Acute Tubular Injury Research Articles

Clinicopathological features and short outcomes of oliguric acute tubular injury.

To explore the clinicopathological features and analyze the relevant risk factors and short-term renal outcomes of acute tubular injury (ATI) patients. A total of 83 patients with biopsy-proven ATI were included in this retrospective cohort study. Clinical characteristic and histological feature data were collected, and renal recovery at 1 month postbiopsy was recorded. The severity of renal dysfunction, percentage of acute tubular lesions, interstitial inflammation and fibrosis of oliguric ATI patients were all significantly higher than those of nonoliguric patients. In the subgroup analysis of the oliguric patients, the serum creatinine and urinary microalbumin levels, severity of epithelial cell degeneration and cast formation of patients in the polyuric phase at biopsy were significantly lower than those of patients in the oliguric phase. A total of 59 patients had 1-month follow-up records, and complete renal recovery was observed in 42 patients. In the multivariate analysis, the total acute tubular injury area at biopsy was the most important independent risk factor for poor renal outcomes. Oliguric ATI patients had severe clinicopathological conditions. The severity of tubular lesions seriously influenced renal function recovery, demonstrating the importance of renal biopsy in assessing the prognosis of patients with kidney disease.

S3046 Hepatitis B Causing Severe Hemolysis and Multi-Organ Failure in Patients With Undiagnosed G6PD

Introduction: Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. WHO estimates 1.5 million new infections annually. Most people remain asymptomatic; however, some people have acute illness that lasts several weeks, which can at times be complicated with acute liver failure. Glucose-6-phosphate dehydrogenase (G6PD) X-linked deficiency is the most common human enzymopathy. Case Description/Methods: A 73-year-old male presented with loss of appetite, and dark colored urine. On examination, vitals were within normal range. Scleral icterus was present, along with hepatomegaly. Patient was alert and oriented. Patient's lab work was concerning for AST was 3017 unit/L, ALT 2712 Unit/L, BUN 74 mg/dL, Cr 3.6 mg/dL, total bilirubin 72.4 mg/dL, direct bilirubin 41.8 mg/dL, indirect bilirubin 30.6 mg/dL, hemoglobin 12.9 g/dL, white count 17,000 per microliter and platelet count of 173,000 per microliter (mcL). Patient’s hepatitis panel was positive for Hepatitis B Core Antibody Total, Hepatitis B Core Antibody IgM, Hepatitis B Surface Antibody, log 10 HBV IU/mL 2914. Hematological work up was done which was concerning for LDH 4,875, ferritin > 7500, reticulocyte, Peripheral smear did not show schistocytes. Erythrocyte G6PD level was performed which was low Patient was started on hemodialysis due to electrolyte derangement and oliguria. The patient was given intravenous fluids and was started on Entecavir for acute complicated Hepatitis B infection, Renal Biopsy was done which was suggestive of acute tubular injury. Patient liver function, labs as well as renal function continued to improve and no longer required dialysis. Discussion: Hemolytic anemia has been associated with viral hepatitis, but the degree is usually mild to moderate. With cases of severe intravascular hemolysis, a diagnosis in addition to hepatitis should be sought out. Our case is unique since this is the first reported case of severe hemolysis and renal failure precipitated by acute HBV in an undiagnosed G6PD deficient patient and treatment with Entecavir causing marked improvement. With early recognition and establishing diagnosis of complicated hepatitis B leading to severe hemolysis as well as renal failure, prompt treatment with anti-viral as well as supportive treatment for G6PD deficiency can help with early recovery of patients and prevent life threatening organ failure.

Spontaneous Renal Allograft Rupture of Unknown Etiology - A Case Report

Rupture of renal allograft is a rare but serious complication of transplantation. This is usually attributed to acute rejection, acute tubular necrosis, or renal vein thrombosis. Some other causes such as renal graft biopsy and lymphatic obstruction are also mentioned as possible causes. This usually occurs during the first 1–3 weeks following transplantation, but cases occurring as late as 72 months have been reported. A 23-year-old male with established chronic kidney disease stage 5, underwent live-related renal transplantation using a kidney from a 46-year-old donor (mother). The laparoscopic donor nephrectomy was uneventful. The patient had an uneventful intraoperative course with usual early postoperative recovery. The patient was having a good early postoperative course. On postoperative day (POD) 2, there was sudden decrease in urine output to 100 ml/h. Ultrasonography Doppler on the same day evening showed normal color flow in the renal artery and renal vein. At around 7 p.m., there was sudden increase in drain output with fresh blood as content (500 ml in 10 min) with tachycardia and hypotension. In view of increased drain output, the patient was taken to operating room and reexploration was done. At reexploration, the renal allograft was found to have two longitudinal ruptures of around 8 cm × 1 cm × 2 cm and 5 cm × 1 cm × 1 cm (length × width × depth) with active bleed. The initial attempt was made to achieve hemostasis and salvage the graft kidney, but due to uncontrolled bleed, explantation was performed. Histology showed features of acute tubular injury. However, there was no evidence of acute rejection, acute tubular necrosis, or vascular thrombosis. This case demonstrates that early diagnosis and prompt treatment of a life-threatening condition such as renal allograft rupture with explantation of the graft may be required in certain conditions as a life-saving procedure.

Non-glomerular Tip Lesion Focal Segmental Glomerulosclerosis as a Negative Predictor in Idiopathic Membranous Nephropathy

ObjectiveTo assess the significance of focal segmental glomerulosclerosis (FSGS) variants on clinicopathological characteristics and short-term outcomes in idiopathic membranous nephropathy (IMN) patients.MethodsThe clinicopathological data of 146 IMN patients diagnosed between December 2016 and March 2019 in our center were collected and analyzed. These patients were divided into the pure IMN group, IMN with glomerular tip lesion (GTL) group, and IMN with non-GTL FSGS group.ResultsThe IMN with non-GTL FSGS and IMN with GTL groups both had higher proportions of patients with hypertension, lower serum albumin, and severe proteinuria, while the IMN with non-GTL FSGS group additionally showed higher blood pressure and serum cholesterol, and lower serum IgG than the IMN group (all P<0.05). As for pathology, the IMN with non-GTL FSGS group had higher proportions of patients with acute tubular injury and moderate to severe chronic injuries than the IMN group (all P<0.05). In the IMN, IMN with GTL, and IMN with non-GTL FSGS groups, the overall one-year remission rates were 81.6%, 76%, and 58.8%, respectively. Furthermore, the IMN with non-GTL FSGS group showed the lowest cumulative incidence to reach remission within one year. Multivariate Cox logistic analysis demonstrated that higher level of serum anti-M-type phospholipase A2 receptor antibody and the existence of non-GTL FSGS lesion were independent predictors for no remission in IMN patients.ConclusionThe non-GTL FSGS lesion was a novel negative predictor in IMN and should be taken into account in the management of IMN.

Lithium-induced nephropathy; One medication with multiple side effects: a case report

BackgroundLithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare.Case presentationWe herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started.ConclusionBased on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.

216.2: Acute Tubular Injury and Necrosis Do Not Lead to Meaningful Elevations in Donor-Derived Cell-free DNA (dd-cfDNA)

KOAR registry. Introduction: Associations between non-rejection histologic diagnoses and dd-cfDNA have not been extensively characterized. We explored these associations inkidney transplant recipients enrolled in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076). Methods: For-cause and surveillance biopsies with NR (no rejection or other abnormalities, except IF/TA) or acute tubular injury/necrosis (ATI/ATN), and paireddd-cfDNA within 30 days were included. The incidence of a composite outcome (eGFR decline > 25%, rejection, and de novo donor-specific antibody detection) at 12 months after biopsy was also assessed. Results: 166 biopsies (141 patients) with NR and 70 biopsies (64 patients) with ATI/ATN were included; compared to patients with ATI/ATN, patients with NRhad lower KDPI (49% vs 64%, p <0.05) and shorter cold ischemia time (13 vs 18 hours, p<0.01). ATI/ATN biopsies were more likely to be for-cause (91.4% vs59.6%, p<0.001), earlier post-transplant (83.0 vs 116.5 days, p<0.001), and occur at lower eGFRs (43 vs 32 mL/min, p<0.001) (Table 1). There was no significant difference in median dd-cfDNA between NR (0.23%, IQR: 0.11 - 0.53) and ATI/ATN (0.21%, IQR: 0.13 - 0.55) biopsies (p = 0.993) (Figure 1). When patients were stratified by dd-cfDNA at the time of their first biopsy (< 0.5% vs ≥ 0.5%), there was a non-significant trend towards a higher incidence of the 12-month clinical composite among those with dd-cfDNA ≥ 0.5% (27.5% vs 12.9%, p=0.53), with eGFR decline being most common (78.5% of events). Conclusions: Our findings suggest that acute tubular injury/necrosis is not associated with substantial elevations in dd-cfDNA. The use of dd-cfDNA to identify patients with non-actionable histologic findings (including ATI/ATN) may allow more nuanced clinical decision-making and reduce the number of unnecessary biopsies.

Clinicopathologic, Gross Necropsy, and Histopathologic Effects of High-Dose, Repeated Meloxicam Administration in Rhode Island Red Chickens (Gallus gallus domesticus).

Meloxicam is a commonly prescribed non-steroidal anti-inflammatory drug for backyard poultry that has demonstrated pharmacodynamic efficacy at a single high dose of 5 mg/ kg. This study characterized the adverse effects of meloxicam administered in chickens at an approximate dose of 5 mg/kg orally twice daily for 5 days. Twenty-one adult Rhode Island Red hens (Gallus gallus domesticus), judged to be healthy based on an external physical examination, complete blood count (CBC), and plasma biochemistry panel, were recruited for this study. The subject birds were randomly assigned to a treatment (n = 11) or control group (n = 10) and received a 15-mg tablet of meloxicam or a nonmedicated feed pellet, respectively, orally twice daily. Physical examinations and body weight measurements were performed daily, and observation for clinical signs occurred twice daily. Following completion of the 5-day treatment course, an external physical examination, blood collection for a CBC and plasma biochemistry panel, euthanasia, necropsy, and measurement of meloxicam tissue residues were performed. During the treatment course, 1 hen from the treatment group died with peracute clinical signs, 2 hens from the treatment group died suddenly with no clinical signs, and 1 hen from the treatment group became acutely lethargic and was euthanized. Within the meloxicam group, 7 out of 11 hens had gross and histologic evidence of varying levels of renal acute tubular injury and gout. Plasma uric acid concentrations were above the species reference intervals in all affected hens in the treatment group that were still available for testing. The control group had no evidence of renal injury or gout based on postmortem examinations. Based on the results of this study, repeated oral dosing of meloxicam in chickens at 5 mg/kg twice daily is not recommended.

Experimental malaria-associated acute kidney injury is independent of parasite sequestration and resolves upon antimalarial treatment.

Malaria remains a important global disease with more than 200 million cases and 600 000 deaths each year. Malaria-associated acute kidney injury (MAKI) may occur in up to 40% of patients with severe malaria and is associated with increased mortality. Histopathological characteristics of AKI in malaria are acute tubular injury, interstitial nephritis, focal segmental glomerulosclerosis, collapsing glomerulopathy and glomerulonephritis. We observed that C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) develop MAKI in parallel with malaria-associated acute respiratory distress syndrome (MA-ARDS). MAKI pathology was associated with proteinuria, acute tubular injury and collapse of glomerular capillary tufts, which resolved rapidly after treatment with antimalarial drugs. Importantly, parasite sequestration was not detected in the kidneys in this model. Furthermore, with the use of skeleton binding protein-1 (SBP-1) KO PbNK65 parasites, we found that parasite sequestration in other organs and its subsequent high parasite load are not required for the development of experimental MAKI. Similar proteinuria, histopathological features, and increases in kidney expression of interferon-γ, TNF-α, kidney injury molecule-1 (KIM-1) and heme oxygenase-1 (HO-1) was observed in both infected groups despite a significant difference in parasite load. Taken together, we introduce a model of experimental AKI in malaria with important similarities to AKI in malaria patients. Therefore, this mouse model might be important to further study the pathogenesis of AKI in malaria.

Role of protease‐activated receptor‐1 (PAR‐1) in the glomerular filtration barrier integrity

Protease‐activated receptors (PAR) play an important role in the regulation of cellular function by the coagulation system, and they are activated by thrombin. PAR‐1 is expressed in both endothelial cells and podocytes in the kidney. The role of PAR1 in the maintenance of the glomerular filtration barrier is not clear. Anticoagulant‐related nephropathy (ARN) is a kidney disease with glomerular hematuria and red blood cell tubular casts. We validated 5/6 nephrectomy (5/6NE) in rats as a model of ARN and had demonstrated that direct thrombin inhibitor (dabigatran) induces ARN. The aim of this study was to investigate the role of PAR‐1 in the ARN pathogenesis. 5/6NE rats were treated with dabigatran (150 mg/kg/day), PAR‐1 inhibitor SCH79797 (1 and 3 mg/kg/day) and PAR‐1 agonist TFLLR‐NH2 (0.25 and 0.50 µmol/kg/day) for 7 days. Serum creatinine and hematuria were assessed daily. Kidney morphology was evaluated at the end of the study. In 5/6NE rats treated with either dabigatran or combination with a PAR‐1 modulator, there was an elevation in serum creatinine, glomerular hematuria, red blood casts in the tubules, and acute tubular epithelial cell injury. Interestingly, both PAR‐1 modulators in a dose‐depended manner had similar effects on the serum creatinine levels and hematuria as those of dabigatran. Dabigatran‐induced increase in the systolic blood pressure was not affected by PAR‐1 modulators. In conclusion, the normal function of PAR‐1 is crucial to maintain the glomerular filtration barrier integrity. Either activation or blockage of PAR‐1 leads to glomerular hematuria and subsequent acute tubular epithelial cell injury.

Drug-Induced Acute Kidney Injury.

Medications are a common cause of AKI, especially for patients admitted to hospital wards and the intensive care unit. Although drug-related kidney injury occurs through different mechanisms, this review will focus on three specific types of tubulointerstitial injury. Direct acute tubular injury develops from several medications, which are toxic to various cellular functions. Their excretory pathways through the proximal tubules contribute further to AKI. Drug-induced AKI may also develop through induction of inflammation within the tubulointerstitium. Medications can elicit a T cell-mediated immune response that promotes the development of acute interstitial nephritis leading to AKI. Although less common, a third pathway to kidney injury results from the insolubility of drugs in the urine leading to their precipitation as crystals within distal tubular lumens, causing a crystalline-related AKI. Intratubular obstruction, direct tubular injury, and localized inflammation lead to AKI. Clinicians should be familiar with the pathogenesis and clinical-pathologic manifestations of these forms of kidney injury. Prevention and treatment of AKI relies on understanding the pathogenesis and judiciously using these agents in settings where AKI risk is high.

Incidence and Importance of Calcium Deposition in Kidney Biopsy Specimens

Introduction: Calcification on native kidney biopsy specimens is often noted by pathologists, but the consequence is unknown. Methods: We searched the pathology reports in the Biopsy Biobank Cohort of Indiana for native biopsy specimens with calcification. Results: Of the 4,364 specimens, 416 (9.8%) had calcification. We compared clinical and histopathology findings in those with calcification (n = 429) compared to those without calcification (n = 3,936). Patients with calcification were older, had more comorbidities, lower estimated glomerular filtration rates (eGFR), were more likely to have hyaline arteriosclerosis, interstitial fibrosis/tubular atrophy, and a primary pathologic diagnosis of acute tubular injury or acute tubular necrosis when compared to patients without calcification. Patients with calcium oxalate deposition alone, compared to calcium phosphate or mixed calcifications, had fewer comorbidities but were more likely to have a history of gastric bypass surgery or malabsorption and take vitamin D. In patients with two or more years of follow-up, multivariate analyses showed the presence of calcification (HR 0.59, 0.38–0.92, p = 0.02) and higher eGFR (HR 0.76, 0.73–0.79, p < 0.001), was associated with decreased likelihood of progressing to end-stage renal disease. The presence of calcification was also associated with a reduced slope/decline in eGFR compared to known biopsy and clinical risk factors for decline in kidney function. We hypothesized this was due to more recoverable acute kidney injury (AKI) and found more severe acute kidney injury network stage in patients with kidney calcification but also greater improvement over time. Discussion/Conclusion: In summary, we demonstrated that calcification on kidney biopsy specimens was associated with a better prognosis than those without calcification due to the association with recoverable AKI.

Non-diabetic urine glucose in idiopathic membranous nephropathy

This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-β-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% (p < 0.005). Patients who got urine glucose remission also had better renal survival. In conclusion, non-diabetic urine glucose was closely related to proteinuria. It could be applied as a tubular injury marker to predict renal function.

Kidney xenotransplantation in a brain-dead donor: Glass half-full or half-empty?

Kidney xenotransplantation in a brain-dead donor: Glass half-full or half-empty?

Yellow Lamb Disease (Clostridium perfringens Type A Enterotoxemia of Sheep): A Review.

Simple SummaryYellow lamb disease is a poorly researched and understood condition that seems to affect young sheep. The disease is characterized by hemolysis and is thought to be caused by alpha toxin-producing Clostridium perfringens type A, although a definitive association with this microorganism has not been confirmed. This is due, in part, to the ubiquitous nature of C. perfringens type A, which is naturally present in the intestine of healthy sheep, a fact that complicates the diagnosis. In this review, we summarize the available information on the etiology, clinical signs, lesions, diagnosis, prevention and prophylaxis of yellow lamb disease.Yellow lamb disease is an infrequent disease in sheep for which there is scant literature, and that has been reported in the US, Australia, New Zealand, South Africa and Europe, although anecdotal evidence indicates that it may have also been diagnosed in South America. The disease is produced by some strains of Clostridium perfringens type A that produce unusually high levels of alpha- toxin. Because C. perfringens type A is ubiquitous and is found in the intestine of most clinically healthy sheep, diagnosis of yellow lamb disease is challenging and requires quantitating the amount of this microorganism present in feces and/or intestinal content. Clinically, yellow lamb disease is characterized by depression, anemia, icterus and hemoglobinuria. Occasionally, sudden death may occur. Gross findings include generalized icterus, red urine in the bladder, enlarged, pale, and friable spleen, enlarged liver with an acinar pattern, and dark, swollen kidneys. Microscopically, yellow lamb disease is characterized by centrilobular necrosis of the liver, hemoglobinuria-associated acute tubular injury, splenic congestion, pulmonary congestion and edema. Although there are no vaccines specifically designed to prevent yellow lamb disease, several vaccines against the different types of C. perfringens may afford at least some level of protection against yellow lamb disease.

Hypercalciuria may predict better response to immunosuppressive therapyin renal sarcoidosis: a case series.

Renal sarcoidosis is a rare cause of tubulointerstitial nephritits(TIN). The clinical and pathological characteristics, as well as outcomes, of renal sarcoidosis remain unclear. This single-center study retrospectively analyzed 18 patients affected bysarcoidosis with tubulointerstitial nephritis (TIN) and 53 patients with tubulointerstitial nephritisnot related to sarcoidosis.Patientswere further stratified into the granulomatous (12 sarcoidosis and 6 non-sarcoidosis) and non-granulomatous (6 sarcoidosis and 47 non-sarcoidosis) TIN groups. Half of the patients with renal sarcoidosis had signs ofacute kidneyinjury at kidneybiopsy, 94% of whom presented with extra-renal involvement. The prevalence of hypercalcemia, hypercalciuria, and elevated serum angiotensin-converting enzyme levels was 27.6%, 33.3%, and 31.3%, respectively. Renal sarcoidosis patients with eGFR < 30mL/min/1.73 m2 scored higher for total chronic tubulointerstitial injury (p = 0.044) and glomerular sclerosis (p = 0.027). Compared to non-sarcoidosispatients, higher urinary calcium levels (for patients with GFR [Formula: see text] 40mL/min/1.73 m2, p = 0.034), lower scores of acute tubular injury (p = 0.008), and more prominent glomerular sclerosis were observed in renal sarcoidosis. Similar characteristics of chronicity and hypercalciuria were also identified in granulomatous interstitial nephritis; however, interstitial inflammation was obvious (p = 0.001). Patients with renal sarcoidosis were initially treated with corticosteroids. Five patients receiving immunosuppressive agents showed better long-term renal recovery. High 24-h urine calcium (adjusted by weight) was identified as a factor associated with long-term remission. Renal sarcoidosis is a systemic disease of insidious onset and chronic progression, sharing similar features of chronicity and hypercalciuria with granulomatous interstitial nephritisof other cause. Hypercalciuria may predict a better response toimmunosuppressive therapy, presumablyindicating active interstitial inflammation; thus, strengthened immunosuppression might be considered.

ACE2 Promoted by STAT3 Activation Has a Protective Role in Early-Stage Acute Kidney Injury of Murine Sepsis.

Sepsis-induced AKI (SIAKI) is the most common complication with unacceptable mortality in hospitalized and critically ill patients. The pathophysiology of the development of SIAKI is still poorly understood. Our recent work has demonstrated the role of signal transducer and activator of transcription 3 (STAT3) pathways in regulating inflammation and coagulation in sepsis. We hypothesized that STAT3 activation has a critical role in early-stage SIAKI. The early-stage SIAKI model was established in cecal ligation and puncture (CLP) mice, which recapitulates the clinical and renal pathological features of early-stage AKI patients. Brush border loss (BBL) was the specific pathological feature of acute tubular injury in early-stage AKI. The role of STAT3 signaling and angiotension system in early-stage SIAKI was evaluated. The STAT3 activation (increased pSTAT3) and increased angiotensin-converting enzyme 2 (ACE2) expressions were observed in CLP mice. The low responsive expressions of pSTAT3 and ACE2 to septic inflammation in CLP AKI mice were associated with BBL. Correlation analysis of proteins' expressions showed pSTAT3 expression was significantly positively related to ACE2 expression in CLP mice. Reduced pSTAT3 after S3I201 intervention, which blocked STAT3 phosphorylation, decreased ACE2 expression, and exacerbated tubular injury in early-stage SIAKI. Our data indicate that endogenous increase of ACE2 expression upregulated by STAT3 activation in early-stage SIAKI play protective role against acute tubular injury.

Double glomerulopathies or two-faced janus? A challenging case in the COVID-19 era.

SARS-CoV-2 very often causes kidney involvement through various mechanisms including: acute tubular injury, virus cell invasion, vascular damage due to hypercoagulability and finally dysregulation of the immune system. Even though there are no pathognomonic morphologic features that can rule out or confirm direct damage by SARS-CoV-2, the latest literature suggests that there may be some association. SARS-CoV-2 infection represents a poor prognostic factor, regardless of pulmonary involvement. We report a challenging case with complex renal biopsy findings suggestive of collapsing glomerulopathy and focal proliferative IgA-dominant glomerulonephritis in a patient affected by active hepatitis C virus (HCV), SARS-CoV-2 infection and personal history of cocaine abuse.

Advances in laboratory detection of acute kidney injury

Recent advances have improved our understanding of the epidemiology and pathophysiology of acute kidney injury (AKI). So far, the Kidney Disease: Improving Global Outcome guidelines define and stratify kidney injury based on increases in serum creatinine level and/or decreases in urine output. Although the term AKI acknowledges the existence of cellular injury, its diagnosis is still only defined by the reduced excretory function of the kidney. New biomarkers that aid a better understanding of the relationship between acute tubular injury and kidney dysfunction have been identified, reflecting the advances in molecular biology. The expression of some of these novel biomarkers precedes changes in conventional biomarkers or can increase their predictive power. Therefore, they might enhance the clinical accuracy of the definition of AKI. This review summarizes the limitations of the current AKI classification and a panel of candidate biomarkers for augmenting AKI classification and recognition of AKI subphenotypes. We expect that the integration of appropriately selected biomarkers in routine clinical practice can improve AKI care.

Early loss of glutathione -s- transferase (GST) activity during diverse forms of acute renal tubular injury.

Glutathione‐S‐transferases (GSTs) are a diverse group of phase II detoxification enzymes which primarily evoke tissue protection via glutathione conjugation to xenobiotics and reactive oxygen species. Given their cytoprotective properties, potential changes in GST expression during AKI has pathophysiologic relevance. Hence, we evaluated total GST activity, and the mRNA responses of nine cytosolic GST isotypes (GST alpha1, kappa1, mu1/5, omega1, pi1 sigma1, theta1, zeta1 mRNAs), in five diverse mouse models of AKI (glycerol, ischemia/reperfusion; maleate, cisplatin, endotoxemia). Excepting endotoxemia, each AKI model significantly reduced GST activity (~35%) during both the AKI “initiation” (0‐4 h) and “maintenance” phases (18 or 72 h). During the AKI maintenance phase, increases in multiple GST mRNAs were observed. However, no improvement in GST activity resulted. Increased urinary GST excretion followed AKI induction. However, this could not explain the reduced renal GST activity given that it also fell in response to ex vivo renal ischemia (i.e., absent urinary excretion). GST alpha, a dominant proximal tubule GST isotype, manifested 5–10‐fold protein increases following AKI, arguing against GST proteolysis as the reason for the GST activity declines. Free fatty acids (FFAs) and lysophospholipids, which markedly accumulate during AKI, are known to bind to, and suppress, GST activity. Supporting this concept, arachidonic acid addition to renal cortical protein extracts caused rapid GST activity reductions. Based on these results, we conclude that diverse forms of AKI significantly reduce GST activity. This occurs despite increased GST transcription/translation and independent of urinary GST excretion. Injury‐induced generation of endogenous GST inhibitors, such as FFAs, appears to be a dominant cause.

Asparagus falcatus L. (Asparagaceae) leaf extracts attenuate doxorubicin-induced renal toxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways

The search for therapeutic agents that improve kidney function against doxorubicin-induced renal toxicity is important. Herein, the potential nephroprotective activity by Asparagus falcatus L. (AF, Asparagaceae) leaf extracts against doxorubicin-induced renal toxicity (5 mg/kg, ip) in Wistar rats (n = 6/group) after oral administration of hexane (55 mg/kg), ethyl acetate (35 mg/kg), butanol (75 mg/kg), and aqueous (200 mg/kg) extracts of AF for 28 consecutive days was investigated. It was noticed that the treatment with the selected extracts of AF significantly attenuated doxorubicin-induced elevations of serum creatinine, urea nitrogen, β2-microglobulin, cystatin C, and proteinuria in experimental rats. The histology showed attenuation of the features of acute tubular injury. Treatment regimens significantly reversed the doxorubicin-induced reduction in total antioxidant status, glutathione peroxidase, and glutathione reductase activity in renal tissue homogenates. A suppression in lipid peroxidation was noted with hexane, ethyl acetate, and butanol extracts of AF. Moreover, a reduction in the concentration of the pro-inflammatory mediator TNF-α (p < 0.05), and immunohistochemical expression of COX-2 were observed. The immunohistochemical expression of pro-apoptotic Bax protein was decreased and the anti-apoptotic BCL-2 was increased in renal tissues following the treatments. In conclusion, it was revealed that, hexane, ethyl acetate, butanol, and aqueous extracts of AF attenuate doxorubicin-induced renal toxicity in Wistar rats through antioxidant, anti-inflammatory, and anti-apoptotic pathways. The plant, AF could be recommended as a promising therapeutic agent to minimize renal toxicity induced by doxorubicin in cancer patients, however, subsequent clinical trials are warranted.