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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.

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.

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.

C1q nephropathy is a rare glomerulopathy characterized by mesangial deposition of the complement component C1q. These deposits can be isolated or associated with immunoglobulins or complement fractions, which are observed by immunofluorescence or immunohistochemical microscopy. In ultramicroscopy, dense mesangial deposits and alterations of the podocyte are observed. Clinically it presents as a nephrotic syndrome (NS) or by alterations of the urinalysis such as proteinuria and/or hematuria in children and young adults. In light microscopy, it is expressed with a morphological pattern of minimal change disease (MCD), mesangial proliferative glomerulonephritis or focal segmental glomerulosclerosis (FSGS). The NS during its evolution usually evolve in steroid resistance or steroid dependency, often requiring the association of immunosuppressants to obtain remission. We report a 14 years old male with a history of NS and its evolution under various treatments during a 12-year follow-up.

Background Monoclonal gammopathy of renal significance (MGRS)-related lesions are infrequent entities. There are no publications on these disorders in Latin America (LA). The aim of this study was to describe epidemiological and clinical characteristics of these patients in LA. Methods We performed a multicentre retrospective study. Patients with diagnosis of MGRS between 2012 and 2018 were included. Epidemiological and clinical data were collected from clinical records. Results Twenty-seven patients from Chile, Argentina, Ecuador and Uruguay were included. Half debuted with a nephrotic syndrome, and 32% required dialysis. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits was found in 33%, amyloidosis in 26% and monoclonal immunoglobulin deposition disease also in 26%. The immunoglobulin most frequently found in renal biopsies was IgG kappa. In 67% a paraprotein was found. Twenty patients received an anti-plasma cell regimen, and 3 a rituximab-based regimen (IgM-MGRS). Renal response (RR) was achieved in 56%. Early treatment (≤3 months) was associated with higher RR (75% vs 43%). Three patients relapsed within 21.5 months, and 3 progressed: 1 to multiple myeloma, 1 to systemic amyloidosis and another to systemic light-chain deposition disease. Two patients died, both due to infection during induction treatment. Conclusion There was a higher than expected frequency of patients requiring dialysis. The most common MGRS-related lesion was PGNMD. Early treatment was associated with better response. As a rare disease, increasing awareness and promoting early diagnosis are necessary in LA to improve outcomes. SUMMARY AT A GLANCE A collection of 27 cases of MGRS from Latin America with information on epidemiology, clinical characteristics, treatment and outcome of patients diagnosed of MGRS-related renal lesions.

Background Lupus nephritis (LN) is a complication of systemic lupus erythematosus that requires renal biopsy (RB). Proliferative classes III, IV-S, IV-G have especial clinical and pathological characteristics. Aim To determine the association between pathological features in RB with serum creatinine and urine protein levels. Material and Methods We analyzed 186 RB performed in adults aged 18 to 73 years, from a renal pathology reference center. Histopathological variables such as class and subclass of proliferative LN, endocapillary and extracapillary proliferation, activity and chronicity indexes, and vascular sclerosis were correlated with serum creatinine and urine protein levels, at the time of diagnosis. Results As compared with LN III, all the morphological and laboratory values were significantly more deteriorated in LN IV, with special focus on vascular sclerosis. Serum creatinine was the only variable that significantly differentiated LN IV-S from LN IV-G. Proteinuria was non-significantly higher in LN IV-G compared to LN IV-S. However, the difference became significant when proteinuria was compared between LN IV-G and LN III. Conclusions The significant difference in serum creatinine between LN IV-S and LN IV-G supports the concept that they are different subclasses. Proteinuria is a variable that differentiates classes III from IV-G, being significantly higher in the second. Severe arteriosclerosis is a constant and significant finding that differentiates LN III from LN IV. Thus, we propose its usefulness for distinguishing LN classes, and eventually, to be considered in the chronicity index.

Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.

Granulomatous lobular mastitis is a rare disease whose origin is still unknown and shows an increase in its frequency. Morphological, microbiological, and molecular biology studies have linked this disease to lipophilic and fastidious corynebacteria, suggesting its possible infectious etiology. This series describes and reviews in detail the distinctive morphological characteristics of the bacteria present in the granulomas of this disease, the usefulness of histochemical techniques for their identification, and our proposal for a tissue quantification score for the bacteria. The MacCallum-Goodpasture method of Gram’s stain turned out to be the gold standard for examination, but we also highlight the efficiency of hematoxylin and eosin stain when it is exhaustively examined as well as the Grocott stain to evaluate the bacterial pleomorphism method, which is often underutilized.

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.

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.To describe the clini cal and laboratory characteristics of a series of pediatric cases with AAV.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.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.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.

Prostate cancer (PCa) is a multifocal neoplasm in which different cancer foci can be found within a single organ. This feature represents a technical difficulty when obtaining highly-enriched primary cultures of human prostate stroma cells (HPSCs), since their isolation involves enzymatic digestion of large pieces of tissue, resulting in an unknown proportion of benign- (BAF) and carcinoma-associated fibroblasts (CAF). Here we report an efficient tissue explant methodology to obtain highly-enriched populations of BAFs or CAFs from benign and malignant human prostate specimens, including needle biopsies. Also, we investigated whether different histological/pathological origins of the prostate tissue determine the activation of distinct transcription programs in HPSCs. Analysis of gene expression profiles revealed that CAFs exhibited a unique transcriptional program characterized by up-regulation of genes involved in proliferation, migration and cell adhesion. CAFs, but not BAFs, expressed typical activation markers such as α-smooth muscle actin, tenascin C and collagen 1 and stimulated tumor growth of PCa cells in vivo. Our study indicated that gene expression profile of HPSCs was determined mostly by the zone rather than the pathological state of the prostate tissue and that tissue explants from needle biopsies provide a valuable tool to obtain highly enriched primary cultures of HPSCs.

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.

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.

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.To emphasize the risk of renal involvement in this susceptible population by describing the case of a patient with long-term follow-up.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.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.

Background One of the devastating consequences of monoclonal gammopathies is the development of end-stage kidney disease, which can be prevented with an early diagnosis. Renal involvement can be secondary to saturation of paraproteins with intratubular precipitation or the glomerular deposition of paraproteins with secondary inflammation and destruction. These conditions can also be associated with monoclonal gammopathies that do not meet hematological treatment criteria, called monoclonal gammopathies of renal significance (MGRS). Aim To report a retrospective analysis of patients who underwent a renal biopsy and whose final diagnosis was a form of monoclonal gammopathy. Material and methods We reviewed the clinical and laboratory features and response to treatment of 22 patients aged 63 ± 12 years (55% women) with a pathological diagnosis of a nephropathy associated with paraproteinemia. Results The most common hematological diagnosis was amyloidosis in 50% of patients, followed by cast nephropathy. The predominant clinical presentations were proteinuria (without nephrotic syndrome) and nephritic syndrome. Classic criteria such as erythrocyte sedimentation rate > 100 mm/h and protein-albumin gap were unusual. Serum light chain quantification was the test with the best yield to detect paraproteins. Conclusions In this group of patients, light chains tend to affect the kidney more commonly than heavy chains. The prognosis of multiple myeloma is much worse than MGRS.

One of the devastating consequences of monoclonal gammopathies is the development of end-stage kidney disease, which can be prevented with an early diagnosis. Renal involvement can be secondary to saturation of paraproteins with intratubular precipitation or the glomerular deposition of paraproteins with secondary inflammation and destruction. These conditions can also be associated with monoclonal gammopathies that do not meet hematological treatment criteria, called monoclonal gammopathies of renal significance (MGRS).To report a retrospective analysis of patients who underwent a renal biopsy and whose final diagnosis was a form of monoclonal gammopathy.We reviewed the clinical and laboratory features and response to treatment of 22 patients aged 63 ± 12 years (55% women) with a pathological diagnosis of a nephropathy associated with paraproteinemia.The most common hematological diagnosis was amyloidosis in 50% of patients, followed by cast nephropathy. The predominant clinical presentations were proteinuria (without nephrotic syndrome) and nephritic syndrome. Classic criteria such as erythrocyte sedimentation rate100 mm/h and protein-albumin gap were unusual. Serum light chain quantification was the test with the best yield to detect paraproteins.In this group of patients, light chains tend to affect the kidney more commonly than heavy chains. The prognosis of multiple myeloma is much worse than MGRS.

Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE). Based on studies showing the potential role of heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme and has anti-inflammatory properties in SLE development, we decided to explore HO-1 in LN. Accordingly, we evaluated HO-1 levels and function in circulating and infiltrating monocytes and neutrophils of LN patients. HO-1 levels were assessed in peripheral monocytes of LN patients and controls by flow cytometry and immunofluorescence microscopy. Phagocytosis and the production of reactive oxygen species (ROS) were evaluated to determine the effect of HO-1 in monocyte function. In addition, renal biopsies with proliferative LN were used to identify HO-1 in infiltrating cells and renal tissue by immunofluorescence and immunohistochemistry. Biopsies of healthy controls (HC) and patients who underwent nephrectomy were included as controls. Circulating pro-inflammatory monocytes and activated neutrophils were increased in LN patients. HO-1 levels were decreased in all subsets of monocytes and in activated neutrophils. LN monocytes showed increased phagocytosis and higher production of ROS than those of HC. When HO-1 was induced, phagocytosis and ROS levels became similar to those of HC. HO-1 was mostly expressed in renal tubular epithelial cells (RTEC). Renal tissue of LN patients showed lower levels of HO-1 than HC, whereas infiltrating immune cells of LN showed lower levels of HO-1 than biopsies of patients who had renal surgery. HO-1 is decreased in circulating monocytes and activated neutrophils of LN patients. HO-1 levels modulate the phagocytosis of LN monocytes and ROS production. HO-1 expression in RTEC might be an attempt of self-protection from inflammation.

Las vasculitis asociadas a ANCA (AAV) son enfermedades infrecuentes en la edad pediátrica. La literatura internacional en pediatría es escasa y la mayoría de las publicaciones se refieren a otras vasculitis de mayor incidencia en la infancia, como la vasculitis IgA y enfermedad de Kawasaki.Objetivo: Describir las características clínicas y de laboratorio de una serie de pacientes pediátricos con diagnóstico de AAV.Pacientes y Método: Estudio retrospectivo, descriptivo, de pacientes con diagnóstico de AAV atendidos en un centro terciario de salud en Santiago, Chile, entre los años 2000 y 2020. Se revisaron fichas electrónicas recolectando datos epidemiológicos, de laboratorio, imágenes y biopsias.Resultados: Se presentan cinco pacientes pediátricos con AAV de severidad variable, rango de edad al debut 5,5 a 13,5 años. Destaca una frecuencia elevada de compromiso renal en casos de poliangeítis microscópica (MPA) y el compromiso orbitario de tipo pseudotumor inflamatorio en pacientes con granulomatosis con poliangeítis (GPA); manifestación poco frecuente en series pediátricas internacionales. Los pacientes fueron tratados según recomendaciones extrapoladas de ensayos clínicos en población adulta con respuesta clínica satisfactoria; en su mayoría con corticoides sistémicos y ciclofosfamida o rituximab en etapa de inducción. Durante la mantención, la mayoría de pacientes se mantuvo estable con rituximab, azatioprina o metotrexato. Ningún paciente evolucionó con secuelas en órganos afectados y todos lograron suspender la terapia corticoidal.Conclusión: El presente reporte describe las características clínicas de una serie de pacientes pediátricos con AAV. En esta serie, la afectación renal fue frecuente en MPA y la afectación ocular por pseudotumor inflamatorio en GPA. La respuesta clínica con tratamiento según recomendaciones extrapoladas de población adulta fue favorable.

Tanto el nacimiento prematuro como el bajo peso de nacimiento comprometen el desarrollo nefronal. La menor dotación de nefrones es sometida a hiperfiltración compensadora que sobrecarga a los glomérulos y lleva al círculo vicioso de deterioro progresivo de función renal.Objetivo: Enfatizar el riesgo del compromiso renal en esta población susceptible describiendo el caso de un paciente con seguimiento prolongado.Caso Clínico: Recién nacido prematuro nacido con bajo peso, que a los 3 años de edad presenta hipertensión severa, que logró controlarse con distintos tipos de antihipertensivos. Sin embargo, 10 años más tarde, se detectó proteinuria subnefrótica, con una biopsia renal que confirma una glomeruloesclerosis focal y segmentaria. A pesar de bloquear el sistema renina-angiotensina durante 23 años su función renal se deterioró progresivamente, hasta requerir hemodiálisis crónica durante los últimos 3 años.Conclusión: Es indispensable difundir el riesgo de daño renal en recién nacidos prematuros y de bajo peso para instalar un manejo que se extienda desde la gestación hasta la vida adulta y lograr un impacto individual y epidemiológico en la salud renal.

IgG4 disease is a multi-systemic condition involving pancreas, salivary glands and lymph nodes. Less frequently, it causes interstitial nephritis and involves the lungs. We report a 58 years old male with a four years history of hemoptysis and renal dysfunction characterized by hematuria and proteinuria, responsive to steroidal therapy. The renal biopsy established the diagnosis of IgG4 associated interstitial nephritis. Lung involvement was considered secondary to the same systemic disease.

The patient was an 18-year-old man who developed nephrotic syndrome after a ‘wheat spider’ bite (Latrodectus mactans). Due to this atypical manifestation of latrodectism, a renal biopsy was performed showing minimal change disease. The nephrotic syndrome subsided after 1 week without specific treatment. This self-limited evolution suggests that the mechanism of podocyte damage was temporary and potentially mediated by a secondary mechanism of hypersensitivity or direct effect of the α-latrotoxin. The patient did not show signs of relapse in subsequent checkup. This is the first reported case of nephrotic syndrome due to a minimal change lesion secondary to latrodectism.

C1q nephropathy is a rare glomerulopathy characterized by mesangial deposition of the complement component C1q. These deposits can be isolated or associated with immunoglobulins or complement fractions, which are observed by immunofluorescence or immunohistochemical microscopy. In ultramicroscopy, dense mesangial deposits and alterations of the podocyte are observed. Clinically it presents as a nephrotic syndrome (NS) or by alterations of the urinalysis such as proteinuria and/or hematuria in children and young adults. In light microscopy, it is expressed with a morphological pattern of minimal change disease (MCD), mesangial proliferative glomerulonephritis or focal segmental glomerulosclerosis (FSGS). The NS during its evolution usually evolve in steroid resistance or steroid dependency, often requiring the association of immunosuppressants to obtain remission. We report a 14 years old male with a history of NS and its evolution under various treatments during a 12-year follow-up.

The diagnosis of a mycosis is often established through a biopsy, which allows to differentiate invasive and non-invasive lesions, and also to identify hyaline and dematiaceous fungi. However, pigmented fungal elements that do not correspond to dematiaceous fungi, which we have called pseudodematiaceous, can occasionally be present in biopsies. Herein, we present 2 cases of mycosis caused by pseudodematiaceous fungi in rhinosinusal biopsies. A new classification for fungi identified in biopsies is proposed, dividing them into 3 groups: hyaline, dematiaceous, and pseudodematiaceous.

Resumen La esquistomiasis urinaria es producida por Schistosoma haematobium. Es una enfermedad endémica en muchas regiones del mundo, no existente en Chile. Se presenta el caso de un hombre joven que viajó a Malawi, en África meridional, y que a su regreso al país, años después, presentó un síndrome miccional con hematuria macroscópica. La biopsia de vejiga mostró una cistitis granulomatosa y eosinofílica con huevos de Schistosoma haematobium.

Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.

We report a 23 year old woman presenting with a nephrotic syndrome due to minimal change disease, central diabetes insipidus, primary hypothyroidism, vitiligo and universal alopecia. Eleven years later, she presented secondary amenorrhea due to hypogonadotropic hypogonadism, with mild hyperprolactinemia and central adrenal insufficiency. A magnetic resonance imaging of the sella turcica showed a pituitary mass with suprasellar extension that was resected using a transsphenoidal approach. Pathology confirmed the presence of a lymphoplasmacytic hypophysitis. She needed a second surgical resection due to mass growth and neuro-ophthalmologic impairment. One year later, systemic lupus erythematosus, arterial hypertension and type 2 diabetes mellitus were diagnosed. Two years later, due to back pain, constipation and renal failure, retroperitoneal fibrosis was found, satisfactorily treated with glucocorticoids and colchicine. Hence, this clinical vignette shows the coexistence of autoimmune polyglandular syndrome with retroperitoneal fibrosis and lymphoplasmacytic hypophysitis. Tissue analysis showed the presence of IgG4 producing plasma cells in the pituitary and retroperitoneum, which constitute a basis for the diagnosis of IgG4 related disease.

Background Lupus nephritis (LN) is a complication of systemic lupus erythematosus that requires renal biopsy (RB). Proliferative classes III, IV-S, IV-G have especial clinical and pathological characteristics. Aim To determine the association between pathological features in RB with serum creatinine and urine protein levels. Material and Methods We analyzed 186 RB performed in adults aged 18 to 73 years, from a renal pathology reference center. Histopathological variables such as class and subclass of proliferative LN, endocapillary and extracapillary proliferation, activity and chronicity indexes, and vascular sclerosis were correlated with serum creatinine and urine protein levels, at the time of diagnosis. Results As compared with LN III, all the morphological and laboratory values were significantly more deteriorated in LN IV, with special focus on vascular sclerosis. Serum creatinine was the only variable that significantly differentiated LN IV-S from LN IV-G. Proteinuria was non-significantly higher in LN IV-G compared to LN IV-S. However, the difference became significant when proteinuria was compared between LN IV-G and LN III. Conclusions The significant difference in serum creatinine between LN IV-S and LN IV-G supports the concept that they are different subclasses. Proteinuria is a variable that differentiates classes III from IV-G, being significantly higher in the second. Severe arteriosclerosis is a constant and significant finding that differentiates LN III from LN IV. Thus, we propose its usefulness for distinguishing LN classes, and eventually, to be considered in the chronicity index.

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.

HIV infection has different clinical presentations. We report a 21 years old male with longstanding isolated microscopic hematuria attributed to thin glomerular basement membrane disease, who after 15 years of follow-up presented with significant proteinuria. A kidney biopsy was performed, revealing the presence of tubulo-reticular inclusions in the glomerular endothelial cells. This finding led to suspect an HIV infection, which was verified. Antiretroviral therapy, angiotensin-converting enzyme and angiotensin II receptor blockers were prescribed. At 6 years of diagnosis the patient is asymptomatic and has normal kidney function. Microscopic hematuria and low level proteinuria persists.

Background Patients with systemic lupus erythematosus (SLE) and anti-ribosomal P (anti-P) antibodies may present lupus psychosis, cognitive impairment and lupus nephritis (LN). Our group provided a molecular mechanism to explain the neuronal alterations in SLE identifying the neuronal-surface P-antigen (NSPA) as an anti-P target involved in the regulation of synaptic glutamatergic transmission (Bravo-Zehnder et al. A and R 2015; Segovia-Miranda et al. A and R 2015). There is evidence suggesting that anti-P and anti-dsDNA antibodies have the potential to perturb the function of renal cells in addition to complement activation. The mechanism of anti-P association with lupus nephritis remains unclear. It is possible that direct anti-P interaction with cell surface components activates intracellular signalling pathways resulting in renal cell damage. As a first approximation to this hypothesis we study whether and where NSPA is expressed in the kidney. Methods NSPA expression was assessed by RT-PCR, immunoblot and anti-NSPA immunohistochemistry in C57WT mice, s-galactosidase (s-gal) histochemistry staining in transgenic mice bearing a LacZ gene under the promotor of NSPA gene and anti-P staining in the surface of primary cultures of PTEC and the human kidney cell line HK2. NSPA polarized distribution was studied in Madin-Darby canine kidney (MDCK) cells transfected with NSPA-GFP expression plasmid. The pathogenic potential of anti-P antibodies was analyzed by immunizing C57WT and NSPAKO mice with recombinant P0 ribosomal bearing (P0wt) or not the P epitope (P0tr) and testing anti-P and anti-dsDNA presence, proteinuria and renal pathology by histochemistry and electron microscopy. Results NSPA is expressed in PTEC cells and display a mainly apical distribution in vivo and in vitro, including the transfected MDCK cells. Both P0wt and P0tr generated high levels of anti-P antibodies and some mice also developed anti-dsDNA antibodies. Mice presented mild proteinuria at 6 months of immunization. C57WT and NSPAKO mice immunized with either P0wt or P0tr also displayed perivenular lymphocytic infiltration, a mild renal pathology change. In addition, NSPAKO mice, even in absence of anti-dsDNA, showed mesangial electron dense-deposits with discrete effacement of foot processes. Conclusions NSPA is expressed in both PTEC and polarized MDCK epithelial cells with a polarized distribution that precludes direct interaction with circulating anti-P antibodies, which might access to this target only after glomerular filtration. Circulating anti-P can associate with mild kidney damage independently of NSPA expression, at least in non-lupus prone mice. Acknowledgements CONICYT Basal grant PFB12/2007 and FONDECYT Grant 1160513.

We report a 23 year old woman presenting with a nephrotic syndrome due to minimal change disease, central diabetes insipidus, primary hypothyroidism, vitiligo and universal alopecia. Eleven years later, she presented secondary amenorrhea due to hypogonadotropic hypogonadism, with mild hyperprolactinemia and central adrenal insufficiency. A magnetic resonance imaging of the sella turcica showed a pituitary mass with suprasellar extension that was resected using a transsphenoidal approach. Pathology confirmed the presence of a lymphoplasmacytic hypophysitis. She needed a second surgical resection due to mass growth and neuro-ophthalmologic impairment. One year later, systemic lupus erythematosus, arterial hypertension and type 2 diabetes mellitus were diagnosed. Two years later, due to back pain, constipation and renal failure, retroperitoneal fibrosis was found, satisfactorily treated with glucocorticoids and colchicine. Hence, this clinical vignette shows the coexistence of autoimmune polyglandular syndrome with retroperitoneal fibrosis and lymphoplasmacytic hypophysitis. Tissue analysis showed the presence of IgG4 producing plasma cells in the pituitary and retroperitoneum, which constitute a basis for the diagnosis of IgG4 related disease.

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.

Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare disorder, first described by Destombes in 1965 and then Rosai and Dorfman reported the first clinical series in 1969. The etiology of RDD is unknown, and the treatment is not standardized. There is no data about the true number of cases that exist worldwide. This disease occurs mainly in children and young adults, however, it may occur at any age. It is more common in males and individuals of African descent. RDD, presents clinically as painful bilateral massive cervical lymphadenopathies, with fever, night sweats and weight loss. Mediastinum, inguinal region and retroperitoneum lymph nodes may also be involved. The course of the disease is unpredictable, usually characterized by episodes of exacerbation and remission. It can last for many years and is usually self-limited, with good outcomes. Extranodal compromise is unusual but can affect almost any organ. Involvement of the kidney has been stated as a poor prognostic predictor.1 We present an unusual case of RDD in a 64 year old woman with a literature review of renal RDD.

Objective:The detection of adrenal incidentalomas is increasing. Current European guidelines suggest that all adrenal incidentalomas (AI) should be screened for excess cortisol and cathecolamines, but excess aldosterone only in the presence of hypertension and/or hypokalemia. Consistently, the repor

The association of granulomatous lobular mastitis and carcinoma of the breast is very infrequent. We present the case of a 44-year-old woman with concurrent granulomatous lobular mastitis with coryneform bacteria and ductal carcinoma in situ in the same breast.

Background Monoclonal gammopathy of renal significance (MGRS) is a recently defined entity. It is a group of renal diseases due to paraprotein deposition from a small B lymphocyte or plasma cell clon, not meeting the criteria for an overt gammopathy-associated neoplasm. Despite this feature, the secondary kidney damage may be severe and irreversible; therefore, its early recognition and treatment are crucial. There are few studies on MGRS in the international literature, and no reported data from Latin America (LA). Aims To describe epidemiological and clinical characteristics of patients diagnosed with MGRS in LA. To evaluate patients outcomes. Material and methods This is an international multicentric retrospective case series study. All members of GELAMM (Grupo de estudio latinoamericano de Mieloma Múltiple) were invited to participate. Patients with diagnosis of MGRS according to the IMWG definition were included. All cases had pathological diagnosis provided by a renal biopsy. Epidemiological and clinical data were collected from clinical records in a standardized report form. Renal response was arbitrarily defined as the partial or total recovery of renal failure or renal symtoms at the end of treatment. Statistical analysis was performed by descriptive statistics using STATA 12. Results We received data from 18 patients, from centers in Chile, Argentina and Uruguay. Median follow up was 22,5 months. The patients characteristics are shown in table 1. The median age was 58 years (36 to 78 years). Male to female ratio was 1:1,25. Twelve had history of hypertension and one patient of renal transplantation. Anemia was present in 78% of cases (mean 10,7g/dL +/-2,3), hypoalbuminemia in 72% (mean 2,8g/dL +/-0,7), renal failure in 83% (mean creatinine of 4,6mg/dL +/- 4,8) with 47% of these (7 patients) requiring renal replacement therapy (RRT). Proteinuria was measured in 16 patients. Its average was 4,4gr (range 0,12 - 11,5gr/24hrs). LDH and calcemia were normal in all cases. Half of the patients presented as a nephrotic syndrome. Regarding histological subtypes, the most frequently diagnosed was the proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). The paraprotein most frequently found was Kappa, and in the renal biopsy was IgG Kappa deposition (table 1). Serum protein electrophoresis (sPEP) was performed in all cases. Only 8 out 18 patients underwent urine protein electrophoresis (uPEP) and 14 had urine and serum immunofixation (IFX) done. Serum free light chain (sFLC) were performed in 94% of the patients. The paraprotein identification according to each of this exams is shown in figure 1. Seventeen patients received treatment; 13 received an anti-plasma cell drug, 7 a thalidomide based regimen and 6 a bortezomib based regimen. The patient with IgM MGRS was treated with a rituximab based regimen. Regarding renal responses, there were no data in 5 patients. Nine out 13 of the patients achieved renal response: 3 achieved partial recovery and 9 complete recovery. Three patients become RRT independent. There was no mortality in our cohort. No patient relapsed, but 3 progressed: 1 to multiple myeloma (MM), 1 to systemic amyloidosis and another to systemic light chain deposition disease (LCDD). Discussion Only 18 cases from 3 South American countries were collected. The lack of hematologists in some countries, difficulties in achieving a renal biopsy, non-availability of immunofluorescence in the histological studies and few experienced pathologists could be some of the problems in our region. Our cohort is of rather young patients, which is probably related to the fact that these patients are mostly undergoing renal biopsy. We believe, however, that the incidence of MGRS (similar to what happens with MGUS), increases with age, which could mean a problem of underdiagnoses. As expected, nephropathies frequently associated with MM were found: AL amyloidosis and LCDD. However, the most common renal pathology was PGNMID, a rare entity. This data must be corroborated with a larger study. The high sensitivity of sFLC to identify the paraprotein was corroborated and highlighted the importance of this test in the follow up. Half of patients achieved a renal response, which reinforces the fact that they must be promptly treated. Conclusion According to our knowledge, this is the larger cases series study in LA, and we hope it will be a contribution to the knowledge of this pathology. Disclosures No relevant conflicts of interest to declare.

ANCA mediated vasculitis mainly occur between the fourth and fifth decade of life; therefore, it is very uncommon to see pregnant patients with the disease. Vasculitis may affect significantly the course of pregnancy; in turn pregnancy can change the course of vasculitis. We report a 20 years old woman with ANCA-mediated renal vasculitis lasting 10 years who consulted with a pregnancy of 15 weeks. She was in remission and had amenorrhea attributed to ovarian toxicity due to cyclophosphamide. Pregnancy had an uneventful course with spontaneous delivery at the 37th week, giving birth to a healthy newborn. Proteinuria increased during the course of pregnancy with a mild deterioration of kidney function. During the year after delivery, she had nephrotic proteinuria and a worsening of renal function.

ANCA mediated vasculitis mainly occur between the fourth and fifth decade of life; therefore, it is very uncommon to see pregnant patients with the disease. Vasculitis may affect significantly the course of pregnancy; in turn pregnancy can change the course of vasculitis. We report a 20 years old woman with ANCA-mediated renal vasculitis lasting 10 years who consulted with a pregnancy of 15 weeks. She was in remission and had amenorrhea attributed to ovarian toxicity due to cyclophosphamide. Pregnancy had an uneventful course with spontaneous delivery at the 37th week, giving birth to a healthy newborn. Proteinuria increased during the course of pregnancy with a mild deterioration of kidney function. During the year after delivery, she had nephrotic proteinuria and a worsening of renal function.

HIV infection has different clinical presentations. We report a 21-year-old male with longstanding isolated microscopic hematuria attributed to thin glomerular basement membrane disease, who after 15 years of follow-up presented with significant proteinuria. A kidney biopsy was performed, revealing the presence of tubulo-reticular inclusions in the glomerular endothelial cells. This finding led to suspect an HIV infection, which was verified. Antiretroviral therapy, angiotensin-converting enzyme and angiotensin II receptor blockers were prescribed. At 6 years of diagnosis the patient is asymptomatic and has normal kidney function. Microscopic hematuria and low level proteinuria persists.

A 31-year-old woman with nephronophthisis received a cadaveric kidney transplant, and was immunosuppressed with cyclosporine, azathioprine and steroids. Twelve days after transplant a biopsy showed acute rejection with vascular damage. She was treated with 3 pulses of methylprednisolone and change of immunosuppression to mycophenolate mofetil and tacrolimus, without improving graft function. At day 21, a second biopsy showed accentuation of interstitial and vascular rejection. Antibody-mediated rejection was suspected and plasmapheresis and rituximab were prescribed. Graft function improved rapidly. Staining for C4d was negative and there were no circulating antibodies against the donor. In the interstitial infiltrate there were clusters of B lymphocytes that accounted for 40% of cells, which was thought to be an ominous sign, as it has been associated with poor graft outcome. Acute T-cell-mediated rejection grade III (Banff 07) was diagnosed. Thirty-nine months after transplant her kidney function is stable with no other complication. This clinical case generates the hypothesis that rituximab may have a beneficial role in the therapy of acute cellular rejection when there are clusters of B lymphocytes in the infiltrate and a good response has not been obtained to conventional anti-rejection therapy.

Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment.