Assessment and management of oral health in liver transplant candidates

Liver transplantation has become a standard treatment for end-stage liver disease and the number of recipients has grown rapidly in the last few years. Dental care during pre-transplant workup is important to reduce potential sources of infection in the drug-induced immunosuppression phase of liver transplantation. Objectives: The objectives of this study were to document the prevalence of oral abnormalities in patients on a liver transplant waiting list presenting to an urban dental school clinic, discuss the appropriate dental treatment according their systemic conditions and compare their oral manifestations with those of healthy individuals. Material and Methods: A pilot study was conducted involving 16 end-stage liver disease individuals (study group- SG) attending the Special Care Dentistry Center of the University of So Paulo and 16 control individuals (control group- CG) with no liver diseases, receiving dental care at the Dental School of the University of So Paulo. These individuals were assessed for their dental status (presence of oral disease or abnormalities), coagulation status, and dental treatment indications. Results: The patients from SG exhibited a greater incidence of oral manifestations compared with CG (p=0.0327) and were diagnosed with at least one oral disease or condition that required treatment. Coagulation abnormalities reflecting an increased risk of bleeding were found in 93.75% of the patients. However, no bleeding complications occurred after dental treatment. Conclusions: The patients with chronic liver diseases evaluated in this study exhibited a higher incidence of oral manifestations compared with the control group and had at least one oral disease or abnormality which required dental treatment prior to liver transplantation. Careful oral examination and evaluation of the patient, including laboratory tests, will ensure correct oral preparation and control of oral disease prior to liver transplantation.

The association between coronary artery calcification progression and loss of bone density in non-dialyzed CKD patients

Background: Coronary artery calcification (CAC) and low bone density are coexisting deleterious conditions commonly shared by chronic kidney disease (CKD) patients. In the present study, we aimed to investigate whether the progression of CAC was associated with overtime reduction in bone density in non-dialyzed CKD patients. Methods: This is a prospective study of 24 months including 72 non-dialyzed CKD patients Stages 2 - 4 (age 57.6 +/- 10.3 years, 62% male, 22% diabetics). CAC and vertebral bone density (VBD) were measured by computed tomography. Results: At baseline, 46% of the patients had CAC (calcified group) and calcification was not identified in 54% of the patients (non-calcified group). The calcified group was older, predominantly male, and had lower VBD in comparison to non-calcified group. CAC progression was observed only in the calcified group (91% of the patients increased calcium score). The multiple regression analysis revealed loss of VBD as the independent determinant of CAC progression in these patients. Conclusion: CAC progression was associated with loss of VBD in non-dialyzed CKD patients.

Can we predict which patients will evolve to chronic kidney disease after nephrectomy for cortical renal tumors?

Introduction: While some studies show that patients submitted to radical nephrectomy have a higher risk of developing chronic kidney disease (CKD), some studies report that carefully selected living kidney donors do not present a higher risk for CKD. Here, we aim to study predictive factors of CKD after radical nephrectomy. Materials and Methods: Between January 2006 to January 2010, 107 patients submitted to radical nephrectomy for cortical renal tumors at our institution were enrolled in this study. Demographic data were recorded, modified Charlson-Romano Index was calculated, and creatinine clearance was estimated using abbreviated Modification of Diet in Renal Disease (MDRD) study equation. Pathological characteristics, surgical access and surgical complications were also reviewed. The end-point of the current study was new onset estimated glomerular filtration rate (eGFR) less than 60 and less than 45 mL/minute/1.73 m(2). Results: Age, preoperative eGFR, Charlson-Romano Index and hypertension were predictive factors of renal function loss, when the end-point considered was eGFR lower than 60 mL/minute/1.73 m(2). Age and preoperative eGFR were predictive factors of renal function loss, when the end-point considered was eGFR lower than 45 mL/minute/1.73 m2. Moreover, each year older increased 1.1 times the risk of eGFR lower than 60 and 45 mL/minute/1.73 m(2). After multivariate logistic regression, only age remained as an independent predictive factor of eGFR loss. Conclusion: Age is an independent predictive factor of GFR loss for patients submitted to radical nephrectomy for cortical renal tumors.

Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy

Chronic kidney diseasemineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-?B ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy. (C) 2012 American Society for Bone and Mineral Research.

Facial lesions caused by renal osteodystrophy in a patient with chronic renal insufficiency: a case report

PURPOSE: Chronic renal insufficiency (CRI) is the last stage of a chronic renal condition in which the kidney loses its filtration and endocrine functions. Chronic endocrine hypofunction causes generalized damage to the body known as Uremic Syndrome, which affects the central nervous system as well as the cardiovascular, hematologic, dermatologic, ophthalmic, endocrine, respiratory, gastrointestinal and skeletal systems. The present study reports the case of a female patient with CRI who presented facial osteodystrophy of the osteitis fibrosa type, and highlights the main features of this condition. CASE DESCRIPTION: A 24-year old, female, Caucasian patient presented chronic glomerulonephritis recurrence and lost the transplanted kidney five years before, undergoing arteriovenous fistula hemodialysis three times a week. She presented swelling of the left masseter area with a hard consistency on palpation, covered by intact skin, swelling at the bottom of the left atrium, with a hard consistency on palpation, a mucosa-like color and absence of inflammation signs, suggesting expansive bone lesions on the face. These features were compatible with hyperparathyroidism brown tumor and/or osteodystrophy. The CT scan showed expansive bone lesions of heterogeneous appearance on the left jaw, maxilla/nasal floor, and right frontotemporal suture areas. The clinical and histopathological characteristics of the lesion, in association with PHT hormone high serum levels led to renal osteodystrophy diagnosis. The patient was referred to the nephrology services. CONCLUSION: Osteodystrophic bone alterations have a high prevalence in renal disease patients, and the dentist must take these alterations into consideration in bone lesion diagnosis for this specific group of patients.

Oral Lesions in Renal Transplant

To prevent rejection of kidney transplants, patients must be kept in immunosuppressive therapy for a long time, which includes the use of drugs such as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of these drugs reduces the general immune response of transplant patients and thus increases their susceptibility to infections. Moreover, these drugs increase the potential of developing lesions. Therefore, oral hygiene in kidney transplant recipients contributes to maintenance of the transplanted organ and its function. Thus, an investigation of oral lesions could be counted as a notable work. The aim of this study was to investigate oral lesions in a group of 21 kidney transplant patients under immunosuppressive therapy attended during a 1-year period in the Nephrology Department of the Federal University of Sergipe, Brazil. Data related to sex, age, etiology of renal disease, types of renal transplant, time elapsed after transplantation, immunosuppressive treatment, use of concomitant agents, and presence of oral lesions were obtained. All patients received a kidney transplant from a living donor, and the mean posttransplantation follow-up time was 31.6 months; 71.5% used triple immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten patients were also treated with calcium-channel blockers. Of the 21 transplant patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most common alteration, followed by candidiasis and superficial ulcers. One case of spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a variety of manifestations related to renal transplantation under immunosuppressive therapy.

Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of Diabetes

Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p < 0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p < 0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p < 0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p < 0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p < 0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.

Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

Background: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.

Beyond "Cirrhosis" A Proposal From the International Liver Pathology Study Group

Cirrhosis is a moiphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure. However, recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly. This consensus document by the International Liver Pathology Study Group challenges the usefulness of the word cirrhosis in modern medicine and suggests that this is an appropriate time to consider discontinuing the use of this term. The role of pathologists should evolve to the diagnosis of advanced stage of chronic liver disease, with emphasis on etiology, grade of activity, features suggestive of progression or regression, presence of other diseases, and risk factors for malignancy, within the perspective of an integrated clinicopathologic assessment.

Airway disease: similarities and differences between asthma, COPD and bronchiectasis

Airway diseases are highly prevalent worldwide; however, the prevalence of these diseases is underestimated. Although these diseases present several common characteristics, they have different clinical outcomes. The differentiation between asthma, chronic obstructive pulmonary disease and bronchiectasis in the early stage of disease is extremely important for the adoption of appropriate therapeutic measures. However, because of the high prevalence of these diseases and the common pathophysiological pathways, some patients with different diseases may present with similar symptoms. The objective of this review is to highlight the similarities and differences between these diseases in terms of the risk factors, pathophysiology, symptoms, diagnosis and treatment.

Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.

In search of mechanisms associated with mesenchymal stem cell-based therapies for acute kidney injury

Acute kidney injury (AKI) is classically described as a rapid loss of kidney function. AKI affects more than 15% of all hospital admissions and is associated with elevated mortality rates. Although many advances have occurred, intermittent or continuous renal replacement therapies are still considered the best options for reversing mild and severe AKI syndrome. For this reason, it is essential that innovative and effective therapies, without side effects and complications, be developed to treat AKI and the end-stages of renal disease. Mesenchymal stem cell (MSC) based therapies have numerous advantages in helping to repair inflamed and damaged tissues and are being considered as a new alternative for treating kidney injuries. Numerous experimental models have shown that MSCs can act via differentiation-independent mechanisms to help renal recovery. Essentially, MSCs can secrete a pool of cytokines, growth factors and chemokines, express enzymes, interact via cell-to-cell contacts and release bioagents such as microvesicles to orchestrate renal protection. In this review, we propose seven distinct properties of MSCs which explain how renoprotection may be conferred: 1) anti-inflammatory; 2) pro-angiogenic; 3) stimulation of endogenous progenitor cells; 4) anti-apoptotic; 5) anti-fibrotic; 6) anti-oxidant; and 7) promotion of cellular reprogramming. In this context, these mechanisms, either individually or synergically, could induce renal protection and functional recovery. This review summarises the most important effects and benefits associated with MSC-based therapies in experimental renal disease models and attempts to clarify the mechanisms behind the MSC-related renoprotection. MSCs may prove to be an effective, innovative and affordable treatment for moderate and severe AKI. However, more studies need to be performed to provide a more comprehensive global understanding of MSC-related therapies and to ensure their safety for future clinical applications.

Changes in renal glucose transporters in an animal model of metabolic syndrome

Considering the similarity between structural, hemodynamic, and functional changes of obesity-related renal disease and diabetic nephropathy, we hypothesized that renal glucose transporter changes occur in obesity as in diabetes. The aim of the work was to evaluate GLUT1 and GLUT2 in kidneys of an animal model of metabolic syndrome. Neonate spontaneously hypertensive rats (SHR), n=15/group, were treated with monosodium glutamate (5 mg/g) (MetS) for 9 days and compared with saline-treated Wistar-Kyoto (C) and SHR (H) rats. Lee index, systolic arterial pressure (SAP), glycemia, insulin resistance, triglycerides, and HDL cholesterol were evaluated at 3 and 6 months. Medullar GLUT1 and cortical GLUT2 were analyzed by Western blot. MetS vs. C and H rats had the highest Lee index (p<0.001) and insulin resistance (3-months C: 4.3±0.7, H: 3.9±0.9, MetS: 2.7±0.6; 6-months C: 4.2±0.6, H: 3.8±0.5, MetS: 2.4±0.6% • min−1, p<0.001), similar glycemia, and the lowest HDL-cholesterol at 6-months (p<0.001). In the MetS and H rats, SAP was higher vs. C at 3-months (p<0.001) and 6-months (C: 151±15, H: 190±11, MetS: 185±13 mm Hg, p<0.001) of age. GLUT1 was ̴ 13× lower (p<0.001) at 3-months, reestablishing its content at 6-months in MetS group, while GLUT2 was 2× higher (p<0.001) in this group at 6-months of age. Renal GLUT1 and GLUT2 are modulated in kidney of rats with metabolic syndrome, where obesity, insulin resistance and hypertension coexist, despite normoglycemia. Like in diabetes, cortical GLUT2 overexpression may contribute to the development of kidney disease

Dental calculus formation in children and adolescents undergoing hemodialysis

This study aimed to determine whether dental calculus formation is really higher among patients with chronic kidney disease undergoing hemodialysis than among controls. Furthermore, the study evaluated correlations between dental calculus formation and dental plaque, variables that are related to renal disease and/or saliva composition. The Renal Group was composed of 30 patients undergoing hemodialysis, whereas the Healthy Group had 30 clinically healthy patients. Stimulated whole saliva and parotid saliva were collected. Salivary flow rate and calcium and phosphate concentrations were determined. In the Renal Group the saliva collection was carried out before and after a hemodialysis session. Patients from both groups received intraoral exams, oral hygiene instructions, and dental scaling. Three months later, the dental calculus was measured by the Volpe-Manhold method to determine the rate of dental calculus formation. The Renal Group presented a higher rate of dental calculus formation (p < 0.01). Correlation was observed between rate of dental calculus formation and whole saliva flow rate in the Renal Group after a hemodialysis session (r = 0.44, p < 0.05). The presence of dental calculus was associated with phosphate concentration in whole saliva from the Renal Group (p < 0.05). In conclusion, patients undergoing hemodialysis presented accelerated dental calculus formation, probably due to salivary variables.

The first cardiac transplant experience in a patient with mucopolysaccharidosis

Hunter syndrome (MPSII) is a rare X-linked lysosomal storage disorder that can affect multiple systems but primarily affects the heart. We report the case of a previously asymptomatic 23-year-old patient who had an attenuated form of MPSII and presented with refractory heart failure that required a heart transplant. The diagnosis was confirmed by detection of an increase in urinary excretion of glycosaminoglycans, a deficiency in enzymatic activity, and molecular analysis. A myocardial biopsy revealed hypertrophic cardiomyocytes, mild fibrosis, and lysosomal storage in interstitial cells. Molecular analysis identified a novel mutation in the iduronate-2-sulfatase gene. Although the clinical outcome was not favorable, we believe that this approach may be valid in end-stage heart failure. (C) 2012 Elsevier Inc. All rights reserved.