Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery

Husain‐Syed, Faeq; Ferrari, Fiorenza; Sharma, Aashish; Danesi, Tommaso Hinna; Bezerra, Pércia; López-Giacoman, Salvador; Samoni, Sara; Cal, Massimo de; Corradi, Valentina; Virzì, Grazia Maria; Rosa, Silvia De; Bermejo, M.; Estremadoyro, Carla; Villa, Gianluca; Zaragoza, José J.; Caprara, Carlotta; Brocca, Alessandra; Birk, Horst‐Walter; Walmrath, Hans‐Dieter; Seeger, Werner; Nalesso, Federico; Zanella, Monica; Brendolan, Alessandra; Giavarina, Davide; Salvador, Loris; Bellomo, Rinaldo; Rosner, Mitchell H.; Kellum, John A.; Ronco, Claudio

doi:10.1093/ndt/gfy227

Cited by 64 publications

(47 citation statements)

References 37 publications

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“…Our results show a positive treatment impact on sepsis survival with delayed administration of UPHD186, together with increased indicators of tissue proliferation and reduced fibrosis. Interestingly, serum creatinine and cytokines were insensitive to these pathological features-consistent with clinical observations [6,7]. Maladaptive repair and fibrosis are important mechanisms leading to CKD, apparently across AKI syndromes.…”

Section: Discussionsupporting

confidence: 77%

“…Often, this relationship is obvious-CKD results when renal function remains low following an AKI episode. However, more complicated patterns of recovery following AKI have been reported [7] and concerns have been raised that renal functional recovery may belie ongoing insidious injury or progression [6]. Thus, AKI may develop into CKD, even in the cases where there is an appearance of renal recovery measured by conventional renal indicators.…”

Section: Discussionmentioning

confidence: 99%

“…These deficiencies are compounded by the fact that patients often present with S-AKI after the injury has already occurred [3], and the development of maladaptive repair is often insidious. However, when renal recovery does occur, survival is dramatically enhanced [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Time-dependent effects of histone deacetylase inhibition in sepsis-associated acute kidney injury

Wen

Frank

et al. 2020

ICMx

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Background: Sepsis, a dysregulated host response to infection with results in organ dysfunction, has been a major challenge to the development of effective therapeutics. Sepsis-associated acute kidney injury (S-AKI) results in a 3-5-fold increase in the risk of hospital mortality compared to sepsis alone. The development of therapies to reverse S-AKI could therefore significantly affect sepsis outcomes. However, the translation of therapies from preclinical studies into humans requires model systems that recapitulate clinical scenarios and the development of renal fibrosis indicative of the transition from acute to chronic kidney disease. Results: Here we characterized a murine model of S-AKI induced by abdominal sepsis developing into a chronic phenotype. We applied a small molecule histone deacetylase-8 inhibitor, UPHD186, and found that early treatment, beginning at 48 h post-sepsis, worsened renal outcome accompanied by decreasing mononuclear cell infiltration in the kidney, skewing cells into a pro-inflammatory phenotype, and increased pro-fibrotic gene expression, while delayed treatment, beginning at 96 h post-sepsis, after the acute inflammation in the kidney had subsided, resulted in improved survival and kidney histology presumably through promoting proliferation and inhibiting fibrosis. Conclusions: These findings not only present a clinically relevant S-AKI model, but also introduce a timing dimension into S-AKI therapeutic interventions that delayed treatment with UPHD186 may enhance renal histologic repair. Our results provide novel insights into successful repair of kidney injury and sepsis therapy.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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Time-dependent effects of histone deacetylase inhibition in sepsis-associated acute kidney injury

Wen

Frank

et al. 2020

ICMx

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“…4 To overcome this problem, it would be necessary to identify a marker able to detect a renal damage even in the absence of GFR alterations, discovering episodes of sub-clinical AKI 5 compensated by the renal functional reserve that can be lost after a pathological noxa, as heart surgery. 6 In this point of view, in the last years, several studies focused on the identification of new biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL18), liver-type fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinases-2 (TIMP-2), and insulin-like growth factorbinding protein 7 (IGFBP-7). 7,8 In this spectrum of new markers, urinary insulin-like growth factor-binding protein (IGFBP-7) and tissue inhibitor of metalloproteinase (TIMP-2) have been proven as the best-performing.…”

Section: Introductionmentioning

confidence: 99%

<p>Evaluating Nephrocheck<sup>®</sup> as a Predictive Tool for Acute Kidney Injury</p>

Nalesso¹,

Cattarin²,

Gobbi³

et al. 2020

IJNRD

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Acute kidney injury (AKI) is a common complication in critically ill patients in the intensive settings with increased risks of short-and long-term complications and mortality. AKI is also associated with an increased length of stay in intensive care units (ICU) and worse kidney function recovery at hospital discharge. The management of AKI is one of the major challenges for nephrologists and intensivists overall for its early diagnosis. The current KDIGO criteria used to define AKI include the serum creatinine and urinary output that are neither sensitive nor specific markers of kidney function, since they can be altered only after hours from the kidney injury. In order to allow an early AKI detection, in the last years, several studies focused on the identification of new biomarkers. Among all these markers, urinary insulin-like growth factor-binding protein (IGFBP-7) and tissue inhibitor of metalloproteinase (TIMP-2) have been proven as the best-performing and have been proposed as a predictive tool for the AKI detection in the critical settings in order to perform an early diagnosis. Patients undergoing major surgery, cardiac surgery, those with hemodynamic instability or those with sepsis are believed to be the top priority patient populations for the biomarker test. In this view, the urinary [TIMP-2] x [IGFBP-7] becomes an important tool for the early detection of patients at high risk for AKI and its integration with the local ICU experience has to provide a multidisciplinary management of AKI with the institution of a rapid response team in order to assess patients and customize AKI management.

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“…The NC urinary biomarker appears to be more of a kidney ''stress'' indicator, although recent evidence has suggested that patients with NC elevations have some evidence of long-term decrease in renal functional reserve (the normal increase in glomerular filtration rate after a protein load). 4 Just as importantly, this test had a 100% negative predictive value, as none of those patients with a negative NC went on to develop significant AKI postoperatively.…”

mentioning

confidence: 96%

Commentary: Looking to prevent acute kidney injury after cardiac surgery? Just check the urine

Engelman

Germain

2019

The Journal of Thoracic and Cardiovascular Surgery

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Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery

Cited by 64 publications

References 37 publications

Time-dependent effects of histone deacetylase inhibition in sepsis-associated acute kidney injury

Time-dependent effects of histone deacetylase inhibition in sepsis-associated acute kidney injury

<p>Evaluating Nephrocheck<sup>®</sup> as a Predictive Tool for Acute Kidney Injury</p>

Commentary: Looking to prevent acute kidney injury after cardiac surgery? Just check the urine

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