Faculty Opinions recommendation of Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury.

Abstract Background The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high. Nevertheless, data are lacking about the determinants of acute kidney injury (AKI) and the combined effect of chronic kidney disease (CKD) and AKI in COVID-19 patients. Methods We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution. Chronic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or proteinuria at urinalysis within 180 days prior to hospital admission. AKI was defined according to KDIGO criteria. The primary and secondary outcomes were the development of AKI and death. Results Of 777 patients eligible for the study, acute kidney injury developed in 176 (22.6%). Of these, 79 (45%) showed an acute worsening of a preexisting CKD, and 21 (12%) required kidney replacement therapy. Independent associates of AKI were chronic kidney disease, C-reactive protein (CRP) and ventilation support. Among patients with acute kidney injury, 111 died (63%) and its occurrence increased the risk of death by 60% (HR 1.60 [95% IC 1.21–2.49] p = 0.002) independently of potential confounding factors including hypertension, preexisting kidney damage, and comorbidities. Patients with AKI showed a significantly higher rate of deaths attributed to bleeding compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively). Conclusion Awareness of kidney function, both preexisting CKD and development of acute kidney injury, may help to identify those patients at increased risk of death.

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Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

Nature Reviews Nephrology ◽

10.1038/s41581-021-00418-2 ◽

2021 ◽

Author(s):

John R. Prowle ◽

Lui G. Forni ◽

Max Bell ◽

Michelle S. Chew ◽

Mark Edwards ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Kidney Disease ◽

Kidney Injury ◽

Adverse Outcomes ◽

Baseline Risk ◽

Major Surgery ◽

Increased Risk

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

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Developing better mouse models to study cisplatin-induced kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00285.2017 ◽

2017 ◽

Vol 313 (4) ◽

pp. F835-F841 ◽

Cited By ~ 36

Author(s):

Cierra N. Sharp ◽

Leah J. Siskind

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Kidney Injury ◽

Therapeutic Interventions ◽

Low Doses ◽

Dosing Regimen ◽

Risk Of Mortality ◽

Increased Risk ◽

Novel Therapeutic

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury.

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Acute Kidney Injury in Patients Receiving Systemic Treatment for Cancer: A Population-Based Cohort Study

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djy167 ◽

2018 ◽

Vol 111 (7) ◽

pp. 727-736 ◽

Cited By ~ 13

Author(s):

Abhijat Kitchlu ◽

Eric McArthur ◽

Eitan Amir ◽

Christopher M Booth ◽

Rinku Sutradhar ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Angiotensin Converting Enzyme ◽

Systemic Therapy ◽

Kidney Injury ◽

Population Based ◽

Converting Enzyme ◽

Angiotensin Receptor ◽

Increased Risk

Abstract Background Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment. Methods We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007–2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence. Results We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014. Conclusion Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population.

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ACUTE KIDNEY INJURY FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT IS ASSOCIATED WITH AN INCREASED RISK OF CHRONIC KIDNEY DISEASE AT 1 YEAR

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(14)61742-3 ◽

2014 ◽

Vol 63 (12) ◽

pp. A1739 ◽

Cited By ~ 1

Author(s):

Justin Fried ◽

Ben Lerman ◽

Ming Liao ◽

Jacob Kriegel ◽

Eelin Wilson ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Aortic Valve ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Transcatheter Aortic Valve Replacement ◽

Kidney Injury ◽

Transcatheter Aortic Valve ◽

Increased Risk

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Genetic deficiency of Smad3 protects against murine ischemic acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00162.2011 ◽

2011 ◽

Vol 301 (2) ◽

pp. F436-F442 ◽

Cited By ~ 26

Author(s):

Karl A. Nath ◽

Anthony J. Croatt ◽

Gina M. Warner ◽

Joseph P. Grande

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Kidney Injury ◽

Acute Ischemia ◽

Heme Oxygenase 1 ◽

Increased Risk ◽

Genetic Deficiency ◽

Ischemic Acute Kidney Injury ◽

Tgf Β1

TGF-β1 contributes to chronic kidney disease, at least in part, via Smad3. TGF-β1 is induced in the kidney following acute ischemia, and there is increasing evidence that TGF-β1 may protect against acute kidney injury. As there is a paucity of information regarding the functional significance of Smad3 in acute kidney injury, the present study explored this issue in a murine model of ischemic acute kidney injury in Smad3+/+ and Smad3−/− mice. We demonstrate that, at 24 h after ischemia, Smad3 is significantly induced in Smad3+/+ mice, whereas Smad3−/− mice fail to express this protein in the kidney in either the sham or postischemic groups. Compared with Smad3+/+ mice, and 24 h following ischemia, Smad3−/− mice exhibited greater preservation of renal function as measured by blood urea nitrogen (BUN) and serum creatinine; less histological injury assessed by both semiquantitative and qualitative analyses; markedly suppressed renal expression of IL-6 and endothelin-1 mRNA (but comparable expression of MCP-1, TNF-α, and heme oxygenase-1 mRNA); and no increase in plasma IL-6 levels, the latter increasing approximately sixfold in postischemic Smad3+/+ mice. We conclude that genetic deficiency of Smad3 confers structural and functional protection against acute ischemic injury to the kidney. We speculate that these effects may be mediated through suppression of IL-6 production. Finally, we suggest that upregulation of Smad3 after an ischemic insult may contribute to the increased risk for chronic kidney disease that occurs after acute renal ischemia.

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Toll-Like Receptors in Acute Kidney Injury

International Journal of Molecular Sciences ◽

10.3390/ijms22020816 ◽

2021 ◽

Vol 22 (2) ◽

pp. 816

Author(s):

Cristina Vázquez-Carballo ◽

Melania Guerrero-Hue ◽

Cristina García-Caballero ◽

Sandra Rayego-Mateos ◽

Lucas Opazo-Ríos ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Pathological Condition ◽

Kidney Injury ◽

Preclinical Studies ◽

Toll Like Receptors ◽

Middle Income ◽

Increased Risk

Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

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Does Intragastric Balloon Treatment for Obesity in Chronic Kidney Disease Heighten Acute Kidney Injury Risk?

American Journal of Nephrology ◽

10.1159/000450765 ◽

2016 ◽

Vol 44 (6) ◽

pp. 411-418 ◽

Cited By ~ 3

Author(s):

Helen L. MacLaughlin ◽

Iain C. Macdougall ◽

Wendy L. Hall ◽

Tracy Dew ◽

Konstantinos Mantzoukis ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Weight Loss ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Body Mass ◽

Intragastric Balloon ◽

Gastrointestinal Symptoms ◽

Kidney Injury ◽

Obese Patients ◽

Increased Risk

Background: The outcomes of intragastric balloon (IGB) placement to achieve weight loss in obese patients with chronic kidney disease (CKD) have not been reported to date. This study aimed to assess the safety and efficacy of the IGB as a weight-loss treatment among this patient population. Methods: A prospective, single-arm, ‘first in CKD' interventional study was conducted in patients with a body mass index >35 kg/m2 and CKD stages 3-4, referred for weight loss. After clinical assessment, the IGB was endoscopically inserted into the stomach and kept in place for 6 months. Complications, adverse events, acceptability, weight loss and metabolic responses were monitored over 6 months. Results: Eleven participants were recruited over 18 months. Two patients withdrew (1 prior to IGB insertion and 1 early removal after 3 days due to persistent vomiting) from the study; 9 patients completed the study. There were 5 episodes of acute kidney injury (AKI), occurring in 3 patients. After 6 months, the mean body mass decreased by 9.6% (SD ±6.8). Median waist circumference and total cholesterol decreased significantly (-7.7 cm; interquartile range (IQR) -15.3 to -3.9; and -0.2 mmol/l; IQR -0.6 to -0.05, respectively), with no changes in estimated glomerular filtration rate, blood pressure, triglycerides, adipokines, inflammation, or arterial stiffness measured by carotid-femoral pulse wave velocity. At IGB removal, there was 1 new case each of gastritis and esophagitis. Conclusions: Treatment with IGB has only moderate efficacy on weight loss; yet it results in a high rate of complications in obese patients with established CKD. The risk of AKI may be raised due to increased risk of dehydration secondary to gastrointestinal symptoms associated with IGB placement and reduced baseline kidney function.

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