Sepsis-associated acute kidney injury

Acute kidney injury (AKI) is a condition that develops as a result of a rapid decrease in the glomerular filtration rate, which leads to the accumulation of nitrogenous, including urea and creatinine, and non-nitrogenous metabolic products with electrolytic disorders, impairment of the acid-base balance, and the volume of fluid excreted by the kidneys. Objective: to provide a review of the literature concerning sepsis-associated acute kidney injury. We presented the problems of diagnosis, risk factors, the pathogenesis of sepsis-associated acute kidney injury, as well as to outline terminologically the clinical form of sepsis-associated acute kidney injury: the paradigm shifts from ischemia and vasoconstriction to hyperemia and vasodilation, from acute tubular necrosis to acute tubular apoptosis. Sepsis contributes significantly to the development of AKI: in sepsis, it occurs in 19 % of patients; nevertheless, it is much more frequent in septic shock (45 % of cases), the mortality of individuals with AKI is especially high in non-septic and septic conditions (45 and 73 %, respectively). To effectively diagnose the functional state of the kidneys and conduct nephroprotective therapy, stratification scales for assessing the severity of acute kidney damage are applied, which are based on the determination of plasma creatinine level and urine output: RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure), AKIN (Acute Kidney Injury Network), KDIGO (Kidney Disease Improving Global Outcomes); the experts considered KDIGO scale more modern and perfect. It has been found that plasma creatinine is not an early biomarker of AKI that indicates the advisability of using other integral indicators. AKI biomarkers are substances that either participate in the pathological process or witness it allowing diagnose AKI even before an increase in plasma creatinine level. The characteristics of the structure, role of functions of such biomarkers as neutrophil gelatinase-associated lipocalin, cystatin C, interleukin-18, kidney injury molecule-1 and others are given. Intensive care for sepsis-associated acute kidney injury includes the standard therapy corresponding to 2016 Surviving Sepsis Campaign and KDIGO guidelines. Also, the paper focuses on renal replacement therapy (RRT): renal and extrarenal indications for the initiation, factors affecting the initiation of RRT, the timing of initiation, ways of optimization, the timing of RRT discontinuation, recommendations for the dose of RRT, the dose of renal replacement therapy in sepsis-associated AKI, choice of method, advantages and disadvantages of continuous RRT and intermittent hemodialysis, medication support for continuous therapy, the role of hemodialysis machine in the intensive care unit.

Plasma Creatinine Level Does Not Predict Respiratory Function in Amyotrophic Lateral Sclerosis

In amyotrophic lateral sclerosis (ALS) lower plasma creatinine level has been associated with shorter survival and faster functional decline. It has not been clear if creatinine is associated with respiratory outcome. We analyzed retrospectively a population of unselected ALS patients. Multiple-regression and Cox-regression analyses were performed. We included 233 patients, mean age 62.8, mean disease duration of 18.6 months. At baseline, creatinine was significantly associated with ALSFRS-R, but not with its decline rate. No predictive value was disclosed for FVC, or their decline rate, or with survival. We did not confirm that creatinine is a marker of respiratory outcome.

Use of Intra-Aortic Balloon Pump During Coronary Artery Bypass Graft Surgery. Current Questions and Few Answers.

The intra-aortic balloon pump (IABP) is used to prevent complications after coronary artery bypass grafting (CABG) surgery; although some results are controversial nowadays even contradictory. A new article on this field is published in this edition and shows that the risk factors for in-hospital mortality are the preoperative plasma creatinine level and cardiopulmonary bypass time in 177 patients. About the prophylactic use of the IABP regarding mortality the results reflected so far in meta-analyses have been highly contradictory between them, and the risk factors associated with it have been several and different. This lack of evidence has resulted in the continued variation of IABP use in these procedures. A large, multicenter RCT is certainly required to take the next step towards more definitive evidence, either for or against, the use of IABP in high-risk CABG. Until then, the unanswered questions regarding this topic will remain.

Transplanted senescent renal scattered tubular-like cells induce injury in the mouse kidney

Cellular senescence, a permanent arrest of cell proliferation, is characterized by a senescence-associated secretory phenotype (SASP), which reinforces senescence and exerts noxious effects on adjacent cells. Recent studies have suggested that transplanting small numbers of senescent cells suffices to provoke tissue inflammation. We hypothesized that senescent cells can directly augment renal injury. Primary scattered tubular-like cells (STCs) acquired from pig kidneys were irradiated by 10 Gy of cesium radiation, and 3 wk later cells were characterized for levels of senescence and SASP markers. Control or senescent STCs were then prelabeled and injected (5 × 105 cells) into the aorta of C57BL/6J mice. Four weeks later, renal oxygenation was studied in vivo using 16.4-T magnetic resonance imaging and function by plasma creatinine level. Renal markers of SASP, fibrosis, and microvascular density were evaluated ex vivo. Per flow cytometry, irradiation induced senescence in 80–99% of STCs, which showed increased gene expression of senescence and SASP markers, senescence-associated β-galactosidase staining, and cytokine levels (especially IL-6) secreted in conditioned medium. Four weeks after injection, cells were detected engrafted in the mouse kidneys with no evidence for rejection. Plasma creatinine and renal tissue hypoxia increased in senescent compared with control cells. Senescent kidneys were more fibrotic, with fewer CD31+ endothelial cells, and showed upregulation of IL-6 gene expression. Therefore, exogenously delivered senescent renal STCs directly injure healthy mouse kidneys. Additional studies are needed to determine the role of endogenous cellular senescence in the pathogenesis of kidney injury and evaluate the utility of senolytic therapy.

Dose and Exposure Time-Dependent Renal and Hepatic Effects of Intraperitoneally Administered Fumonisin B1 in Rats

Male Wistar rats were treated intraperitoneally (i.p.) with fumonisin B1 (FB1; 0, 20, 50 and 100 mg/kg dietary dose equivalent) for 5 and 10 days (n = 24–24 in each setting) to gain dose- and time-dependent effects on antioxidant status and oxidative stress response, clinical chemical endpoints and liver, kidney and lung histopathology and lymphocyte damage (genotoxicity). FB1 decreased feed intake, body weight gain and absolute liver weight, irrespective of the toxin dose. Relative kidney weight increased in the 10-day setting. Linear dose response was found for plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol, urea and creatinine, and exposure time-dependence for plasma creatinine level. The latter was coupled with renal histopathological findings, tubular degeneration and necrosis and the detachment of tubular epithelial cells. The pronounced antioxidant response (reduced glutathione accretion, increasing glutathione peroxidase activity) referred to renal cortical response (5–10 days exposure at 50–100 ppm FB1). Hepatic alterations were moderate, referring to initial phase lipid peroxidation (exposure time dependent difference of conjugated diene and triene concentrations), and slight functional disturbance (↑ total cholesterol). Lymphocyte DNA damage was moderate, supporting a mild genotoxic effect of FB1.

Abstract 298: Protective Role of Endogenous 20-HETE in Renal Ischemia-Reperfusion Injury

The present study compared renal ischemia-reperfusion (IR) injury in Dahl salt-sensitive (SS) rats that have a deficiency in the renal formation of 20-HETE versus CYP4A1 transgenic SS (SS.4A1) rats in which the renal production of 20-HETE is restored. The concentrations of free 20-HETE in the renal cortex and outer medulla were significantly greater in SS.4A1 than in SS rats. Renal 20-HETE levels rose to a greater extent in SS.4A1 than in SS rats following renal IR. Plasma creatinine level rose to 3.7 ± 0.1 in SS versus 1.8 ± 0.3 mg/dl in SS.4A1 rats (respectively, n=6) following 30 min of ischemia and 24 h reperfusion. The % of necrotic tubules and apoptotic cells were 4-fold higher in SS than in SS.4A1 rats. Administration of the 20-HETE synthesis inhibitor (HET0016, 10 mg/kg) abolished the resistance of SS.4A1 rats to renal IR injury and plasma creatinine level rose to 3.8 ± 0.1 mg/dl (n=6). Cortical blood flow in SS, SS.4A1 and HET0016 treated SS.4A1 rats immediately returned to control following IR. However, medullary blood flow in SS and HET0016 treated SS.4A1 rats fell to 30 % of control 3 h after IR (n=5), and it remained depressed for 24 h. In contrast, medullary blood flow did not decline following IR in SS.4A1 rats. Proximal intratubular pressure rose from 13 to approximately 40 mmHg, 2 h after IR in both SS and SS.4A1 rats. Proximal intratubular pressure remained much higher in SS than in SS.4A1 rats 24 h after IR (32 vs 19 mmHg). These data indicate that normalization of renal CYP4A activity and 20-HETE production opposes renal IR injury by preventing secondary fall in medullary blood flow and the prolonged renal medullary ischemia.

Abstract 482: Renoprotective Effects of Exercise Training in Dahl Salt-sensitive Rats

Exercise training (Ex) slows the progression of hypertension and renal failure in some animal models. We and other groups have reported that Ex ameliorated hypertension and renal dysfunction in spontaneously hypertensive rats. Since little has been reported on the effects of Ex on renal disorder in salt-sensitive hypertension, we investigated the effects of Ex on blood pressure and renal function in Dahl salt-sensitive (DS) rats. Six-week-old male DS rats were divided into three groups: 1) Normal salt (0.5% NaCl) diet (NS) (NS group, n=10), 2) High salt (8% NaCl) diet (HS) (HS group, n=11), 3) HS plus moderate Ex with treadmill running (HE group, n=11). After 8 weeks, HS induced severe hypertension, and Ex did not affect systolic blood pressure (114±3, 209±6 and 205±8 mmHg in the NS, HS and HE groups, respectively). Plasma creatinine was significantly higher in the HS and HE groups than in the NS group, but not different between the HS and HE groups (0.22±0.01, 0.44±0.03 and 0.40±0.03 mg/dl). Urinary protein and albumin significantly increased in the HS and HE groups, but these were significantly lower in the HE group compared with the HS group (Protein: 15.9±1.6, 432.8±36.8 and 327.2±22.3 mg/day. Albumin: 3.9±0.8, 195.2±15.2 and 154.2±11.1mg/day). Urinary TBARS, an index of oxidative stress, significantly increased in the HS and HE groups, but this was significantly lower in the HE group compared with the HS group (0.30±0.02, 0.75±0.06 and 0.53±0.03 mg/day); there was no significant difference in plasma TBARS among all groups. CYP4A1 and CYP4A2 protein expressions in the outer medulla were significantly lowered by 37% and 48% in the HS group compared with the NS group, and were significantly elevated by 40% and 150% in the HE group compared with the HS group. There was no significant difference in cortical CYP4A1 protein expression among all groups. Although there was no difference in cortical CYP4A2 between the NS and HS groups, it was significantly increased by 35% in the HE group compared with the HS group. These results suggest that Ex attenuated HS-induced proteinuria independently of blood pressure or plasma creatinine level in DS rats. The improvement of oxidative stress and CYP4A expression in the kidneys may contribute to the renoprotective effects of Ex in DS rats.

Effects of Pleurotus ostreatus on Blood Pressure and Glycemic Status of Hypertensive Diabetic Male Volunteers

Different species of mushrooms are being used increasingly for their nutritional and medicinal values. They are used in traditional medical practice in the treatment and prevention of diabetes, obesity, heart diesaes, hyperacidity, cancer and hypertension. This study was designed to see the effects of Pleurotus ostreatus on blood pressure and glycemic status of hypertensive diabetic male volunteers. The study was carried out in the National Mushroom development and Extension Center (NAMDEC) laboratory, Savar, Dhaka in collaboration with the Department of Pharmacy along with the Department of Biochemistry and Molecular Biology, Jahangirnagar University. A total of 27 hypertensive male volunteers suffering from type 2 diabetes mellitus with age range of 32 to 68 years, who were free from renal impairment and other known acute or chronic diseases were included in the study. Blood pressure, fasting plasma glucose, HbA1c and serum creatinine were measured before and after 3 months of regular intake of 3 grams mushroom powder capsule daily in in 3 divided doses. However they were allowed to continue the drugs they were taking already. The study showed that after 3 months of regular intake of Pleurotus ostreatus mushroom, both systolic and diastolic blood pressure decreased significantly (p<0.001). It was also observed that, Pleurotus ostreatus decreased fasting plasma glucose level significantly (p<0.001). Reduction of HbA1c % observed after 3 months of mushroom intake was found to be significant (p<0.001). But there was no significant change of plasma creatinine level (p>0.05) indicating Pleurotus ostreatus has no detrimental effect on renal system. From the study, it can be said that, Pleurotus ostreatus mushroom intake improves glycemic status and blood pressure control in diabetic hypertensive subjects. DOI: http://dx.doi.org/10.3329/bjmb.v6i1.13280 Bangladesh J Med Biochem 2013; 6(1): 5-10

Pseudorenal Failure Secondary to Reversed Intraperitoneal Autodialysis

A 16-year-old boy was admitted for anuria, ascites, and abdominal pain. The patient had undergone a laparoscopic appendectomy two days prior to admission. Initial laboratory analysis revealed a plasma creatinine level of 5,07 mg/dL and blood urea nitrogen level of 75 mg/dL. Computed tomography imaging revealed diffuse abdominal ascites with normal kidneys without signs of hydronephrosis. Laprascopic revision found a 3 mm bladder tear and yielded an aspirate of 1,8 litre abdominal fluid. The abdominal fluid exhibited a fluid : serum creatinine ratio exceeding 1, indicating uroperitoneum. This case underscores the importance of bladder ruptures causing uroperitoneum presenting with azotemia.

Renal stones and calcifications in patients with primary hyperparathyroidism: associations with biochemical variables

ObjectiveTo study the prevalence of renal stones and nephrocalcinosis in patients with primary hyperparathyroidism (PHPT) and to appraise biochemical variables as risk factors for developing renal calcifications.DesignCross-sectional.Materials and methodsAll patients (n=177) undergoing diagnostic evaluation and surgery for PHPT at Aarhus University Hospital between 2007 and 2009. All patients underwent routine spiral CT scans of the abdomen to determine the presence or absence of renal calcifications.ResultsA total of 45 patients (25.4%, 95% confidence intervals: 19.0–31.4%) had renal stones (15.3%) and/or renal calcifications (10.2%) on the CT scans. Compared with those without calcification (n=132), the group with calcification had a significantly lower plasma creatinine level (67.0±25.1 vs 74.6±17.5 μmol/l, 2P=0.03). Moreover, CaE was higher in PHPT patients with renal calcification than in PHPT patients without (0.91±0.28 vs 0.74±0.40 mmol/mmol, 2P=0.02). The other measured or derived biochemical variables were similar in the two groups. No biochemical variable was predictive for renal calcifications in a multiple regression analysis.ConclusionWe found a high prevalence of renal calcifications among PHPT patients but no deterioration of renal function. The occurrence of calcifications was related to low plasma creatinine and a high urine calcium/creatinine ratio. However, biochemical markers in general were poor predictors for the risk of renal stones or nephrocalcinosis indicating that routine image diagnostics may be needed for the identification of these complications in order to establish indication for surgery and ensure proper treatment.