Precil Diego Miranda de Menezes Neves

An Overview of Molecular Mechanism of Nephrotic Syndrome

Podocytopathies (minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS)) together with membranous nephropathy are the main causes of nephrotic syndrome. Some changes on the expression of nephrin, podocin, TGF-β, and slit diaphragm components as well as transcription factors and transmembrane proteins have been demonstrated in podocytopathies. Considering the pathogenesis of proteinuria, some elucidations have been directed towards the involvement of epithelial-mesenchymal transition. Moreover, the usefulness of some markers such as TGF-β1, nephrin, synaptopodin, dystroglycans, and malondialdehyde have been determined in the differentiation between MCD and FSGS. Experimental models and human samples indicated an essential role of autoantibodies in membranous glomerulonephritis, kidney damage, and proteinuria events. Megalin and phospholipase-A2-receptor have been described as antigens responsible for the formation of the subepithelial immune complexes and renal disease occurrence. In addition, the complement system seems to play a key role in basal membrane damage and in the development of proteinuria in membranous nephropathy. This paper focuses on the common molecular changes involved in the development of nephrotic proteinuria.

Fibrinogen A alpha-chain amyloidosis: report of the first case in Latin America.

Abstract Background: Hereditary fibrinogen A alpha-chain (AFib) amyloidosis affects different organs, especially the kidneys. No case of this disease has been reported in Latin America. Case report: A 52-year-old previously healthy Brazilian woman presented with a seven-month history of proteinuria in the absence of hematuria. The patient had normal blood pressure and reported no other symptoms. A renal biopsy was obtained and light microscopy revealed the presence of Congo red positive deposits (apple-green birefringence under polarized light) only in the glomerular compartment. These deposits were strongly immunoreactive to fibrinogen in all glomeruli. Electron microscopy showed the presence of organized deposits compatible with AFib. The diagnosis was confirmed by DNA analysis of the AFib gene, which demonstrated a Glu526Val mutation in one allele. Conclusion: This first description of hereditary AFib amyloidosis in Latin America highlights the need to include this type of amyloidosis in the differential diagnosis, especially in Brazil where the degree of miscegenation is high.

Acute glomerulonephritis after upper airway or skin infection: descriptive analysis of 82 cases between 14 and 64 years-old

INTRODUCAO: A glomerulonefrite aguda (GNA) apos infeccao de vias aereas superiores ou pele e uma doenca renal causada geralmente por cepas estreptococicas nefritogenicas, podendo cursar com quadro subito de hematuria macroscopica, hipertensao arterial, edema e, ocasionalmente, insuficiencia renal aguda, sendo comum na infância e pouco incidente em adultos e individuos mais jovens. OBJETIVO: Analisar, de forma descritiva, os dados da apresentacao inicial da GNA apos infeccao de vias aereas superiores ou pele em pacientes com mais de 14 anos de [...]

Schistosoma mansoni and membranous nephropathy

Figure 2 | Ultrastructural findings showing glomerular capillaries with subepithelial and intramembranous electron-dense deposits besides intervening projections (spikes) regularly distributed on the glomerular basement membrane. Original magnification 8000. A 53-year-old Brazilian man presented with lower limb edema that progressed to anasarca. He had no personal or family history of renal disease. Laboratory tests revealed urea level, 35 mg/dl; hemoglobin value, 9.8 g/dl; leukocyte count, 7500/mm; platelet count, 204,000/mm; serum albumin level, 1.2 g/dl; total cholesterol level, 239 mg/dl; and low-density lipoprotein cholesterol level, 92 mg/dl. Urinalysis showed no leukocyturia or hematuria; the 24-hour urinary protein level was 19.7 g. Serum complement levels were normal. Autoantibody testing and serologic test results were negative for hepatitis B, hepatitis C, and HIV. Light microscopy in a renal biopsy sample revealed mesangial hypercellularity, diffuse chain-like thickening with some spikes of the basement membrane, and interstitial lymphocytes (Supplementary Figure S1 online). A foreign body giant cell reaction was seen around an elliptical structure with a lateral spicule, consistent with a Schistosoma mansoni egg (Figure 1). Immunofluorescence showed granular deposits of IgG, IgA, IgM, C1q, C3, kappa, and lambda in the glomerular capillary loop. The pathologic diagnosis was of stage III membranous nephropathy (Figure 2) with tubulointerstitial

Coronary Artery Calcification Seen Through Chest Radiography

Patients with end-stage renal disease (ESRD) on dialysis have poor overall survival, and cardiovascular (CV) is the main cause of mortality among these patients. Coronary calcification is an independent predictor of mortality and CV events in dialysis patients and can be accessed by using a computerized tomography scanning. The high cost of this procedure, however, precludes routine implementation of this method for the purposes of risk stratification. Aortic arch calcification has been associated with CV mortality in the general population. Also, vascular calcification beyond the thoracic aorta has been shown to be associated with mortality in ESRD patients. We presented here a case of a young patient with ESRD in which the coronary calcification could be cleared seen through simple chest radiography. This is a 35-year-old man with a history of ESRD secondary to pyelonephritis, who was receiving conventional hemodialysis thrice a week for the last 5 years. He was submitted to chest radiography as part of routine annual cardiac screening. His blood pressure was within the target limits, although much higher in lower limbs, generating a high ankle brachial index of 1.3. He also had secondary hyperparathyroidism. His physical examination was unremarkable, except for the presence of non-functioning arteriovenous fistulas in both arms and a central venous catheter. The last routine blood test showed calcium 9.0 mg/dL, phosphate 5.7 mg/dL, potassium 4.7 mEq/L, creatinine 7.4 mg/dL, alkaline phosphatase 175 U/L, and parathyroid hormone 1,745 pg/mL. Surprisingly, the chest radiography revealed a calcified aortic valve and a calcified coronary artery. This patient had sudden cardiac death few months after this radiography had been taken. We present here a case of coronary calcification that can be seen through simple chest radiography. Such images are not usually seen, although the risk of vascular calcification is high in this population, and is closely related to CV risk. Chest radiographs, nearly universally available provide a method for assessing coronary artery calcification. Such a finding is intriguing and should alert nephrologists and cardiologists for the high risk of CV death in these patients.

Piperacillin/tazobactam-induced neurotoxicity in a hemodialysis patient: a case report.

Antibiotics are potentially a cause of neurotoxicity in dialysis patients, the most common are the beta‐lactams as ceftazidime and cefepime, and few cases have been reported after piperacillin/tazobactam use. This report presents a case of a hypertensive and diabetic 67‐year‐old woman in regular hemodialysis, which previously had a stroke. She was hospitalized presenting pneumonia, which was initially treated with cefepime. Two days after treatment, she presented dysarthria, left hemiparesis, ataxia, and IX and X cranial nerves paresis. Computed tomography showed no acute lesions and cefepime neurotoxicity was hypothesized, and the antibiotic was replaced by piperacillin/tazobactam. The neurologic signs disappeared; however, 4 days after with piperacillin/tazobactam treatment, the neurological manifestations returned. A new computed tomography showed no new lesions, and the second antibiotic regimen withdrawn. After two hemodialysis sessions, the patient completely recovered from neurological manifestations. The patient presented sequentially neurotoxicity caused by two beta‐lactams antibiotics. This report meant to alert clinicians that these antibiotics have dangerous neurological effects in chronic kidney disease patients.

Dialysis as a Treatment Option for a Patient With Normal Kidney Function and Familial Tumoral Calcinosis Due to a Compound Heterozygous FGF23 Mutation

Primary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%. Parathyroid hormone was suppressed (15 pg/mL), associated with a low-normal 25-hydroxyvitamin D (26 ng/mL) concentration but high 1,25-dihydroxyvitamin D concentration (92 pg/mL). Serum intact FGF-23 (fibroblast growth factor 23) was undetectable. Genetic analysis revealed tumoral calcinosis due to a compound heterozygous mutation in FGF23, c.201G>C (p.Gln67His) and c.466C>T (p.Gln156*). Due to lack of other treatment options and because the patient was facing severe vascular complications, we initiated a daily hemodialysis program even in the setting of normal kidney function. This unusual therapeutic option successful controlled hyperphosphatemia and reduced metastatic tumoral lesions. This is a report of a new mutation in FGF23 in which dialysis was an effective treatment option for tumoral calcinosis with normal kidney function.

Research of multiarterial atherosclerotic disease in hypertensive patients with renal artery stenosis

INTRODUCTION The detection of the renal artery stenosis in hypertensive patients can be a signal of systemic arterial atherosclerosis. AIMS To identify and characterize clinical-epidemiologically the hypertensive patients with renal artery stenosis, evaluating factors of cardiovascular risk and presence of symptomatic multiarterial atherosclerotic. METHOD Were selected the hypertensive patients who were assisted at the Nephrological Clinic of Universidade Federal do Triângulo Mineiro (UFTM) between 2000-2010, with diagnosis of renal artery stenosis of atherosclerotic etiology. Epidemiological data were evaluated (gender, age, ethnicity), factors of cardiovascular risk (diabetes, hypercholesterolemia, hypertriglyceridemia, tabagism, metabolic syndrome), information on hypertension (time of diagnosis, family report, number of used medicines), previous cardiovascular events (acute myocardial infarctation, ischemic stroke, peripheral arterial disease). Blood pressure levels, global cardiovascular risk and Score Framingham were stratified. RESULTS Casuistry of 30 patients, feminine majority (73.3%), average of 66 year-old age, 86.67% white, medium time of hypertension of 19.94 years, 89.92 without family report, 13.8 with diabetes, 65.51% smoking, 17.25% hypertriglyredemia, 62.06% with hypercholesterolemia and 66.7% with metabolic syndrome. Average number of medicines in use: 3.26. Dominant right-sided renal artery stenosis separately (46.7%) and in proximal third (56.7%). High creatinine levels in 40% of the patients. As for the hypertension phase, majority phase 2 (47%) and 73.3% with high global cardiovascular risk. Average Framingham Score of 13%. 66.7% presented atherosclerotic disease in another place, being infarctation the main one (53.3%). CONCLUSION The most common correlation was with acute myocardial infarctation, what implicates in the search of the coronary compromising to the diagnosis of renal artery stenosis in hypertensive patients to try avoid future damages to the patient.

Giant Renal Angiomyolipoma Following Ovarian Stimulation Therapy

Renal angiomyolipomas (AMLs) are benign tumors with higher prevalence in women. Female hormones have been shown to induce AML enlargement. This case refers to a 40-year-old woman with 4 left kidney AMLs, the larger ones with 1.0 and 1.3 cm. Ten months after ovarian stimulation for egg harvesting, a computed tomography revealed an 18-cm AML with large-caliber vessels. Given her high risk of AML bleeding, the patient was submitted to selective arterial embolization, which turned out unsuccessful, supporting a plan of nephron-sparing surgery. Our case highlights the pro-growth effects of female hormones on AML, with particular emphasis to ovarian stimulation.

Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases

Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders.