The protective effect of 1400W against ischaemia and reperfusion injury is countered by transient medullary kidney endothelial dysregulation.

Renal ischaemia and reperfusion (I/R) is caused by a sudden temporary impairment of the blood flow. I/R is a prevalent cause of acute kidney injury. As nitric oxide generated by inducible nitric oxide synthase (iNOS) has detrimental effects during I/R, the pharmacological blockade of iNOS has been proposed as a potential strategy to prevent I/R injury. The aim of this study was to improve the understanding of 1400W (an iNOS inhibitor) on renal I/R as a pharmacological strategy against kidney disease. BALB/c mice received 30 min of bilateral ischaemia, followed by 48 h or 28 days of reperfusion. Vehicle or 1400W (10 mg/kg) was administered 30 min before inducing ischaemia. We found that after 48 h of reperfusion 1400W decreased the serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin and proliferating cell nuclear antigen 3 in the I/R animals. Unexpectedly, we observed mRNA upregulation of genes involved in kidney injury, cell-cycle arrest, inflammation, mesenchymal transition and endothelial activation in the renal medulla of sham animals treated with 1400W. We also explored if 1400W promoted chronic kidney dysfunction 28 days after I/R and did not find significant alterations in renal function, fibrosis, blood pressure or mortality. The results provide evidence that 1400W may have adverse effects in the renal medulla. Importantly, our data point to 1400W-induced endothelial dysfunction, establishing therapeutic limitations for its use. KEY POINTS: Acute kidney injury is a global health problem associated with high morbidity and mortality. The pharmacological blockade of inducible nitric oxide synthase (iNOS) has been proposed as a potential strategy to prevent AKI induced by ischaemia and reperfusion (I/R). Our main finding is that 1400W, a selective and irreversible iNOS inhibitor with low toxicity that is proposed as a therapeutic strategy to prevent kidney I/R injury, produces aberrant gene expression in the medulla associated to tissue injury, cell cycle arrest, inflammation, mesenchymal transition and endothelial activation. The negative effect of 1400W observed in the renal medulla at 48 h from drug administration, is transient as it did not translate into a chronic kidney disease condition.

Relapsing nephrotic syndrome with acute renal failure following a unique episode of multiple bee stings: A case report.

The commonest renal involvement after bee stings is acute kidney injury due to rhabdomyolysis. Nephrotic syndrome combined with AKI is unusual complication of Hymenoptera stings. We diagnosed a minimal change disease and six-year follow up relapses.

Galectin-8 counteracts folic acid-induced acute kidney injury and prevents its transition to fibrosis.

Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.

Vascular malformation simulating a gastric subepithelial lesion: The risks of the bite-on-bite biopsy technique.

We present a case of a healthy 64-year-old man whose endoscopy showed an irregular subepithelial lesion in the gastric antrum. This lesion was covered by normal mucosa. Biopsies were taken by a bite-on-bite technique. After biopsies, the patient developed arterial bleeding, which was controlled. The anatomopathological study showed a tortuous artery in the submucosa, with a marked hyperplasia of the intima and the internal elastic lamina. These findings were consistent with a gastric arteriovenous malformation versus a Dieulafoy's lesion. This case demonstrates the risk of the bite-on-bite biopsy technique. In our country we have endoscopic ultrasound to assess these lesions, however its availability is low.

1400W Prevents Renal Injury in the Renal Cortex But Not in the Medulla in a Murine Model of Ischemia and Reperfusion Injury.

BACKGROUND/AIMS: Acute kidney injury (AKI) carries high morbidity and mortality, and the inducible nitric oxide synthase (iNOS) is a potential molecular target to prevent kidney dysfunction. In previous work, we reported that the pharmacological inhibitions of iNOS before ischemia/reperfusion (I/R) attenuate the I/R-induced AKI in mice. Here, we study the iNOS inhibitor 1400W [N-(3-(Aminomethyl)benzyl] acetamide, which has been described to be much more specific to iNOS inhibition than other compounds. METHODS: We used 30 minutes of bilateral renal ischemia, followed by 24 hours of reperfusion in Balb/c mice. 1400w (10 mg/kg i.p) was applied before I/R injury. We measured the expression of elements associated with kidney injury, inflammation, macrophage polarization, mesenchymal transition, and nephrogenic genes by qRT-PCR in the renal cortex and medulla. The Periodic Acid-Schiff (PAS) was used to study the kidney morphology. RESULTS: Remarkably, we found that 1400W affects the renal cortex and medulla in different ways. Thus, in the renal cortex, 1400W prevented the I/R-upregulation of 1. NGAL, Clusterin, and signs of morphological damage; 2. IL-6 and TNF-α; 3. TGF-ß; 4. M2(Arg1, Erg2, cMyc) and M1(CD38, Fpr2) macrophage polarization makers; and 5. Vimentin and FGF2 levels but not in the renal medulla. CONCLUSION: 1400W conferred protection in the kidney cortex compared to the kidney medulla. The present investigation provides relevant information to understand the opportunity to use 1400W as a therapeutic approach in AKI treatment.

Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico / Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

COVID-19, glomerulonefritis ANCA y anti-membrana basal glomerular. Caso clínico / Association of COVID-19 and glomerulonephritis with ANCA and anti-glomerular basement membrane antibodies. Report of one case

Renal involvement in COVID-19 infection is varied and worsens its outcome and prognosis. However, the association of COVID-19 infection with glomerulonephritis is exceptional. We report a 46-year-old woman with COVID-19 who had an acute kidney injury and ANCA associated glomerulonephritis two weeks after the onset of the disease. The kidney biopsy showed a crescentic glomerulo-nephritis and the presence of anti-glomerular basement membrane antibodies (GBM-Abs). She was treated with steroids and oral cyclophosphamide with good response without requiring plasmapheresis. Plasma anti GBM-Abs were negative. This case suggests that the presence of anti-GBM-Abs in the kidney, was temporally related to COVID-19 pulmonary damage. The absence of plasma antibodies is probably due to transient production and glomerular adsorption, but with unknown pathogenic role.

[Association of COVID-19 and glomerulonephritis with ANCA and anti-glomerular basement membrane antibodies. Report of one case]. / COVID-19, glomerulonefritis ANCA y anti-membrana basal glomerular. Caso clínico.

Renal involvement in COVID-19 infection is varied and worsens its outcome and prognosis. However, the association of COVID-19 infection with glomerulonephritis is exceptional. We report a 46-year-old woman with COVID-19 who had an acute kidney injury and ANCA associated glomerulonephritis two weeks after the onset of the disease. The kidney biopsy showed a crescentic glomerulo-nephritis and the presence of anti-glomerular basement membrane antibodies (GBM-Abs). She was treated with steroids and oral cyclophosphamide with good response without requiring plasmapheresis. Plasma anti GBM-Abs were negative. This case suggests that the presence of anti-GBM-Abs in the kidney, was temporally related to COVID-19 pulmonary damage. The absence of plasma antibodies is probably due to transient production and glomerular adsorption, but with unknown pathogenic role.

[Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case]. / Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico.

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

[Acute phosphate nephropathy secondary to the use of oral sodium phosphate laxatives. Report of one case]. / Nefropatía aguda por fosfatos secundaria al uso de laxantes con fosfato de sodio: caso clínico-patológico.

Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.

Clinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A 4-Decade Experience.

PURPOSE: Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades. METHODS: Demographic, clinical, biochemical, and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980-2019 period. Data were organized into 4 periods by decade. RESULTS: Age at diagnosis, gender, tumor size and percentage of bilaterality, percentage of paragangliomas, and metastases remained stable across the 4 decades. The proportion of genetic testing and incidentalomas increased in recent decades (all P < 0.001). Therefore, we compared PPGLs diagnosed as incidentalomas (36%) with those clinically suspected (64%). Incidentalomas had fewer adrenergic symptoms (38 vs. 62%; P < 0.001) and lower rates of hypertension (64% vs. 80%; P = 0.01) and hypertensive crisis (28% vs. 44%; P = 0.02); also, they had lower functionality (79% vs. 100%; P = 0.01) and lower catecholamines levels (8.4-fold vs. 12.5-fold above upper cutoffs; P = 0.04). Regarding management of all PPGLs over the decades, we observed significant increases in both perioperative doxazosin dose (P = 0.003) and laparoscopic approach rates (P < 0.001), along with a decrease in the length of hospital stays (P = 0.007). CONCLUSIONS: We observed a change in the clinical presentation of PPGL in recent decades, with a marked increase in incidental cases and milder symptoms. The implementation of a multidisciplinary program for adrenal disorders in our institution has translated into more timely diagnoses, more genetic testing, and improvements in perioperative management.

Diagnosis of light chain cast nephropathy through immunostaining of the urine: Perfecting the "liquid biopsy".

Light chain (LC) cast nephropathy is the main cause of kidney injury and an important determinant of poor survival in patients with multiple myeloma (MM). It is usually suspected when an MM patient with elevated serum concentration of free LC presents kidney failure, but it often requires confirmation by kidney biopsy. We report the case of a 73-year-old woman who presented with fatigue, weight loss, and constipation. Laboratory exams revealed anemia, hypercalcemia, and kidney failure. Urine sediment analysis demonstrated irregular crystalline "waxy type" casts. With the hypothesis of LC cast nephropathy, immunostaining of the urine sediment was performed. The analysis revealed several rectangular and irregular casts with intense and bright stain for λ LCs only. A myelogram was performed, showing extensive occupation of the bone marrow by plasma cells; and immunofixation in urine and serum revealed monoclonal IgG-λ component, confirming the diagnosis of IgG-λ MM. This case highlights the potential utility of the urine sediment analysis and immuno-staining as a reliable non-invasive alternative method for diagnosis of cast nephropathy in patients with monoclonal gammopathies.

Immune Dysregulation Mimicking Systemic Lupus Erythematosus in a Patient With Lysinuric Protein Intolerance: Case Report and Review of the Literature.

Lysinuric protein intolerance (LPI) is an inborn error of metabolism caused by defective transport of cationic amino acids in epithelial cells of intestines, kidneys and other tissues as well as non-epithelial cells including macrophages. LPI is caused by biallelic, pathogenic variants in SLC7A7. The clinical phenotype of LPI includes failure to thrive and multi-system disease including hematologic, neurologic, pulmonary and renal manifestations. Individual presentations are extremely variable, often leading to misdiagnosis or delayed diagnosis. Here we describe a patient that clinically presented with immune dysregulation in the setting of early-onset systemic lupus erythematosus (SLE), including renal involvement, in whom an LPI diagnosis was suspected post-mortem based on exome sequencing analysis. A review of the literature was performed to provide an overview of the clinical spectrum and immune mechanisms involved in this disease. The precise mechanism by which ineffective amino acid transport triggers systemic inflammatory features is not yet understood. However, LPI should be considered in the differential diagnosis of early-onset SLE, particularly in the absence of response to immunosuppressive therapy.

[A secondary focal segmental glomerulosclerosis due to prematurity]. / Glomeruloesclerosis focal y segmentaria secundaria a la oligonefronia del prematuro.

INTRODUCTION: Both premature birth and low birth weight compromise nephron development. The lower nephron endowment is subjected to compensatory hyperfiltration that overloads the glomeruli and leads to the vicious circle of progressive deterioration of renal function. OBJECTIVE: To emphasize the risk of renal involvement in this susceptible population by describing the case of a patient with long-term follow-up. CLINICAL CASE: Low-weight premature newborn, who presented at 3 years of age severe hypertension, which was controlled with different types of antihypertensive drugs. However, 10 years later subnephrotic proteinuria was detected; a renal biopsy confirmed a focal and segmental glome rulosclerosis. Despite blocking the renin-angiotensin system for 23 years, his renal function progres sively deteriorated, until requiring chronic hemodialysis during the last 3 years. CONCLUSION: It is essential to increase the awareness of the risk of renal damage in premature and low weight newborns in order to establish management that covers from gestation to adult life and to achieve an individual and epidemiological impact on renal health.

Nefropatía aguda por fosfatos secundaria al uso de laxantes con fosfato de sodio: caso clínico-patológico / Acute phosphate nephropathy secondary to the use of oral sodium phosphate laxatives: report of one case

Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.

Takayasu's arteritis and secondary membranous nephropathy: an exceptional association.

The association between Takayasu's arteritis and membranous nephropathy is uncommon. We present the case of a 46-year-old man with Takayasu's arteritis treated over 10 years by a multidisciplinary medical team. He had an atrophic left kidney due to arterial stenosis, with a basal creatinine of 1.59 mg/dL (140.55 µmol/l). Three years ago, he presented with full nephrotic syndrome, uncontrolled blood pressure, creatinine increases to 4.5 mg/dL (basal: 1.59 mg/dL), severe hypoalbuminaemia (1.4 g/dL) and albuminuria of 24.6 g per day. He underwent percutaneous biopsy of the right kidney that showed membranous nephropathy with negative PLA2R1 and positive IgG 1, 3 and 4 subclasses. After therapy with oral prednisone and cyclophosphamide, the patient's kidney function improved, without recurrence of disease after 3 years of follow-up. Here, we present this extremely uncommon association of Takayasu's arteritis and membranous nephropathy.

Bladder squamous cell carcinoma in a pregnant woman: case report and review of the literature.

BACKGROUND: Bladder tumors in pregnancy are extremely rare. No more than 50 cases have been published to date, including all histologic variants, and only three cases of bladder squamous cell carcinoma have been described. CASE PRESENTATION: We present a clinical case of a 31-year-old woman with bladder squamous cell carcinoma in the second trimester of pregnancy. After a C-section at 30 weeks, we performed radical cystectomy with extended bilateral lymphadenectomy, hysterectomy and right oophorectomy. The Studer neobladder technique was performed for urinary tract reconstruction. Definitive pathology showed invasive bladder squamous cell carcinoma, Grade 2, with microscopic infiltration of the perivesical fat, negative margins, and 3/28 lymph nodes with carcinoma (pT3aN2M0). The patient underwent 18 months of surveillance after radical cystectomy, without recurrence by PET-CT. CONCLUSIONS: Bladder cancer in pregnant women is extremely rare but must be considered in those with recurrent gross hematuria and/or recurrent urinary tract infection. To our knowledge, this case involves the longest recurrence-free survival of a pregnant woman with squamous cell bladder cancer published thus far.

[Pediatric ANCA-associated vasculitis, a case series]. / Vasculitis asociadas a ANCA en pediatría, serie de casos clínicos.

INTRODUCTION: ANCA-associated vasculitis (AAV) is an infrequent disease in childhood. International literature about pediatric vasculitis is scarce, and it mainly refers to other systemic vasculitides with a higher incidence in childhood, such as IgA vasculitis and Kawasaki disease. OBJECTIVE: To describe the clini cal and laboratory characteristics of a series of pediatric cases with AAV. PATIENTS AND METHOD: Re trospective, descriptive study of patients with diagnosis of AAV treated at a tertiary health center from Santiago, Chile, between 2000 and 2020. Electronic medical records were reviewed collecting epidemiological, laboratory, images, and biopsies data. RESULTS: There were five cases of pediatric pa tients with AAV, with varying degrees of severity, and the age range at the onset was 5.5 to 13.5 years. We observed frequent renal involvement in microscopic polyangiitis (MPA) and eye involvement due to orbital pseudotumor in patients with granulomatosis with polyangiitis (GPA), an infrequent manifestation in the international pediatric literature. Patients were treated according to recommen dations extrapolated from clinical trials in adult populations, showing excellent clinical response to induction therapy with systemic corticosteroids and cyclophosphamide or rituximab. During main tenance therapy, most of the patients were stable on rituximab, azathioprine, or methotrexate. No patient developed organ damage and all cases achieved discontinuation of the corticosteroid therapy. CONCLUSION: This report describes the clinical characteristics of AAV in a series of pediatric patients. In this series, renal involvement was common in MPA and eye involvement due to orbital pseudotu mor in GPA. The clinical response with treatment according to recommendations extrapolated from the adult population was favorable.

Acute liver failure and liver transplantation secondary to flutamide treatment in a prostate cancer patient.

Flutamide is a first-generation nonsteroidal antiandrogen, used for treatment of advanced prostate cancer (PCa). We present the clinical case of a patient with localized high-risk PCa who started flutamide before radical prostatectomy and evolved with acute liver failure and liver transplantation. Hepatotoxicity induced by antiandrogen therapy, and current indications for first generation anti-androgen therapy were reviewed. To our knowledge, this is the first report of a man diagnosed with PCa who evolved with acute liver failure secondary to flutamide, and finally required liver transplantation.