Pathophysiology of Acute Kidney Injury

2017 ◽  
Author(s):  
Shalini Bumb ◽  
Andrew Malone ◽  
Matthew A. Sparks

Acute kidney injury (AKI) is defined as the abrupt loss of kidney excretory function with the accumulation of nitrogenous waste products and fluid overload. The etiologies of AKI are numerous and can largely be classified as prerenal, intrinsic, or postrenal. Complex pathways involving inflammatory mediators, vascular compromise, and direct cellular injury are triggered, and equally as complex pathways, including autophagy and fibrosis, are involved in the recovery. Prerenal azotemia is caused by a reduction in tissue perfusion with resulting AKI. Although acute tubular necrosis is the most common intrinsic etiology, other nephrotoxins and exposures can result in intrinsic injury as well. Postrenal AKI is due to obstruction of urinary flow. Herein, in further detail, the mechanisms, pathophysiology, and manifestations of these causes of AKI are discussed. Research into the mechanisms and development of markers and techniques to advance clinical practice is ongoing.

2020 ◽  
pp. 4807-4829
Author(s):  
John D. Firth

Definition—for practical clinical purposes, acute kidney injury (AKI) is defined as a significant decline in renal excretory function occurring over hours or days, detected by either a fall in urinary output or a rise in the serum concentration of creatinine. Oliguria—defined (arbitrarily) as a urinary volume of less than 400 ml/day—is usually present, but not always. Clinical approach: diagnosis—all patients admitted to hospital with acute illness, but particularly older people and those with pre-existing chronic kidney disease, should be considered at risk of developing AKI. The most common precipitant is volume depletion. Serum creatinine and electrolytes should be measured on admission in all acutely ill patients, and repeated daily or on alternate days in those who remain so. Assessment—after treatment of life-threatening complications, the initial assessment of a patient who appears to have AKI must answer three questions: (1) is the kidney injury really acute? (2) Is urinary obstruction a possibility? And (3) is there a renal inflammatory cause? General aspects of management—the immediate management of a patient with renal impairment is directed towards three goals: (1) recognition and treatment of any life-threatening complications of AKI, (2) prompt diagnosis and treatment of hypovolaemia, and (3) specific treatment of the underlying condition—if this persists untreated then renal function will not improve. Specific causes of acute kidney injury—there are many possible causes of AKI, but in any given clinical context few of these are likely to require consideration. By far the most frequent are prerenal failure and acute tubular necrosis, which together account for 80 to 90% of cases of AKI seen by physicians.


2015 ◽  
Vol 122 (1) ◽  
pp. 72-86 ◽  
Author(s):  
Chenfang Luo ◽  
Dongdong Yuan ◽  
Xiaoyun Li ◽  
Weifeng Yao ◽  
Gangjian Luo ◽  
...  

Abstract Background: Postliver transplantation acute kidney injury (AKI) severely affects patient survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion induced enhancement of connexin32 (Cx32) gap junction plays a critical role in mediating postliver transplantation AKI and that pretreatment/precondition with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. Methods: Male Sprague–Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx32 inhibitor, 2-aminoethoxydiphenyl borate or propofol (50 mg/kg) (n = 8 per group). Also, kidney tubular epithelial (NRK-52E) cells were subjected to hypoxia–reoxygenation and the function of Cx32 was manipulated by three distinct mechanisms: cell culture in different density; pretreatment with Cx32 inhibitors or enhancer; Cx32 gene knock-down (n = 4 to 5). Results: AOLT resulted in significant increases of renal Cx32 protein expression and gap junction, which were coincident with increases in oxidative stress and impairment in renal function and tissue injury as compared to sham group. Similarly, hypoxia–reoxygenation resulted in significant cellular injury manifested as reduced cell growth and increased lactate dehydrogenase release, which was significantly attenuated by Cx32 gene knock-down but exacerbated by Cx32 enhancement. Propofol inhibited Cx32 function and attenuated post-AOLT AKI. In NRK-52E cells, propofol reduced posthypoxic reactive oxygen species production and attenuated cellular injury, and the cellular protective effects of propofol were reinforced by Cx32 inhibition but cancelled by Cx32 enhancement. Conclusion: Cx32 plays a critical role in AOLT-induced AKI and that inhibition of Cx32 function may represent a new and major mechanism whereby propofol reduces oxidative stress and subsequently attenuates post-AOLT AKI.


2019 ◽  
Vol 9 (1) ◽  
pp. 42-48
Author(s):  
Ali Ayaash ◽  
Dipesh Maan ◽  
Anastasios Kapetanos ◽  
Mark Bunker ◽  
Mary Chester Wasko ◽  
...  

Crescentic glomerulonephritis (GN) without immune reactants or deposits (referred to as pauci-immune) is typically characterized by the presence of anti-neutrophilic cytoplasmic antibodies (ANCA). While ANCA-negative patients might be expected to have a more benign course, they often have poor renal outcomes, especially without treatment with steroids and immune-modulating therapy. Pauci-immune crescentic GN can also co-exist with other autoimmune conditions, including rheumatoid arthritis (RA). Here, we describe an ANCA-negative patient with RA who developed dialysis-requiring acute kidney injury (AKI) with findings consistent with focal pauci-immune crescentic GN (i.e., no IgG or immune complex on kidney biopsy). Coexistent conditions included Klebsiella sepsis attributed to pneumonia, rhabdomyolysis, leukocytoclastic immune-mediated skin vasculitis, and positive ANA. He had spontaneous improvement in renal function without immunosuppressive therapy. This crescentic GN was not associated with poor renal outcome as AKI resolved with supportive care and treatment of his infection. The AKI was likely multifactorial with co-existing acute tubular necrosis in the setting of Kebsiella sepsis and rhabdomyolysis, and the crescentic GN was felt more likely to be related to the infection rather than having a primary role. This case highlights the importance of viewing crescentic GN in the context of the clinical picture, as it may not always lead to the need of aggressive immune suppression and is not a universally poor prognostic kidney finding. However, these cases do warrant close follow-up as our patient had recurrent RA disease manifestations over the next 2 years that eventually led to his death from severe pulmonary hypertension.


2020 ◽  
Vol 58 (228) ◽  
Author(s):  
Pukar Thapa ◽  
Sudhamshu KC ◽  
Achyut Bikram Hamal ◽  
Dilip Sharma ◽  
Sandip Khadka ◽  
...  

Introduction: Acute kidney injury is a common and life-threatening event in patients with liver cirrhosis occurring in approximately 20-50% of hospitalized patients of liver cirrhosis. Pre-renal acute kidney injury, the hepatorenal syndrome type of acute kidney injury and acute tubular necrosis represent the common causes. The aim of this study was to study the profile of acute kidney injury in patients with liver cirrhosis. Methods: Consecutive patients of liver cirrhosis admitted in Liver unit of Bir Hospital were studied to see the presence of acute kidney injury in this hospital based descriptive cross-sectional study. Clinical and laboratory parameters along with various clinical outcome were compared between different groups categorized by the severity of liver disease and renal dysfunction. Results: Out of 302 liver cirrhosis patients, 56 (18.5%) had acute kidney injury among which 23 (46%) were found to have pre-renal acute kidney injury, 15 (30%) with hepatorenal syndrome– acute kidney injury and 12 (24%) with intrinsic renal disease. Patients with higher stages of acute kidney injury had longer duration of hospital stay and hepatorenal syndrome-acute kidney injury was seen in patients with higher grade of ascites and with hyponatremia. Conclusions: Acute kidney injury is a common occurrence in patients with advanced liver cirrhosis with pre-renal acute kidney injury being the commonest cause. Median hospital stay is directly affected by the severity of acute kidney injury and hepatorenal syndrome–acute kidney injury was seen in patients with higher grade of ascites and hyponatremia. Early identification of patients at high risk for acute kidney injury may help to reduce mortality and contain costs.  


2021 ◽  
Author(s):  
Arshpal Gill ◽  
Ra’ed Nassar ◽  
Ruby Sangha ◽  
Mohammed Abureesh ◽  
Dhineshreddy Gurala ◽  
...  

Hepatorenal Syndrome (HRS) is an important condition for clinicians to be aware of in the presence of cirrhosis. In simple terms, HRS is defined as a relative rise in creatinine and relative drop in serum glomerular filtration rate (GFR) alongside renal plasma flow (RPF) in the absence of other competing etiologies of acute kidney injury (AKI) in patients with hepatic cirrhosis. It represents the end stage complication of decompensated cirrhosis in the presence of severe portal hypertension, in the absence of prerenal azotemia, acute tubular necrosis or others. It is a diagnosis of exclusion. The recognition of HRS is of paramount importance for clinicians as it carries a high mortality rate and is an indication for transplantation. Recent advances in understanding the pathophysiology of the disease improved treatment approaches, but the overall prognosis remains poor, with Type I HRS having an average survival under 2 weeks. Generally speaking, AKI and renal failure in cirrhotic patients carry a very high mortality rate, with up to 60% mortality rate for patients with renal failure and cirrhosis and 86.6% of overall mortality rates of patients admitted to the intensive care unit. Of the various etiologies of renal failure in cirrhosis, HRS carries a poor prognosis among cirrhotic patients with acute kidney injury. HRS continues to pose a diagnostic challenge. AKI can be either pre-renal, intrarenal or postrenal. Prerenal causes include hypovolemia, infection, use of vasodilators and functional due to decreased blood flow to the kidney, intra-renal such as glomerulopathy, acute tubular necrosis and post-renal such as obstruction. Patients with cirrhosis are susceptible to developing renal impairment. HRS may be classified as Type 1 or rapidly progressive disease, and Type 2 or slowly progressive disease. There are other types of HRS, but this chapter will focus on Type 1 HRS and Type 2 HRS. HRS is considered a functional etiology of acute kidney injury as there is an apparent lack of nephrological parenchymal damage. It is one several possibilities for acute kidney injury in patients with both acute and chronic liver disease. Acute kidney injury (AKI) is one of the most severe complications that could occur with cirrhosis. Up to 50% of hospitalized patients with cirrhosis can suffer from acute kidney injury, and as mentioned earlier an AKI in the presence of cirrhosis in a hospitalized patient has been associated with nearly a 3.5-fold increase in mortality. The definition of HRS will be discussed in this chapter, but it is characterized specifically as a form of acute kidney injury that occurs in patients with advanced liver cirrhosis which results in a reduction in renal blood flow, unresponsive to fluids this occurs in the setting of portal hypertension and splanchnic vasodilation. This chapter will discuss the incidence of HRS, recognizing HRS, focusing mainly on HRS Type I and Type II, recognizing competing etiologies of renal impairment in cirrhotic patients, and the management HRS.


2020 ◽  
Vol 10 (4) ◽  
pp. 30471.1-30471.9
Author(s):  
Roghayeh Rashidi ◽  

Background: Acute Kidney Injury (AKI) is an abrupt decrease in kidney function, leading to the retention of urea and other nitrogenous waste products. Poisoned patients admitted to the Intensive Care Unit (ICU) may develop AKI due to some reasons. This study was done to evaluate the AKI in poisoned patients admitted to ICU. Methods: 146 patients, admitted to the ICU of Imam Reza Hospital from March 2017 to March 2018 were studied. AKI status was assessed using Acute Kidney Injury Network (AKIN) and Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) classification. Data analysis was done through SPSS V. 22 software. Results: Opioids, organophosphates, aluminum phosphide, multiple drugs, and other types of poisoning were the main five poisoning classes. Opioid toxicity was had the highest frequency with 51 patients; cases in this group experienced longer length of hospitalization stay and higher serum creatinine level than others did. Among 146 patients, 19 patients (12.8%) died, and 97 patients (66%) were transferred to the ICU. Of all cases, 18 patients (12.3%) had renal dysfunction (six patients were at risk, five patient at injury, and seven patients were at failure phase based on the RIFLE criteria). Renal replacement therapy was required in 24 cases (16.4%). Conclusion: It is unlikely to detect a significant difference in the occurrence of AKI between the main poisoning classes. Being the largest group of intoxicated patients admitted to the ICU, the opioid poisoning had the highest rate of AKI


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew S. Allegretti ◽  
Guillermo Ortiz ◽  
Julia Wenger ◽  
Joseph J. Deferio ◽  
Joshua Wibecan ◽  
...  

Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality.Methods. Prospective cohort study at a major US liver transplant center. A nephrologist’s review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other.Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35%) with prerenal azotemia, 20/35 (57%) with hepatorenal syndrome, 21/36 (58%) with acute tubular necrosis, and 1/9 (11%) with other (p=0.04overall). Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (p=0.99). Mortality was lower in prerenal azotemia compared to hepatorenal syndrome (p=0.05) and acute tubular necrosis (p=0.04). Ten participants (22%) were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment.Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management.


2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e96-e97
Author(s):  
Nikoo Niknafs

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Infants undergoing abdominal surgery, particularly those born preterm, are at risk of postoperative fluid overload and acute kidney injury due to immature cardiac and renal functions, which could contribute to increased morbidity and mortality. Objectives The purpose of this study was to evaluate the burden of fluid overload and acute kidney injury among newborns undergoing abdominal surgery and the association with adverse neonatal outcomes. Design/Methods Newborns who had undergone laparotomy from January 2017 to June 2019 admitted to a tertiary level Neonatal Intensive Care Unit were included in this retrospective cohort study. Fluid overload was assessed by the maximum percentage change in body weight and the difference between actual and prescribed fluid intake post-operatively. Acute kidney injury was defined as an increase in serum creatinine >1.5 times of baseline or >26 mmol/L, or oliguria (< 0 .5mL/kg/hr over 24-hour). Results There were 60 eligible infants with medians [IQR] gestational age (GA) and birth weight being 29 weeks [25–36] and 1240 grams [721–2871], respectively. Indications for laparotomy included small bowel obstruction (45%), necrotizing enterocolitis (23%), and large bowel obstruction (11.7%). In the first three post-operative days, 24/60 (40%) required inotropes, 5/59 (8.5%) had hyponatremia (<130 mmol/L), and 15/31(48.4%) developed hypoalbuminemia (<20 g/L). 52/60 (86.7%) infants had serum creatinine measured and 4 (6.7%) fulfilled our AKI criteria. The median of actual fluid intake was significantly higher than the prescribed fluid intake in the first 7 post-operative days (p<0.01) [Figure 1]. Medians [IQR] of maximum % change of body weight within the first 3- and 7-days post operation were 6 [3–13] and 11 [5 –17], respectively. While we did not identify any associations between post-operative fluid overload and mortality/bronchopulmonary dysplasia in this cohort, we found that every 1% increase in weight gain within the first 3 days post-operation were associated with an increase in 0.6 day of invasive ventilator support (p=0.012) [Figure 2]. Such correlation still exists after adjusting for GA (p=0.033). Conclusion In our cohort of newborns undergoing abdominal surgery, weight gain within the first three post-operative days was associated with an increase in duration of invasive ventilator support. Fluid overload does not seem to be associated with acute kidney injury. Careful attention to intra and early postoperative fluid balance may play an important role in optimizing outcomes of newborns undergoing abdominal surgery.


ASAIO Journal ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Katja M. Gist ◽  
Andrew Misfeldt ◽  
Rashmi D. Sahay ◽  
Stephen M. Gorga ◽  
David J. Askenazi ◽  
...  

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