in hypertensives as compared to non-hypertensives at preserved eGFR but a steeper relative risk gradient among non-hypertensives than hypertensives at eGFR range 45-75 ml/min/1.73m2 led to similar mortality risk at lower eGFR. With a reference eGFR of 95 mL/min/1.73m2 in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min/1.73m2 was 1.77 (95% CI, 1.57-1.99) in non-hypertensives versus 1.24 (1.11-1.39) in hypertensives (P for overall interaction =0.0003). Similarly, for albumin-creatinine ratio (ACR) of 300 mg/g (vs. 5 mg/g), HRs were 2.30 (1.98-2.68) in non-hypertensives versus 2.08 (1.84-2.35) in hypertensives (P for overall interaction=0.019). Similar results were observed for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results in CKD cohorts were comparable to results in general and high-risk population cohorts. Interpretation Low eGFR and elevated albuminuria were more strongly associated with mortality among individuals without hypertension than in those with hypertension, but the associations with ESRD were similar. CKD should be considered at least an equally relevant risk factor for mortality and ESRD in non-hypertensive as it is in hypertensive individuals. Funding The US National Kidney Foundation (sources include Abbott and Amgen).

886 Partial nephrectomy for the treatment of renal cell carcinoma and the risk of end stage renal disease

“…A step-wise relationship was demonstrated between worsening renal function (decreased eGFR, increased albuminuria) and all-cause mortality, cardiovascular mortality, and development of ESRD regardless of hypertensive status. 144 A similar study demonstrated an increased risk of ESRD and all-cause or cardiovascular death, regardless of whether or not a patient had a diagnosis of DM. 145 Decreased eGFR remained a strong risk factor for the development ESRD and death despite specifically controlling for HTN and DM.…”

Renal Hyperfiltration as a Novel Marker of All-Cause Mortality

“…These observations are consistent with previous studies reporting a J-shaped association between serum creatininebased eGFR and mortality. [11][12][13][14][15][16][17] The J-shaped association between eGFR and mortality has been explained by the overestimation of the true GFR in individuals in the high-risk group because of muscle wasting. Previous studies defined high GFR as above a certain absolute value, irrespective of age, sex, and muscle mass, and could not exclude the possibility of the confounding effects of muscle wasting in the high-risk group or the misclassification of normal GFR in young subjects as higher GFR or higher GFR in older subjects as normal GFR.…”

“…However, the increased mortality associated with a higher GFR was commonly regarded as an overestimation of GFR because of muscle wasting in a high-risk group. [11][12][13][14][15][16][17] The disappearance of the J-shaped association between GFR and mortality within a younger age group in the higher GFR range is considered as supporting evidence for the overestimation of the true GFR …”

Aspirin and cardiovascular primary prevention in non-endstage chronic kidney disease: A meta-analysis

“…Whilst the heterogeneity of these co-morbidities may potentially limit the findings of this meta-analysis, CKD remains a potent CV risk factor regardless of the presence or absence of DM or hypertension. This has been confirmed in large individual patient level meta-analyses in CKD compared to non- 18 CKD individuals for both all-cause and cardiovascular mortality and morbidity [24,25,26].…”