A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury

doi:10.1053/j.ajkd.2015.02.338

American Journal of Kidney Diseases

Volume 66, Issue 4, October 2015, Pages 602-612

https://doi.org/10.1053/j.ajkd.2015.02.338 Get rights and content

Background

Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.

Study Design

Meta-analysis of cohort studies.

Setting & Population

8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.

Selection Criteria for Studies

Cohorts participating in the CKD Prognosis Consortium.

Predictors

Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.

Outcome

Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

Results

During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80 mL/min/1.73 m² in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs > 60 mL/min/1.73 m² than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.

Limitations

AKI identified by diagnostic code.

Conclusions

Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

Section snippets

Study Selection Criteria

Studies were selected according to criteria of the CKD Prognosis Consortium (CKD-PC), as previously described.¹⁵ We included studies of general-population and CKD cohorts with baseline information about eGFR and albuminuria and at least 50 AKI events. We restricted all analyses to adults 18 years or older. Data transfer and analyses were done from October 2013 through June 2014. The Institutional Review Board (IRB) at the Johns Hopkins Bloomberg School of Public Health approved the study (IRB

Participant Characteristics

We included 1,285,045 participants from 8 general-population cohorts (mean follow-up, 4-13 years) and 79,519 participants from 5 CKD cohorts (mean follow-up, 1-5 years; Table 1). The prevalence of diabetes and hypertension ranged from 4% to 34% and 20% to 82%, respectively, in the general-population cohorts and 14% to 89% and 42% to 93%, respectively, in the CKD cohorts. Among the general-population cohorts, there were 16,480 AKI events, and 0.2% to 6% of the individual study populations

Discussion

In this meta-analysis, lower eGFRs and higher levels of albuminuria were independently associated with increased risks of AKI in individuals with and without diabetes and hypertension, with the highest risks of AKI consistently observed in individuals with low eGFRs and high albuminuria regardless of the presence or absence of these conditions. Persons with diabetes generally had higher risks of AKI compared with individuals without diabetes at any level of eGFR, but this difference was

Acknowledgements

CKD-PC investigators and collaborators (expansions of acronyms/ abbreviations are listed in Item S2): AKDN: Marcello Tonelli, MD, SM, Brenda R. Hemmelgarn, MD, PhD, Matthew T. James, MD, PhD, and Tanvir Chowdhury Turin, MD, PhD, University of Calgary, Canada; ARIC: Josef Coresh, MD, PhD, Kunihiro Matsushita, MD, PhD, Morgan Grams, MD, PhD, and Yingying Sang, MS, Johns Hopkins University, United States; CHS: Michael Shlipak, MD, MPH, University of California, San Francisco and San Francisco

References (29)

C.Y. Hsu et al.
Community-based incidence of acute renal failure
Kidney Int
(2007)
S.G. Coca et al.
Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis
Am J Kidney Dis
(2009)
S.G. Coca et al.
Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis
Kidney Int
(2012)
C.Y. Hsu et al.
The risk of acute renal failure in patients with chronic kidney disease
Kidney Int
(2008)
M.T. James et al.
Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study
Lancet
(2010)
B.K. Mahmoodi et al.
Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis
Lancet
(2012)
C.S. Fox et al.
Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis
Lancet
(2012)
R. Mehran et al.
A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation
J Am Coll Cardiol
(2004)
R.T. Gansevoort et al.
Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes in both general and high-risk populations. A collaborative meta-analysis of general and high-risk population cohorts
Kidney Int
(2011)
B. Bartholomew et al.
Impact of nephropathy after percutaneous coronary intervention and a method for risk stratification
Am J Cardiol
(2004)

S.S. Waikar et al.

Declining mortality in patients with acute renal failure, 1988 to 2002

J Am Soc Nephrol

(2006)

J.L. Xue et al.

Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001

J Am Soc Nephrol

(2006)

S.S. Waikar et al.

Diagnosis, epidemiology, and outcomes of acute kidney injury

Clin J Am Soc Nephrol

(2008)

T. Huang et al.

Preoperative proteinuria predicts adverse renal outcomes after coronary artery bypass grafting

J Am Soc Nephrol

(2011)

Cited by (210)

Festivity: The Effects of Traditional Holidays on the Graft Function Among Stable Kidney Recipients
2024, Transplantation Proceedings
We observed transient elevations in creatinine levels among kidney recipients after three traditional holidays in Taiwan. This retrospective cohort study aimed to compare the changes in eGFR levels after Chinese New Year, Dragon Boat Festival, and Mid-Autumn Festival, all of which are associated with high-calorie and high-fat diets.
We conducted a retrospective analysis of 364 kidney recipients with stable graft function who were following at Chang Gung Memorial Hospital Linkou from 2018 to 2020. The graft function before and after the festival was determined by calculating the eGFR level using the serum creatinine measured during clinic visits prior to and following the festival. The patients were then categorized into subgroups based on their sex, BMI, and co-morbidities. The eGFR levels before and after the festival were evaluated and compared within these subgroups.
A total of 301 kidney recipients have been finally included in this retrospective cohort study. The analysis showed a significant decrease in overall eGFR levels after Chinese New Year (from 56.92 ± 29.70 to 55.14 ± 24.79, P = .006), Mid-Autumn Festival (from 54.03 ± 24.61 to 53.35 ± 24.33, P = .008), and Dragon Boat Festival only in 2020 (from 50.98 ± 24.35 to 49.99 ± 23.45, P = .018). The analysis of subgroups suggested a tendency of renal function decline after all 3 traditional holidays in patient groups with DM or hypertension or nonoverweight status.
In this study, we observed a significant decline in renal function among kidney recipients following traditional holidays in Taiwan, particularly among recipients with hypertension or diabetes mellitus or those who were not overweight.
Prevalence of Adult Type 2 Diabetes Mellitus and Related Complications in Alberta, Canada: A Retrospective, Observational Study Using Administrative Data
2024, Canadian Journal of Diabetes
Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease and a leading cause of morbidity/mortality in Canada. We evaluated the burden of T2DM in Alberta, Canada, by estimating the 5-year period prevalence of T2DM and rates of comorbidities and complications/conditions after T2DM.
We conducted a population-based, retrospective study linking administrative health databases. T2DM patients (≥18 years of age) were identified between 2008–09 and 2018–19 using a published algorithm, with follow-up data to March 2020. The 5-year period prevalence was estimated for 2014–15 to 2018–19. Patients with newly identified T2DM, ascertained between 2010–11 and 2017–18 with a lookback period between 2008–09 and 2009–10 and a minimum 1 year of follow-up data, were evaluated for subsequent cardiovascular, diabetic, renal, and other complication/condition frequencies (%) and rates (per 100 person years). Complications/conditions were stratified by atherosclerotic cardiovascular disease (ASCVD) status at index and age.
The 5-year period prevalence of T2DM was 11,051 per 100,000 persons, with the highest prevalence in men 65 to <75 years of age. There were 195,102 patients included in the cohort (mean age 56.7±14.7 years). The most frequently reported complications/conditions (rates per 100 person years) were acute infection (23.10, 95% confidence interval [CI] 23.00 to 23.30), hypertension (17.30, 95% CI 16.80 to 17.70), and dyslipidemia (12.20, 95% CI 11.90 to 12.40). Patients who had an ASCVD event/procedure and those ≥75 years of age had higher rates of complications/conditions.
We found that over half of the patients had hypertension or infection after T2DM. Also, those with ASCVD had higher rates of complications/conditions. Strategies to mitigate complications/conditions after T2DM are required to reduce the burden of this disease on patients and health-care systems.
Le diabète sucré de type 2 (DT2) est une maladie chronique prévalente et l'une des principales causes de morbidité/mortalité au Canada. Nous avons évalué la charge associée au DT2 en Alberta, au Canada, en estimant la prévalence du DT2 sur cinq ans et les taux de comorbidités et de complications/affections avec un DT2.
Nous avons mené une étude rétrospective basée sur la population en liant des bases de données administratives de santé. Les patients atteints de DT2 (≥18 ans) ont été identifiés pour la période comprise entre 2008/09 et 2018/19 en utilisant un algorithme publié, avec des données de suivi allant jusqu'en mars 2020. La prévalence sur cinq ans a été estimée entre 2014/15 et 2018/19. Les patients avec un DT2 nouvellement identifié, établi entre 2010/11 et 2017/18 avec une période de rétrospection comprise entre 2008/09 et 2009/10 et comportant un minimum d'un an de données de suivi, ont été évalués pour la fréquence (%) et les taux (/100 personnes-années) de complications/affections cardiovasculaires, diabétiques, rénales, et autres. Les complications/affections ont été stratifiées en fonction du statut de la maladie cardiovasculaire athérosclérotique (MCAS) au moment de l'indexation et par âge.
La prévalence du DT2 sur une période de cinq ans était de 11,051 pour 100,000 personnes, avec la plus haute prévalence chez les hommes âgés de 65-<75 ans. La cohorte comptait 195,102 patients (âge moyen de 56.7±14.7 ans). Les complications/affections les plus fréquemment rapportées (taux /100 personnes-années) étaient les suivantes: l'infection aiguë (23.10, intervalle de confiance [IC] à 95%: 23.00-23.30), l'hypertension (17.30, IC à 95%: 16.80-17.70), et la dyslipidémie (12.20, IC à 95%: 11.90-12.40). Ceux qui avaient vécu un événement/procédure de MCAS et ceux âgés de ≥75 ans avaient des taux plus élevés de complications/affections.
Notre étude a trouvé que plus de la moitié des patients avec un DT2 ont souffert d'hypertension ou d'infection. De plus, ceux avec une MCAS présentaient des taux plus élevés de complications/affections. Des stratégies visant à atténuer les complications/affections associées au DT2 sont nécessaires pour réduire la charge que représente le DT2 pour les patients et les systèmes de santé.
Long-term Visit-to-Visit Variability in Hemoglobin A<inf>1c</inf> and Kidney-Related Outcomes in Persons With Diabetes
2023, American Journal of Kidney Diseases
To characterize associations between long-term visit-to-visit variability of hemoglobin A_1c (HbA_1c) and risk of adverse kidney outcomes in patients with diabetes.
Observational study.
93,598 adults with diabetes undergoing routine care in Stockholm, Sweden.
Categories of baseline and time-varying HbA_1c variability score (HVS, the percentage of total HbA_1c measures that vary by >0.5% [5.5 mmol/mol] during a 3-year window): 0-20%, 21%-40%, 41%-60%, 61%-80%, and 81%-100%, with 0-20% as the reference group.
Chronic kidney disease (CKD) progression (composite of >50% estimated glomerular filtration rate [eGFR] decline and kidney failure), acute kidney disease (AKI by clinical diagnosis or transient creatinine elevations according to KDIGO criteria), and worsening of albuminuria.
Multivariable Cox proportional hazards regression.
Compared with persons showing low HbA_1c variability (HVS 0-20%), any increase in variability was associated with a higher risk of adverse kidney outcomes beyond mean HbA_1c. For example, for patients with a baseline HbA_1c variability of 81%-100%, the adjusted HR was 1.6 (95% CI, 1.47-1.74) for CKD progression, 1.23 [1.16-1.3] for AKI, and 1.28 [1.21-1.36] for worsening of albuminuria. The results were consistent across subgroups (diabetes subtypes, baseline eGFR, or albuminuria categories), in time-varying analyses and in sensitivity analyses including time-weighted average HbA_1c or alternative metrics of variability.
Observational study, limitations of claims data, lack of information on diet, body mass index, medication changes, and diabetes duration.
Higher long-term visit-to-visit HbA_1c variability is consistently associated with the risks of CKD progression, AKI, and worsening of albuminuria.
The evidence for current guideline recommendations derives from clinical trials that focus on a single HbA_1c as the definitive measure of efficacy of an intervention. However, long-term visit-to-visit fluctuations of HbA_1c may provide additional value in the prediction of future kidney complications. We evaluated the long-term fluctuations in glycemic control in almost 100,000 persons with diabetes undergoing routine care in Stockholm, Sweden. We observed that higher long-term HbA_1c fluctuation is consistently associated with the risks of chronic kidney disease progression, worsening of albuminuria and acute kidney injury. This finding supports a role for long-term glycemic variability in the development of kidney complications and illustrates the potential usefulness of this metric for risk stratification at the bedside beyond a single HbA_1c test.
Acute kidney injury with sodium-glucose co-transporter-2 inhibitors across the cardiovascular and renal outcome trials: Foe or friend?
2023, Nefrologia
Leptospirosis kidney disease: Evolution from acute to chronic kidney disease
2023, Biomedical Journal
Leptospirosis is a neglected bacterial disease caused by leptospiral infection that carries a substantial mortality risk in severe cases. Research has shown that acute, chronic, and asymptomatic leptospiral infections are closely linked to acute and chronic kidney disease (CKD) and renal fibrosis. Leptospires affect renal function by infiltrating kidney cells via the renal tubules and interstitium and surviving in the kidney by circumventing the immune system. The most well-known pathogenic molecular mechanism of renal tubular damage caused by leptospiral infection is the direct binding of the bacterial outer membrane protein LipL32 to toll-like receptor-2 expressed in renal tubular epithelial cells (TECs) to induce intracellular inflammatory signaling pathways. These pathways include the production of tumor necrosis factor (TNF)-α and nuclear factor kappa activation, resulting in acute and chronic leptospirosis-related kidney injury. Few studies have investigated the relationship between acute and chronic renal diseases and leptospirosis and further evidence is necessary. In this review, we intend to discuss the roles of acute kidney injury (AKI) to/on CKD in leptospirosis. This study reviews the molecular pathways underlying the pathogenesis of leptospirosis kidney disease, which will assist in concentrating on potential future research directions.
Ambient air pollution and incidence, progression to multimorbidity and death of hypertension, diabetes, and chronic kidney disease: A national prospective cohort
2023, Science of the Total Environment
The link between ambient air pollution and the incidence of hypertension, diabetes, and chronic kidney disease (CKD) has been widely studied. However, the associations of air pollution with the dynamic progression to multimorbidity and mortality of these diseases are unknown.
This study included 162,334 participants from the UK Biobank. Multimorbidity was defined as the coexistence of at least two of hypertension, diabetes, and CKD. Land use regression was used to estimate annual concentrations of particulate matter (PM_2.5), PM₁₀, nitrogen dioxide (NO₂), and nitrogen oxides (NO_x). Multi-state models were used to assess the association between ambient air pollutants and the dynamic progression of hypertension, diabetes, and CKD.
During a median follow-up of 11.7 years, 18,496 participants experienced at least one of hypertension, diabetes, and CKD, 2216 experienced multimorbidity, and 302 died afterwards. We observed differential associations of four air pollutants on different transitions from healthy status to incident disease (hypertension, diabetes, or CKD), to multimorbidity, and to death. The hazard ratios (HRs) of each IQR increment in PM_2.5, PM₁₀, NO₂, and NO_x for the transition to incident disease were 1.07 [95 % confidence intervals (CI): 1.04, 1.09], 1.02 (1.00, 1.03), 1.07 (1.04, 1.09), and 1.05 (1.03, 1.07), but the associations with the transition to death were significant for NO_x only [HR: 1.04 (95 % CI: 1.01, 1.08)].
Air pollution exposure might be one important determinant for the incidence and dynamic progression of hypertension, diabetes, and CKD, suggesting that more attention should be paid to ambient air pollution control in the prevention of hypertension, diabetes, and CKD, as well as their progression.

View all citing articles on Scopus

: Because an author of this article is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Beth Piraino, MD) who served as Acting Editor-in-Chief. Details of the journal’s procedures for potential editor conflicts are given in the Information for Authors & Journal Policies.

^∗: A list of the CKD Prognosis Consortium investigators and collaborators appears in the Acknowledgements.

View full text

Original InvestigationPathogenesis and Treatment of Kidney DiseaseA Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury

Background

Study Design

Setting & Population

Selection Criteria for Studies

Predictors

Outcome

Results

Limitations

Conclusions

Section snippets

Study Selection Criteria

Participant Characteristics

Discussion

Acknowledgements

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int

Lancet

Lancet

Lancet

J Am Coll Cardiol

Kidney Int

Am J Cardiol

Declining mortality in patients with acute renal failure, 1988 to 2002

J Am Soc Nephrol

Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001

J Am Soc Nephrol

Diagnosis, epidemiology, and outcomes of acute kidney injury

Clin J Am Soc Nephrol

Preoperative proteinuria predicts adverse renal outcomes after coronary artery bypass grafting

J Am Soc Nephrol

Original Investigation
Pathogenesis and Treatment of Kidney Disease
A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury