Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions

https://doi.org/10.1016/j.jdiacomp.2019.107465Get rights and content

Highlights

  • Optimal glycaemic control reduces microvascular complications in outpatients. This is not well characterised in inpatients.

  • Diabetes and higher HbA1c are strongly associated with adverse renal outcomes in patients with multiple hospital admissions.

  • All inpatients with diabetes, regardless of glycaemic control, should be targeted for structured renoprotective interventions.

Abstract

Objective

To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions.

Design

A prospective observational cohort study.

Participants

All inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital.

Main outcomes

We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2.

Results

Of 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18–1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20–1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03–1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01–1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05–1·18;p < 0·001).

Conclusions

In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

Introduction

Diabetes is the leading cause of chronic kidney disease (CKD) worldwide.1 1·2 million Australians were reported to have diabetes in 2014–15. There were over one million hospitalisations with diabetes as the principal or additional diagnosis in 2015–16 in Australia.2 People with diabetes have higher hospital readmission rates compared to people without diabetes which is a major driver of impaired health related quality of life and significant socioeconomical costs.3 The role of glucose control in reducing micro and macrovascular complications of diabetes in the outpatient setting is well established4; however, there are no studies examining the relationship between glycaemic status leading to the initial hospital admission in people with multiple re-hospitalisation episodes and the risk of future decline in renal function. Studies related to the inpatient population have been generally confined to single admission episodes in the cardiac surgery setting or to critically ill patients looking at short term strict glycaemic control during the inpatient pre and post-operative periods.5,6 Thus, whether diabetes and glycaemic control prior to an initial admission are independently associated with adverse renal outcomes in future hospitalisation episodes is currently unknown.

Estimates of glomerular filtration rate using eGFR equations have been used as a surrogate endpoint in clinical studies,7 with the Food and Drug Administration (FDA) accepting a 30% decline in eGFR as a surrogate endpoint in clinical trials of new medications for diabetes.8 In this regard, the typical annual absolute age related eGFR decline in the outpatient population is approximately 0·4–1·2 mL/min per 1·73 m2 per year but this is approximately 2·1–2·7 mL/min per 1·73 m2 per year in those with diabetes.9 While chronic decline in renal function is important, shorter term decline in renal function provides important prognostic information as it has been demonstrated that an eGFR nadir at any time point is associated with increased cardiovascular events and all-cause mortality.10,11 Furthermore, more rapid declines in eGFR (>5 ml/min per 1·73 m2 per year)12 are strongly associated with progression to end stage kidney disease (ESKD) in the outpatient setting but there are no studies evaluating this outcome following recent hospitalisation.13 However, despite the likely importance of long term glycaemic control in patients with diabetes and their risk of diabetic kidney disease, the role of HbA1c14 as a prognostic factor in progression of renal function decline over short follow-up times in those who have had an inpatient admission is unclear.

We hypothesised that the presence of diabetes and higher HbA1c levels would, over the medium term, be independently associated with adverse renal outcomes in patients with multiple hospital admissions. To test this hypothesis, we evaluated the association between baseline glycaemic status defined categorically or using HbA1c as a continuous variable, with medium-term decline in renal function in patients re-admitted to a tertiary referral hospital.

Section snippets

Study design

This project was approved by the health service Human Research Ethics Committee and individual consent was waived due to the nature of the study. In this prospective observational cohort study, an automated HbA1c test was generated by the Cerner Millennium Electronic Medical Record® (CERNER, North Kansas City, Missouri), for all inpatients aged ≥54 years admitted to Austin hospital, Melbourne, Australia, between July 2013 and January 2016, who did not have an HbA1c measurement recorded within

Results

Following exclusion of patients who met exclusion criteria or with missing data (Fig. 1), 4126 study patients were identified. The follow-up period was a median of 465 days (254, 740). The baseline characteristics of patients included and excluded were compared and were not statistically different (Table 1).

The baseline characteristics of included patients with diabetes and no diabetes are shown in Table 2. During their index admission, 26% of inpatients had diabetes and 59% were male. Median

Main findings

We investigated the association between glycaemic status and renal functional decline over the medium term in a prospective observational study of 4126 in-patients with multiple hospital admissions. We found that the presence of diabetes was strongly and consistently associated with a greater decline in renal function over time. Moreover, we found that higher HbA1c levels were associated with higher odds of decline in renal function. Finally, we showed that such findings were consistent for

Conclusion

In this large prospective cohort study, we evaluated the independent association between baseline glycaemic status defined using HbA1c, with decline in renal function over a little more than a year in patients with multiple admissions to a tertiary referral hospital. We found that the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function

Declaration of competing interests

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors report no conflict of interest.

The data from this research is available to be shared upon request.

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