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Special Article
Acute kidney injury in China Yi FANG, Jie TENG, Xiaoqiang DING Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Abstract China has a large population and bears a heavy burden of kidney diseases. Acute kidney injury (AKI) is increasingly prevalent in China and is associated with severe morbidity and mortality. The inadequacies of early diagnosis and management remain the major challenges to Chinese nephrologists. There is an urgent need for a nationwide, or even a global effort to increase an awareness of the devastating effects of AKI, to develop professional preventive strategies, as well as to achieve early diagnosis and early intervention. In this article, we review the increasing incidence of AKI and complexity behind prevention and management, focusing on differences in various clinical settings in China. Key words: Acute kidney injury (AKI), China, diagnosis, management
INTRODUCTION In the past 10 years, kidney diseases have been established as a clear threat not only to human health, but also to development and economic growth.1 An increase in the incidence of acute kidney injury (AKI) has been reported in both developing and developed countries. AKI is associated with severe morbidity and mortality.2,3 China is a developing country with the largest population in the world. The epidemiological data on AKI in China, as well as the current status of AKI clinical practice in China, have attracted increasing attention worldwide in the last decade. However, there have not been many Correspondence to: X. Ding, M.D., PhD, Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China. E-mail: [email protected] Conflict of Interest: No conflicts of interest, financial or otherwise, are declared by the authors. Grants: We thank the National Clinical Key Subject Construction Projects, the Shanghai Health System Promotion Projects of Appropriate Use of Advanced Technology (2013SY048), and the Project of Technology Committee in Shanghai (12DJ1400200) for funding this work.
articles published on the epidemiology of AKI in China until recently.4 Early epidemiology studies were confounded by varying definitions of AKI until recent consensus guidelines (RIFLE [Risk, Injury, Failure, Loss, End stage kidney disease], AKIN [Acute Kidney Injury Network] and KDIGO [Kidney Disease: Improving Global Outcomes]) standardized its definition.5–8 Unfortunately, the nationwide incidence of AKI is still not well defined because of underreporting, regional disparities, and differences in case mix, as indicated by Zhihong Liu, President of the Chinese Society of Nephrology.4 On July 2013, the Chinese Acute Kidney Injury Network was established, with the goal of developing a more accurate database concerning the incidence of AKI in China and to increase the awareness of AKI by governments, the public, general physicians, and other health-care professionals to help prevent the disease.
AKI in the hospital setting AKI is encountered in multiple settings, mostly in the community or the hospital setting. The pattern of hospital-acquired AKI occurring in high-level tertiary hospitals in some of the largest cities in China might be equivalent to that in high-income developed countries.5–9
© 2014 International Society for Hemodialysis DOI:10.1111/hdi.12193
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AKI in China
Reported incidences of AKI in hospitalized patients in China are mostly single-center based. Incidences of AKI reported in English-language journals were mainly from tertiary metropolitan hospitals in large cities. Recent single-centre studies have shown that AKI is a complicating factor in 2.4%–8.1% of all hospital adult admissions and up to 30%–50% in intensive care unit (ICU) patients, with an associated mortality rate of 18.6%–28.5% in those affected.5–10 An increase in AKI incidence was reported based on a 10-year hospital admission database (1994– 2003) from a single center, and Wang et al. reported that hospital-acquired AKI incidence doubled in the last 5 years, compared with that of the previous 5 years.11 AKI after cardiac surgery AKI is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is one of the most common causes of AKI in the ICU. The incidence of cardiac surgery associated AKI (CSA-AKI) varies from 6.7% to 68.5%,8,12–14 based on the definition used at the time it was applied (Table 1). Che et al.12 reported an incidence of 31.1% among 1056 patients who underwent cardiac surgery. Their cohort, consisting of 2.5 years’ admissions to the cardiac department, demonstrates that patients meeting the definition of AKIN AKI were 2.4 times as likely to die during hospitalization (mortality rate: AKI vs. non-AKI, 11.6% vs. 0.7%; hazard ratio, 2.40, 95% confidence interval 1.73–3.31). Using the same definition of AKI, in a study of 6665 postcardiac surgery patients, Yang et al. reported that 26.7% cases met the diagnostic criteria of AKIN. Hospital mortality rate among AKI patients and non-AKI patients was 2.47% and 0.29%, respectively.13 The incidence of CSA-AKI was even higher in the elderly. Data from 457 consecutive elderly patients (≥60 years) who underwent cardiac surgery with CPB showed an incidence of AKI of 68.5%.14 More recently, Teng et al.8 reported that the incidence of CSA-AKI was much higher in the elderly (39.9%), especially in senile patients over 80 years (42.1%), compared with that in the young and the middle aged (23.1%). Multivariate logistic regression analysis showed that male gender, old age (every 10 years), preoperative serum creatinine (Scr) > 1.2 mg/dL and postoperative use of adrenaline for hypotension were independent risk factors for AKI after cardiac surgery in patients over 65 years old. Drug-induced AKI Drug-induced kidney injury is becoming a major cause of AKI in China. Based on an AKI registry originating from 17 hospitals in Shanghai, drug-induced AKI accounted for
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28.9% of 1200 cases. Antibiotics were the leading cause of drug-induced AKI (47.8%), followed by diuretics (22.2%) and radiocontrast agents (13.3%). About one-third of the affected patients needed renal replacement therapy (RRT). The in-hospital mortality was 28.8%, and only 54.2% of the surviving patients completely recovered their renal function.15 In a single-center study involving 1440 patients with AKI, drug-induced AKI was the most common etiology.16 Of the 5619 AKI cases among 176,155 admissions to our hospital, we found 381 episodes of AKI were attributed to toxic effects of medications on renal tubules or decreases in renal blood flow. The most common medications implicated were contrast medium, chemotherapeutics (especially cisplatin and its analogues) and antibiotics. In some cases, AKI developed after using nonsteroidal anti-inflammatory drugs (NSAIDs), diuretics and angiotensin-converting enzyme inhibitors.5 Contrast-induced nephropathy (CIN) is one of the leading causes of hospital-acquired renal insufficiency.20 Reports of CIN after coronary angiography and percutaneous coronary intervention (PCI) have estimated the overall incidence at between 2% and 50% depending mainly on the presence of risk factors17,18,21 (Table 1). A newly published single-center retrospective study reported that 418 (16.7%) of 2500 consecutive patients who underwent PCI developed CIN within 5 days after exposure to contrast medium.18 The majority of the study population was from the north of the country and may represent a particular ethnic background. Interestingly, a diagnostic Scr value was presented on days 3–5 after PCI in 20% of the patients. It suggests the 48-hour time window for CIN diagnosis might need to be modified. AKI in ICU The incidence of AKI in ICU patients is much higher than that of non-ICU patients. The overall incidence of AKI in the ICU is approximately 20%–50% and can have a mortality over 50%.5,7,19 Zhou7 carried out a retrospective multicenter study of a total of 4642 patients admitted to five ICU centers in Sichuan province (located in the southwest of China). AKI was identified in 34.1% of ICU patients during the entire stay in ICU based on AKIN criteria and the 28-day mortality was 54.4%. More recently, a prospective multicenter observational study that enrolled 3063 consecutive patients from 22 ICUs across mainland China revealed an AKI incidence of 31.6%, according to the RIFLE criteria. The adjusted hazard ratios for 90-day mortality were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the failure group.19
3
4
5
3063
Wen et al.19 Multiple
single
Multiple
Single
multiple
Single Single
Single
Single
single
Multiple single
Single
Single
Single/ multicenter
31.6
16.7
8.63
3.17
UKN
26.69 68.5
31.1
UKN
2.41
34.1 26.2
6.13
3.19
AKI incidence (%)
ICU
CIN
CIN
Mixed
CSA-AKI CSA-AKI, >60 years Durg induced AKI
CSA-AKI
Mixed
Mixed
ICU CSA-AKI
Burn injury
Mixed
Patient population
An increase of ≥25% or ≥0.5 mg/dL Scr within 72 h after PCI An increase of ≥25% or ≥0.5 mg/dL Scr within 5 d after PCI RIFLE
Rise in SCr >177 μmol/L (≥50% if prior mild renal dysfunction [SCr ≤264 μmol/l]) AKIN
AKIN RIFLE
Scr increased to 176 uml/L or above; 50% increase in Scr, when baseline Scr > 132 uml/L AKIN
AKIN
AKIN KDIGO-AKI
RIFLE
AKIN
AKI definition used
A lack of consensus in the determination of baseline creatinine levels; did not investigate the exact AKI pathogenic factors; relatively small sample size
Patients selection bias
Patients selection bias; short-term retrospective study; incorrect classification with ICD-10 code Male predominance; misclassifications of baseline Scr; confounding bias Retrospective; patient selection bias Small sample size; no data on long-term prognosis Retrospective; do not have an accurate evaluation of baseline Scr Only involved patients diagnosed with acute renal failure from ICD-9 codes; limitations in AKI definition; no data for the entire population Retrospective; not have an accurate measurement of preoperative GFR; unselected cohort-value Retrospective; short-term study Small sample, retrospective; misclassifications of baseline Scr Patients with severe renal injury were excluded; nonrandomized, no data for the entire population Short-term retrospective study; not have an accurate measurement of baseline Scr Small sample size; not randomized; confounding bias
Study limitations
a Article published in Chinese. AKIN = Acute Kidney Injury Network; CIN = contrast-induced nephropathy; CSA-AKI = cardiac surgery associated AKI; GFR = glomerular filtration rate; ICD = International Classification of Diseases and Related Health Problems; ICU = intensive care unit; PCI = percutaneous coronary intervention; RIFLE = Risk, Injury, Failure, Loss, End stage kidney disease; KDIGO = Kidney Disease: Improving Global Outcomes; Scr = serum creatinine; UKN = unable to determine due to inability to access source.
2500
45376
Liao et al.16a
Chen et al.18
1200
Che et al.15a
197
6665 457
Yang et al.13 Hu et al.14
Zhang et al.17a
1056
Che et al.12
38734
Lu et al.10a
211
4642 3896
Zhou et al.7 Teng et al.8a
Wang et al.11
2479
176,155
Number of subjects
Hu et al.6
Fang et al.
Author
Table 1 Summary of original reports describing the incidence of adult AKI in the hospital setting
Fang et al.
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AKI in China
AKI in the elderly and in children As a result of the decline of renal compensatory ability, the kidneys of the elderly are much more vulnerable to injuries induced by ischemia/hypoxia or toxins.22 In the elderly, the incidence of AKI is reported to be >14%, with hypovolemia, nephrotoxic drugs, cardiac dysfunction and respiratory failure being the most common etiologies.23,24 Our data, which were from a tertiary metropolitan hospital in Shanghai, indicated an incidence of AKI of 4.10% in patients aged 60–80 years and of 6.17% in patients aged >80 years.5 Large-sample epidemiological studies on pediatric AKI were not reported until a prospective multicenter study by Cao et al.25 published in 2013. Pediatric patients (≤18 years) were enrolled from 14 provincial or municipal children’s hospitals and departments of pediatrics of 13 general hospitals affiliated with medical universities in China. Of the 388,736 pediatric patients involved, 1257 (0.32%) patients were identified as having AKI based on the AKIN criteria. Among the 1257 AKI pediatric patients, 632 were less than 1 year old. The most common causes of AKI were renal causes (57.52%) (Table 2), whereas Table 2 Primary causes of pediatric intrinsic AKI Primary disease Acute glomerulonephritis Nephritic syndrome Neonatal jaundice Sepsis Drug poisoning Henoch–Schonlein prupura Hemolytic uremic syndrome Asphyxia DIC SLE Pneumonia Tumor Acute interstitial nephritis Urinary tract infection IgA nephropathy HIE Traffic accident Hemolytic anemia Renal tubular acidosis Epidemic hemorrhagic fever Renal vein thrombosis Intubation of umbilical cord others
Cases Constituent ratio (%) 127 78 67 62 58 57 43 43 41 32 26 24 14 5 5 5 5 4 3 3 3 3 15
17.6 10.8 9.3 8.6 8.0 7.9 5.9 5.9 5.7 4.4 3.6 3.3 1.9 0.7 0.7 0.7 0.7 0.6 0.4 0.4 0.4 0.4 2.1
DIC = disseminated intravascular coagulation; SLE = systemic lupus erythematosus; HIE = hypoxic ischemic encephalopathy; IgA = immunoglobulin A.
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postrenal (25.69%) and prerenal (14.96%) causes were less common. A total of 43 AKI patients (3.4%) died during their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis.
AKI in the community setting While AKI in hospitalized patients, especially severely ill patients, often has multiple causes, community-acquired AKI is more likely to have a single identifiable cause.26 There are no reliable statistics about the incidence of community-acquired AKI, especially in low-income areas, because of late presentation of patients to tertiary centers, underreporting, and a reduced capacity to provide intensive care to severely ill patients. Data available are mostly from sporadic regional reports and are probably biased because it represents only the cases encountered in large hospital by enthusiastic physicians who want to report them. Venomous snake bites,27 organophosphorus pesticides/ paraquat poisoning,28,29 bee sting,30 and indigenous delicacies such as mushrooms and fish guts31 lead to AKI in some rural area. Renal injury induced by heavy metals (mercury, cadmium, lead, and arsenic) was usually associated with occupational exposure or environmental pollution.32 Aristolochic acid-associated nephropathy can occur in people who have consumed certain amounts of traditional Chinese herbs containing aristolochic acid.33 The data shown earlier came from case reports or small sample size studies, mostly published in Chinese. Glomerulonephritis after infection is declining in most regions, but is still an important cause of pediatric AKI.25 In a large cohort of Chinese patients with biopsy-proven lupus nephritis, AKI, as an independent risk factor for renal outcome was identified with an incidence of 20.5%.34
AKI in earthquake China is an earthquake-prone country. In the past 10 years, more than 14 significant earthquakes struck some regions in 23 seismic belts, some of which were catastrophic, especially the 2008 event. AKI is one of the most lethal, but reversible complications of crush syndrome occurring after an earthquake. The incidence of AKI after earthquake was hard to estimate as many severely injured victims died before medical care facilities could be reached. The 2008 Sichuan earthquake was a deadly earthquake, killing 69,277 people, with 17,923 missing and 96,655 wounded (according to China’s State Council Information Official statement on September 25, 2008).
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Victims severely injured or with special health-care needs such as with AKI were sent to large peripheral hospitals in Mianyang City and Chengdu City.35–37 The Wenchuan earthquake-related AKI Study Group designed a questionnaire in accordance with the recommendations of the International Society of Nephrology’s Renal Disaster Relief Task Force (RDRTF). The questionnaire was sent to 17 hospitals, in which the casualties were accepted and dialysis was available. Among the 10,845 injured patients hospitalized in 10 reference hospitals during the earthquake, crush-related AKI occurred in 228 (2.1%) patients. One hundred thirteen (53.6%) of 211 adult AKI patients needed hemodialysis (HD) treatment.36 Taken as a whole, the most common trauma was limb crush injury (82.9%), followed by fractures (49.8%), and thoracic traumas (22.3%). Twenty-five patients (10.96%) died during the hospitalization period.37
Early diagnosis and biomarkers New biomarkers, as early predictors of structural AKI, might allow detection of AKI up to 48 hours earlier than with an increase in Scr. A variety of promising biomarkers for AKI have been identified in the published literature. Relevant substances, such as neutrophil gelatinaseassociated lipocalin, liver-type fatty acid binding protein, cystatin C, kidney injury molecule-1, N-acetyl-beta-Dglucosaminidase, nestin, and interleukin-18 have all been well studied in the clinical setting in China.38–43 In addition to those protein or peptide biomarkers, nucleic acids such as circulating microRNA have been added to the growing list of potentially useful biomarkers of AKI.44 In a study involving 120 adult patients undergoing cardiac surgery, urinary and plasma microRNA-21(miR-21) were identified to be associated with severe AKI and other poor postoperative outcomes of cardiac surgery, indicating their potential use as prognostic markers.45 In addition to its role as a biomarker of AKI, miR-21 appears to have antiapoptotic properties, in part by targeting the expression of programmed cell death protein 4 in renal ischemic preconditioning (IPC), based on our research work on AKI mechanism.46 Although studies of biomarkers are evolving rapidly, routine application is not yet recommended because their added value to clinical models is not well established.
Prevention and management Nondialytic management Prevention of AKI starts in the community with prompt assessment of those at risk and timely referral. Regular
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drug therapy can compound that risk and quite a few people taking NSAIDs or renin-angiotensin system blockers should be educated to discontinue them temporarily in the face of acute intercurrent illness. Active surveillance for changes in creatinine can automate alerts to guide drug dosing and reduce the incidence of drug-induced kidney injury. In some cases, awareness of the specific infectious or venomous organisms in certain areas will allow environmental protection, vaccines, pharmacologic prophylaxis, and early administration of antivenom. General practitioners and care providers should be educated about AKI and the tools to manage these patients timely and effectively. The key elements in any AKI prevention strategy for hospitalized patients, whenever feasible, are avoidance of hypovolemia, avoidance of nephrotoxins and preventive maneuvers for particular diseases or conditions causing AKI. Effective measures must include hospital-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management (Figure 1). CIN is a common form of hospital-acquired AKI that has been studied extensively. Numerous investigators, including our team, have found that baseline renal dysfunction, diabetes, heart failure, and old age are significant risk factors for CIN.21,47,48 A number of clinical studies on the pharmacological preventative strategies have been done in China. Hydration, drug intervention with N-acetylcysteine,49 probucol,50 angiotensin-converting
Figure 1 Hospital-wide surveillance for acute kidney injury. Active hospital-wide surveillance system should be established to monitor AKI risk factors and to early identify AKI patients. The surveillance system consists of two parts: AKI registration system and AKI Cooperative Network. AKI, acute kidney injury; ICU, intensive care unit.
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enzyme inhibitor,51 statins,52 M-choline receptor blockers,53 ascorbic acid,54 and prostaglandin E155 were reported to be clinically effective in some small-sized studies. IPC has been shown to have promising results in preventing renal injury in animal studies.46,56,57 The actual mechanisms is not quite clear and several hypotheses have been proposed including activation of hypoxia-induced factor55 and suppression of nuclear factor-κβ.56 Our team recently provided additional evidence for the importance of microRNAs in regulating the response of the kidney to injury in vivo.57 However, IPC was never considered an intervention for AKI because of its need for pretreatment. A more practical approach may be achieved using remote IPC (RIPC). RIPC has been shown to provide renal protection to patients undergoing cardiac and vascular interventions.58 Recently a group of Chinese urologists reported that slight lower limb ischemia significantly reduced renal impairment within 1 month after laparoscopic partial nephrectomy.59 Mechanism by which RIPC protects the kidney is unclear, requiring large-scale clinical trials to further clarify the underlying mechanism as well as validate its clinical benefits. Dialytic management Various techniques for RRT, either intermittent or continuous, are available for patients with AKI.60–62 A continuous approach to RRT (CRRT) for critically ill patients was introduced in 1977 and hailed almost immediately as an improved alternative to intermittent HD (IHD). CRRT was introduced to China in 1985, by Professor Liao Lvtan, the founder and the first director of the Department of Nephrology at Zhongshan Hospital Fudan University, and one of the main founders of blood purification technology in China.60 Afterwards, CRRT was widely adopted in China as an alternative modality in treating critically ill patients.62 IHD is less expensive than continuous RRT and has similar efficacy in patients with hemodynamic stability.63 For indicated patients, slow low-efficiency daily dialysis (SLEDD) was performed and was reported to have an equal efficacy as CRRT.64,65 Hemoperfusion, immunoadsorption, plasmapheresis, and artificial liver support methods were used alone or in combination with other blood purification techniques in AKI patients with special problems.66,67 The optimal management of RRT in critical AKI patients remains debatable. Nonetheless, little is known about the current practices and beliefs of intensivists or nephrologists in China. To our knowledge, RRTs are mostly performed by nephrologists in China, unlike that in the United States or Europe where intensivists are in charge of RRT practice. Continuous blood purification
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(CBP) is mainly performed in ICU in China while IHD and SLEDD are performed both within and outside ICU. Possible reasons might be that patients receiving CBP usually have much worse medical conditions, such as those requiring mechanical ventilation supports or other life supports, which limits CBP practice outside ICU.63–65,68 A good functioning vascular access is an essential component for adequate RRT. Most acute RRT is performed with a double-lumen temporary dialysis catheter (TDC) inserted into a large vein.69,70 The right jugular vein is the first choice while femoral vein was preferred for patients with critical respiratory condition or when the insertion site of jugular vein was “heavily catheterized.” In a cohort of 1028 patients treated with CRRT or IHD, the total number of TDC placement procedure and the catheterdays was 215 and 3665 for jugular vein, 908 and 13,580 for femoral vein. Catheter-related local infection incidence density was statistically higher for femoral than for jugular (4.79% vs. 2.72%, P < 0.05).69 In the past 5 years, a few studies focusing on the application of peritoneal dialysis (PD) in the treatment of adult AKI/acute renal failure in China have been published.68,71,72 At present, PD is comparatively rarely used in treating critically ill AKI patients, especially in highincome areas in China. Possible reasons might include application of new advanced blood purification techniques. Under certain circumstances where patients present with active bleeding or HD apparatus is not available, PD is a safe, feasible, and efficient alternative to HD.71,72 We have limited data on the proportion of AKI patients receiving HD versus PD. In a single-center study involving 148 patients with CSA-AKI and receiving RRTs, He et al.68 reported that the number of patients who received PD, IHD, and CBP was 28, 77, and 43, respectively (ratio 1: 2.6: 1.5). But the situation is quite different in the setting of pediatric ICU, where PD is the most widely used dialysis modality in treating the critically ill AKI children.73–75 Some PD modalities, like high volume PD, tidal PD, or continuous flow PD may achieve dramatic volume removal and solute clearance, but has not been validated in large sample populations in China.
CONCLUSIONS The total population of China is more than 1.3 billion, and its renal disease health-care system is possibly the largest in the world. In the past decade, the development of nephrology in the field of AKI in China has been boosted by rapid progress in cutting-edge research covering the entire spectrum of renal medicine, from basic science to clinical epidemiological studies. However, the
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academic achievement gap between China and the developed countries still exists, highlighting the need for a larger number of high-quality multicenter randomized controlled trials, as well as clinical epidemiology studies to evaluate the evidence and support regional guideline development.
ACKNOWLEDGMENTS We would like to express our gratitude to Prof. Mingyu Liang, Department of Physiology, Medical College of Wisconsin (USA), and Dave L Roerig, Professor Emeritus of Anesthesiology, Pharmacology and Toxicology, Medical College of Wisconsin (USA), for their critical reading of our article. Manuscript received March 2014; revised June 2014.
REFERENCES 1 Eckardt KU, Coresh J, Devuyst O, et al. Evolving importance of kidney disease: From subspecialty to global health burden. Lancet. 2013; 382:158–169. 2 Li PK, Burdmann EA, Mehta RL. Acute kidney injury: Global health alert. J Nephropathol. 2013; 2:90–97. 3 Lameire NH, Bagga A, Cruz D, et al. Acute kidney injury: An increasing global concern. Lancet. 2013; 382:170– 179. 4 Liu ZH. Nephrology in China. Nat Rev Nephrol. 2013; 9:523–528. 5 Fang Y, Ding X, Zhong Y, et al. Acute kidney injury in a Chinese hospitalized population. Blood Purif. 2010; 30:120–126. 6 Hu JY, Meng XC, Han J, et al. Relation between proteinuria and acute kidney injury in patients with severe burns. Crit Care. 2012; 16:R172. 7 Zhou J, Yang L, Zhang K, Liu Y, Fu P. Risk factors for the prognosis of acute kidney injury under the Acute Kidney Injury Network definition: A retrospective, multicenter study in critically ill patients. Nephrology. 2012; 17:330– 337. 8 Teng J, Xu JR, Fang Y, et al. [Preliminary research on acute kidney injury after cardiac surgery in elderly people]. Chin J Blood Purif. 2013; 12:21–24 (In Chinese). 9 Meier P, Bonfils RM, Vogt B, Burnand B, Burnier M. Referral patterns and outcomes in noncritically ill patients with hospital-acquired acute kidney injury. Clin J Am Soc Nephrol. 2011; 6:2215–2225. 10 Lu RH, Fang Y, Gao JH, et al. [The incidence and risk factors associated with prognosis of acute kidney injury in hospitalized patients]. Chin J Nephrol. 2012; 28:194– 200 (In Chinese).
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11 Wang Y, Cui Z, Fan M. Hospital-acquired and community-acquired acute renal failure in hospitalized Chinese: A ten-year review. Ren Fail. 2007; 29:163–168. 12 Che M, Li Y, Liang X, et al. Prevalence of acute kidney injury following cardiac surgery and related risk factors in Chinese patients. Nephron Clin Pract. 2011; 117:c305– c311. 13 Yang XM, Wang CS, Liu L, et al. [Risk factors for acute kidney injury after adult cardiac surgery with cardiopulmonary bypass]. Clin J Thorac Cardiovasc Surg. 2013; 29:147–150 (In Chinese). 14 Hu PH, Liang XL, Chen YH, et al. [Acute kidney injury after cardiac surgery in elderly patients: Focus on modifiable risk factors]. Clin J Thorac Cardiovasc Surg. 2012; 28:599–602 (In Chinese). 15 Che ML, Yan YC, Zhang W, et al. [Analysis of druginduced acute renal failure in Shanghai]. Zhonghua Yi Xue Za Zhi. 2009; 89:744–749 (In Chinese). 16 Liao XH, Zhang L, Zhong L, et al. [Etiology and prognosis of in patients with acute kidney injury]. Chongqing Med. 2010; 39:1250–1253 (In Chinese). 17 Zhang P, Ni ZH, Wang L, et al. [Investigation of risk factors of contrast—Induced nephropathy in multicenters after coronary artery intervention]. CJITWN. 2010; 11:214–218 (In Chinese). 18 Chen YL, Fu NK, Xu J, et al. A simple preprocedural score for risk of contrast-induced acute kidney injury after percutaneous coronary intervention. Catheter Cardiovasc Interv. 2014; 83:E8–E16. 19 Wen Y, Jiang L, Xu Y, et al. Prevalence, risk factors, clinical course, and outcome of acute kidney injury in Chinese intensive care units: A prospective cohort study. Chin Med J (Engl). 2013; 126:4409–4416. 20 McCullough PA, Adam A, Becker CR, et al. Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol. 2006; 98(6A):5K–13K. 21 Song W, Zhang T, Pu J, et al. Incidence and risk of developing contrast-induced acute kidney injury following intravascular contrast administration in elderly patients. Clin Interv Aging. 2014; 9:85–93. 22 Martin JE, Sheaff MT. Renal ageing. J Pathol. 2007; 211:198–205. 23 Wen J, Cheng Q, Zhao J, et al. Hospital-acquired acute kidney injury in Chinese very elderly persons. J Nephrol. 2013; 26:572–579. 24 Gong Y, Zhang F, Ding F, Gu Y. Elderly patients with acute kidney injury (AKI): Clinical features and risk factors for mortality. Arch Gerontol Geriatr. 2012; 54:e47–e51. 25 Cao Y, Yi ZW, Zhang H, Dang XQ, Wu XC, Huang AW. Etiology and outcomes of acute kidney injury in Chinese children: A prospective multicentre investigation. BMC Urol. 2013; 21:41. 26 Ali T, Khan I, Simpson W, et al. Incidence and outcomes in acute kidney injury: A comprehensive populationbased study. J Am Soc Nephrol. 2007; 18:1292–1298.
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27 Zou RL, Zhang YM. [Acute renal failure caused by viper: Report of 48 cases]. Chin J Surg. 1994; 32:119–120 (In Chinese). 28 Mao SM, Gao Y. [Hemoperfusion combined with hemodialysis in treatment of critically ill organophosphorus poisoning patients: A 9-case report]. Chin J Blood Purif. 2004; 3:33 (In Chinese). 29 Hu F, Zhang H, Chen J, et al. [Clinical features of acute kindey injury in patients with acute paraquat poisoning]. J Nephrol Dial Transplant. 2012; 21:341–345 (In Chinese). 30 He XP, Wu P, Liu L. [Blood purification in the treatment of acute renal failure caused by beetoxin: A report of 37 cases]. Acta Acade Med Mil Tert. 2004; 26:816–819 (In Chinese). 31 Zhou SL, Yang XC, Wang L, et al. [An analysis of 100 patients with acute renal failure caused by food poisoning in west China]. J Nephrol Dial Transplant. 2002; 11:133– 137 (In Chinese). 32 Zhang L, Zhang Y, Lin Q, et al. Acute kidney injury, hematuria, and orange skin pigmentation caused by arsine poisoning. Am J Kidney Dis. 2008; 52:A33–A36. 33 Yang L, Li X, Wang H. Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis. Nephrol Dial Transplant. 2007; 22:445–456. 34 Zhu D, Qu Z, Tan Y, Yu F, Zhao MH. Acute kidney injury in Chinese patients with lupus nephritis: A large cohort study from a single center. Lupus. 2011; 20:1557–1565. 35 Zhang L, Fu P, Wang L, et al. The clinical features and outcome of crush patients with acute kidney injury after the Wenchuan earthquake: Differences between elderly and younger adults. Injury. 2012; 43:1470–1475. 36 Chunguang Z, Rigao C, Fuguo H, et al. Characteristics of crush syndrome caused by prolonged limb compression longer than 24 h in the Sichuan earthquake. Emerg Med J. 2010; 27:627–630. 37 Hu Z, Zeng X, Fu P, et al. Predictive factors for acute renal failure in crush injuries in the Sichuan earthquake. Injury. 2012; 43:613–618. 38 Ling W, Zhaohui N, Ben H, et al. Urinary IL-18 and NGAL as early predictive biomarkers in contrast-induced nephropathy after coronary angiography. Nephron Clin Pract. 2008; 108:c176–c181. 39 Xu X, Zou JZ, Ding XQ, et al. Clinical value of serum cystatin C by ELISA for estimation of glomerular filtration rate. J Clin Lab Anal. 2004; 18:61–64. 40 Xu XH, Xu X, Zhong J, et al. Clinical value of urinary kidney biomarkers for estimation of renal impairment in elderly Chinese with essential hypertension. J Clin Lab Anal. 2008; 22:86–90. 41 Zeng XF, Li JM, Tan Y, et al. Performance of urinary NGAL and L-FABP in predicting acute kidney injury and subsequent renal recovery: A cohort study based on major surgeries. Clin Chem Lab Med. 2014; 52:671–8.
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42 Zhang W, Zhang L, Chen YX, et al. Identification of Nestin as a urinary biomarker for acute kidney injury. Am J Nephrol. 2014; 39:110–121. 43 Shao X, Tian L, Xu W, et al. Diagnostic value of urinary kidney injury molecule 1 for acute kidney injury: A metaanalysis. PLoS ONE. 2014; 9:e84131. 44 Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008; 18:997– 1006. 45 Du J, Cao X, Zou L, et al. MicroRNA-21 and risk of severe acute kidney injury and poor outcomes after adult cardiac surgery. PLoS ONE. 2013; 8:e63390. 46 Xu X, Kriegel AJ, Liu Y, et al. Delayed ischemic preconditioning contributes to renal protection by upregulation of miR-21. Kidney Int. 2012; 82:1167–1175. 47 Ji J, Ding XQ, Xu XH, et al. [Effect of the low osmolality nonionic contrast media on renal function in patients undergoing coronary intervention: A prospective study]. Chin J Nephrol. 2006; 22:388–392 (In Chinese). 48 Yang D, Lin S, Yang D, Wei L, Shang W. Effects of shortand long-term hypercholesterolemia on contrast-induced acute kidney injury. Am J Nephrol. 2012; 35:80–89. 49 Chen SL, Zhang J, Yei F, et al. Clinical outcomes of contrast-induced nephropathy in patients undergoing percutaneous coronary intervention: A prospective, multicenter, randomized study to analyze the effect of hydration and acetylcysteine. Int J Cardiol. 2008; 126:407–413. 50 Li G, Yin L, Liu T, et al. Role of probucol in preventing contrast-induced acute kidney injury after coronary interventional procedure. Am J Cardiol. 2009; 103:512– 514. 51 Li XM, Cong HL, Li TT, He LJ, Zhou YJ. Impact of benazepril on contrast-induced acute kidney injury for patients with mild to moderate renal insufficiency undergoing percutaneous coronary intervention. Chin Med J (Eng). 2011; 124:2101–2106. 52 Jia XW, Fu XH, Zhang J, et al. Comparison of usefulness of simvastatin 20 mg versus 80 mg in preventing contrast-induced nephropathy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2009; 104:519–524. 53 Geng W, Fu XH, Gu XS, et al. Preventive effects of anisodamine against contrast-induced nephropathy in type 2 diabetics with renal insufficiency undergoing coronary angiography or angioplasty. Chin Med J (Engl). 2012; 125:3368–3372. 54 Zhou L, Chen H. Prevention of contrast-induced nephropathy with ascorbic acid. Intern Med. 2012; 51:531– 535. 55 Liu WJ, Zhang BC, Guo R, Wei YD, Li WM, Xu YW. Renoprotective effect of alprostadil in combination with statins in patients with mild to moderate renal failure undergoing coronary angiography. Chin Med J (Engl). 2013; 126:3475–3480.
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Fang et al.
56 Cao CC, Ding XQ, Ou ZL, et al. In vivo transfection of NF-kappaB decoy oligodeoxynucleotides attenuate renal ischemia/reperfusion injury in rats. Kidney Int. 2004; 65:834–845. 57 Jiang S, Chen Y, Zou J, et al. Diverse effects of ischemic pretreatments on the long-term renal damage induced by ichemia-reperfusion. Am J Nephrol. 2009; 30:440– 449. 58 Li L, Li G, Yu C, Li Y. The role of remote ischemic preconditioning on postoperative kidney injury in patients undergoing cardiac and vascular interventions: A meta-analysis. J Cardiothorac Surg. 2013; 8:43–51. 59 Huang J, Chen Y, Dong B, et al. Effect of remote ischaemic preconditioning on renal protection in patients undergoing laparoscopic partial nephrectomy: A “blinded” randomised controlled trial. BJU Int. 2013; 112:74–80. 60 Liao LV, Cai ZH, Chen KJ, et al. Continuous ambulatory peritoneal dialysis-clinical report of 62 cases. Chin Med J (Engl). 1985; 998:281–286. 61 Xu JR, Teng J, Zou JZ, et al. [Goal-directed renal replacement therapy for acute kidney injury after cardiac surgery]. Chin Crit Care Med. 2011; 23:749–754 (In Chinese). 62 Zhang P, Yang Y, Lv R, Zhang Y, Xie W, Chen J. Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: A singlecenter randomized clinical trial. Nephrol Dial Transplant. 2012; 27:967–973. 63 Ji D, Gong D, Xie H, Xu B, Liu Y, Li L. A retrospective study of continuous renal replacement therapy versus intermittent hemodialysis in severe acute renal failure. Chin Med J (Engl). 2001; 114:1157–1161. 64 Shen B, Teng J, Liu ZH, et al. [Comparison of therapeutic effects between extended daily hemodialysis and extended daily hemofiltration for acute kidney injury after orthotopic cardiac transplantation]. Shanghai Med J. 2009; 32:47–49 (In Chinese). 65 Lu RH, Yan YC, Gu Y, et al. [Effects of CVVH and SLED in patients with acute renal failure after liver
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transplantation]. J Shanghai Jiaotong Univ. 2008; 28:1010–1014 (In Chinese). Bo H, Zhang L, Huang S, Zhu T, Yu RC. Continuous venovenous hemofiltration and hemoperfusion in successful treatment of a patient with crush syndrome and acute pancreatitis. Ren Fail. 2012; 34:383–386. Teng J, Chen LM, Zou JZ, et al. [Protein A immunoadsorption for the therapy of rapidly progressive gIomeruIonephritis—5 case reports]. Chin J Blood Purif. 2005; 4:472–475 (In Chinese). He CS, Shi W, Liang XL, et al. [The therapeutic effects of various blood purification techniques for acute renal failure after cardiac surgery]. Chin J Blood Purif. 2004; 3:188–191 (In Chinese). Liang HB, Liang XL, Wang WJ, et al. [A retrospective analysis of catheter-related infections in 1028 critical cases with blood purification]. Chin J Blood Purif. 2012; 11:523–526 (In Chinese). Zhou F, Song Q, Peng Z, et al. Effects of continuous venous–venous hemofiltration on heat stroke patients: A retrospective study. J Trauma. 2011; 71:1562–1568. Gan HB, Dong J, Wang M, et al. [Peritoneal dialysis and continuous renal replacement therapy in critical ill patients]. Chin J Crit Care. 2003; 23:379–381 (In Chinese). Yan WX, Liu J, Wang CC, et al. [Therapeutic effects of different dialysis modality on the outcomes of AKI patients complicated with cerebral hemorrhage]. Chin J Postgrad Med. 2011; 34:32–33 (In Chinese). Zeng M, Li SJ, Wang X, et al. [Early peritoneal dialysis after repair of congenital heart disease in children]. Chin J Thorac Cardiovasc. 2013; 29:73–75 (In Chinese). Zheng J, Xiao Y, Chong M, et al. The effect of cardiopulmonary bypass duration on renal injury after congenital heart surgery in infants and young children. Adv Clin Exp Med. 2013; 22:693–698. Li LL, Lu GP. [Surveying the status of continuous blood purification technology application in Chinese pediatric intensive care unit]. Chin J Pediatr. 2014; 52:201–203 (In Chinese).
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Special Article
Acute kidney injury in China Yi FANG, Jie TENG, Xiaoqiang DING Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Abstract China has a large population and bears a heavy burden of kidney diseases. Acute kidney injury (AKI) is increasingly prevalent in China and is associated with severe morbidity and mortality. The inadequacies of early diagnosis and management remain the major challenges to Chinese nephrologists. There is an urgent need for a nationwide, or even a global effort to increase an awareness of the devastating effects of AKI, to develop professional preventive strategies, as well as to achieve early diagnosis and early intervention. In this article, we review the increasing incidence of AKI and complexity behind prevention and management, focusing on differences in various clinical settings in China. Key words: Acute kidney injury (AKI), China, diagnosis, management
INTRODUCTION In the past 10 years, kidney diseases have been established as a clear threat not only to human health, but also to development and economic growth.1 An increase in the incidence of acute kidney injury (AKI) has been reported in both developing and developed countries. AKI is associated with severe morbidity and mortality.2,3 China is a developing country with the largest population in the world. The epidemiological data on AKI in China, as well as the current status of AKI clinical practice in China, have attracted increasing attention worldwide in the last decade. However, there have not been many Correspondence to: X. Ding, M.D., PhD, Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China. E-mail: [email protected] Conflict of Interest: No conflicts of interest, financial or otherwise, are declared by the authors. Grants: We thank the National Clinical Key Subject Construction Projects, the Shanghai Health System Promotion Projects of Appropriate Use of Advanced Technology (2013SY048), and the Project of Technology Committee in Shanghai (12DJ1400200) for funding this work.
articles published on the epidemiology of AKI in China until recently.4 Early epidemiology studies were confounded by varying definitions of AKI until recent consensus guidelines (RIFLE [Risk, Injury, Failure, Loss, End stage kidney disease], AKIN [Acute Kidney Injury Network] and KDIGO [Kidney Disease: Improving Global Outcomes]) standardized its definition.5–8 Unfortunately, the nationwide incidence of AKI is still not well defined because of underreporting, regional disparities, and differences in case mix, as indicated by Zhihong Liu, President of the Chinese Society of Nephrology.4 On July 2013, the Chinese Acute Kidney Injury Network was established, with the goal of developing a more accurate database concerning the incidence of AKI in China and to increase the awareness of AKI by governments, the public, general physicians, and other health-care professionals to help prevent the disease.
AKI in the hospital setting AKI is encountered in multiple settings, mostly in the community or the hospital setting. The pattern of hospital-acquired AKI occurring in high-level tertiary hospitals in some of the largest cities in China might be equivalent to that in high-income developed countries.5–9
© 2014 International Society for Hemodialysis DOI:10.1111/hdi.12193
2
AKI in China
Reported incidences of AKI in hospitalized patients in China are mostly single-center based. Incidences of AKI reported in English-language journals were mainly from tertiary metropolitan hospitals in large cities. Recent single-centre studies have shown that AKI is a complicating factor in 2.4%–8.1% of all hospital adult admissions and up to 30%–50% in intensive care unit (ICU) patients, with an associated mortality rate of 18.6%–28.5% in those affected.5–10 An increase in AKI incidence was reported based on a 10-year hospital admission database (1994– 2003) from a single center, and Wang et al. reported that hospital-acquired AKI incidence doubled in the last 5 years, compared with that of the previous 5 years.11 AKI after cardiac surgery AKI is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is one of the most common causes of AKI in the ICU. The incidence of cardiac surgery associated AKI (CSA-AKI) varies from 6.7% to 68.5%,8,12–14 based on the definition used at the time it was applied (Table 1). Che et al.12 reported an incidence of 31.1% among 1056 patients who underwent cardiac surgery. Their cohort, consisting of 2.5 years’ admissions to the cardiac department, demonstrates that patients meeting the definition of AKIN AKI were 2.4 times as likely to die during hospitalization (mortality rate: AKI vs. non-AKI, 11.6% vs. 0.7%; hazard ratio, 2.40, 95% confidence interval 1.73–3.31). Using the same definition of AKI, in a study of 6665 postcardiac surgery patients, Yang et al. reported that 26.7% cases met the diagnostic criteria of AKIN. Hospital mortality rate among AKI patients and non-AKI patients was 2.47% and 0.29%, respectively.13 The incidence of CSA-AKI was even higher in the elderly. Data from 457 consecutive elderly patients (≥60 years) who underwent cardiac surgery with CPB showed an incidence of AKI of 68.5%.14 More recently, Teng et al.8 reported that the incidence of CSA-AKI was much higher in the elderly (39.9%), especially in senile patients over 80 years (42.1%), compared with that in the young and the middle aged (23.1%). Multivariate logistic regression analysis showed that male gender, old age (every 10 years), preoperative serum creatinine (Scr) > 1.2 mg/dL and postoperative use of adrenaline for hypotension were independent risk factors for AKI after cardiac surgery in patients over 65 years old. Drug-induced AKI Drug-induced kidney injury is becoming a major cause of AKI in China. Based on an AKI registry originating from 17 hospitals in Shanghai, drug-induced AKI accounted for
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28.9% of 1200 cases. Antibiotics were the leading cause of drug-induced AKI (47.8%), followed by diuretics (22.2%) and radiocontrast agents (13.3%). About one-third of the affected patients needed renal replacement therapy (RRT). The in-hospital mortality was 28.8%, and only 54.2% of the surviving patients completely recovered their renal function.15 In a single-center study involving 1440 patients with AKI, drug-induced AKI was the most common etiology.16 Of the 5619 AKI cases among 176,155 admissions to our hospital, we found 381 episodes of AKI were attributed to toxic effects of medications on renal tubules or decreases in renal blood flow. The most common medications implicated were contrast medium, chemotherapeutics (especially cisplatin and its analogues) and antibiotics. In some cases, AKI developed after using nonsteroidal anti-inflammatory drugs (NSAIDs), diuretics and angiotensin-converting enzyme inhibitors.5 Contrast-induced nephropathy (CIN) is one of the leading causes of hospital-acquired renal insufficiency.20 Reports of CIN after coronary angiography and percutaneous coronary intervention (PCI) have estimated the overall incidence at between 2% and 50% depending mainly on the presence of risk factors17,18,21 (Table 1). A newly published single-center retrospective study reported that 418 (16.7%) of 2500 consecutive patients who underwent PCI developed CIN within 5 days after exposure to contrast medium.18 The majority of the study population was from the north of the country and may represent a particular ethnic background. Interestingly, a diagnostic Scr value was presented on days 3–5 after PCI in 20% of the patients. It suggests the 48-hour time window for CIN diagnosis might need to be modified. AKI in ICU The incidence of AKI in ICU patients is much higher than that of non-ICU patients. The overall incidence of AKI in the ICU is approximately 20%–50% and can have a mortality over 50%.5,7,19 Zhou7 carried out a retrospective multicenter study of a total of 4642 patients admitted to five ICU centers in Sichuan province (located in the southwest of China). AKI was identified in 34.1% of ICU patients during the entire stay in ICU based on AKIN criteria and the 28-day mortality was 54.4%. More recently, a prospective multicenter observational study that enrolled 3063 consecutive patients from 22 ICUs across mainland China revealed an AKI incidence of 31.6%, according to the RIFLE criteria. The adjusted hazard ratios for 90-day mortality were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the failure group.19
3
4
5
3063
Wen et al.19 Multiple
single
Multiple
Single
multiple
Single Single
Single
Single
single
Multiple single
Single
Single
Single/ multicenter
31.6
16.7
8.63
3.17
UKN
26.69 68.5
31.1
UKN
2.41
34.1 26.2
6.13
3.19
AKI incidence (%)
ICU
CIN
CIN
Mixed
CSA-AKI CSA-AKI, >60 years Durg induced AKI
CSA-AKI
Mixed
Mixed
ICU CSA-AKI
Burn injury
Mixed
Patient population
An increase of ≥25% or ≥0.5 mg/dL Scr within 72 h after PCI An increase of ≥25% or ≥0.5 mg/dL Scr within 5 d after PCI RIFLE
Rise in SCr >177 μmol/L (≥50% if prior mild renal dysfunction [SCr ≤264 μmol/l]) AKIN
AKIN RIFLE
Scr increased to 176 uml/L or above; 50% increase in Scr, when baseline Scr > 132 uml/L AKIN
AKIN
AKIN KDIGO-AKI
RIFLE
AKIN
AKI definition used
A lack of consensus in the determination of baseline creatinine levels; did not investigate the exact AKI pathogenic factors; relatively small sample size
Patients selection bias
Patients selection bias; short-term retrospective study; incorrect classification with ICD-10 code Male predominance; misclassifications of baseline Scr; confounding bias Retrospective; patient selection bias Small sample size; no data on long-term prognosis Retrospective; do not have an accurate evaluation of baseline Scr Only involved patients diagnosed with acute renal failure from ICD-9 codes; limitations in AKI definition; no data for the entire population Retrospective; not have an accurate measurement of preoperative GFR; unselected cohort-value Retrospective; short-term study Small sample, retrospective; misclassifications of baseline Scr Patients with severe renal injury were excluded; nonrandomized, no data for the entire population Short-term retrospective study; not have an accurate measurement of baseline Scr Small sample size; not randomized; confounding bias
Study limitations
a Article published in Chinese. AKIN = Acute Kidney Injury Network; CIN = contrast-induced nephropathy; CSA-AKI = cardiac surgery associated AKI; GFR = glomerular filtration rate; ICD = International Classification of Diseases and Related Health Problems; ICU = intensive care unit; PCI = percutaneous coronary intervention; RIFLE = Risk, Injury, Failure, Loss, End stage kidney disease; KDIGO = Kidney Disease: Improving Global Outcomes; Scr = serum creatinine; UKN = unable to determine due to inability to access source.
2500
45376
Liao et al.16a
Chen et al.18
1200
Che et al.15a
197
6665 457
Yang et al.13 Hu et al.14
Zhang et al.17a
1056
Che et al.12
38734
Lu et al.10a
211
4642 3896
Zhou et al.7 Teng et al.8a
Wang et al.11
2479
176,155
Number of subjects
Hu et al.6
Fang et al.
Author
Table 1 Summary of original reports describing the incidence of adult AKI in the hospital setting
Fang et al.
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AKI in China
AKI in the elderly and in children As a result of the decline of renal compensatory ability, the kidneys of the elderly are much more vulnerable to injuries induced by ischemia/hypoxia or toxins.22 In the elderly, the incidence of AKI is reported to be >14%, with hypovolemia, nephrotoxic drugs, cardiac dysfunction and respiratory failure being the most common etiologies.23,24 Our data, which were from a tertiary metropolitan hospital in Shanghai, indicated an incidence of AKI of 4.10% in patients aged 60–80 years and of 6.17% in patients aged >80 years.5 Large-sample epidemiological studies on pediatric AKI were not reported until a prospective multicenter study by Cao et al.25 published in 2013. Pediatric patients (≤18 years) were enrolled from 14 provincial or municipal children’s hospitals and departments of pediatrics of 13 general hospitals affiliated with medical universities in China. Of the 388,736 pediatric patients involved, 1257 (0.32%) patients were identified as having AKI based on the AKIN criteria. Among the 1257 AKI pediatric patients, 632 were less than 1 year old. The most common causes of AKI were renal causes (57.52%) (Table 2), whereas Table 2 Primary causes of pediatric intrinsic AKI Primary disease Acute glomerulonephritis Nephritic syndrome Neonatal jaundice Sepsis Drug poisoning Henoch–Schonlein prupura Hemolytic uremic syndrome Asphyxia DIC SLE Pneumonia Tumor Acute interstitial nephritis Urinary tract infection IgA nephropathy HIE Traffic accident Hemolytic anemia Renal tubular acidosis Epidemic hemorrhagic fever Renal vein thrombosis Intubation of umbilical cord others
Cases Constituent ratio (%) 127 78 67 62 58 57 43 43 41 32 26 24 14 5 5 5 5 4 3 3 3 3 15
17.6 10.8 9.3 8.6 8.0 7.9 5.9 5.9 5.7 4.4 3.6 3.3 1.9 0.7 0.7 0.7 0.7 0.6 0.4 0.4 0.4 0.4 2.1
DIC = disseminated intravascular coagulation; SLE = systemic lupus erythematosus; HIE = hypoxic ischemic encephalopathy; IgA = immunoglobulin A.
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postrenal (25.69%) and prerenal (14.96%) causes were less common. A total of 43 AKI patients (3.4%) died during their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis.
AKI in the community setting While AKI in hospitalized patients, especially severely ill patients, often has multiple causes, community-acquired AKI is more likely to have a single identifiable cause.26 There are no reliable statistics about the incidence of community-acquired AKI, especially in low-income areas, because of late presentation of patients to tertiary centers, underreporting, and a reduced capacity to provide intensive care to severely ill patients. Data available are mostly from sporadic regional reports and are probably biased because it represents only the cases encountered in large hospital by enthusiastic physicians who want to report them. Venomous snake bites,27 organophosphorus pesticides/ paraquat poisoning,28,29 bee sting,30 and indigenous delicacies such as mushrooms and fish guts31 lead to AKI in some rural area. Renal injury induced by heavy metals (mercury, cadmium, lead, and arsenic) was usually associated with occupational exposure or environmental pollution.32 Aristolochic acid-associated nephropathy can occur in people who have consumed certain amounts of traditional Chinese herbs containing aristolochic acid.33 The data shown earlier came from case reports or small sample size studies, mostly published in Chinese. Glomerulonephritis after infection is declining in most regions, but is still an important cause of pediatric AKI.25 In a large cohort of Chinese patients with biopsy-proven lupus nephritis, AKI, as an independent risk factor for renal outcome was identified with an incidence of 20.5%.34
AKI in earthquake China is an earthquake-prone country. In the past 10 years, more than 14 significant earthquakes struck some regions in 23 seismic belts, some of which were catastrophic, especially the 2008 event. AKI is one of the most lethal, but reversible complications of crush syndrome occurring after an earthquake. The incidence of AKI after earthquake was hard to estimate as many severely injured victims died before medical care facilities could be reached. The 2008 Sichuan earthquake was a deadly earthquake, killing 69,277 people, with 17,923 missing and 96,655 wounded (according to China’s State Council Information Official statement on September 25, 2008).
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Victims severely injured or with special health-care needs such as with AKI were sent to large peripheral hospitals in Mianyang City and Chengdu City.35–37 The Wenchuan earthquake-related AKI Study Group designed a questionnaire in accordance with the recommendations of the International Society of Nephrology’s Renal Disaster Relief Task Force (RDRTF). The questionnaire was sent to 17 hospitals, in which the casualties were accepted and dialysis was available. Among the 10,845 injured patients hospitalized in 10 reference hospitals during the earthquake, crush-related AKI occurred in 228 (2.1%) patients. One hundred thirteen (53.6%) of 211 adult AKI patients needed hemodialysis (HD) treatment.36 Taken as a whole, the most common trauma was limb crush injury (82.9%), followed by fractures (49.8%), and thoracic traumas (22.3%). Twenty-five patients (10.96%) died during the hospitalization period.37
Early diagnosis and biomarkers New biomarkers, as early predictors of structural AKI, might allow detection of AKI up to 48 hours earlier than with an increase in Scr. A variety of promising biomarkers for AKI have been identified in the published literature. Relevant substances, such as neutrophil gelatinaseassociated lipocalin, liver-type fatty acid binding protein, cystatin C, kidney injury molecule-1, N-acetyl-beta-Dglucosaminidase, nestin, and interleukin-18 have all been well studied in the clinical setting in China.38–43 In addition to those protein or peptide biomarkers, nucleic acids such as circulating microRNA have been added to the growing list of potentially useful biomarkers of AKI.44 In a study involving 120 adult patients undergoing cardiac surgery, urinary and plasma microRNA-21(miR-21) were identified to be associated with severe AKI and other poor postoperative outcomes of cardiac surgery, indicating their potential use as prognostic markers.45 In addition to its role as a biomarker of AKI, miR-21 appears to have antiapoptotic properties, in part by targeting the expression of programmed cell death protein 4 in renal ischemic preconditioning (IPC), based on our research work on AKI mechanism.46 Although studies of biomarkers are evolving rapidly, routine application is not yet recommended because their added value to clinical models is not well established.
Prevention and management Nondialytic management Prevention of AKI starts in the community with prompt assessment of those at risk and timely referral. Regular
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drug therapy can compound that risk and quite a few people taking NSAIDs or renin-angiotensin system blockers should be educated to discontinue them temporarily in the face of acute intercurrent illness. Active surveillance for changes in creatinine can automate alerts to guide drug dosing and reduce the incidence of drug-induced kidney injury. In some cases, awareness of the specific infectious or venomous organisms in certain areas will allow environmental protection, vaccines, pharmacologic prophylaxis, and early administration of antivenom. General practitioners and care providers should be educated about AKI and the tools to manage these patients timely and effectively. The key elements in any AKI prevention strategy for hospitalized patients, whenever feasible, are avoidance of hypovolemia, avoidance of nephrotoxins and preventive maneuvers for particular diseases or conditions causing AKI. Effective measures must include hospital-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management (Figure 1). CIN is a common form of hospital-acquired AKI that has been studied extensively. Numerous investigators, including our team, have found that baseline renal dysfunction, diabetes, heart failure, and old age are significant risk factors for CIN.21,47,48 A number of clinical studies on the pharmacological preventative strategies have been done in China. Hydration, drug intervention with N-acetylcysteine,49 probucol,50 angiotensin-converting
Figure 1 Hospital-wide surveillance for acute kidney injury. Active hospital-wide surveillance system should be established to monitor AKI risk factors and to early identify AKI patients. The surveillance system consists of two parts: AKI registration system and AKI Cooperative Network. AKI, acute kidney injury; ICU, intensive care unit.
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AKI in China
enzyme inhibitor,51 statins,52 M-choline receptor blockers,53 ascorbic acid,54 and prostaglandin E155 were reported to be clinically effective in some small-sized studies. IPC has been shown to have promising results in preventing renal injury in animal studies.46,56,57 The actual mechanisms is not quite clear and several hypotheses have been proposed including activation of hypoxia-induced factor55 and suppression of nuclear factor-κβ.56 Our team recently provided additional evidence for the importance of microRNAs in regulating the response of the kidney to injury in vivo.57 However, IPC was never considered an intervention for AKI because of its need for pretreatment. A more practical approach may be achieved using remote IPC (RIPC). RIPC has been shown to provide renal protection to patients undergoing cardiac and vascular interventions.58 Recently a group of Chinese urologists reported that slight lower limb ischemia significantly reduced renal impairment within 1 month after laparoscopic partial nephrectomy.59 Mechanism by which RIPC protects the kidney is unclear, requiring large-scale clinical trials to further clarify the underlying mechanism as well as validate its clinical benefits. Dialytic management Various techniques for RRT, either intermittent or continuous, are available for patients with AKI.60–62 A continuous approach to RRT (CRRT) for critically ill patients was introduced in 1977 and hailed almost immediately as an improved alternative to intermittent HD (IHD). CRRT was introduced to China in 1985, by Professor Liao Lvtan, the founder and the first director of the Department of Nephrology at Zhongshan Hospital Fudan University, and one of the main founders of blood purification technology in China.60 Afterwards, CRRT was widely adopted in China as an alternative modality in treating critically ill patients.62 IHD is less expensive than continuous RRT and has similar efficacy in patients with hemodynamic stability.63 For indicated patients, slow low-efficiency daily dialysis (SLEDD) was performed and was reported to have an equal efficacy as CRRT.64,65 Hemoperfusion, immunoadsorption, plasmapheresis, and artificial liver support methods were used alone or in combination with other blood purification techniques in AKI patients with special problems.66,67 The optimal management of RRT in critical AKI patients remains debatable. Nonetheless, little is known about the current practices and beliefs of intensivists or nephrologists in China. To our knowledge, RRTs are mostly performed by nephrologists in China, unlike that in the United States or Europe where intensivists are in charge of RRT practice. Continuous blood purification
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(CBP) is mainly performed in ICU in China while IHD and SLEDD are performed both within and outside ICU. Possible reasons might be that patients receiving CBP usually have much worse medical conditions, such as those requiring mechanical ventilation supports or other life supports, which limits CBP practice outside ICU.63–65,68 A good functioning vascular access is an essential component for adequate RRT. Most acute RRT is performed with a double-lumen temporary dialysis catheter (TDC) inserted into a large vein.69,70 The right jugular vein is the first choice while femoral vein was preferred for patients with critical respiratory condition or when the insertion site of jugular vein was “heavily catheterized.” In a cohort of 1028 patients treated with CRRT or IHD, the total number of TDC placement procedure and the catheterdays was 215 and 3665 for jugular vein, 908 and 13,580 for femoral vein. Catheter-related local infection incidence density was statistically higher for femoral than for jugular (4.79% vs. 2.72%, P < 0.05).69 In the past 5 years, a few studies focusing on the application of peritoneal dialysis (PD) in the treatment of adult AKI/acute renal failure in China have been published.68,71,72 At present, PD is comparatively rarely used in treating critically ill AKI patients, especially in highincome areas in China. Possible reasons might include application of new advanced blood purification techniques. Under certain circumstances where patients present with active bleeding or HD apparatus is not available, PD is a safe, feasible, and efficient alternative to HD.71,72 We have limited data on the proportion of AKI patients receiving HD versus PD. In a single-center study involving 148 patients with CSA-AKI and receiving RRTs, He et al.68 reported that the number of patients who received PD, IHD, and CBP was 28, 77, and 43, respectively (ratio 1: 2.6: 1.5). But the situation is quite different in the setting of pediatric ICU, where PD is the most widely used dialysis modality in treating the critically ill AKI children.73–75 Some PD modalities, like high volume PD, tidal PD, or continuous flow PD may achieve dramatic volume removal and solute clearance, but has not been validated in large sample populations in China.
CONCLUSIONS The total population of China is more than 1.3 billion, and its renal disease health-care system is possibly the largest in the world. In the past decade, the development of nephrology in the field of AKI in China has been boosted by rapid progress in cutting-edge research covering the entire spectrum of renal medicine, from basic science to clinical epidemiological studies. However, the
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academic achievement gap between China and the developed countries still exists, highlighting the need for a larger number of high-quality multicenter randomized controlled trials, as well as clinical epidemiology studies to evaluate the evidence and support regional guideline development.
ACKNOWLEDGMENTS We would like to express our gratitude to Prof. Mingyu Liang, Department of Physiology, Medical College of Wisconsin (USA), and Dave L Roerig, Professor Emeritus of Anesthesiology, Pharmacology and Toxicology, Medical College of Wisconsin (USA), for their critical reading of our article. Manuscript received March 2014; revised June 2014.
REFERENCES 1 Eckardt KU, Coresh J, Devuyst O, et al. Evolving importance of kidney disease: From subspecialty to global health burden. Lancet. 2013; 382:158–169. 2 Li PK, Burdmann EA, Mehta RL. Acute kidney injury: Global health alert. J Nephropathol. 2013; 2:90–97. 3 Lameire NH, Bagga A, Cruz D, et al. Acute kidney injury: An increasing global concern. Lancet. 2013; 382:170– 179. 4 Liu ZH. Nephrology in China. Nat Rev Nephrol. 2013; 9:523–528. 5 Fang Y, Ding X, Zhong Y, et al. Acute kidney injury in a Chinese hospitalized population. Blood Purif. 2010; 30:120–126. 6 Hu JY, Meng XC, Han J, et al. Relation between proteinuria and acute kidney injury in patients with severe burns. Crit Care. 2012; 16:R172. 7 Zhou J, Yang L, Zhang K, Liu Y, Fu P. Risk factors for the prognosis of acute kidney injury under the Acute Kidney Injury Network definition: A retrospective, multicenter study in critically ill patients. Nephrology. 2012; 17:330– 337. 8 Teng J, Xu JR, Fang Y, et al. [Preliminary research on acute kidney injury after cardiac surgery in elderly people]. Chin J Blood Purif. 2013; 12:21–24 (In Chinese). 9 Meier P, Bonfils RM, Vogt B, Burnand B, Burnier M. Referral patterns and outcomes in noncritically ill patients with hospital-acquired acute kidney injury. Clin J Am Soc Nephrol. 2011; 6:2215–2225. 10 Lu RH, Fang Y, Gao JH, et al. [The incidence and risk factors associated with prognosis of acute kidney injury in hospitalized patients]. Chin J Nephrol. 2012; 28:194– 200 (In Chinese).
8
11 Wang Y, Cui Z, Fan M. Hospital-acquired and community-acquired acute renal failure in hospitalized Chinese: A ten-year review. Ren Fail. 2007; 29:163–168. 12 Che M, Li Y, Liang X, et al. Prevalence of acute kidney injury following cardiac surgery and related risk factors in Chinese patients. Nephron Clin Pract. 2011; 117:c305– c311. 13 Yang XM, Wang CS, Liu L, et al. [Risk factors for acute kidney injury after adult cardiac surgery with cardiopulmonary bypass]. Clin J Thorac Cardiovasc Surg. 2013; 29:147–150 (In Chinese). 14 Hu PH, Liang XL, Chen YH, et al. [Acute kidney injury after cardiac surgery in elderly patients: Focus on modifiable risk factors]. Clin J Thorac Cardiovasc Surg. 2012; 28:599–602 (In Chinese). 15 Che ML, Yan YC, Zhang W, et al. [Analysis of druginduced acute renal failure in Shanghai]. Zhonghua Yi Xue Za Zhi. 2009; 89:744–749 (In Chinese). 16 Liao XH, Zhang L, Zhong L, et al. [Etiology and prognosis of in patients with acute kidney injury]. Chongqing Med. 2010; 39:1250–1253 (In Chinese). 17 Zhang P, Ni ZH, Wang L, et al. [Investigation of risk factors of contrast—Induced nephropathy in multicenters after coronary artery intervention]. CJITWN. 2010; 11:214–218 (In Chinese). 18 Chen YL, Fu NK, Xu J, et al. A simple preprocedural score for risk of contrast-induced acute kidney injury after percutaneous coronary intervention. Catheter Cardiovasc Interv. 2014; 83:E8–E16. 19 Wen Y, Jiang L, Xu Y, et al. Prevalence, risk factors, clinical course, and outcome of acute kidney injury in Chinese intensive care units: A prospective cohort study. Chin Med J (Engl). 2013; 126:4409–4416. 20 McCullough PA, Adam A, Becker CR, et al. Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol. 2006; 98(6A):5K–13K. 21 Song W, Zhang T, Pu J, et al. Incidence and risk of developing contrast-induced acute kidney injury following intravascular contrast administration in elderly patients. Clin Interv Aging. 2014; 9:85–93. 22 Martin JE, Sheaff MT. Renal ageing. J Pathol. 2007; 211:198–205. 23 Wen J, Cheng Q, Zhao J, et al. Hospital-acquired acute kidney injury in Chinese very elderly persons. J Nephrol. 2013; 26:572–579. 24 Gong Y, Zhang F, Ding F, Gu Y. Elderly patients with acute kidney injury (AKI): Clinical features and risk factors for mortality. Arch Gerontol Geriatr. 2012; 54:e47–e51. 25 Cao Y, Yi ZW, Zhang H, Dang XQ, Wu XC, Huang AW. Etiology and outcomes of acute kidney injury in Chinese children: A prospective multicentre investigation. BMC Urol. 2013; 21:41. 26 Ali T, Khan I, Simpson W, et al. Incidence and outcomes in acute kidney injury: A comprehensive populationbased study. J Am Soc Nephrol. 2007; 18:1292–1298.
Hemodialysis International 2015; 19:2–10
AKI in China
27 Zou RL, Zhang YM. [Acute renal failure caused by viper: Report of 48 cases]. Chin J Surg. 1994; 32:119–120 (In Chinese). 28 Mao SM, Gao Y. [Hemoperfusion combined with hemodialysis in treatment of critically ill organophosphorus poisoning patients: A 9-case report]. Chin J Blood Purif. 2004; 3:33 (In Chinese). 29 Hu F, Zhang H, Chen J, et al. [Clinical features of acute kindey injury in patients with acute paraquat poisoning]. J Nephrol Dial Transplant. 2012; 21:341–345 (In Chinese). 30 He XP, Wu P, Liu L. [Blood purification in the treatment of acute renal failure caused by beetoxin: A report of 37 cases]. Acta Acade Med Mil Tert. 2004; 26:816–819 (In Chinese). 31 Zhou SL, Yang XC, Wang L, et al. [An analysis of 100 patients with acute renal failure caused by food poisoning in west China]. J Nephrol Dial Transplant. 2002; 11:133– 137 (In Chinese). 32 Zhang L, Zhang Y, Lin Q, et al. Acute kidney injury, hematuria, and orange skin pigmentation caused by arsine poisoning. Am J Kidney Dis. 2008; 52:A33–A36. 33 Yang L, Li X, Wang H. Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis. Nephrol Dial Transplant. 2007; 22:445–456. 34 Zhu D, Qu Z, Tan Y, Yu F, Zhao MH. Acute kidney injury in Chinese patients with lupus nephritis: A large cohort study from a single center. Lupus. 2011; 20:1557–1565. 35 Zhang L, Fu P, Wang L, et al. The clinical features and outcome of crush patients with acute kidney injury after the Wenchuan earthquake: Differences between elderly and younger adults. Injury. 2012; 43:1470–1475. 36 Chunguang Z, Rigao C, Fuguo H, et al. Characteristics of crush syndrome caused by prolonged limb compression longer than 24 h in the Sichuan earthquake. Emerg Med J. 2010; 27:627–630. 37 Hu Z, Zeng X, Fu P, et al. Predictive factors for acute renal failure in crush injuries in the Sichuan earthquake. Injury. 2012; 43:613–618. 38 Ling W, Zhaohui N, Ben H, et al. Urinary IL-18 and NGAL as early predictive biomarkers in contrast-induced nephropathy after coronary angiography. Nephron Clin Pract. 2008; 108:c176–c181. 39 Xu X, Zou JZ, Ding XQ, et al. Clinical value of serum cystatin C by ELISA for estimation of glomerular filtration rate. J Clin Lab Anal. 2004; 18:61–64. 40 Xu XH, Xu X, Zhong J, et al. Clinical value of urinary kidney biomarkers for estimation of renal impairment in elderly Chinese with essential hypertension. J Clin Lab Anal. 2008; 22:86–90. 41 Zeng XF, Li JM, Tan Y, et al. Performance of urinary NGAL and L-FABP in predicting acute kidney injury and subsequent renal recovery: A cohort study based on major surgeries. Clin Chem Lab Med. 2014; 52:671–8.
Hemodialysis International 2015; 19:2–10
42 Zhang W, Zhang L, Chen YX, et al. Identification of Nestin as a urinary biomarker for acute kidney injury. Am J Nephrol. 2014; 39:110–121. 43 Shao X, Tian L, Xu W, et al. Diagnostic value of urinary kidney injury molecule 1 for acute kidney injury: A metaanalysis. PLoS ONE. 2014; 9:e84131. 44 Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008; 18:997– 1006. 45 Du J, Cao X, Zou L, et al. MicroRNA-21 and risk of severe acute kidney injury and poor outcomes after adult cardiac surgery. PLoS ONE. 2013; 8:e63390. 46 Xu X, Kriegel AJ, Liu Y, et al. Delayed ischemic preconditioning contributes to renal protection by upregulation of miR-21. Kidney Int. 2012; 82:1167–1175. 47 Ji J, Ding XQ, Xu XH, et al. [Effect of the low osmolality nonionic contrast media on renal function in patients undergoing coronary intervention: A prospective study]. Chin J Nephrol. 2006; 22:388–392 (In Chinese). 48 Yang D, Lin S, Yang D, Wei L, Shang W. Effects of shortand long-term hypercholesterolemia on contrast-induced acute kidney injury. Am J Nephrol. 2012; 35:80–89. 49 Chen SL, Zhang J, Yei F, et al. Clinical outcomes of contrast-induced nephropathy in patients undergoing percutaneous coronary intervention: A prospective, multicenter, randomized study to analyze the effect of hydration and acetylcysteine. Int J Cardiol. 2008; 126:407–413. 50 Li G, Yin L, Liu T, et al. Role of probucol in preventing contrast-induced acute kidney injury after coronary interventional procedure. Am J Cardiol. 2009; 103:512– 514. 51 Li XM, Cong HL, Li TT, He LJ, Zhou YJ. Impact of benazepril on contrast-induced acute kidney injury for patients with mild to moderate renal insufficiency undergoing percutaneous coronary intervention. Chin Med J (Eng). 2011; 124:2101–2106. 52 Jia XW, Fu XH, Zhang J, et al. Comparison of usefulness of simvastatin 20 mg versus 80 mg in preventing contrast-induced nephropathy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2009; 104:519–524. 53 Geng W, Fu XH, Gu XS, et al. Preventive effects of anisodamine against contrast-induced nephropathy in type 2 diabetics with renal insufficiency undergoing coronary angiography or angioplasty. Chin Med J (Engl). 2012; 125:3368–3372. 54 Zhou L, Chen H. Prevention of contrast-induced nephropathy with ascorbic acid. Intern Med. 2012; 51:531– 535. 55 Liu WJ, Zhang BC, Guo R, Wei YD, Li WM, Xu YW. Renoprotective effect of alprostadil in combination with statins in patients with mild to moderate renal failure undergoing coronary angiography. Chin Med J (Engl). 2013; 126:3475–3480.
9
Fang et al.
56 Cao CC, Ding XQ, Ou ZL, et al. In vivo transfection of NF-kappaB decoy oligodeoxynucleotides attenuate renal ischemia/reperfusion injury in rats. Kidney Int. 2004; 65:834–845. 57 Jiang S, Chen Y, Zou J, et al. Diverse effects of ischemic pretreatments on the long-term renal damage induced by ichemia-reperfusion. Am J Nephrol. 2009; 30:440– 449. 58 Li L, Li G, Yu C, Li Y. The role of remote ischemic preconditioning on postoperative kidney injury in patients undergoing cardiac and vascular interventions: A meta-analysis. J Cardiothorac Surg. 2013; 8:43–51. 59 Huang J, Chen Y, Dong B, et al. Effect of remote ischaemic preconditioning on renal protection in patients undergoing laparoscopic partial nephrectomy: A “blinded” randomised controlled trial. BJU Int. 2013; 112:74–80. 60 Liao LV, Cai ZH, Chen KJ, et al. Continuous ambulatory peritoneal dialysis-clinical report of 62 cases. Chin Med J (Engl). 1985; 998:281–286. 61 Xu JR, Teng J, Zou JZ, et al. [Goal-directed renal replacement therapy for acute kidney injury after cardiac surgery]. Chin Crit Care Med. 2011; 23:749–754 (In Chinese). 62 Zhang P, Yang Y, Lv R, Zhang Y, Xie W, Chen J. Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: A singlecenter randomized clinical trial. Nephrol Dial Transplant. 2012; 27:967–973. 63 Ji D, Gong D, Xie H, Xu B, Liu Y, Li L. A retrospective study of continuous renal replacement therapy versus intermittent hemodialysis in severe acute renal failure. Chin Med J (Engl). 2001; 114:1157–1161. 64 Shen B, Teng J, Liu ZH, et al. [Comparison of therapeutic effects between extended daily hemodialysis and extended daily hemofiltration for acute kidney injury after orthotopic cardiac transplantation]. Shanghai Med J. 2009; 32:47–49 (In Chinese). 65 Lu RH, Yan YC, Gu Y, et al. [Effects of CVVH and SLED in patients with acute renal failure after liver
10
66
67
68
69
70
71
72
73
74
75
transplantation]. J Shanghai Jiaotong Univ. 2008; 28:1010–1014 (In Chinese). Bo H, Zhang L, Huang S, Zhu T, Yu RC. Continuous venovenous hemofiltration and hemoperfusion in successful treatment of a patient with crush syndrome and acute pancreatitis. Ren Fail. 2012; 34:383–386. Teng J, Chen LM, Zou JZ, et al. [Protein A immunoadsorption for the therapy of rapidly progressive gIomeruIonephritis—5 case reports]. Chin J Blood Purif. 2005; 4:472–475 (In Chinese). He CS, Shi W, Liang XL, et al. [The therapeutic effects of various blood purification techniques for acute renal failure after cardiac surgery]. Chin J Blood Purif. 2004; 3:188–191 (In Chinese). Liang HB, Liang XL, Wang WJ, et al. [A retrospective analysis of catheter-related infections in 1028 critical cases with blood purification]. Chin J Blood Purif. 2012; 11:523–526 (In Chinese). Zhou F, Song Q, Peng Z, et al. Effects of continuous venous–venous hemofiltration on heat stroke patients: A retrospective study. J Trauma. 2011; 71:1562–1568. Gan HB, Dong J, Wang M, et al. [Peritoneal dialysis and continuous renal replacement therapy in critical ill patients]. Chin J Crit Care. 2003; 23:379–381 (In Chinese). Yan WX, Liu J, Wang CC, et al. [Therapeutic effects of different dialysis modality on the outcomes of AKI patients complicated with cerebral hemorrhage]. Chin J Postgrad Med. 2011; 34:32–33 (In Chinese). Zeng M, Li SJ, Wang X, et al. [Early peritoneal dialysis after repair of congenital heart disease in children]. Chin J Thorac Cardiovasc. 2013; 29:73–75 (In Chinese). Zheng J, Xiao Y, Chong M, et al. The effect of cardiopulmonary bypass duration on renal injury after congenital heart surgery in infants and young children. Adv Clin Exp Med. 2013; 22:693–698. Li LL, Lu GP. [Surveying the status of continuous blood purification technology application in Chinese pediatric intensive care unit]. Chin J Pediatr. 2014; 52:201–203 (In Chinese).
Hemodialysis International 2015; 19:2–10
