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Marrapu S, Kumar R. Transition from acute kidney injury to chronic kidney disease in liver cirrhosis patients: Current perspective. World J Nephrol 2025; 14:102381. [DOI: 10.5527/wjn.v14.i1.102381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 12/22/2024] [Accepted: 01/11/2025] [Indexed: 01/20/2025] Open
Abstract
In liver cirrhosis patients, acute kidney injury (AKI) is a common and severe complication associated with significant morbidity and mortality, often leading to chronic kidney disease (CKD). This progression reflects a complex interplay of renal and hepatic pathophysiology, with AKI acting as an initiator through maladaptive repair mechanisms. These mechanisms—such as tubular cell cycle arrest, inflammatory cascades, and fibrotic processes—are exacerbated by the hemodynamic and neurohormonal disturbances characteristic of cirrhosis. Following AKI episodes, persistent kidney dysfunction or acute kidney disease (AKD) often serves as a bridge to CKD. AKD represents a critical phase in renal deterioration, characterized by prolonged kidney injury that does not fully meet CKD criteria but exceeds the temporal scope of AKI. The progression from AKD to CKD is further influenced by recurrent AKI episodes, impaired renal autoregulation, and systemic comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease, which compound kidney damage. The clinical management of AKI and CKD in cirrhotic patients requires a multidimensional approach that includes early identification of kidney injury, the application of novel biomarkers, and precision interventions. Recent evidence underscores the inadequacy of traditional biomarkers in predicting the AKI-to-CKD progression, necessitating novel biomarkers for early detection and intervention.
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Affiliation(s)
- Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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Guo L, Wu X, Cui X, Li M, Yang L, Feng Y, Zhan Q, Huang L. Clinical Characteristics and the Prognostic Impact of Acute Kidney Injury in Critically Ill Patients with Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Retrospective, Single-Center Study. KIDNEY DISEASES (BASEL, SWITZERLAND) 2024; 10:262-273. [PMID: 39131885 PMCID: PMC11309762 DOI: 10.1159/000539139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 04/23/2024] [Indexed: 08/13/2024]
Abstract
Introduction The incidence and impact of acute kidney injury (AKI) in patients with invasive pulmonary aspergillosis (IPA) admitted to the intensive care unit (ICU) are unknown. Methods This retrospective study included 140 patients who were diagnosed with IPA and admitted to the medical ICU of China-Japan Friendship Hospital in Beijing, China. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. Data on demographic characteristics, comorbidities, laboratory tests, treatments, and prognosis at ICU admission were collected. Results The rate of AKI was 71.4% (n = 100), and approximately 30% of the patients had preadmission acute kidney dysfunction. Of the 100 patients with AKI, 19, 8, and 73 patients had stage I, II, and III AKI, respectively, and 64 (87.6%) patients required continuous renal replacement therapy. Overall ICU mortality rate was 52.1%. Irreversible AKI was a strong independent risk factor for ICU mortality (odds ratio 13.36, 95% confidence interval 4.52-39.48, p < 0.001), followed by chronic lung disease, use of intermittent positive-pressure ventilation, and long-term corticosteroid treatment within 1 year prior to ICU admission. Higher cardiac troponin I levels at admission and worse volume control during the first 7 days of ICU stay were potential predictive factors of irreversible kidney dysfunction. Patients with irreversible AKI and those who died during the ICU stay had greater volume overload during the first 14 days of ICU stay. Patients who survived received earlier renal replacement therapy support after ICU admission compared to those who died (median, 2 vs. 5 days; p = 0.026). Conclusion Compared to the patients with IPA in the absence of AKI, those with AKI presented with more volume overload, worse disease burden, and required stronger respiratory support, while experiencing worse prognosis. Irreversible AKI was a strong predictor of mortality in patients with critical IPA. Better volume control and earlier CRRT initiation should be considered key points in AKI management and prognostic improvement.
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Affiliation(s)
- Lingxi Guo
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
| | - Xiaojing Wu
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
| | - Xiaoyang Cui
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
| | - Meiyuan Li
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
| | - Lu Yang
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
| | - Yiming Feng
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
| | - Qingyuan Zhan
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
| | - Linna Huang
- National Center for Respiratory Medicine, Beijing, PR China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, PR China
- National Clinical Research Center for Respiratory Diseases, Beijing, PR China
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China
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Taylor KM, Au AYM, Herath S, Succar L, Wong J, Erlich JH, Endre ZH. Kidney functional reserve and damage biomarkers in subclinical chronic kidney disease and acute kidney injury. Am J Physiol Renal Physiol 2023; 325:F888-F898. [PMID: 37733876 DOI: 10.1152/ajprenal.00133.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 09/01/2023] [Accepted: 09/15/2023] [Indexed: 09/23/2023] Open
Abstract
Significant loss of kidney function is not easily identified by serum creatinine (sCr)-based measurements. In the presence of normal sCr, decreased kidney functional reserve (KFR) may identify a significant loss of function. We evaluated KFR in experimental subclinical chronic kidney disease (sCKD) before and after brief ischemia-reperfusion injury (IRI). Using fluorescein isothiocyanate-labeled sinistrin, glomerular filtration rate (GFR) was measured transcutaneously before and after adenine-induced sCKD, and 1 and 2 wk after brief IRI, and compared with urinary kidney damage biomarkers. sCKD reduced stimulated and unstimulated GFR by ∼20% while reducing KFR by 50%. IRI reduced unstimulated GFR for 14 days, but KFR remained relatively unchanged in sCKD and transiently increased in control kidneys at 7 days. sCr increased and creatinine clearance (CrCl) decreased only immediately after IRI; sCr and CrCl correlated poorly with measured GFR except on day 1 after IRI. Heterogeneity in sCr and CrCl resulted from variation in tubular creatinine secretion. The increase in damage biomarker concentrations persisted for up to 14 days after IRI, allowing retrospective detection of sCKD before AKI by urine clusterin/urine kidney injury molecule-1 with an area under the curve of 1.0. sCr and CrCl are unreliable unless sCr is acutely elevated. Measurement of KFR and urine damage biomarker excretion detected sCKD despite normal sCr and CrCl. After IRI, the urine clusterin-to-urine kidney injury molecule-1 ratio may identify prior sCKD.NEW & NOTEWORTHY Early kidney function loss is poorly identified by serum creatinine (sCr)-based measurements. Direct kidney functional reserve (KFR) measurement before kidney injury and elevated urinary biomarkers clusterin and kidney injury molecule-1 detect subclinical chronic kidney disease (sCKD) after kidney injury despite normal range sCr and creatinine clearance. Reliance on sCr masks underlying sCKD. Acute kidney injury risk evaluation requires direct glomerular filtration rate measurement and KFR, whereas kidney damage biomarkers facilitate identification of prior subclinical injury.
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Affiliation(s)
- Kylie M Taylor
- Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Amy Y M Au
- Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
- Department of Nephrology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Sanjeeva Herath
- Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Lena Succar
- Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Jasmine Wong
- Department of Nephrology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Jonathan H Erlich
- Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
- Department of Nephrology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Zoltán H Endre
- Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
- Department of Nephrology, Prince of Wales Hospital, Sydney, New South Wales, Australia
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Ohlmeier C, Schuchhardt J, Bauer C, Brinker M, Kong SX, Scott C, Vaitsiakhovich T. Risk of chronic kidney disease in patients with acute kidney injury following a major surgery: a US claims database analysis. Clin Kidney J 2023; 16:2461-2471. [PMID: 38046015 PMCID: PMC10689184 DOI: 10.1093/ckj/sfad148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Indexed: 12/05/2023] Open
Abstract
Background Acute kidney injury (AKI) is a common complication after major surgery. This study assessed the risk of developing or worsening of chronic kidney disease (CKD) and other clinical outcomes in patients experiencing AKI after major surgery. Methods This retrospective observational study used Optum's de-identified Clinformatics Data Mart Database to investigate cardiorenal outcomes in adult patients at the first AKI event following major surgery. The primary outcome was CKD stage ≥3; secondary outcomes included myocardial infarction (MI), stroke, heart failure, all-cause hospitalization, end-stage kidney disease, need for dialysis or kidney transplant and composite measures. Follow-up was up to 3 years. Additionally, the effect of intercurrent events on the risk of clinical outcomes was assessed. Results Of the included patients (N = 31 252), most were male (61.9%) and White (68.9%), with a median age of 72 years (interquartile range 64-79). The event rates were 25.5 events/100 patient-years (PY) for CKD stage ≥3, 3.1 events/100 PY for end-stage kidney disease, 3.0 events/100 PY for dialysis and 0.1 events/100 PY for kidney transplants. Additionally, there were 6.9 events/100 PY for MI, 8.7 events/100 PY for stroke and 49.8 events/100 PY for all-cause hospitalization during follow-up. Patients with AKI relapses as intercurrent events were more likely to develop CKD stage ≥3 than those with just one AKI event after major surgery. Conclusion This analysis demonstrated that patients experiencing AKI following major surgery are at high risk of developing severe CKD or worsening of pre-existing CKD and other cardiorenal clinical outcomes such as MI and stroke.
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Affiliation(s)
- Christoph Ohlmeier
- Medical Affairs & Pharmacovigilance, Pharmaceuticals, Bayer AG, Berlin, Germany
| | | | | | - Meike Brinker
- Research & Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany
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Muiru A, Hsu J, Zhang X, Appel L, Chen J, Cohen DL, Drawz PE, Freedman BI, Go AS, He J, Horwitz E, Hsu RK, Lash JP, Liu KD, McCoy IE, Porter A, Rao P, Ricardo AC, Rincon-Choles H, Sondheimer J, Taliercio J, Unruh M, Hsu CY. Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study. Ann Intern Med 2023; 176:961-968. [PMID: 37429030 PMCID: PMC10829039 DOI: 10.7326/m22-3617] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not. OBJECTIVE To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD). DESIGN Multicenter prospective cohort study. SETTING United States. PARTICIPANTS Patients with CKD (n = 3150). MEASUREMENTS Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits. RESULTS During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m2) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m2) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m2 per year) also had CI bounds that included the possibility of no effect. LIMITATIONS Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge. CONCLUSION After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small. PRIMARY FUNDING SOURCE National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
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Affiliation(s)
- Anthony Muiru
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - Jesse Hsu
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Xiaoming Zhang
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Larry Appel
- Division of General Internal Medicine, The Johns Hopkins University, Baltimore, MD
| | - Jing Chen
- Section of Nephrology & Hypertension, Tulane University School of Medicine, New Orleans, LA
| | - Debbie L. Cohen
- Division of Nephrology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Paul E. Drawz
- Division of Nephrology and Hypertension, University of Minnesota Medical School, Minneapolis, MN
| | - Barry I. Freedman
- Section on Nephrology, Wake Forest University, Winston-Salem, North Carolina
| | - Alan S. Go
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Jiang He
- Tulane University School of Public Health & Tropical Medicine, New Orleans, LA
| | - Ed Horwitz
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Raymond K. Hsu
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - James P. Lash
- Division of Nephrology, University of Illinois Health, Chicago, IL
| | - Kathleen D. Liu
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - Ian E. McCoy
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - Anna Porter
- Division of Nephrology, University of Illinois Health, Chicago, IL
| | - Panduranga Rao
- Division of Nephrology, University of Michigan Health, Ann Arbor, MI
| | - Ana C. Ricardo
- Division of Nephrology, University of Illinois Health, Chicago, IL
| | | | - James Sondheimer
- Division of Nephrology and Hypertension, Wayne State University School of Medicine, Detroit, MI
| | | | - Mark Unruh
- University of New Mexico Health Sciences, Albuquerque, NM
| | - Chi-yuan Hsu
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
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Bonde SS, Zaman W, Cuomo R, Malhotra R, Macedo E. Risk of de novo proteinuria following hospitalization with acute kidney injury. BMC Nephrol 2023; 24:176. [PMID: 37322414 PMCID: PMC10273748 DOI: 10.1186/s12882-023-03209-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 05/21/2023] [Indexed: 06/17/2023] Open
Abstract
BACKGROUND Acute Kidney Injury (AKI) incidence has continued to rise and is recognized as a major risk factor for kidney disease progression and cardiovascular complications. Early recognition of factors associated with post-AKI complications is fundamental to stratifying patients that could benefit from closer follow-up and management after an episode of AKI. Recent studies have shown that proteinuria is a prevalent sequela after AKI and a strong predictor of complications post-AKI. This study aims to evaluate the frequency and timing of the development of de-novo proteinuria after an AKI episode in patients with known kidney function and no prior history of proteinuria. METHODS We retrospectively analyzed data from adult AKI patients with pre- and post-kidney function information between Jan 2014 and March 2019. The presence of proteinuria determined before and after index AKI encounter was based on ICD-10 code and/or urine dipstick and UPCR during the follow-up period. RESULTS Of 9697 admissions with AKI diagnoses between Jan 2014 and March 2019, 2120 eligible patients with at least one assessment of Scr and proteinuria before AKI index admission were included in the analysis. The median age was 64 (IQR 54-75) years, and 57% were male. 58% (n-1712) patients had stage 1 AKI, 19% (n = 567) stage 2 AKI, and 22% (n = 650) developed stage 3 AKI. De novo proteinúria was found in 62% (n = 472) of patients and was already present by 90 days post-AKI in 59% (209/354). After adjusting for age and comorbidities, severe AKI (stage 2/3 AKI) and diabetes, were independently associated with increased risk for De novo proteinuria. CONCLUSION Severe AKI is an independent risk factor for subsequent de novo proteinuria post-hospitalization. Further prospective studies are needed to determine whether strategies to detect AKI patients at risk of proteinuria and early therapeutics to modify proteinuria can delay the progression of kidney disease.
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Affiliation(s)
- Saniya S Bonde
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Warda Zaman
- East Bay Nephrology Medical Group, Berkeley, CA, USA
| | - Raphael Cuomo
- Department of Anesthesiology, School of Medicine, University of California San Diego, San Diego, CA, USA
| | - Rakesh Malhotra
- Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Etienne Macedo
- Department of Medicine, University of California San Diego, San Diego, CA, USA.
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Shin J, Lee CH. The roles of sodium and volume overload on hypertension in chronic kidney disease. Kidney Res Clin Pract 2021; 40:542-554. [PMID: 34922428 PMCID: PMC8685361 DOI: 10.23876/j.krcp.21.800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 10/18/2021] [Indexed: 11/24/2022] Open
Abstract
Chronic kidney disease (CKD) is associated with increased risk of cardiovascular (CV) events, and the disease burden is rising rapidly. An important contributor to CV events and CKD progression is high blood pressure (BP). The main mechanisms of hypertension in early and advanced CKD are renin-angiotensin system activation and volume overload, respectively. Sodium retention is well known as a factor for high BP in CKD. However, a BP increase in response to total body sodium or volume overload can be limited by neurohormonal modulation. Recent clinical trial data favoring intensive BP lowering in CKD imply that the balance between volume and neurohormonal control could be revisited with respect to the safety and efficacy of strict volume control when using antihypertensive medications. In hemodialysis patients, the role of more liberal use of antihypertensive medications with the concept of functional dry weight for intensive BP control must be studied.
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Affiliation(s)
- Jinho Shin
- Division of Cardiology, Department of Internal Medicine, Hanyang University Medical Center, Seoul, Republic of Korea
| | - Chang Hwa Lee
- Division of Nephrology, Department of Internal Medicine, Hanyang University Medical Center, Seoul, Republic of Korea
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Macedo E, Hemmila U, Sharma SK, Claure-Del Granado R, Mzinganjira H, Burdmann EA, Cerdá J, Feehally J, Finkelstein F, García-García G, Jha V, Lameire NH, Lee E, Levin NW, Lewington A, Lombardi R, Rocco MV, Aronoff-Spencer E, Tonelli M, Yeates K, Remuzzi G, Mehta RL. Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study. PLoS Med 2021; 18:e1003408. [PMID: 33444372 PMCID: PMC7808595 DOI: 10.1371/journal.pmed.1003408] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 12/03/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries. METHODS AND FINDINGS Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily. CONCLUSIONS This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.
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Affiliation(s)
- Etienne Macedo
- Division of Nephrology, Department of Medicine, University of California San Diego, San Diego, California, United States of America
| | - Ulla Hemmila
- College of Medicine, University of Malawi, Blantyre, Malawi
| | - Sanjib Kumar Sharma
- Department of Internal Medicine, B.P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - Rolando Claure-Del Granado
- Division of Nephrology, Hospital Obrero #2–Caja Nacional de Salud, School of Medicine, Universidad Mayor de San Simón, Cochabamba, Bolivia
| | | | - Emmanuel A. Burdmann
- LIM 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil
| | - Jorge Cerdá
- Division of Nephrology, Department of Medicine, Albany Medical College, Albany, New York, United States of America
| | | | | | - Guillermo García-García
- Hospital Civil de Guadalajara, University of Guadalajara Health Science Center, Guadalajara, Jalisco, Mexico
| | - Vivekanand Jha
- George Institute for Global Health, University of New South Wales, New Delhi, India
- School of Public Health, Imperial College London, London, United Kingdom
- Manipal Academy of Higher Education, Manipal, India
| | - Norbert H. Lameire
- Nephrology Section, Department of Internal Medicine, University Hospital, Ghent, Belgium
| | - Euyhyun Lee
- Altman Clinical and Translational Research Institute, University of California San Diego, La Jolla, California, United States of America
| | - Nathan W. Levin
- Mount Sinai School of Medicine, Renal Research Institute, New York, New York, United States of America
| | - Andrew Lewington
- Department of Nephrology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- NIHR Leeds In Vitro Diagnostics Co-operative, Leeds, United Kingdom
| | - Raúl Lombardi
- Department of Critical Care Medicine, Servicio Médico Integral, Montevideo, Uruguay
| | - Michael V. Rocco
- Section of Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America
| | - Eliah Aronoff-Spencer
- Division of Nephrology, Department of Medicine, University of California San Diego, San Diego, California, United States of America
| | | | - Karen Yeates
- Division of Nephrology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri, Istituto di Ricovero e Cura a Carattere Scientifico, Bergamo, Italy
| | - Ravindra L. Mehta
- Division of Nephrology, Department of Medicine, University of California San Diego, San Diego, California, United States of America
- * E-mail:
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Belli M, Martin RM, Brescia MDG, Nascimento CP, Massoni Neto LM, Arap SS, Ferraz-de-Souza B, Moyses RMA, Peacock M, Montenegro FLDM. Acute and long-term kidney function after parathyroidectomy for primary hyperparathyroidism. PLoS One 2020; 15:e0244162. [PMID: 33382714 PMCID: PMC7774859 DOI: 10.1371/journal.pone.0244162] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 12/03/2020] [Indexed: 01/22/2023] Open
Abstract
Background In kidney transplant patients, parathyroidectomy is associated with an acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been extensively studied in primary hyperparathyroidism (PHPT). Methods This retrospective cohort study included 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post-parathyroidectomy and were stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up. Results A total of 391 (79.1%) patients were female, and 422 (85.4%) were non-African American. The median age was 58 years old. The median (first and third quartiles) preoperative serum creatinine, PTH and total calcium levels were 0.81 mg/dL (0.68–1.01), 154.5 pg/mL (106–238.5), and 10.9 mg/dL (10.3–11.5), respectively. The median (first and third quartiles) preoperative eGFR was 86 mL/min/1.73 m2 (65–101.3). After surgery, the median acute decrease in the eGFR was 21 mL/min/1.73 m2 (p<0.0001). Acutely, 41.1% of patients developed stage 1 AKI, 5.9% developed stage 2 AKI, and 1.8% developed stage 3 AKI. The acute eGFR decrease (%) was correlated with age and PTH, calcium and preoperative creatinine levels in univariate analysis. Multivariate analysis showed that the acute change was related to age and preoperative values of ionized calcium, phosphorus and creatinine. The change at 12 months was related to sex, preoperative creatinine and 25OHD. Permanent reduction in the eGFR occurred in 60.7% of patients after an acute episode. Conclusion There was significant acute impairment in renal function after parathyroidectomy for PHPT, and almost half of the patients met the criteria for AKI. Significant eGFR recovery was observed during the first month after surgery, but a small permanent reduction may occur. Patients treated for PHPT seemed to present with prominent renal dysfunction compared to patients who underwent thyroidectomy.
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Affiliation(s)
- Marcelo Belli
- Division of Head and Neck Surgery, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
- * E-mail:
| | - Regina Matsunaga Martin
- Divison of Endocrinology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
| | | | - Climério Pereira Nascimento
- Division of Head and Neck Surgery, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
| | - Ledo Mazzei Massoni Neto
- Division of Head and Neck Surgery, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
| | - Sergio Samir Arap
- Division of Head and Neck Surgery, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
| | - Bruno Ferraz-de-Souza
- Divison of Nephrology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
| | - Rosa Maria Affonso Moyses
- Divison of Nephrology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
| | - Munro Peacock
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Fábio Luiz de Menezes Montenegro
- Division of Head and Neck Surgery, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
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10
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Holmes J, Geen J, Williams JD, Phillips AO. Recurrent acute kidney injury: predictors and impact in a large population-based cohort. Nephrol Dial Transplant 2020; 35:1361-1369. [PMID: 31377810 DOI: 10.1093/ndt/gfz155] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 07/03/2019] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND This study examined the impact of recurrent episodes of acute kidney injury (AKI) on patient outcomes. METHODS The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients ≥18 years of age between April 2015 and September 2018. Patients were grouped according to the number of AKI episodes they experienced with each patient's first episode described as their index episode. We compared the demography and patient outcomes of those patients with a single AKI episode with those patients with multiple AKI episodes. Analysis included 153 776 AKI episodes in 111 528 patients. RESULTS Of those who experienced AKI and survived their index episode, 29.3% experienced a second episode, 9.9% a third episode and 4.0% experienced fourth or more episodes. Thirty-day mortality for those patients with multiple episodes of AKI was significantly higher than for those patients with a single episode (31.3% versus 24.9%, P < 0.001). Following a single episode, recovery to baseline renal function at 30 days was achieved in 83.6% of patients and was significantly higher than for patients who had repeated episodes (77.8%, P < 0.001). For surviving patients, non-recovery of renal function following any AKI episode was significantly associated with a higher probability of a further AKI episode (33.4% versus 41.0%, P < 0.001). Furthermore, with each episode of AKI the likelihood of a subsequent episode also increased (31.0% versus 43.2% versus 51.2% versus 51.7% following a first, second, third and fourth episode, P < 0.001 for all comparisons). CONCLUSIONS The results of this study provide an important contribution to the debate regarding the need for risk stratification for recurrent AKI. The data suggest that such a tool would be useful given the poor patient and renal outcomes associated with recurrent AKI episodes as highlighted by this study.
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Affiliation(s)
- Jennifer Holmes
- Welsh Renal Clinical Network, Cwm Taf Morgannwg University Health Board, Caerphilly, UK
| | - John Geen
- Department of Clinical Biochemistry, Cwm Taf Morgannwg University Health Board, Merthyr, UK.,Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK
| | - John D Williams
- Institute of Nephrology, Cardiff University School of Medicine, Cardiff, UK
| | - Aled O Phillips
- Institute of Nephrology, Cardiff University School of Medicine, Cardiff, UK
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11
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Long-term Outcomes of Postoperative Kidney Injury: Reply. Anesthesiology 2020; 133:1155. [PMID: 32833692 DOI: 10.1097/aln.0000000000003526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Abstract
INTRODUCTION There are little data about renal follow-up of neonates after cardiovascular surgery and no guidelines for long-term renal follow-up. Our objectives were to assess renal function follow-up practice after neonatal cardiac surgery, evaluate factors that predict follow-up serum creatinine measurements including acute kidney injury following surgery, and evaluate the estimated glomerular filtration rate during follow-up using routinely collected laboratory values. METHODS Two-centre retrospective cohort study of children 5-7 years of age with a history of neonatal cardiac surgery. Univariable and multivariable analyses were performed to determine factors associated with post-discharge creatinine measurements. Glomerular filtration rate was estimated for each creatinine using a height-independent equation. RESULTS Seventeen of 55 children (30%) did not have any creatinine measured following discharge after surgery until the end of study follow-up, which occurred at a median time of 6 years after discharge. Of the 38 children who had the kidney function checked, 15 (40%) had all of their creatinine drawn only in the context of a hospitalisation or emergency department visit. Acute kidney injury following surgery did not predict the presence of follow-up creatinine measurements. CONCLUSIONS A large proportion of neonates undergoing congenital heart repair did not have a follow-up creatinine measured in the first years following surgery. In those that did have a creatinine measured, there did not appear to be any identified pattern of follow-up. A follow-up system for children who are discharged from cardiac surgery is needed to identify children with or at risk of chronic kidney disease.
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Maiwall R, Pasupuleti SSR, Bihari C, Rastogi A, Singh PK, Naik V, Singh A, Jain P, Kumar A, Mukund A, Mathur RP, Kumar G, Sarin SK. Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study. Hepatology 2020; 71:1009-1022. [PMID: 31313333 DOI: 10.1002/hep.30859] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 07/07/2019] [Indexed: 02/06/2023]
Abstract
Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End-Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow-up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR], 1.58; 1.07-2.33), episodes of previous AKI (SHR, 1.26; 1.02-1.56), and AKI stage at enrollment (no AKI [SHR, 1] vs. stage 1 [SHR, 3.28; 1.30-8.25] vs. stage 2 [SHR, 4.33; 1.76-10.66] vs. stage 3 [SHR, 4.5; 1.59-12.73]) were identified as baseline risk factors for CKD development. On time-varying competing risk analysis, MELD (SHR, 1.01; 1.00-1.03), number of AKI episodes (SHR, 1.25; 1.15-1.37), and CysC (SHR, 1.38; 1.01-1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate (GFR) not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%. Conclusion: Almost two-thirds of patients with cirrhosis develop episodes of AKI and reduction in GFR; one-third progress to CKD, resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Vini Naik
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akanksha Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Priyanka Jain
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Awinash Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amar Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - R P Mathur
- Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Cho JS, Shim JK, Lee S, Song JW, Choi N, Lee S, Kwak YL. Chronic progression of cardiac surgery associated acute kidney injury: Intermediary role of acute kidney disease. J Thorac Cardiovasc Surg 2019; 161:681-688.e3. [PMID: 31959433 DOI: 10.1016/j.jtcvs.2019.10.101] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 10/24/2019] [Accepted: 10/25/2019] [Indexed: 10/25/2022]
Abstract
OBJECTIVE The association between acute kidney injury (AKI) and chronic kidney disease (CKD) remains elusive in cardiac surgery. We investigated the association between postoperative AKI and CKD development, emphasizing the intermediary role of acute kidney disease (AKD), in patients undergoing valvular heart surgery. METHODS We assessed the occurrence of postoperative AKI (7 days postsurgery), AKD (3 months postsurgery), and CKD (12 months postsurgery) in 1386 patients. The primary outcome was the development of AKD and CKD according to AKI occurrence. Relevant risk factors of AKI, AKD, and CKD were identified through multivariable regression analysis. RESULTS AKI occurred in 23.9% of patients with normal preoperative renal function. Even with early recovery of renal function within 3 days, AKI increased the risk of AKD (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.98-5.20, P < .001) and CKD (OR, 2.86; 95% CI, 1.68-4.86, P < .001), whereas persistent AKI further increased the risk of AKD (OR, 12.07; 95% CI, 5.56-26.21, P < .001) and CKD (OR, 10.54; 95% CI, 4.01-27.76, P < .001). We also found these relationships in patients with pre-existing renal dysfunction. Multivariable analysis identified 3-month postoperative heart failure and high right ventricular systolic pressure as independent risk factors for CKD. CONCLUSIONS Even after early recovery, postvalvular heart surgery AKI was associated with increased risk of CKD via AKD in a graded manner related to AKI severity and persistence. Postoperative cardiac dysfunction assessed 3 months postsurgery also significantly influenced CKD development, indicating a need for close follow-up of cardiac and renal function to improve patient outcomes.
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Affiliation(s)
- Jin Sun Cho
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae-Kwang Shim
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sak Lee
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong-Wook Song
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Nakcheol Choi
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sugeun Lee
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young-Lan Kwak
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Increase of endocan, a new marker for inflammation and endothelial dysfunction, in acute kidney injury. North Clin Istanb 2018; 6:124-128. [PMID: 31297477 PMCID: PMC6593909 DOI: 10.14744/nci.2018.70446] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Accepted: 04/07/2018] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE: In this study, the clinical relevance of the levels of serum endocan and 25-hydroxyvitamin D [25(OH)D] was investigated in patients with acute kidney injury (AKI). Endocan or the endothelial cell-specific molecule 1 is a soluble proteoglycan secreted by vascular endothelial cells. It plays a significant role in immunity, inflammation, and endothelial function. METHODS: A total of 39 patients with AKI (19 females, 20 males) and 38 healthy individuals (18 females, 20 males) were included in the study. The levels of serum endocan, vitamin D, and other biochemical parameters were compared between the two groups. RESULTS: In the AKI group, the values of serum creatinine, endocan, parathormone, phosphorus, and uric acid were found to be higher, and the total protein, albumin, and calcium levels were lower compared to the control group. There was no difference between the two groups in terms of the serum vitamin D, magnesium, alkaline phosphatase, and gamma-glutamyl transferase. CONCLUSION: In patients with AKI, an increased endocan level is a significant marker of inflammation and endothelial injury. In addition, these patients experience vitamin D deficiency.
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Hu Y, Liu H, Du L, Wan J, Li X. Serum Cystatin C Predicts AKI and the Prognosis of Patients in Coronary Care Unit: a Prospective, Observational Study. Kidney Blood Press Res 2017; 42:961-973. [PMID: 29179178 DOI: 10.1159/000485341] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 11/16/2017] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Acute Kidney Injury (AKI) is a serious clinical state associated with high morbidity and mortality, particularly in critical ill patients. We investigated the hypothesis that serum Cystatin C (sCysC) is a good predictor for AKI and may affect the short-term prognosis of coronary care unit (CCU) patients. METHODS In this prospective, observational study, we screened 412 adults admitted to the CCU from January 1, 2014 to June 1, 2015 at Zhongnan Hospital of Wuhan University. Serum samples were obtained at the time of admission, and sCysC was quantified through nephelometry. AKI was defined based on KDIGO-AKI criteria. After the patients' hospital discharge, the survivors in this study were followed up for up to 2 years. The primary endpoint was the incidence of AKI stratified by severity stage, while the second endpoints included 2-year mortality, rehospitalization and failure in renal recovery rates, as well as the progression of AKI to CKD. RESULTS According to the KDIGO-AKI criteria, AKI occurred in 130 (31.6%) patients. After multivariate adjustments, the highest quartile of sCysC was associated with a 9-fold increased risk of incident AKI compared with the lowest quartile. For predicting AKI, sCysC [area under the receiver operating characteristic curve (AUC=0.842)] outperformed β2-micro globulin (AUC=0.813) and the clinical model (AUC=0.777), and a cutoff of 1.255 mg/L yielded good sensitivity and specificity. After a median 19.8-month follow-up, 112 (27.2%) patients died within 2 years after admission. The sCysC independently predicted the risk of 2-year mortality [adjusted odds ratio (OR), 4.955; 95% confidence interval (95% CI), 2.853 to 8.603] and rehospitalization (OR, 3.128; 95% CI, 2.011 to 4.867), as well as renal recovery failure (OR, 3.618, 95% CI, 1.753 to 7.463). CONCLUSIONS Serum CysC is a strong predictor of AKI and the short-term prognosis of CCU patients.
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Affiliation(s)
- Yugang Hu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Huilan Liu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Liguo Du
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jing Wan
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiaoning Li
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
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Vanmassenhove J, Vanholder R, Lameire N. Points of Concern in Post Acute Kidney Injury Management. Nephron Clin Pract 2017; 138:92-103. [PMID: 29131132 DOI: 10.1159/000484146] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 10/11/2017] [Indexed: 01/16/2023] Open
Abstract
The incidence of acute kidney injury (AKI) will in the future remain high, partly due to an increase in comorbidities and other AKI favoring factors such as the rise in high-risk diagnostic and therapeutic interventions. AKI has emerged as a major public health concern with high human and financial costs. It has recently been demonstrated that patients surviving an AKI episode show increased all-cause mortality, chronic kidney disease (CKD), ESRD, cardiovascular events, and reduced quality of life. Although it is important to acknowledge that, after an AKI episode, the risk of dying by far exceeds the risk of developing incident or progressive CKD and/or entering a maintenance renal replacement therapy (RRT) program, currently only a minority of patients are referred for renal follow-up, even after AKI-requiring RRT. On the other hand, renal follow-up for all AKI survivors might not be necessary and would represent an overwhelming work load for the health care system. There are at present no clear guidelines on which patients should be referred and on the elements of post AKI care that may improve non-renal and renal outcomes. In this review, we discuss several points of concern in post-AKI management and propose an algorithm on post-AKI care, mainly based on the renal recovery pattern at discharge from the hospital. Potential opportunities to improve care include appropriate risk stratification, close monitoring of kidney function, management of CKD complications, blood pressure control, medication reconciliation, and education of patients and non-nephrologists on AKI and its downstream complications.
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Horne KL, Packington R, Monaghan J, Reilly T, Selby NM. Three-year outcomes after acute kidney injury: results of a prospective parallel group cohort study. BMJ Open 2017; 7:e015316. [PMID: 28360257 PMCID: PMC5372023 DOI: 10.1136/bmjopen-2016-015316] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVES Using a prospective study design, we aimed to characterise the effect of acute kidney injury (AKI) on long-term changes in renal function in a general hospital population. PARTICIPANTS Hospitalised patients with AKI (exposed) and hospitalised patients without AKI (non-exposed), recruited at 3 months after hospital admission. DESIGN Prospective, matched parallel group cohort study, in which renal function and proteinuria were measured at 3 months, 1 year and 3 years. SETTING Single UK centre. CLINICAL END POINTS Clinical end points at 3 years were comparison of the following variables between exposed and non-exposed groups: renal function, prevalence of proteinuria and albuminuria and chronic kidney disease (CKD) progression/development at each time point. CKD progression was defined as a decrease in the estimated glomerular filtration rate (eGFR) of ≥25% associated with a decline in eGFR stage. RESULTS 300 exposed and non-exposed patients were successfully matched 1:1 for age and baseline renal function; 70% of the exposed group had AKI stage 1. During follow-up, the AKI group had lower eGFR than non-exposed patients at each time point. At 3 years, the mean eGFR was 60.7±21 mL/min/1.73 m2 in the AKI group compared with 68.4±21 mL/min/1.73 m2 in the non-exposed group, p=0.003. CKD development or progression at 3 years occurred in 30 (24.6%) of the AKI group compared with 10 (7.5%) of the non-exposed group, p<0.001. Albuminuria was more common in the AKI group, and increased with AKI severity. Factors independently associated with CKD development/progression after AKI were non-recovery at 90 days, male gender, diabetes and recurrent AKI. CONCLUSIONS AKI is associated with deterioration in renal function to 3 years, even in an unselected population with predominantly AKI stage 1. Non-recovery from AKI is an important factor determining long-term outcome.
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Affiliation(s)
- Kerry L Horne
- Department of Renal Medicine, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK
| | - Rebecca Packington
- Department of Renal Medicine, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK
| | - John Monaghan
- Department of Chemical Pathology, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK
| | - Timothy Reilly
- Department of Informatics, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK
| | - Nicholas M Selby
- Department of Renal Medicine, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK
- Centre for Kidney Research and Innovation, School of Medicine, University of Nottingham, Nottingham, UK
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Stryckers M, Nagler EV, Van Biesen W. The Need for Accurate Risk Prediction Models for Road Mapping, Shared Decision Making and Care Planning for the Elderly with Advanced Chronic Kidney Disease. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2016; 37:33-42. [PMID: 27883315 DOI: 10.1515/prilozi-2016-0014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
As people age, chronic kidney disease becomes more common, but it rarely leads to end-stage kidney disease. When it does, the choice between dialysis and conservative care can be daunting, as much depends on life expectancy and personal expectations of medical care. Shared decision making implies adequately informing patients about their options, and facilitating deliberation of the available information, such that decisions are tailored to the individual's values and preferences. Accurate estimations of one's risk of progression to end-stage kidney disease and death with or without dialysis are essential for shared decision making to be effective. Formal risk prediction models can help, provided they are externally validated, well-calibrated and discriminative; include unambiguous and measureable variables; and come with readily applicable equations or scores. Reliable, externally validated risk prediction models for progression of chronic kidney disease to end-stage kidney disease or mortality in frail elderly with or without chronic kidney disease are scant. Within this paper, we discuss a number of promising models, highlighting both the strengths and limitations physicians should understand for using them judiciously, and emphasize the need for external validation over new development for further advancing the field.
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Urinary retinol-binding protein as a risk factor of poor prognosis in acute-on-chronic renal injury. J Nephrol 2016; 29:827-833. [DOI: 10.1007/s40620-016-0331-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 06/24/2016] [Indexed: 12/14/2022]
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Abstract
In recent times the use of larger doses of vancomycin aimed at curbing the increasing incidence of resistant strains of Staphylococcus aureus has led to a wider report of acute kidney injury (AKI). Apart from biological plausibility, causality is implied by the predictive association of AKI with larger doses, longer duration, and graded plasma concentrations of vancomycin. AKI is more likely to occur with the concurrent use of nephrotoxic agents, and in critically ill patients who are susceptible to poor renal perfusion. Although most vancomycin-induced AKI cases are mild and therefore reversible, their occurrence may be associated with greater incidence of end-stage kidney disease and higher mortality rate. The strategy for its prevention includes adequate renal perfusion and therapeutic drug monitoring in high-risk individuals. In the near future, there is feasibility of renoprotective use of antioxidative substances in the delivery of vancomycin.
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Omata M, Doke Y, Yamada C, Kawashima K, Sho R, Enomoto K, Furuya M, Inomata N. Hepatocyte Nuclear Factor-1β Induces Redifferentiation of Dedifferentiated Tubular Epithelial Cells. PLoS One 2016; 11:e0154912. [PMID: 27196561 PMCID: PMC4873210 DOI: 10.1371/journal.pone.0154912] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 04/21/2016] [Indexed: 11/19/2022] Open
Abstract
Tubular epithelial cells (TECs) can be dedifferentiated by repetitive insults, which activate scar-producing cells generated from interstitial cells such as fibroblasts, leading to the accumulation and deposition of extracellular matrix molecules. The dedifferentiated TECs play a crucial role in the development of renal fibrosis. Therefore, renal fibrosis may be attenuated if dedifferentiated TECs are converted back to their normal state (re-epithelialization). However, the mechanism underlying the re-epithelialization remains to be elucidated. In the present study, TGF-β1, a profibrotic cytokine, induced dedifferentiation of cultured TECs, and the dedifferentiated TECs were re-epithelialized by the removal of TGF-β1 stimulation. In the re-epithelialization process, transcription factor hepatocyte nuclear factor 1, beta (HNF-1β) was identified as a candidate molecule involved in inducing re-epithelialization by means of DNA microarray and biological network analysis. In functional validation studies, the re-epithelialization by TGF-β1 removal was abolished by HNF-1β knockdown. Furthermore, the ectopic expression of HNF-1β in the dedifferentiated TECs induced the re-epithelialization without the inhibition of TGF-β/Smad signaling, even in the presence of TGF-β1 stimulation. In mouse renal fibrosis model, unilateral ureteral obstruction model, HNF-1β expression in the TECs of the kidney was suppressed with fibrosis progression. Furthermore, the HNF-1β downregulated TECs resulted in dedifferentiation, which was characterized by expression of nestin. In conclusion, HNF-1β suppression in TECs is a crucial event for the dedifferentiation of TECs, and the upregulation of HNF-1β in TECs has a potential to restore the dedifferentiated TECs into their normal state, leading to the attenuation of renal fibrosis.
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Abstract
Alpha-Klotho (αKlotho) protein is encoded by the gene, Klotho, and functions as a coreceptor for endocrine fibroblast growth factor-23. The extracellular domain of αKlotho is cleaved by secretases and released into the circulation where it is called soluble αKlotho. Soluble αKlotho in the circulation starts to decline in chronic kidney disease (CKD) stage 2 and urinary αKlotho in even earlier CKD stage 1. Therefore soluble αKlotho is an early and sensitive marker of decline in kidney function. Preclinical data from numerous animal experiments support αKlotho deficiency as a pathogenic factor for CKD progression and extrarenal CKD complications including cardiac and vascular disease, hyperparathyroidism, and disturbed mineral metabolism. αKlotho deficiency induces cell senescence and renders cells susceptible to apoptosis induced by a variety of cellular insults including oxidative stress. αKlotho deficiency also leads to defective autophagy and angiogenesis and promotes fibrosis in the kidney and heart. Most importantly, prevention of αKlotho decline, upregulation of endogenous αKlotho production, or direct supplementation of soluble αKlotho are all associated with attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiac function and morphometry, and alleviation of vascular calcification in CKD. Therefore in rodents, αKlotho is not only a diagnostic and prognostic marker for CKD but the enhancement of endogenous or supplement of exogenous αKlotho are promising therapeutic strategies to prevent, retard, and decrease the comorbidity burden of CKD.
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Affiliation(s)
- J A Neyra
- University of Texas Southwestern Medical Center, Dallas, TX, United States; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - M C Hu
- University of Texas Southwestern Medical Center, Dallas, TX, United States; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, United States.
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Thomas B, Wulf S, Bikbov B, Perico N, Cortinovis M, Courville de Vaccaro K, Flaxman A, Peterson H, Delossantos A, Haring D, Mehrotra R, Himmelfarb J, Remuzzi G, Murray C, Naghavi M. Maintenance Dialysis throughout the World in Years 1990 and 2010. J Am Soc Nephrol 2015. [PMID: 26209712 DOI: 10.1681/asn.2014101017] [Citation(s) in RCA: 136] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Rapidly rising global rates of chronic diseases portend a consequent rise in ESRD. Despite this, kidney disease is not included in the list of noncommunicable diseases (NCDs) targeted by the United Nations for 25% reduction by year 2025. In an effort to accurately report the trajectory and pattern of global growth of maintenance dialysis, we present the change in prevalence and incidence from 1990 to 2010. Data were extracted from the Global Burden of Disease 2010 epidemiologic database. The results are on the basis of an analysis of data from worldwide national and regional renal disease registries and detailed systematic literature review for years 1980-2010. Incidence and prevalence estimates of provision of maintenance dialysis from this database were updated using a negative binomial Bayesian meta-regression tool for 187 countries. Results indicate substantial growth in utilization of maintenance dialysis in almost all world regions. Changes in population structure, changes in aging, and the worldwide increase in diabetes mellitus and hypertension explain a significant portion, but not all, of the increase because increased dialysis provision also accounts for a portion of the rise. These findings argue for the importance of inclusion of kidney disease among NCD targets for reducing premature death throughout the world.
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Affiliation(s)
- Bernadette Thomas
- Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, Washington; Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington;
| | - Sarah Wulf
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington
| | - Boris Bikbov
- Nephrology, A. I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russian Federation; Department of Nephrology Issues of Transplanted Kidney, Academician V. I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; Moscow City Nephrology Center, Moscow City Hospital 52, Moscow, Russian Federation
| | - Norberto Perico
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCC), Mario Negri Institute for Pharmacological Research, Bergamo, Italy
| | - Monica Cortinovis
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCC), Mario Negri Institute for Pharmacological Research, Bergamo, Italy
| | | | - Abraham Flaxman
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington
| | - Hannah Peterson
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington
| | - Allyne Delossantos
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington
| | - Diana Haring
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington
| | - Rajnish Mehrotra
- Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, Washington
| | - Jonathan Himmelfarb
- Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, Washington
| | - Giuseppe Remuzzi
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCC), Mario Negri Institute for Pharmacological Research, Bergamo, Italy; Unit of Nephrology, Dialysis and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - Christopher Murray
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington
| | - Mohsen Naghavi
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington
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Vanholder R, Lameire N, Annemans L, Van Biesen W. Cost of renal replacement: how to help as many as possible while keeping expenses reasonable? Nephrol Dial Transplant 2015; 31:1251-61. [PMID: 26109485 DOI: 10.1093/ndt/gfv233] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Accepted: 05/12/2015] [Indexed: 02/06/2023] Open
Abstract
The treatment of kidney diseases consumes a substantial amount of the health budget for a relatively small fraction of the overall population. If the nephrological community and society do not develop mechanisms to contain those costs, it will become impossible to continue assuring optimal outcomes and quality of life while treating all patients who need it. In this article, we describe several mechanisms to maintain sustainability of renal replacement therapy. These include (i) encouragement of transplantation after both living and deceased donation; (ii) stimulation of alternative dialysis strategies besides classical hospital haemodialysis, such as home haemodialysis, peritoneal dialysis or self-care and necessitating less reimbursement; (iii) promotion of educational activities guiding the patients towards therapies that are most suited for them; (iv) consideration of one or more of cost containment incentives such as bundling of reimbursement (if not affecting quality of the treatment), timely patient referral, green dialysis, start of dialysis based on clinical necessity rather than renal function parameters and/or prevention of CKD or its progression; (v) strategically planned adaptations to the expected growth of the ageing population in need of renal replacement; (vi) the necessity for support of research in the direction of helping as large as possible patient populations for acceptable costs; and (vii) the need for more patient-centred approaches. We also extend the discussion to the specific situation of kidney diseases in low- and middle-income countries. Finally, we point to the dramatic differences in accessibility and reimbursement of different modalities throughout Europe. We hope that this text will offer a framework for the nephrological community, including patients and nurses, and the concerned policy makers and caregivers on how to continue reaching all patients in need of renal replacement for affordable expenses.
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Affiliation(s)
- Raymond Vanholder
- Nephrology Section, Department of Internal Medicine, University Hospital Ghent, Ghent, Belgium
| | - Norbert Lameire
- Nephrology Section, Department of Internal Medicine, University Hospital Ghent, Ghent, Belgium
| | - Lieven Annemans
- Department of Public Health, University Ghent, Ghent, Belgium
| | - Wim Van Biesen
- Nephrology Section, Department of Internal Medicine, University Hospital Ghent, Ghent, Belgium
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