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BackgroundThe melanocortinergic pathway orchestrates the energy homeostasis and impairments in this system often lead to an increase in body weight. Rare variants in the melanocortin 4 receptor (MC4R) gene resulting in partial or complete loss of function have been described with autosomal co-dominant inheritance. These mutations are the most common cause of non-syndromic monogenic obesity. In this context, this study aimed to sequence the MC4R gene in a Brazilian cohort of adults with severe obesity.MethodsThis study included 163 unrelated probands with Body Mass Index (BMI) ≥ 35 kg/m2, stratified into three groups, according to the period of obesity onset. From the total sample, 25 patients were enrolled in the childhood-onset group (0–11 years), 19 patients in the adolescence/youth-onset group (12–21 years), and 119 patients in the adult-onset group (>21 years). Blood pressure, anthropometric and biochemical characteristics were obtained, and the MC4R coding region of each subject’s DNA was assessed using automated Sanger sequencing.ResultsSignificant anthropometric differences between the groups were observed. Higher body weight and BMI medians were found in patients with childhood-onset or adolescence/youth-onset when compared to the adulthood-onset obesity group. A total of five mutations were identified, including four missense variants: p.Ser36Thr, p.Val103Ile, p.Ala175Thr, and p.Ile251Leu. Additionally, we observed one synonymous variant (p.Ile198=). The p.Ala175Thr variant was identified in a female case with severe obesity and adulthood-onset. This variant was previously described as a partial loss-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity.ConclusionThis study showed a prevalence of common and rare variants in a cohort of Brazilian adults with severe obesity and candidates to bariatric surgery. We have identified a rare potentially pathogenic MC4R variant in a Brazilian patient with severe and adulthood-onset obesity.

Introduction Amongst Parkinson's disease (PD) genetic factors, mutations in LRRK2, SNCA, VPS35 and GBA genes are recognized causes of PD. Nonetheless, few genetic screenings have been conducted in families with a history of PD consistent with autosomal dominant inheritance (ADPD), and their relevance to the etiology of PD has been poorly explored in Latin American populations, such as the Brazilian one, with a high degree of admixture. Methods In order to assess the contribution of specific mutations in LRRK2, SNCA, VPS35 and GBA genes to ADPD in Brazil, we conducted the first molecular evaluation in a cohort of 141 index cases from families with ADPD. Genomic DNA was isolated from peripheral blood or saliva, and the molecular analysis was performed by TaqMan allelic discrimination assays or bidirectional sequencing. Results Heterozygous mutations in LRRK2 and GBA genes were identified in 10 (7.0%) probands, and all presented typical signs of classical PD. No mutations were found in SNCA or VPS35 genes. Conclusion Our findings in a representative series of index cases from families with ADPD emphasize the important contribution of LRRK2 G2019S and GBA (L444P and N370S) mutations to parkinsonism in Brazilian families. The absence of mutations in VPS35 and SNCA genes reveals that they are uncommon causes of PD in Brazil, corroborating previous studies that also failed to detect these genetic variants in PD patients from other populations. Recent discoveries of novel causative genes of autosomal dominant forms of PD expand the investigative possibilities and should be targeted on future studies.

It is known that the incidence of malignancy in transplant recipients is higher than in the general population, with a more aggressive behavior and a worse outcome. In fact, malignancy is the third most common cause of death among kidney transplant (KT) recipients, after cardiovascular events and infections. The aim of this study was to investigate the incidence and characteristics of malignancies after KT in a single center. A total of 2353 patients who underwent KT between 1987 and 2012 were retrospectively studied. The results were compared with a group without cancer. During the follow-up period leading to August 2014, which included a median duration of 126.3 ± 81.8 months, 223 malignancies (9.4%) were diagnosed, which were the cause of death in 59 patients. Patients with cancer were older, had a longer duration of graft function, and had more episodes of acute rejection (AR), and a higher number of patients were treated with azathioprine and cyclosporine as initial immunosuppressive regime (P = .001). The most frequent malignancy was skin cancer (28.7%), followed by malignant lymphoma (12.1%) and kidney cancer (10.8%). The mean age of patients at diagnosis was 58.0 ± 11.1 years. The average time for development of a cancer was 7.5 ± 5.8 years, with 43.2% detected between 1 and 5 years. Patient survival was significantly lower among subjects with cancer, and censored graft survival was significantly higher in this group (P = .001). Multivariate logistic regression analysis showed that recipients' age and acute rejection episode are risk factors for development of post–kidney transplantation malignancy.

NTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury. Although commonly associated with human immunodeficiency virus (HIV) infection, it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT: We present the case of a 50-year-old man, with chronic kidney disease secondary to focal and segmental glomerulosclerosis, who received a cadaveric kidney transplant in 2007. There were no relevant intercurrences until May 2015, when he presented with nephrotic range proteinuria (± 4 g/d). A graft biopsy was performed and it did not show any significant pathological changes. In September, he developed a full nephrotic syndrome (proteinuria 19 g/d) and a graft biopsy was repeated. CG features were evident with a rich immunofluorescence. Antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies were positive; the remaining immunologic study was normal. Viral markers for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) were negative. The patient was treated with corticosteroid pulses and plasmapheresis (seven treatments). A rapid deterioration of kidney function was seen and he became dialysis dependent. He was discharged with a low-dose immunosuppressive treatment. In October, he was hospitalized with diffuse alveolar hemorrhage (DAH). The auto-immune study was repeated, revealing complement consumption and positive titers of ANA and Anti-dsDNA antibodies. Anti-neutrophil cytoplasmic antibodies (ANCAs) and antiglomerular basement membrane antibody (anti-GBM) were negative. Treatment with intravenous corticosteroids, plasmapheresis, and human immunoglobulin was ineffective and the outcome was fatal. CONCLUSION: This case report highlights the possible association of CG and SLE. To our knowledge, it is the first case of SLE presenting with CG and DAH, with the singularity of occurring in a kidney transplant recipient receiving immunosuppression. info:eu-repo/semantics/publishedVersion

BACKGROUND: The purpose of this study was to determine the incidence of early surgical complications of kidney transplantation in our institution and its association with donor and recipient factors, as well as patient and transplant outcome. METHODS: A retrospective cohort study of all kidney transplants performed during 2015 was made. We evaluated the incidence of surgical complications and the outcome of patients and grafts at a 3-month follow-up interval. RESULTS: During the study period, 141 kidney transplants occurred. Seventeen patients had surgical complications (6 urologic, 6 vascular, and 5 other complications). Five patients lost the graft during the follow-up. Older age was associated with other surgical complications (P = .023), and graft loss was associated with the existence of surgical complications, namely, vascular complications (P

INTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss. info:eu-repo/semantics/publishedVersion

INTRODUCTION: Rehospitalization early post-kidney transplant is common and has a negative impact in morbidity, graft survival, and health costs. Infection is one the most common causes, and identifying the risk factors for early readmission due to infectious complications may guide a preventive program and improve outcome. The aim of this study was to evaluate the incidence, characterize the population, and identify the risk factors associated with early readmission for infectious complications post-kidney transplantation. METHODS: We performed a retrospective cohort study of all the kidney transplants performed during 2015. The primary outcome was readmission in the first 3 months post-transplant due to infectious causes defined by clinical and laboratory parameters. RESULTS: We evaluated 141 kidney transplants; 71% of subjects were men, with an overall mean age of 50.8 ± 15.4 years. Prior to transplant, 98% of the patients were dialysis dependent and 2% underwent pre-emptive living donor kidney transplant. The global readmission rate was 49%, of which 65% were for infectious complications. The most frequent infection was urinary tract infection (n = 28, 62%) and the most common agent detected by blood and urine cultures was Klebsiella pneumonia (n = 18, 40%). The risk factors significantly associated with readmission were higher body mass index (P = .03), diabetes mellitus (P = .02), older donor (P = .007), and longer cold ischemia time (P = .04). There were 3 graft losses, but none due to infectious complications. CONCLUSION: There was a high incidence of early rehospitalization due to infectious complications, especially urinary tract infections to nosocomial agents. The risk factors identified were similar to other series. info:eu-repo/semantics/publishedVersion

Background Parkinson's disease (PD) is a neurodegenerative disorder characterized by remarkable phenotypic variability. Accumulated evidence points that the manifestation of PD clinical signs might be differentially modified by genetic factors, as mutations in LRRK2 and GBA genes. In this sense, the clarification of the genotype-phenotype correlations in PD has important implications in predicting prognosis and can contribute to the development of specific therapeutic approaches. Methods Here, we conducted the first comparative analysis of motor and non-motor features in 17 LRRK2 and 22 GBA mutation carriers and 93 non-carriers unrelated PD patients from Brazil, a highly admixed population. Results Significant differences were found between the three groups. LRRK2 PD patients presented more occurrence of familiar history. Resting tremor was observed in a lower frequency in GBA mutation carries. In contrast, gait freezing and dysautonomia was present in lower frequencies in LRRK2 carriers. Besides that, LRRK2 and GBA mutation carriers showed a higher incidence of depressive symptoms and a younger age at onset, when compared to non-carriers. Conclusion Our results suggest that specific mutations in GBA and LRRK2 influence the clinical signs of the disease, with significant implications for handling of specific patient groups.

Background Patients with multiple myeloma (MM) manifesting acute kidney injury (AKI) and who later recover renal function and independence from renal replacement therapy (RRT) are considered to have a better outcome. The aim of this work was to study the factors associated with renal function recovery (independence of hemodialysis) and longer survival in these patients. Methods A retrospective single center study including patients with a diagnosis of MM and severe AKI, defined as stage 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria: 3.0 times baseline increase in serum creatinine (sCr) or increase in sCr to ≥ 4.0 mg/dL or initiation of RRT, was conducted. Data was registry-based and collected between January 2000 and December 2011. We examined demographic and laboratorial data, presenting clinical features, precipitating factors, need for RRT and chemotherapy. Death was considered the primary endpoint. Results Lower serum β2-microglobulin was the only independent factor associated with recovery of renal function and independence of RRT (OR 0.95, 95% CI: 0.91–0.99, P = 0.02). The median survival after AKI was 10.7 ± 12.1 months. The factors associated with longer survival were independence of RRT (HR 2.21; 95% CI: 1.08–4.49; P = 0.02), lower CRP (HR 1.07; 95% CI: 1.03–1.12; P = 0.001) and younger age (HR 1.03; 95% CI: 1.01–1.06; P = 0.005). Conclusions Our study suggests that MM patients with lower serum β2-microglobulin have a higher likelihood of recovering renal function after severe AKI. Independence of RRT, lower CRP and younger age are associated with longer survival.

Background Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus (SLE) that can lead to end-stage renal disease. According to the Kidney Disease Outcomes Global Improving clinical Guidelines for Glomerulonephritis, spot urine protein/creatinine (P/C) ratio should be used for monitoring LN. However, some reports write that the random spot urine P/C ratio is unreliable in monitoring proteinuria in SLE glomerulonephritis patients. The aim of this study was to evaluate the agreement of these two assay methods. Methods The prospective observational study was performed. Fifty-three paired (total 106) spot and 24-h urine collections were evaluated. Statistical analysis: SPSS 20.0. Results Paired samples t-test did not reveal significant differences between the two-paired assay methods (spot P/C ratio versus 24-h proteinuria and 24-h P/C ratio) and a statistically significant correlation was observed between them: Pearson's coefficient of 0.847 (P < 0.001) and 0.863 (P < 0.001), respectively. However, after stratifying by degrees of proteinuria, a poor correlation was found in the range of 0.05). In fact, only 1% of 24-h measurements could be explained by the spot P/C ratio. Conclusions Our study demonstrated a good correlation between 24-h proteinuria and random P/C ratio among patients with LN. However, this correlation was poor for proteinuria under 500 mg/day and did not exist in a range between 500 and 1000 mg/day. This finding is of greater importance because this range is quite common in patients with LN remission. Until further clarification, to the best of our knowledge, we maintain reluctant to completely substitute the 24-h collection by the P/C ratio especially when a renal flare is suspected, or before any change in therapy.

Diabetes currently accounts for approximately 45% of cases of end-stage renal failure in patients undergoing hemodialysis. Several observational studies have identified a positive correlation between measures of glycemic control and cardiovascular and microvascular benefits. Several randomized prospective studies have been conducted to quantify the impact of strict glycemic control on morbidity and mortality. These studies have consistently demonstrated an association between strict glycemic control and a reduction in microvascular events, but these results contrast with the lack of consistent results regarding macrovascular events. Treating diabetes has always been challenging. This challenge is increased in chronic kidney disease, due to changes in the pharmacokinetics and pharmacodynamics of insulin and most oral antidiabetic agents. The available pharmacotherapeutic arsenal for treating type 2 diabetes mellitus currently involves approximately 6 different pharmacological classes of oral antidiabetic agents and different modalities of insulin therapy.

AL amyloidosis is a clonal plasma cell proliferative disorder characterised by extracellular tissue deposits of insoluble fibrils derived from κ or λ immunoglobulin light chains. The most common organs affected by AL amyloidosis are the kidney, presenting with nephrotic syndrome and/or progressive renal dysfunction, and the heart, with restrictive cardiomyopathy. Hepatic deposition of fibrils occurs in half the cases but the liver is rarely the predominantly affected organ. The most common presentation of hepatic amyloidosis is hepatomegaly with elevated alkaline phosphatase. Acute liver failure with cholestasis and jaundice is a rare complication, with a prevalence of approximately 5%, and is usually associated with a worse prognosis. We report a case of a 39-year-old man admitted to our nephrology department with an unusual presentation of primary amyloidosis with nephrotic syndrome and acute liver failure, complicated by obstructive cholestasis resulting in death 2 months after diagnosis.

Introduction Invasive fungal infections (IFI) affecting transplant recipients are associated with increased mortality and graft dysfunction. Objective Describe the frequency, clinical features, and outcomes of IFI (except pneumocystis infection) in kidney transplant recipients. Method Single-center descriptive study including every kidney transplant recipient with a culture-proven or probable IFI between 2003 and 2013, according to the EORTC-MSG criteria. Results We identified 45 IFI. There were 13 cases of invasive candidiasis (C. albicans: 6 and non–C. albicans candidial spp.: 7), 11 cases of pulmonary aspergillosis (A. fumigatus: 9 and A. flavus: 2); 11 cases of subcutaneous mycosis (Alternaria spp.: 9, Paecilomyces spp.: 1, and Pseudallescheria spp.: 1); 7 cases of cryptococcosis; 2 cases of pneumonia by non-Aspergillus molds (Mucor spp.: 1 and Cunninghamella spp.: 1); and 1 case of Geotrichum capitatum pneumonia. All patients were recipients from deceased donors. Six cases occurred in the first 3 months post-transplant, 15 cases between the third and twelfth months, and 21 cases after the twelfth month. Treatment options were fluconazole for Candida infections, voriconazole or caspofungin for aspergillosis, liposomal amphotericin for cryptococcosis, and itraconazole plus excision or cryotherapy for subcutaneous mycosis. Fifteen patients died (33%). Mortality rates were 15% for invasive candidiasis, 45% for aspergillosis, 71% for cryptococcosis, 100% for non-Aspergillus molds and G. capitatum pneumonia, and 0% for subcutaneous mycosis. Six patients who survived (14%) started regular hemodialysis. Conclusion IFI still have a high mortality and morbidity in kidney transplant recipients, as verified in this report. We reinforce the need for a high index of suspicion and prompt treatment.

In mammals, methyl-CpG binding proteins play a significant role in the control of gene expression through their association with chromatin-remodeling complexes. Mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome and have also been reported in a number of X-linked mental retardation diseases. In this study, DNA samples from 363 male individuals with syndromic and non-syndromic mental retardation and other psychiatric diseases were screened for A140V (419C>T) mutation in the MECP2 gene, considered the most frequent MECP2 mutation in males. No 419C>T was found suggesting that the A140V mutation in the MECP2 gene is not a common cause of mental retardation in males. Recently, a new and abundant isoform of MECP2 was described, which has an alternative N-terminus, translated from exon 1, that was previously thought to be non-coding and has been excluded from many mutational screening, as well, the 5' and 3' UTR regions. We consider essential proceeding further screening in the whole extension of the MECP2 gene using clinically well-documented and larger sized sample to assure the overall contribution of MECP2 to mental retardation.

Cantharidin is a poisonous substance secreted by blister beetles, including the 'Spanish fly'. Historically, cantharidin was used as an aphrodisiac, vesicant and abortifacient. Symptoms of poisoning include gastrointestinal and genitourinary mucosal irritation along with renal dysfunction. We present the case of a reckless 23-year-old soldier who accepted the challenge of eating a beetle (Berberomeloe majalis). Six hours later he was admitted to the emergency room with abdominal pain, dysuria, gross haematuria with clots, hypotension, fever and renal insufficiency. With intravenous fluid therapy, he recovered clinically. Laboratory parameters returned to normal within 1 week.

Background and purpose: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been associated with Parkinson’s disease (PD), and the majority of the pathogenic variants are located in the ROC and MAPKKK domains. Methods: Exons 29–31 and 38–44 (ROC and MAPKKK domains) were sequenced in 204 patients with PD, mostly Brazilian. Results: We identified four polymorphisms, a novel silent variant p.R1398R and four substitutions: p.T1410M, p.G2019S, p.Y2189C and the novel variant p.C2139S. Conclusions: The most prevalent mutation was the p.G2019S (2.4%). We consider that the p.T1410M and the p.Y2189C variants are probably polymorphisms and that the p.C2139S mutation is potentially pathogenic.

The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate are not validated in this population. During the first trimester of gestation, acute kidney injury develops most often due to hyperemesis gravidarum or septic abortion. In the third trimester, the differential diagnosis is more challenging for the obstetrician and the nephrologist and comprises some pathologies that are reviewed in this article: preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies.

Mutations in the Jumonji AT-rich interactive domain 1C (JARID1C/SMCX/KDM5C) gene, located at Xp11.22, are emerging as frequent causes of X-linked intellectual disability (XLID). KDM5C encodes for a member of an ARID protein family that harbors conserved DNA-binding motifs and acts as a histone H3 lysine 4 demethylase, suggesting a potential role in epigenetic regulation during development, cell growth and differentiation. In this study, we describe clinical and genetic findings of a Brazilian family co-segregating a novel nonsense mutation (c.2172C>A) in exon 15 of KDM5C gene with the intellectual disability phenotype. The transition resulted in replacement of the normal cysteine by a premature termination codon at position 724 of the protein (p.Cys724X), leading to reduced levels of KDM5C transcript probably due to nonsense mediated mRNA decay. The clinical phenotype of the proband, who has two affected brothers and a mild cognitively impaired mother, consisted of short stature, speech delay, hyperactivity, violent behavior and high palate, besides severe mental retardation. Our findings extend the number of KDM5C mutations implicated in XLID and highlight its promise for understanding neural function and unexplained cases of XLID.

Point mutations and genomic rearrangements in the MECP2 gene are the major cause of Rett syndrome (RTT), a pervasive developmental disorder affecting almost exclusively females. MECP2 mutations were also identified in patients with autism without RTT. In this study, we present a mutational and gene dosage analysis of the MECP2 in a cohort of 60 Brazilian males with autistic features but not RTT. No duplication or deletion was identified. Sequencing analysis, however, revealed four MECP2 sequence variations. Three of them were previously discussed as non disease causing mutations and one mutation (p.T160S) was novel. It affects a highly conserved amino acid located within the MBD domain, a region of the protein involved in specific recognition and interaction with methylated CpG dinucleotides. The p.T160S variation was not found in the control sample. This mutation may represent a potential genetic factor for autistic phenotype and should be object of further studies.

There is good evidence that long-term graft survival is superior when living donors are used for kidney transplantation. Nevertheless, an assessment of potential risks associated with living donation is of particular interest.In this single-center study, we evaluated the renal function of 31 kidney living donors (1997-2003) at 2-13.2 years after nephrectomy. The purpose of this study was to evaluate perioperative complications, renal function, new-onset proteinuria, and hypertension.Living related donation was performed in all cases. The average time after donation was 5.7 +/- 2.4 years. The mean age at nephrectomy was 46.3 +/- 9.0 years (range, 25-64), and 26 (83.9%) donors were females. Twelve patients (29%) were older than 50 years. The left kidney was used in 25 patients (80.6%). Surgical complications occurred in 2 patients. Glomerular filtration rate (GFR) decreased from 116.9 +/- 23 to 77.7 +/- 19.2 mL/min/1.73 m(2) (P.001). Five patients (16.1%) developed a postdonation GFR between 50 and 60 mL/min/1.73 m(2). Patients with lower GFR values after uninephrectomy showed lower predonation values (P.05). Older patients (50 years) displayed lower postdonation GFR than younger ones. We did not observe an increased prevalence of low postdonation GFR over time nor significant differences in protein excretion and blood pressure.Living donor nephrectomy appears to be an acceptably safe intervention. Despite a reduction in GFR, the postdonation incidence of hypertension was low and proteinuria was not observed in any donor, even among previously hypertensive patients. Rigorous donor follow-up is recommended to identify persons at risk.

Structural variations that affect the copy number of the MECP2 gene were shown to cause mental retardation in males by driving the overexpression of this gene. To access the impact of these rearrangements in males with unexplained mental retardation, we have performed a quantitative real-time polymerase chain reaction assay using SYBR Green I chemistry to quantify MECP2 gene copy number in 145 Brazilian males with mental retardation of unknown cause. Three patients carrying MECP2 duplications (approximately 2%) were identified. The analysis of additional markers flanking the MECP2 region showed that the duplications observed are nonrecurrent. Expression studies in two of these patients revealed the overexpression of the MECP2 gene compared to the expression level observed in controls. These findings corroborate other recent reports in the literature and highlight that the overexpression of MECP2 caused by duplications involving this gene is a relatively frequent genetic cause of mental retardation in males, highlighting the importance of MECP2 gene dosage for diagnostic purposes in such cases.

MeCP2 is a protein that functions as a key factor in epigenetic transcriptional regulation. Mutations in MECP2 gene have been reported as being the major cause of Rett syndrome. These mutations may also cause a wide spectrum of neurological disorders in males. Here, we report the identification of the mutation p.P405L in a 19-year-old Brazilian male with mental retardation. This variant is localized in a highly conserved aminoacid from the carboxy terminal domain and may affect the protein function. Segregation analysis on the patient's mother revealed that this is a de novo mutation and it was not identified in the control sample. The programs SIFT, PolyPhen and A-GVGD considered that the p.P405L may be damaging. Despite the high frequency of non pathogenic variants that have been identified in this gene, our data lead us to consider the p.P405L a disease-causing mutation.

MeCP2 is a protein that selectively binds to methylated cytosines through its methyl-CpG-binding domain (MBD) and connects DNA methylation to transcriptional repression. Mutations in MECP2 gene, located in Xq28, have been reported as being the major cause of Rett syndrome and are also associated with some cases of X-linked mental retardation in both males and females. In this study, we present the first screening in the MECP2 gene in a Brazilian cohort of 239 unrelated males with idiopathic mental retardation. Eight sequence variations were observed in 10 patients: one novel putative pathogenic variant, two never described variants of unknown pathogenic value and five non-pathogenic variations. We conclude that in mentally retarded Brazilian males, non-pathogenic variants in the MECP2 gene are more common than actual pathogenic mutations, and therefore alterations in this gene have a weak relationship with mental retardation in males.

A 38-year-old man with a history of myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presented after 4 days of fever >38°C, red eye, arthralgias and skin lesions. The patient's vasculitis was initially treated with a 7-month course of intravenous cyclophosphamide and oral corticosteroids, reaching complete remission. The patient had been transferred, 2 weeks before, to oral azathioprine (200 mg/day) as maintenance therapy. The physical examination found fever, conjunctivitis and painful erythematous edematous papules, with occasional pustules, involving the neck, upper back and extremities (Figure 1). In the lower legs, there were also erythematous, tender deep nodules (Figure 2). Laboratory findings revealed 12.2 × 109/L leukocytes with 85% neutrophils, elevation of both erythrocyte sedimentation rate and C-reactive protein, acute kidney injury, haematoproteinuria and leukocyturia. Infectious disease was ruled out. A skin biopsy, from an erythematous papule, showed a dense neutrophilic infiltrate in the upper dermis, junctional oedema and focal karyorrhexis. There was no vasculitis in the biopsy specimen and testing for ANCAs was negative. Fig. 1. Erythematous papules, involving the neck and upper back, typical of Sweet syndrome, with occasional pustules. Fig. 2. Erythematous deep nodules in the lower legs (mimic erythema nodosum) typical of the subcutaneous presentation of Sweet syndrome. The diagnosis of Sweet syndrome was established, and the temporal relationship between azathioprine administration and clinical presentation raised the suspicion for drug-induced Sweet syndrome. Azathioprine was withdrawn and high-dose prednisolone was initiated with a rapid and dramatic response of both cutaneous and extracutaneous manifestations. The diagnosis of azathioprine-induced Sweet syndrome was confirmed. Methotrexate was selected as maintenance therapy. Azathioprine treats a variety of autoimmune conditions, and, in nephrology, its main indication is maintenance therapy of ANCA-associated vasculitis. Sweet syndrome is one of the several recognized clinical patterns of azathioprine hypersensitivity syndrome. Sweet syndrome is characterized by fever, constitutional symptoms, peripheral neutrophilia and abrupt onset of erythematous papules, plaques or nodules [1]. Sweet syndrome presents in three clinical settings: classical, malignancy-associated and drug-induced. The criteria for drug-induced Sweet syndrome include: (i) abrupt onset of painful erythematous plaques or nodules, (ii) histopathological evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, (iii) fever >38°C, (iv) temporal relationship between drug ingestion and clinical presentation and (v) temporal resolution of lesions after drug withdrawal or treatment with systemic corticosteroids [2]. The first case of azathioprine-induced Sweet syndrome was reported in 2003 [3] and since then only 18 [4] cases have been described. We emphasize the importance of considering azathioprine-induced Sweet syndrome, within weeks of azathioprine initiation, in the differential diagnosis of infection and disease flare in patients with ANCA-associated vasculitis. Subsequent azathioprine avoidance is crucial as rechallenge can lead to anaphylaxis [5].

Light chain deposition disease (LCDD) and immunoglobulin light chain (AL) amyloidosis are uncommon, and heterogeneous clonal plasma cell (PC) proliferative disorders defined by the different biochemical characteristics of the underlying anomalous immunoglobulin. The deposits are usually multisystemic and the two diseases can coexist. The diagnosis is sometimes made difficult by the absence of a detectable paraprotein by routine immunofixation techniques, and the use of serum-free light chain (FLC) immunoassay brought new value in terms of their diagnosis, prognosis and assessment of treatment response. Association of LCDD and AL amyloidosis with multiple myeloma (MM) at the time of diagnosis is common, but further progression to this condition is considered rare. We present a case of a patient diagnosed with systemic LCDD and AL amyloidosis of atypical biochemical characteristics, with no paraprotein detected in immunoelectrophoresis and immunofixation techniques, who progressed to MM in the later course of her disease.

OBJECTIVE: The impacts of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections on patient and renal graft survivals are controversial. This study sought to evaluate the effects of pretransplantation HCV and HBV infections on renal transplant patients and their grafts at our center. PATIENTS AND METHODS: We retrospectively examined 1224 renal transplantations performed between 1992 and 2006, including 28 HBsAg positive; 64, anti-HCV; 9, anti-HCV plus HBsAg positive; and 1123, negative for anti-HCV and HBsAg. The mean posttransplantation follow-up was 5.6 +/- 4.1 years. RESULTS: The prevalences of HBV infection were 6.2% in 1994 and 2.3% in 2006 and those of HCV infection were 6.8% in 1998 and 5.2% in 2006. The rejection rate was higher among HBV+ (46.4%) and HCV+ (40.6%) groups than the negative groups (31.5%), but it was not significant. There were no significant differences in patient and graft survivals among the groups. The major cause of patient death was liver failure among patients with concomitant HBV+ and HCV+ infections and cardiovascular disease among HCV+ and negative patients. CONCLUSIONS: There has been a decrease in the prevalence of recipients with hepatitis virus infections over the last 15 years. Patient and graft survivals were not affected by HCV or HBV infection.