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

Summary

Background

Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown.

Methods

We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension.

Findings

We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1 127 656 participants, 364 344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1·1–1·2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45–75 mL/min per 1·73 m² led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1·73 m² in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1·73 m² was 1·77 (95% CI 1·57–1·99) in individuals without hypertension versus 1·24 (1·11–1·39) in those with hypertension (p for overall interaction=0·0003). Similarly, for albumin-creatinine ratio of 300 mg/g (vs 5 mg/g), HR was 2·30 (1·98–2·68) in individuals without hypertension versus 2·08 (1·84–2·35) in those with hypertension (p for overall interaction=0·019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results for chronic kidney disease cohorts were similar to those for general and high-risk population cohorts.

Interpretation

Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension.

Funding

US National Kidney Foundation.

Introduction

Chronic kidney disease is a major health problem, affecting 10–16% of the general adult population in Asia, Europe, Australia, and the USA,1, 2, 3, 4, 5, 6 and is associated with increased risk of mortality, cardiovascular disease, and progression to renal failure.6, 7, 8, 9, 10 Decreased glomerular filtration rate (GFR) and increased albuminuria, the two key kidney measures for definition of chronic kidney disease,¹ frequently coexist with traditional cardiovascular risk factors, with hypertension being the most common.5, 11 The prevalence of hypertension ranges from about 22% in stage 1 chronic kidney disease to more than 80% in stage 4 disease.5, 11 Prevalence of hypertension increases with both decreased GFR and increased albuminuria.¹¹ Whereas screening for chronic kidney disease in the general population is a matter of debate,¹² screening high-risk individuals such as those with hypertension is recommended by existing guidelines.13, 14, 15

Since hypertension is not only a cause but also a consequence of chronic kidney disease,¹⁶ individuals who are hypertensive might be expected to encounter a vicious circle of hypertension–chronic kidney disease inter-relation and therefore to have stronger chronic kidney disease-risk associations than those who are not hypertensive. Reliable data directly comparing key kidney measures with either mortality or end-stage renal disease (ESRD) in individuals with and without hypertension, however, is scarce.¹⁷ In fact, presence of chronic kidney disease has been proposed as a marker of hypertension and other traditional cardiovascular risk factors, such as diabetes mellitus, but the relevance of chronic kidney disease as a predictor in the absence of traditional cardiovascular risk factors is uncertain.17, 18 Hence, data for associations of decreased estimated GFR (eGFR) and increased albuminuria with mortality and ESRD in absence versus presence of hypertension will provide important insights for care of patients and for public health. We did a large-scale meta-analysis to assess whether hypertensive status modifies the association of decreased eGFR and increased albuminuria with all-cause mortality, cardiovascular mortality, and ESRD.