Progression from acute kidney injury to chronic kidney disease: a pediatric perspective

Although emerging evidence indicates that the incidence of both acute kidney injury (AKI) and chronic kidney disease (CKD) in children is rising and the etiologies are dramatically changing, relatively little is currently known regarding the potential for transition from AKI to CKD. In both situations, early intervention can significantly improve the dismal prognosis. However, the lack of a uniform AKI definition and the paucity of early, predictive biomarkers have impaired our ability diagnose AKI early to institute potentially effective therapies in a timely manner. Fortunately, recent data has validated a multidimensional AKI classification system for children. In addition, the application of innovative technologies has identified candidates that are emerging as early biomarkers of both AKI and CKD. These include neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, and kidney injury molecule-1. Studies to validate the sensitivity and specificity of these biomarkers in clinical samples from large cohorts and from multiple clinical situations are currently in progress, facilitated by the development of commercial tools for the reproducible measurement of these biomarkers across different laboratories.     

Outcomes of hospital-acquired acute kidney injury in elderly patients: a single-centre study

International Urology and Nephrology - HAAKI is a common clinical problem in hospitalized patients. Its incidence is high in older patients and carries worse prognosis. The presence of multiple...     

Epigenetic regulation in the acute kidney injury to chronic kidney disease transition

Epigenetic modifications have emerged as a new, important contributor to gene expression regulation in both normal and pathophysiological conditions. Epigenetics have been studied in many diseases and conditions such as acute kidney injury (AKI), a syndrome with a high prevalence that carries a poor prognosis with increased morbidity and mortality. In addition, it has recently been shown that AKI increases the risk for the development of chronic kidney disease (CKD). The specific molecular mechanisms by which AKI increases the risk of CKD and end stage renal disease (ESRD) remain unknown, although there is new evidence supporting a role of epigenetic changes. The most studied epigenetic regulations in AKI are chromatin compaction, DNA methylation, and histone acetylation/deacetylation. These modifications predominantly increase the production of pro‐inflammatory and profibrotic cytokines such as: monocyte chemoattractant protein‐1 (MCP‐1), complement protein 3 (C3), transforming growth factor β (TGF‐β) that have been shown for perpetuating inflammation, promoting epithelial‐to‐mesenchymal transition (EMT) and ultimately causing renal fibrosis. A review of epigenetic mechanisms, the pathophysiology of AKI and recent studies that implicate epigenetic modifications in AKI and in the transition to CKD are discussed below.     

The severity of acute kidney injury predicts progression to chronic kidney disease

Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with 'c' statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy ('c' 0.81-0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD.     

Incidence of contrast-induced acute kidney injury in a pediatric setting: a cohort study

Background

Contrast-induced acute kidney injury (CI-AKI) is a common pathology among adult patients, with an incidence ranging from 3–25 % depending on risk factors. Little information is available regarding CI-AKI incidence, risk factors, and prognostic impact in the pediatric population.

Methods

We performed a retrospective study of pediatric patients who underwent computed tomography (CT) scan with iodinated contrast media injection between 2005 and 2014 in five pediatric units of a university hospital. CI-AKI was defined according to Kidney Disease/Improving Global Outcomes (KDIGO) criteria.

Results

Of 346 identified patients, 233 had renal function follow-up and were included in our analyses. CI-AKI incidence was 10.3 % [95 % confidence interval (CI) 6.4–14.2 %]. CI-AKI was associated with 30-day unfavorable outcome before (45.8 % vs. 19.7 %, P?=?0.007) and after [odds ratio (OR) 3.6; 95 % CI 1.4–9.5] adjustment for confounders. No independent risk factors of CI-AKI were identified.

Conclusions

CI-AKI incidence was as high as 10.3 % following intravenous contrast media administration in the pediatric setting. As reported among adults, CI-AKI was associated with unfavorable outcome after adjustment for confounders. Although additional studies are needed in the pediatric setting, our data suggest that physicians should maintain a high degree of suspicion toward this complication among pediatric patients.

     

Preoperative chronic kidney disease and complications after pancreatoduodenectomy: a retrospective cohort study

Background

Chronic kidney disease is a prevalent condition in surgical patients. Possible associations with increased postoperative morbidity and mortality have not been clearly demonstrated in patients undergoing pancreatoduodenectomy. The aim of this study was to assess the risk of postoperative complications in patients with reduced kidney function undergoing pancreatoduodenectomy.

Methods

All patients undergoing pancreatoduodenectomy at Karolinska University Hospital between 2008 and 2019 were retrospectively included. The variable of interest was chronic kidney disease, based on preoperative estimated glomerular filtration rate measurements. Unadjusted and adjusted logistic regression analyses were performed for standardized postoperative complications.

Results

A total of 971 patients were included in the study, of whom 92 (10%) had an estimated glomerular filtration rate < 60 mL/min/1.73m², equivalent to chronic kidney disease Stage 3a or worse. Patients with chronic kidney disease had a higher odds of longer hospital stay (adjusted odds ratio 1.58, 95% confidence interval 1.00–2.50) and postoperative weight increase (adjusted odds ratio 2.02, 1.14–3.56). A 10 unit increase of preoperative estimated glomerular filtration rate was associated to lower odds of intensive care unit admission (adjusted odds ratio 0.81, 0.69–0.95), delayed gastric emptying (adjusted odds ratio 0.90, 0.81–0.99), and post-operative pancreatic fistula (adjusted odds ratio 0.83, 0.74–0.94).

Conclusion

Patients undergoing pancreatoduodenectomy with decreased preoperative kidney function are more likely to experience major postoperative complications, and also postoperative weight increase. Preoperative kidney function assessment is important in risk stratification before pancreatoduodenectomies.     

The long-term prognosis of acute kidney injury: acute renal failure as a cause of chronic kidney disease

There is a widespread opinion that acute kidney injury (AKI) is a rather harmless complication and that survival is determined not by renal dysfunction per se, but by the severity of the underlying disease. This opinion is in sharp contrast to evidence from several recent experimental and clinical investigations indicating that AKI is a condition which exerts a fundamental impact on the course of the disease, the evolution of associated complications and on prognosis, independently from the type and severity of the underlying condition. In conclusion, severe AKI in the critically ill patient is associated with high rates of morbidity, mortality and consumption of health care resources.     

The longitudinal chronic kidney disease study: a prospective cohort study of predialysis renal failure

Chronic kidney disease (CKD) is a significant public health problem: every year the number of Americans living with CKD and requiring renal replacement therapy increases. In addition, individuals with CKD have substantially increased morbidity and mortality compared to the general population. The Longitudinal Chronic Kidney Dialysis (LCKD) Study is a multicenter, prospective, observational study of patients with moderate to severe CKD that was designed to better describe the course of the disease and the determinants of patient outcomes. Patients with moderate to severe CKD (glomerular filtration rate [GFR] < 60 ml/min/m2) from four academic nephrology clinics were enrolled between 2000 and 2002. Special cardiac and vascular testing has recently commenced as phase II of this study. Areas that have been or are currently being studied include anemia management, health-related quality of life (HRQOL), medication use, and markers of cardiovascular disease. This article describes the LCKD Study in the context of current knowledge of CKD.     

Epidemiology of acute kidney injury in Canadian critical care units: a prospective cohort study

Purpose

We undertook this study to characterize the epidemiology of acute kidney injury (AKI) in Canadian critical care units. We aimed to identify predictors of mortality for patients diagnosed with AKI.

Methods

We conducted a prospective cohort study of consecutive patients admitted to critical care units at five Canadian hospitals over a 30-day period. Each patient was followed until hospital discharge or for a maximum of 30?days. The serum creatinine criteria for the Acute Kidney Injury Network (AKIN-SCr) system were used to identify, classify, and characterize patients who developed AKI. We used multivariable logistic regression to predict 30-day mortality among patients with AKI.

Results

We identified 603 patients, 161 (26.7%) of whom developed AKI. Compared to patients without AKI, those with AKI were more likely to die (29.2% vs 8.6%, P?<?0.001). The risk of death increased with increasing AKIN-SCr stage (P?<?0.001). In all, 19 patients (11.8% of those with AKI) commenced dialysis a median of one day (interquartile range, one to two days) after AKI diagnosis. At AKI diagnosis, the blood urea nitrogen (BUN) level (adjusted odds ratio [OR] 1.68, 95% confidence interval [CI] 1.01 to 2.79/10?mmol·L^?1) and serum bicarbonate (adjusted OR 0.88, 95% CI 0.81 to 0.95/1?mmol·L^?1) were associated with 30-day mortality and predicted death with an area under the receiver-operating characteristic curve of 0.79 (95% CI 0.71 to 0.86).

Conclusions

Acute kidney injury is a common complication of critical illness in Canada. The development of even the mildest stage of AKI is associated with a substantially higher risk of death. At AKI diagnosis, routine clinical data may be helpful for predicting adverse outcomes.     

Hyperparathyroidism in chronic kidney disease: a retrospective cohort study of costs and outcomes

Hyperparathyroidism may play a role in the excess morbidity and mortality in chronic kidney disease. This study examined utilization and outcomes of patients with hyperparathyroidism and chronic kidney disease. In a US health maintenance organization (HMO), patients with chronic kidney disease were identified from the electronic medical record. Patients included in the study had at least one intact parathyroid hormone (iPTH) measurement ordered by a nephrologist and were at least 20 years of age with no history of renal replacement therapy (RRT, n = 455). Cohorts were determined by index iPTH level and were followed for 1 year. Rates of health care utilization were compared between cohorts using Poisson regression; costs comparisons were made using linear regression; mortality and RRT were evaluated using Cox regression. Increasing levels of iPTH were associated with a significantly elevated risk of mortality and RRT, even after adjustment for potential confounders such as stage of chronic kidney disease. Compared to iPTH of <110 pg/ml, we found a 66% increase combined mortality-RRT risk (HR 1.66, 95% CI 1.41–1.97) for those with iPTH 110–199 pg/ml, and a HR of 4.57 (95% CI 3.86–5.43) for iPTH ≥300 pg/ml. We did not find a convincing association between iPTH level and utilization. While this study provides no evidence that treating patients with higher levels of iPTH will ameliorate poor outcomes, it suggests that iPTH levels beyond the targets suggested by clinical guidelines are associated with increased harm in patients with chronic kidney disease. This work was presented in part at the National Kidney Foundation 2006 annual meeting and at the 2006 International Society for Pharmacoeconomics and Outcomes Research meeting.     

Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease

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Aliskiren-associated acute kidney injury in a patient with pre-existing chronic kidney disease and dilated cardiomyopathy

We report a case of acute kidney injury (AKI) caused by a novel direct renin inhibitor, aliskiren. A 43-year-old Japanese man with dilated cardiomyopathy on cardiac resynchronization therapy with defibrillator and chronic kidney disease (CKD) was started on aliskiren in addition to enalapril, carvedilol, furosemide, and spironolactone for worsening cardiac function suggested by the elevation of serum brain natriuretic peptide. After 1 month, he noticed general malaise, loss of appetite and his serum creatinine level increased from 2.0 to 7.24 mg/dL. He had no evidence of exacerbation of hemodynamic instability (heart failure or hypotension) or post-renal cause of AKI. Although a cessation of aliskiren did not ameliorate AKI, renal function returned to baseline after withholding enalapril. Careful monitoring is necessary when aliskiren is used in patients with CKD and/or significant systolic dysfunction since it can cause normotensive ischemic AKI, especially when there is a concomitant use of other renin–angiotensin–aldosterone system inhibitors.     

队列研究在慢性肾脏病流行病学研究中的重要性

近10余年来,慢性肾脏病(CKD)的流行病学研究成为肾脏病领域的热点.在这一趋势的带动下,我国各个地区陆续开展了若干关于CKD患病率的横断面研究,为评估我国CKD患病现状提供了大量数据.来自北京、上海、广州3个大城市的研究显示成年人群中CKD患病率为11.8%～13.0%[1-3],与美国的水平接近.CKD的相关因素包括传统危险因素,如高血压、糖尿病、老年等,此外还有具中国特色的危险因素,如肾毒性药物等.时至今日,在此领域国际上已经鲜见针对患病率的横断面研究,取而代之的是各种队列研究提供的关于CKD危险因素、疾病进展、并发症发生等的诸多证据.我们介绍队列研究这一流行病学研究的经典方法,并阐述开展队列研究的注意事项.