The role of basiliximab in the evolving renal transplantation immunosuppression protocol

Basiliximab is a chimeric mouse-human monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor on activated T lymphocytes. It was shown in phase III trials to reduce the number and severity of acute rejection episodes in the first year following renal transplantation in adults and children, with a reasonable cost-benefit ratio. The drug does not increase the incidence of opportunistic infections or malignancies above baseline in patients treated with conventional calcineurin inhibitor-based immunosuppression. In the field of renal transplantation, basiliximab does not increase kidney or patient survival, despite the reduction in the number of rejection episodes. Basiliximab may reduce the incidence of delayed graft function. In comparison with lymphocyte-depleting antibodies basiliximab appears to have equal efficacy in standard immunological risk patients. Recently, IL-2 receptor monoclonal antibodies have been used with the objective of reducing or eliminating the more toxic elements of the standard immunosuppression protocol. Several trials have incorporated basiliximab in protocols designed to avoid or withdraw rapidly corticosteroids, as well as protocols which substitute target-of-rapamycin (TOR) inhibitors for calcineurin inhibitors

O Atendimento odontológico do paciente renal terminal submetido a dialise: uma revisão atual da literatura médica vigente.

Chronic renal failure is a progressive disease characterized by a gradual destruction of the nephrons and a consequent reduction in renal function. End-stage kidney disease (ESRD) requires renal replacement therapy such as peritoneal dialysis, hemodialysis or transplantation. Patients affected by ESRD or on hemodialysis are at risk of developing a series of comorbidities, including hypertension, anemia, risk of bleeding, susceptibility to infection, side effects of medications and oral manifestations associated with the disease itself and treatment on hemodialysis. In this context, oral diseases represent a potential and preventable cause of poor health outcomes in people with ESRD due to their relationship with infection, inflammation and malnutrition.A insuficiência renal crônica é uma doença progressiva caracterizada por uma destruição gradual dos néfrons e uma conseqüente redução da função renal. A doença renal em estágio terminal (DRT) requer terapia de substituição renal como diálise peritoneal, hemodiálise ou transplante. Os pacientes afetados pela DRT ou em hemodiálise correm risco de desenvolver uma série de comorbidades, incluindo hipertensão, anemia, risco de sangramento, suscetibilidade à infecção, efeitos colaterais dos medicamentos e manifestações orais associadas à própria doença e ao tratamento em hemodiálise. Nesse contexto, as doenças bucais representam uma causa potencial e evitável de maus resultados de saúde em pessoas com DRT devido à sua relação com infecção, inflamação e desnutrição

Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis

Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis.BackgroundHyperlipemia characterizes nephrotic syndrome (NS) and contributes to the progression of the underlying nephropathy. The data in the literature support an implication of apolipoprotein E (apoE) in both hyperlipemia and focal segmental glomerulosclerosis (FSGS), a malignant condition associated with NS.MethodsThe apoE genotype was determined in 209 nephrotic patients, who were classified according to age and their response to steroids as resistant children (N = 96) and adults (43), and steroid dependent (33) and steroid responder (37) children. A total of 123 presented the histological features of FSGS. In a subgroup of 28 patients, serum and urinary levels of apoE and renal deposits were evaluated by immunofluorescence.ResultsThe allelic frequencies of the three major haplotypes γ2, γ3, and γ4 were the same in nephrotic patients versus controls, and homozygosity for γ3γ3 was comparably the most frequent genotype (70 vs. 71%) followed by γ3γ4, γ2γ3, γ2γ4, γ4γ4. Serum levels of apoE were fivefold higher in NS and in FSGS patients than in controls, with a direct correlation with hypercholesterolemia and proteinuria. ApoE genotypes did not influence serum levels. Urinary levels were 1/10,000 of serum with an increment in nephrotic urines. Finally, immunofluorescence demonstrated the absence of apoE in sclerotic glomeruli, while comparably nephrotic patients with membranous nephropathy had an increased glomerular expression of apoE.ConclusionsApoE is dysregulated in NS with a marked increment in serum, which is a part of the complex lipid metabolism. Down-regulation of glomerular apoE instead is a peculiarity of FSGS and may contribute to the pathogenesis of the disease. The normal distribution of apoE genotypes in nephrotic patients with FSGS excludes a pathogenetic role of genetic variants

A facility and community-based assessment of scabies in rural Malawi.

Background Scabies is a neglected tropical disease of the skin, causing severe itching, stigmatizing skin lesions and systemic complications. Since 2015, the DerMalawi project provide an integrated skin diseases clinics and Tele-dermatology care in Malawi. Clinic based data suggested a progressive increase in scabies cases observed. To better identify and treat individuals with scabies in the region, we shifted from a clinic-based model to a community based outreach programme. Methodology/principal findings From May 2015, DerMalawi project provide integrated skin diseases and Tele-dermatological care in the Nkhotakota and Salima health districts in Malawi. Demographic and clinical data of all patients personally attended are recorded. Due to a progressive increase in the number of cases of scabies the project shifted to a community-based outreach programme. For the community outreach activities, we conducted three visits between 2018 to 2019 and undertook screening in schools and villages of Alinafe Hospital catchment area. Treatment was offered for all the cases and school or household contacts. Scabies increased from 2.9% to 39.2% of all cases seen by the DerMalawi project at clinics between 2015 to 2018. During the community-based activities approximately 50% of the population was assessed in each of three visits. The prevalence of scabies was similar in the first two rounds, 15.4% (2392) at the first visit and 17.2% at the second visit. The prevalence of scabies appeared to be lower (2.4%) at the third visit. The prevalence of impetigo appeared unchanged and was 6.7% at the first visit and 5.2% at the final visit. Conclusions/significance Prevalence of scabies in our setting was very high suggesting that scabies is a major public health problem in parts of Malawi. Further work is required to more accurately assess the burden of disease and develop appropriate public health strategies for its control

Small molecule membrane transporters in the mammalian podocyte: a pathogenic and therapeutic target

The intriguingly complex glomerular podocyte has been a recent object of intense study. Researchers have sought to understand its role in the pathogenesis of common proteinuric diseases such as minimal change disease and focal segmental glomerular sclerosis. In particular, considerable effort has been directed towards the anatomic and functional barrier to macromolecular filtration provided by the secondary foot processes, but little attention has been paid to the potential of podocytes to handle plasma proteins beyond the specialization of the slit diaphragm. Renal membrane transporters in the proximal tubule have been extensively studied for decades, particularly in relation to drug metabolism and elimination. Recently, uptake and efflux transporters for small organic molecules have also been found in the glomerular podocyte, and we and others have found that these transporters can engage not only common pharmaceuticals but also injurious endogenous and exogenous agents. We have also found that the activity of podocyte transporters can be manipulated to inhibit pathogen uptake and efflux. It is conceivable that podocyte transporters may play a role in disease pathogenesis and may be a target for future drug development

Percutaneous cryoablation of a renal cell carcinoma in a transplanted kidney

In patients who undergo renal transplantation urinary tract tumors have an incidence of approximately 1.5%-3.3%. We report a rare case of renal cell carcinoma occurring in a transplanted kidney 25 years after the transplant. The lesion was treated by CT-guided percutaneous cryoablation with the ablation of renal lesion. This approach offers more accuracy compared with ultrasonography (US), and it is faster compared to magnetic resonance (MR) guidance. In transplanted kidneys CT-guided cryoablation seems to be safe

Percutaneous cryoablation of a renal cell carcinoma in a transplanted kidney

In patients who undergo renal transplantation urinary tract tumors have an incidence of approximately 1.5%-3.3%. We report a rare case of renal cell carcinoma occurring in a transplanted kidney 25 years after the transplant. The lesion was treated by CT-guided percutaneous cryoablation with the ablation of renal lesion. This approach offers more accuracy compared with ultrasonography (US), and it is faster compared to magnetic resonance (MR) guidance. In transplanted kidneys CT-guided cryoablation seems to be safe

Diagnosis of acute intermittent porphyria in a renal transplant patient: A case report

BackgroundAcute intermittent porphyria (AIP) is an inherited disorder of porphyrin metabolism with a worldwide distribution and a prevalence ranging from 1 to 9 per million population. AIP is caused by an autosomal dominant-inherited mutation of low penetrance resulting in a deficiency of porphobilinogen deaminase (PBGD) activity. Acute attacks are provoked by stressors such as certain medications, alcohol, and infection. We herein present the first case report of AIP detected in a post-renal transplant patient.Case summaryThe patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephro-pathy. He subsequently developed diabetes mellitus which required insulin therapy. He had been treated in the recent past with local mesalamine for proctitis. He presented with classic but common symptoms of AIP including intense abdominal pain, hypertension, and anxiety. He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained. His urinary postprandial blood glucose level was 60 mg/24 h (normal, < 2 mg/24 h). He was placed on a high carbohydrate diet, and his symptoms slowly improved.ConclusionThis case report describes a common presentation of an uncommon disease, in which post-transplant complications and medications may have contributed to precipitating the previously undiagnosed AIP. We hypothesize that the low-carbohydrate diet and insulin with which our patient was treated may have led to the attacks of AIP. Alternatively, our patient's mesalamine treatment for proctitis may have led to an acute AIP crisis. A high index of suspicion is needed to consider the diagnosis of a heme synthesis disorder, which presents with the common symptoms of abdominal pain, high blood pressure, and anxiety

Warfarin-related nephropathy: possible role for the warfarin pharmacogenetic profile

Warfarin-related nephropathy (WRN) is a renal complication of warfarin treatment associated with over-anticoagulation. We describe a case of a 73-year-old man affected by chronic kidney disease, essential hypertension and atrial fibrillation treated with warfarin. The patient presented a rapid course of kidney failure after many episodes of over-anticoagulation, and renal biopsy demonstrated WRN. Interestingly, the patient's warfarin pharmacogenetic profile showed that he was warfarin sensitive. This is the first report describing the presence of gene polymorphisms affecting warfarin metabolism in a subject with a biopsy-proven WRN. The patient was treated with corticosteroids obtaining a partial clinical respons

The muscleblind gene participates in the organization of Z-bands and epidermal attachments of Drosophila muscles and is regulated by Dmef2

AbstractWe report the embryonic phenotype ofmuscleblind(mbl), a recently describedDrosophilagene involved in terminal differentiation of adult ommatidia.mblis a nuclear protein expressed late in the embryo in pharyngeal, visceral, and somatic muscles, the ventral nerve cord, and the larval photoreceptor system. All threemblalleles studied exhibit a lethal phenotype and die as stage 17 embryos or first instar larvae. These larvae are partially paralyzed, show a characteristically contracted abdomen, and lack striation of muscles. Our analysis of the somatic musculature shows that the pattern of muscles is established correctly, and they form morphologically normal synapses. Ultrastructural analysis, however, reveals two defects in the terminal differentiation of the muscles: inability to differentiate Z-bands in the sarcomeric apparatus and reduction of extracellular tendon matrix at attachment sites to the epidermis. Failure to differentiate both structures could explain the partial paralysis and contracted abdomen phenotype. Analysis ofmblexpression in embryos that are either mutant forDmef2or ectopically expressDmef2placesmbldownstream ofDmef2function in the myogenic differentiation program.mbl, therefore, may act as a critical element in the execution of twoDmef2-dependent processes in the terminal differentiation of muscles