Sample records for renal cystic diseases

  1. Renal diseases in adults with cystic fibrosis: a 40 year single centre experience.

    PubMed

    Wilcock, M J; Ruddick, A; Gyi, K M; Hodson, M E

    2015-10-01

    There is a sizable literature describing renal disease in patients with cystic fibrosis. Previous studies have focused on single disease processes alone, most commonly renal stone disease or acute kidney injury. In this study we report for the first time on the prevalence of all forms of renal disease in a cystic fibrosis population. A retrospective review of adult patients with cystic fibrosis attending the Adult Cystic Fibrosis Department at the Royal Brompton Hospital was carried out by searching the department's database to identify patients with renal problems and subsequently retrieving clinical information from medical notes. The prevalence of all renal diseases in our population was 5.1 %. The most commonly identified problem was renal stones. At 2.0 % the prevalence of renal stones in adult patients with cystic fibrosis was comparable to the general population. A range of other renal diseases were identified, the next most common being drug-induced acute kidney injury. A range of cystic fibrosis independent and attributable diseases has been identified but no cystic fibrosis specific disease. In contrast to other cystic fibrosis centres no increased prevalence of renal stones was found.

  2. Cystic renal tumors: new entities and novel concepts.

    PubMed

    Moch, Holger

    2010-05-01

    Cystic renal neoplasms and renal epithelial stromal tumors are diagnostically challenging and represent some novel tumor entities. In this article, clinical and pathologic features of established and novel entities are discussed. Predominantly cystic renal tumors include cystic nephroma/mixed epithelial and stromal tumor, synovial sarcoma, and multilocular cystic renal cell carcinoma. These entities are own tumor entities of the 2004 WHO classification of renal tumors. Tubulocystic carcinoma and acquired cystic disease-associated renal cell carcinoma are neoplasms with an intrinsically cystic growth pattern. Both tumor types should be included in a future WHO classification as novel entities owing to their characteristic features. Cysts and clear cell renal cell carcinoma frequently coexist within the kidneys of patients with von Hippel-Lindau disease. Sporadic clear cell renal cell carcinomas often contain cysts, usually as a minor component. Some clear cell renal cell carcinomas have prominent cysts, and multilocular cystic renal cell carcinoma is composed almost exclusively of cysts. Recent molecular findings suggest that clear cell renal cancer may develop through cyst-dependent and cyst-independent molecular pathways.

  3. Frequency of Undiagnosed Cystic Lung Disease in Patients With Sporadic Renal Angiomyolipomas

    PubMed Central

    Hartman, Thomas E.; Torres, Vicente E.; Decker, Paul A.

    2012-01-01

    Objective: The aim of this study was to assess the frequency of undiagnosed cystic lung lesions suggestive of pulmonary lymphangioleiomyomatosis (LAM) in patients who received a diagnosis of sporadic renal angiomyolipomas (AMLs). Methods: We conducted a retrospective review of CT scans of the chest or abdomen for cystic lung lesions on 176 adult patients who received a diagnosis of sporadic renal AML during a 10-year period, 1997 to 2006, and comparison with chest CT scans of 176 control subjects without renal AML but matched for age, sex, and smoking history. Patients presenting with suspected or known pulmonary LAM and those with underlying tuberous sclerosis were excluded. Results: Sporadic renal AML was diagnosed in 176 patients with a median age of 58 years (range, 20-91 years), the majority of whom were women (81.8%). Renal tumor was an incidental finding on imaging studies for most patients (90.3%). Nineteen patients (10.8%) had one or more cystic lung lesions and included nine patients (5.1%) with four or more cysts, all of whom were women. In comparison, eight control subjects (4.6%) had one to three cystic lung lesions and none of them exhibited four or more cysts. None of the patients with renal AML and cystic lung lesions, including six women with 10 or more cysts, had undergone an evaluation of their cystic lung disease. Conclusions: We conclude that a significant portion of women with sporadic renal AMLs exhibit cystic lung lesions suggestive of pulmonary LAM but may remain undiagnosed. Coexistence of pulmonary LAM should be considered in women incidentally found to have sporadic renal AMLs. PMID:21737494

  4. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

    PubMed

    Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

    2012-01-01

    Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

  5. [Cystic renal neoplasms. New entities and molecular findings].

    PubMed

    Moch, H

    2010-10-01

    Renal neoplasms with dominant cysts represent a broad spectrum of known as well as novel renal tumor entities. Established renal tumors with dominant cysts include cystic nephroma, mixed epithelial and stromal tumor, synovial sarcoma and multilocular cystic renal cancer (WHO classification 2004). Novel tumor types have recently been reported, which are also characterized by marked cyst formation. Examples are tubulocystic renal cancer and renal cancer in end-stage renal disease. These tumors are very likely to be included in a future WHO classification due to their characteristic phenotype and molecular features. Cysts and clear cell renal cell carcinoma frequently coexist in the kidneys of patients with von Hippel-Lindau disease. Cysts are also a component of many sporadic clear cell renal cell carcinomas. Multilocular cystic renal cell carcinoma is composed almost exclusively of cysts and is regarded as a specific subtype of clear cell renal cancer. Recent molecular findings suggest that clear cell renal cancer may develop via a cyst-dependent mechanism in von Hippel-Lindau syndrome as well as via cyst-independent molecular pathways in sporadic clear cell renal cancer.

  6. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    ERIC Educational Resources Information Center

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  7. Secondary Hypertension, Erythrocytosis, and Unilateral Renal Cystic Disease in a Submariner: A Case Report.

    PubMed

    Forbes, Angela S; Yeo, Fred E

    Erythrocytosis, or increased red blood cell mass, may be primary as in the case of polycythemia vera (PV), or secondary due to a variety of causes related to erythropoietin (EPO) secretion and hypoxia. Chronic pulmonary disease and certain EPO-secreting tumors should be addressed and excluded early during the course of evaluation for a patient presenting with increased red blood cell mass. Inclusion of the JAK2 V617F gene mutation in the recent World Health Organization criteria for the diagnosis of PV allows for facilitated diagnosis and guides therapy. EPO levels can be helpful in diagnosis and guiding therapy, but in the case of cystic renal diseases, EPO levels are often not elevated, creating diagnostic uncertainty. This report describes a case of symptoms directly attributable to erythrocytosis in the setting of negative JAK2 mutation and normal EPO levels. The subsequent discovery of a large cystic renal kidney and PV were the leading diagnostic considerations. 2016.

  8. Metastatic renal cell carcinoma associated with acquired cystic kidney disease 15 years after successful renal transplantation.

    PubMed

    Lien, Y H; Kam, I; Shanley, P F; Schröter, G P

    1991-12-01

    Renal cell carcinoma (RCC) is a relatively uncommon cancer in renal transplant patients. From 1968 to 1987, 101 cases of RCC of native kidneys have been reported to the Cincinnati Transplant Tumor Registry. We describe here a case of metastatic RCC associated with acquired cystic kidney disease (ACKD) 15 years after successful renal transplantation. The patient presented with a subcutaneous nodule, which led to discovery of a large primary tumor in the left kidney. ACKD was present in the atrophic right kidney. The reported cases of ACKD-associated RCC in renal transplant recipients were reviewed. Most of these cases are middle-aged men with a long posttransplant course, good graft function, and usage of azathioprine and prednisone as immunosuppressive agents. ACKD can develop or persist and progress to RCC many years after successful renal transplantation. Transplant patients with flank pain, hematuria, or other suspicious symptoms should have imaging studies of their native kidneys.

  9. Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases: A Clinical Practice Recommendation With Systematic Literature Reviews.

    PubMed

    Gimpel, Charlotte; Avni, Fred E; Bergmann, Carsten; Cetiner, Metin; Habbig, Sandra; Haffner, Dieter; König, Jens; Konrad, Martin; Liebau, Max C; Pape, Lars; Rellensmann, Georg; Titieni, Andrea; von Kaisenberg, Constantin; Weber, Stefanie; Winyard, Paul J D; Schaefer, Franz

    2018-01-01

    Prenatal and neonatal cystic kidney diseases are a group of rare disorders manifesting as single, multiple unilateral, or bilateral cysts or with increased echogenicity of the renal cortex without macroscopic cysts. They may be accompanied by grossly enlarged kidneys, renal oligohydramnios, pulmonary hypoplasia, extrarenal abnormalities, and neonatal kidney failure. The prognosis is extremely variable from trivial to very severe or even uniformly fatal, which poses significant challenges to prenatal counseling and management. To provide a clinical practice recommendation for fetal medicine specialists, obstetricians, neonatologists, pediatric nephrologists, pediatricians, and human geneticists by aggregating current evidence and consensus expert opinion on current management of cystic nephropathies before and after birth. After 8 systematic literature reviews on clinically relevant questions were prepared (including 90 studies up to mid-2016), recommendations were formulated and formally graded at a consensus meeting that included experts from all relevant specialties. After further discussion, the final version was voted on by all members using the Delphi method. The recommendations were reviewed and endorsed by the working groups on inherited renal disorders of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and European Society for Paediatric Nephrology (ESPN); the German Society of Obstetrics and Gynecology (DGGG), German Society of Perinatal Medicine (DGPM), and German Society of Ultrasound in Medicine (DEGUM); and the alliance of patient organizations, PKD International. The group makes a number of recommendations on prenatal and postnatal imaging by ultrasound and magnetic resonance imaging, genetic testing, prenatal counseling, in utero therapeutic interventions, and postnatal management of prenatal and neonatal cystic kidney diseases, including provision of renal replacement therapy in neonates. In addition to

  10. Network for Early Onset Cystic Kidney Diseases-A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood.

    PubMed

    König, Jens Christian; Titieni, Andrea; Konrad, Martin

    2018-01-01

    Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet-Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype-phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases. To tackle these challenges comprehensive scientific approaches are urgently needed that match the ongoing "revolution" in genetics and molecular biology with an improved efficacy of clinical data collection. Network for early onset cystic kidney diseases (NEOCYST) is a multidisciplinary, multicenter collaborative combining a detailed collection of clinical data with translational scientific approaches addressing the genetic, molecular, and functional background of hereditary cystic kidney diseases. Consisting of seven work packages, including an international registry as well as a biobank, NEOCYST is not only dedicated to current scientific questions, but also provides a platform for longitudinal clinical surveillance and provides precious sources for high-quality research projects and future clinical trials. Funded by the German Federal Government, the NEOCYST collaborative started in February 2016. Here, we would like to introduce the rationale, design, and objectives of the network followed by a short overview on the current state of progress.

  11. Network for Early Onset Cystic Kidney Diseases—A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood

    PubMed Central

    König, Jens Christian; Titieni, Andrea; Konrad, Martin; Bergmann, C.

    2018-01-01

    Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet–Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype–phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases. To tackle these challenges comprehensive scientific approaches are urgently needed that match the ongoing “revolution” in genetics and molecular biology with an improved efficacy of clinical data collection. Network for early onset cystic kidney diseases (NEOCYST) is a multidisciplinary, multicenter collaborative combining a detailed collection of clinical data with translational scientific approaches addressing the genetic, molecular, and functional background of hereditary cystic kidney diseases. Consisting of seven work packages, including an international registry as well as a biobank, NEOCYST is not only dedicated to current scientific questions, but also provides a platform for longitudinal clinical surveillance and provides precious sources for high-quality research projects and future clinical trials. Funded by the German Federal Government, the NEOCYST collaborative started in February 2016. Here, we would like to introduce the rationale, design, and objectives of the network followed by a short overview on the current state of progress. PMID:29497606

  12. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spino, M.; Chai, R.P.; Isles, A.F.

    1985-07-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the resultmore » of enhanced glomerular filtration or tubular secretion.« less

  13. Transitional cell carcinoma arising in a calyceal cyst mimicking a cystic renal tumour.

    PubMed

    Kim, Jeong Ho; Song, Joo Yeon; Lee, Wan

    2014-01-01

    Solitary renal cysts are relatively common. The occurrence of transitional cell carcinoma (TCC) in a renal cyst is rare. We present the case of a 59-year-old man with a medical history of viral hepatitis B. During a workup for his hepatitis, a computed tomography scan revealed a large cystic tumour in the upper region of the left kidney. A radical left nephrectomy was performed. Microscopic examination of the cystic tumour revealed a grade 2 TCC. The cyst was lined by transitional epithelium. This is a case of a TCC growing within a renal calyceal cyst.

  14. Can a Modified Bosniak Classification System Risk Stratify Pediatric Cystic Renal Masses?

    PubMed

    Saltzman, Amanda F; Carrasco, Alonso; Colvin, Alexandra N; Meyers, Mariana L; Cost, Nicholas G

    2018-03-20

    We characterize and apply the modified Bosniak classification system to a cohort of children with cystic renal lesions and known surgical pathology. We identified all patients at our institution with cystic renal masses who also underwent surgery for these lesions. Patients without available preoperative imaging or pathology were excluded. All radiological imaging was independently reviewed by a pediatric radiologist blinded to pathological findings. Imaging characteristics (size, border, septations, calcifications, solid components, vascularity) were recorded from the most recent preoperative ultrasounds and computerized tomograms. The modified Bosniak classification system was applied to these scans and then correlated with final pathology. A total of 22 patients met study criteria. Median age at surgery was 6.1 years (range 11 months to 16.8 years). Of the patients 12 (54.5%) underwent open nephrectomy, 6 (27.3%) open partial nephrectomy, 2 (9.1%) laparoscopic cyst decortication, 1 (4.5%) open renal biopsy and 1 (4.5%) laparoscopic partial nephrectomy. Final pathology was benign in 9 cases (41%), intermediate in 6 (27%) and malignant in 7 (32%). All malignant lesions were modified Bosniak class 4, all intermediate lesions were modified class 3 or 4 and 8 of 9 benign lesions (89%) were modified class 1 or 2. Cystic renal lesions in children with a modified Bosniak class of 1 or 2 were most often benign, while class 3 or 4 lesions warranted surgical excision since more than 90% of masses harbored intermediate or malignant pathology. The modified Bosniak classification system appears to allow for a reasonable clinical risk stratification of pediatric cystic renal masses. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Cystic renal cell carcinoma carries an excellent prognosis regardless of tumor size.

    PubMed

    Winters, Brian R; Gore, John L; Holt, Sarah K; Harper, Jonathan D; Lin, Daniel W; Wright, Jonathan L

    2015-12-01

    Cystic renal cell carcinoma (cystic RCC) is thought to carry an improved prognosis relative to clear cell RCC (CCRCC); however, this is based on small case series. We used a population-based tumor registry to compare clinicopathologic features and cancer-specific mortality (CSM) of cystic RCC with those of CCRCC. The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed and treated for cystic RCC and CCRCC between 2001 and 2010. Clinical and pathologic factors were compared using t tests and chi-square tests as appropriate. Kaplan-Meier survival analysis compared CSM differences between cystic RCC and CCRCC. A total of 678 patients with cystic RCC and 46,677 with CCRCC were identified. The mean follow-up duration was 52 and 40 months, respectively. When compared with CCRCC patients, those with cystic RCC were younger (mean age 58 vs. 61 y, P < 0.001), more commonly black (22% vs. 9%, P < 0.001), and female (45% vs. 41%, P = 0.02). Cystic RCCs were more commonly T1a tumors (66% vs. 55%, P < 0.001), well differentiated (33% vs. 16%, P < 0.001), and smaller (mean size = 3.8 vs. 4.5 cm, P < 0.001). Cystic RCC was associated with a reduction in CSM when compared with CCRCC (P = 0.002). In a subset analysis, this reduction in CSM was seen only for those with T1b/T2 tumors (P = 0.01) but not for those with T1a RCCs lesions (P = 0.31). We report the largest series of cystic RCC and corroborate the findings of improved CSM when compared with CCRCC for larger tumors; however, no difference was noted in smaller tumors, suggesting that tumor biology becomes more relevant to prognosis with increasing size. These data may suggest a role for active surveillance in appropriately selected patients with small, cystic renal masses. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Cystic renal cell carcinoma carries an excellent prognosis regardless of tumor size

    PubMed Central

    Winters, Brian R.; Gore, John L.; Holt, Sarah K.; Harper, Jonathan D.; Lin, Daniel W.; Wright, Jonathan L.

    2016-01-01

    Introduction Cystic renal cell carcinoma (cystic RCC) is thought to carry an improved prognosis relative to clear cell RCC (CCRCC); however, this is based on small case series. We used a population-based tumor registry to compare clinicopathologic features and cancer-specific mortality (CSM) of cystic RCC with those of CCRCC. Materials and methods The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed and treated for cystic RCC and CCRCC between 2001 and 2010. Clinical and pathologic factors were compared using t tests and chi-square tests as appropriate. Kaplan-Meier survival analysis compared CSM differences between cystic RCC and CCRCC. Results A total of 678 patients with cystic RCC and 46,677 with CCRCC were identified. The mean follow-up duration was 52 and 40 months, respectively. When compared with CCRCC patients, those with cystic RCC were younger (mean age 58 vs. 61 y, P < 0.001), more commonly black (22% vs. 9%, P < 0.001), and female (45% vs. 41%, P = 0.02). Cystic RCCs were more commonly T1a tumors (66% vs. 55%, P < 0.001), well differentiated (33% vs. 16%, P < 0.001), and smaller (mean size 3.8 vs. 4.5 cm, P < 0.001). Cystic RCC was associated with a reduction in CSM when compared with CCRCC (P = 0.002). In a subset analysis, this reduction in CSM was seen only for those with T1b/T2 tumors (P = 0.01) but not for those with T1a RCCs lesions (P = 0.31). Conclusions We report the largest series of cystic RCC and corroborate the findings of improved CSM when compared with CCRCC for larger tumors; however, no difference was noted in smaller tumors, suggesting that tumor biology becomes more relevant to prognosis with increasing size. These data may suggest a role for active surveillance in appropriately selected patients with small, cystic renal masses. PMID:26319351

  17. Renal capillary haemangioma associated with renal cell carcinoma and polycythaemia in acquired cystic disease.

    PubMed

    Beamer, Matthew; Love, Matthew; Ghasemian, Seyed

    2017-06-16

    Capillary haemangiomas are relatively common tumours, typically occurring in the subcutaneous tissue during childhood. However, visceral occurrence is very rare. These tumours make up a subset of vascular lesions that have previously, although rarely, been described in case reports in association with the kidney. Here we review the literature and describe a capillary haemangioma occurring in the renal hilum found to be coexistent with end-stage renal disease, renal cell carcinoma and polycythaemia. To our knowledge, this is the first case report to describe the occurrence of this tumour in the renal hilum in association with this constitution of renal pathologies. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Sorting the Alphabet Soup of Renal Pathology: A Review.

    PubMed

    Curran-Melendez, Sheilah M; Hartman, Matthew S; Heller, Matthew T; Okechukwu, Nancy

    2016-01-28

    Diseases of the kidney often have their names shortened, creating an arcane set of acronyms which can be confusing to both radiologists and clinicians. This review of renal pathology aims to explain some of the most commonly used acronyms within the field. For each entity, a summary of the clinical features, pathophysiology, and radiological findings is included to aid in the understanding and differentiation of these entities. Discussed topics include acute cortical necrosis, autosomal dominant polycystic kidney disease, angiomyolipoma, autosomal recessive polycystic kidney disease, acute tubular necrosis, localized cystic renal disease, multicystic dysplastic kidney, multilocular cystic nephroma, multilocular cystic renal cell carcinoma, medullary sponge kidney, paroxysmal nocturnal hemoglobinuria, renal papillary necrosis, transitional cell carcinoma, and xanthogranulomatous pyelonephritis. Copyright © 2016 Mosby, Inc. All rights reserved.

  19. Challenges in pulmonary fibrosis · 3: Cystic lung disease

    PubMed Central

    Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

    2007-01-01

    Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID:17726170

  20. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    PubMed

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. Copyright ©ERS 2015.

  1. Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

    PubMed

    Barr, Maureen M

    2005-02-01

    The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

  2. Liver Disease in Cystic Fibrosis: an Update

    PubMed Central

    Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

    2013-01-01

    Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

  3. Laparoscopic management of cystic disease of the liver.

    PubMed

    Albrink, M H; McAllister, E W; Rosemurgy, A S; Karl, R C; Carey, L C

    1994-04-01

    Laparoscopic surgical procedures are increasing in scope and in variety. The benefits of decreased wound morbidity and pain have been well documented for multiple procedures that have traditionally required laparotomy. Although there are few controlled studies to document them, these benefits may be evident from simple clinical observation. Cystic disease of the liver is a condition that is treated largely for symptomatic reasons. The so-called noninvasive or radiographic guided methods of treatment for cystic disease of the liver are fraught with high recurrence rates. We present four cases of cystic disease of the liver treated laparoscopically, followed with pertinent discussion.

  4. Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient

    PubMed Central

    Penteado, Louise Piva; Osório, Cecília Susin; Balbinotto, Antônio; Dalcin, Paulo de Tarso Roth

    2018-01-01

    In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated. PMID:29742226

  5. Novel NEK8 Mutations Cause Severe Syndromic Renal Cystic Dysplasia through YAP Dysregulation

    PubMed Central

    Grampa, Valentina; Odye, Gweltas; Thomas, Sophie; Elkhartoufi, Nadia; Filhol, Emilie; Niel, Olivier; Silbermann, Flora; Lebreton, Corinne; Collardeau-Frachon, Sophie; Rouvet, Isabelle; Alessandri, Jean-Luc; Devisme, Louise; Dieux-Coeslier, Anne; Cordier, Marie-Pierre; Capri, Yline; Khung-Savatovsky, Suonavy; Sigaudy, Sabine; Salomon, Rémi; Antignac, Corinne; Gubler, Marie-Claire; Benmerah, Alexandre; Terzi, Fabiola; Attié-Bitach, Tania; Jeanpierre, Cécile; Saunier, Sophie

    2016-01-01

    Ciliopathies are a group of genetic multi-systemic disorders related to dysfunction of the primary cilium, a sensory organelle present at the cell surface that regulates key signaling pathways during development and tissue homeostasis. In order to identify novel genes whose mutations would cause severe developmental ciliopathies, >500 patients/fetuses were analyzed by a targeted high throughput sequencing approach allowing exome sequencing of >1200 ciliary genes. NEK8/NPHP9 mutations were identified in five cases with severe overlapping phenotypes including renal cystic dysplasia/hypodysplasia, situs inversus, cardiopathy with hypertrophic septum and bile duct paucity. These cases highlight a genotype-phenotype correlation, with missense and nonsense mutations associated with hypodysplasia and enlarged cystic organs, respectively. Functional analyses of NEK8 mutations in patient fibroblasts and mIMCD3 cells showed that these mutations differentially affect ciliogenesis, proliferation/apoptosis/DNA damage response, as well as epithelial morphogenesis. Notably, missense mutations exacerbated some of the defects due to NEK8 loss of function, highlighting their likely gain-of-function effect. We also showed that NEK8 missense and loss-of-function mutations differentially affect the regulation of the main Hippo signaling effector, YAP, as well as the expression of its target genes in patient fibroblasts and renal cells. YAP imbalance was also observed in enlarged spheroids of Nek8-invalidated renal epithelial cells grown in 3D culture, as well as in cystic kidneys of Jck mice. Moreover, co-injection of nek8 MO with WT or mutated NEK8-GFP RNA in zebrafish embryos led to shortened dorsally curved body axis, similar to embryos injected with human YAP RNA. Finally, treatment with Verteporfin, an inhibitor of YAP transcriptional activity, partially rescued the 3D spheroid defects of Nek8-invalidated cells and the abnormalities of NEK8-overexpressing zebrafish embryos

  6. Atheroembolic renal disease

    MedlinePlus

    Renal disease - atheroembolic; Cholesterol embolization syndrome; Atheroemboli - renal; Atherosclerotic disease - renal ... disorder of the arteries. It occurs when fat, cholesterol, and other substances build up in the walls ...

  7. Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

    PubMed

    Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

    2016-05-01

    Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

  8. Quantitative MRI of kidneys in renal disease.

    PubMed

    Kline, Timothy L; Edwards, Marie E; Garg, Ishan; Irazabal, Maria V; Korfiatis, Panagiotis; Harris, Peter C; King, Bernard F; Torres, Vicente E; Venkatesh, Sudhakar K; Erickson, Bradley J

    2018-03-01

    To evaluate the reproducibility and utility of quantitative magnetic resonance imaging (MRI) sequences for the assessment of kidneys in young adults with normal renal function (eGFR ranged from 90 to 130 mL/min/1.73 m 2 ) and patients with early renal disease (autosomal dominant polycystic kidney disease). This prospective case-control study was performed on ten normal young adults (18-30 years old) and ten age- and sex-matched patients with early renal parenchymal disease (autosomal dominant polycystic kidney disease). All subjects underwent a comprehensive kidney MRI protocol, including qualitative imaging: T1w, T2w, FIESTA, and quantitative imaging: 2D cine phase contrast of the renal arteries, and parenchymal diffusion weighted imaging (DWI), magnetization transfer imaging (MTI), blood oxygen level dependent (BOLD) imaging, and magnetic resonance elastography (MRE). The normal controls were imaged on two separate occasions ≥24 h apart (range 24-210 h) to assess reproducibility of the measurements. Quantitative MR imaging sequences were found to be reproducible. The mean ± SD absolute percent difference between quantitative parameters measured ≥24 h apart were: MTI-derived ratio = 4.5 ± 3.6%, DWI-derived apparent diffusion coefficient (ADC) = 6.5 ± 3.4%, BOLD-derived R2* = 7.4 ± 5.9%, and MRE-derived tissue stiffness = 7.6 ± 3.3%. Compared with controls, the ADPKD patient's non-cystic renal parenchyma (NCRP) had statistically significant differences with regard to quantitative parenchymal measures: lower MTI percent ratios (16.3 ± 4.4 vs. 23.8 ± 1.2, p < 0.05), higher ADCs (2.46 ± 0.20 vs. 2.18 ± 0.10 × 10 -3  mm 2 /s, p < 0.05), lower R2*s (14.9 ± 1.7 vs. 18.1 ± 1.6 s -1 , p < 0.05), and lower tissue stiffness (3.2 ± 0.3 vs. 3.8 ± 0.5 kPa, p < 0.05). Excellent reproducibility of the quantitative measurements was obtained in all cases. Significantly different quantitative MR parenchymal

  9. Expression and function of CLC and cystic fibrosis transmembrane conductance regulator chloride channels in renal epithelial tubule cells: pathophysiological implications.

    PubMed

    Vandewalle, Alain

    2007-01-01

    Cl(-) channels play important roles in the regulation of a variety of functions, including electrical excitability, cell volume regulation, transepithelial transport and acidification of cellular organelles. They are expressed in plasma membranes or reside in intracellular organelles. A large number of Cl(-) channels with different functions have been identified. Some of them are highly expressed in the kidney. They include members of the CLC Cl(-) channel family: ClC-K1 (or ClC-Ka), ClC-K2 (or ClC-Kb) and ClC-5. The identification of mutations responsible for human inherited diseases (Bartter syndrome for ClC-Kb and Dent's disease for ClC-5) and studies on knockout mice models have evidenced the physiological importance of these CLC Cl(-) channels, permitting better understanding on their functions in renal tubule epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel, also expressed in renal tubule epithelial cells, is involved in the transepithelial transport of Cl(-) in the distal nephron. This short review focuses on intrarenal distribution, subcellular localization and function of the ClK(-1), ClC-K2 and ClC-5 Cl(-) channels in renal tubule epithelial cells, and the role of the CFTR Cl(-) channel in chloride fluxes elicited by vasopressin in the distal nephron.

  10. Adult cystic nephroma and mixed epithelial and stromal tumor of the kidney are the same disease entity: molecular and histologic evidence.

    PubMed

    Zhou, Ming; Kort, Eric; Hoekstra, Philip; Westphal, Michael; Magi-Galluzzi, Cristina; Sercia, Linda; Lane, Brian; Rini, Brian; Bukowski, Ronald; Teh, Bin T

    2009-01-01

    Adult cystic nephroma (CN) and mixed epithelial and stromal tumor of the kidney (MEST) are considered as separate entities in the 2004 World Health Organization classification of renal neoplasms. Recent studies suggested that the two share clinicopathologic features and may represent the same disease process of varying morphology. However, definitive genetic evidence is lacking. We examined their relationship using gene expression profiling and histologic analysis. Gene expression profiles of 3 CN and 3 MEST were analyzed using HGU133 Plus 2.0 microarrays (Affymetrix) and were compared with each other and also with 48 other renal tumors and 13 normal kidneys. Histologic examination of 26 CN and 13 MEST focused on the cystic septal thickness, cyst-to-stroma ratio, stromal cellularity and composition, types of epithelial cells lining cysts and glands, and estrogen and progesterone receptors expression. Patients' age, sex distribution, and tumor size were similar between the two. They also shared many histologic features, including lining epithelium of cysts and glands, stromal cellularity and composition. Unsupervised clustering of mRNA expression profiles demonstrated that they had very similar expression profiles that were distinct from other renal tumors. By microarray analysis, progesterone receptor expression was significantly higher in CN and MEST relative to both normal and other renal tumors, while estrogen receptor expression was not. By immunohistochemistry, expression of both receptors was similar between CN and MEST. This study provides the most convincing molecular evidence that CN and MEST represent different parts of the morphologic spectrum of the same disease.

  11. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    PubMed

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  12. Disruption of IFT Complex A Causes Cystic Kidneys without Mitotic Spindle Misorientation

    PubMed Central

    Jonassen, Julie A.; SanAgustin, Jovenal; Baker, Stephen P.

    2012-01-01

    Intraflagellar transport (IFT) complexes A and B build and maintain primary cilia. In the mouse, kidney-specific or hypomorphic mutant alleles of IFT complex B genes cause polycystic kidneys, but the influence of IFT complex A proteins on renal development is not well understood. In the present study, we found that HoxB7-Cre–driven deletion of the complex A gene Ift140 from collecting ducts disrupted, but did not completely prevent, cilia assembly. Mutant kidneys developed collecting duct cysts by postnatal day 5, with rapid cystic expansion and renal dysfunction by day 15 and little remaining parenchymal tissue by day 20. In contrast to many models of polycystic kidney disease, precystic Ift140-deleted collecting ducts showed normal centrosomal positioning and no misorientation of the mitotic spindle axis, suggesting that disruption of oriented cell division is not a prerequisite to cyst formation in these kidneys. Precystic collecting ducts had an increased mitotic index, suggesting that cell proliferation may drive cyst expansion even with normal orientation of the mitotic spindle. In addition, we observed significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis in highly cystic, but not precystic, kidneys. Taken together, these studies indicate that loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression. PMID:22282595

  13. Eosinophilic, Solid, and Cystic Renal Cell Carcinoma: Clinicopathologic Study of 16 Unique, Sporadic Neoplasms Occurring in Women.

    PubMed

    Trpkov, Kiril; Hes, Ondrej; Bonert, Michael; Lopez, Jose I; Bonsib, Stephen M; Nesi, Gabriella; Comperat, Eva; Sibony, Mathilde; Berney, Daniel M; Martinek, Petr; Bulimbasic, Stela; Suster, Saul; Sangoi, Ankur; Yilmaz, Asli; Higgins, John P; Zhou, Ming; Gill, Anthony J; Przybycin, Christopher G; Magi-Galluzzi, Cristina; McKenney, Jesse K

    2016-01-01

    A unique renal neoplasm characterized by eosinophilic cytoplasm and solid and cystic growth was recently reported in patients with tuberous sclerosis complex (TSC). We searched multiple institutional archives and consult files in an attempt to identify a sporadic counterpart. We identified 16 morphologically identical cases, all in women, without clinical features of TSC. The median age was 57 years (range, 31 to 75 y). Macroscopically, tumors were tan and had a solid and macrocystic (12) or only solid appearance (4). Average tumor size was 50 mm (median, 38.5 mm; range, 15 to 135 mm). Microscopically, the tumors showed solid areas admixed with variably sized macrocysts and microcysts that were lined by cells with a pronounced hobnail arrangement. The cells had voluminous eosinophilic cytoplasm with prominent granular cytoplasmic stippling and round to oval nuclei with prominent nucleoli. Scattered histiocytes and lymphocytes were invariably present. Thirteen of 16 patients were stage pT1; 2 were pT2, and 1 was pT3a. The cells demonstrated a distinct immunoprofile: nuclear PAX8 expression, predominant CK20-positive/CK7-negative phenotype, patchy AMACR staining, but no CD117 reactivity. Thirteen of 14 patients with follow-up were alive and without disease progression after 2 to 138 months (mean: 53 mo; median: 37.5 mo); 1 patient died of other causes. Although similar to a subset of renal cell carcinomas (RCCs) seen in TSC, we propose that sporadic "eosinophilic, solid, and cystic RCC," which occurs predominantly in female individuals and is characterized by distinct morphologic features, predominant CK20-positive/CK7-negative immunophenotype, and indolent behavior, represents a novel subtype of RCC.

  14. Cystic fibrosis liver disease - from diagnosis to risk factors.

    PubMed

    Ciucă, Ioana Mihaiela; Pop, Liviu; Tămaş, Liviu; Tăban, Sorina

    2014-01-01

    Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmitted, characterized by an impressive clinical polymorphism and appreciative fatal prospective. Liver disease is the second non-pulmonary cause of death in cystic fibrosis, which, with increasing life expectancy, became an important management problem. Predisposing factors like male gender, pancreatic insufficiency, meconium ileus and severe mutation are incriminated to influence the occurrence of cystic fibrosis associated liver disease (CFLD). Our study included 174 patients with CF, monitored in the National Cystic Fibrosis Centre, Timisoara, Romania. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and other methods like transient elastography, biopsy, in selected cases. Sixty-six patients, with median age at diagnosis 4.33 years, diagnosed with CFLD, without significant gender gap. CFLD was frequent in patients aged over eight years, with meconium ileus history, carriers of severe mutations (p=0.002). Pancreatic insufficiency, although present in 75% of patients with CFLD was not confirmed as risk factor, not male gender, in our study. CF children older than eight years, carriers of a severe genotype, with a positive history of meconium ileus, were more likely predisposed to CFLD.

  15. Magnetic resonance imaging (MRI) of the renal sinus.

    PubMed

    Krishna, Satheesh; Schieda, Nicola; Flood, Trevor A; Shanbhogue, Alampady Krishna; Ramanathan, Subramaniyan; Siegelman, Evan

    2018-04-09

    This article presents methods to improve MR imaging approach of disorders of the renal sinus which are relatively uncommon and can be technically challenging. Multi-planar Single-shot T2-weighted (T2W) Fast Spin-Echo sequences are recommended to optimally assess anatomic relations of disease. Multi-planar 3D-T1W Gradient Recalled Echo imaging before and after Gadolinium administration depicts the presence and type of enhancement and relation to arterial, venous, and collecting system structures. To improve urographic phase MRI, concentrated Gadolinium in the collecting systems should be diluted. Diffusion-Weighted Imaging (DWI) should be performed before Gadolinium administration to minimize T2* effects. Renal sinus cysts are common but can occasionally be confused for dilated collecting system or calyceal diverticula, with the latter communicating with the collecting system and filling on urographic phase imaging. Vascular lesions (e.g., aneurysm, fistulas) may mimic cystic (or solid) lesions on non-enhanced MRI but can be suspected by noting similar signal intensity to the blood pool and diagnosis can be confirmed with MR angiogram/venogram. Multilocular cystic nephroma commonly extends to the renal sinus, however, to date are indistinguishable from cystic renal cell carcinoma (RCC). Solid hilar tumors are most commonly RCC and urothelial cell carcinoma (UCC). Hilar RCC are heterogeneous, hypervascular with epicenter in the renal cortex compared to UCC which are centered in the collecting system, homogeneously hypovascular, and show profound restricted diffusion. Diagnosis of renal sinus invasion in RCC is critically important as it is the most common imaging cause of pre-operative under-staging of disease. Fat is a normal component of the renal sinus; however, amount of sinus fat correlates with cardiovascular disease and is also seen in lipomatosis. Fat-containing hilar lesions include lipomas, angiomyolipomas, and less commonly other tumors which engulf sinus

  16. The Epidemiology and Management of Lung Diseases in Sickle Cell Disease: Lessons Learned from Acute and Chronic Lung Disease in Cystic Fibrosis.

    PubMed

    Willen, Shaina M; DeBaun, Michael R

    2018-06-01

    Although sickle cell disease and cystic fibrosis are two of the most common monogenic diseases presenting in childhood worldwide, cystic fibrosis and sickle cell disease enjoy vastly different funding and collaborative research efforts. Pulmonary complications in cystic fibrosis have well established guidelines and multidisciplinary involvement focusing on comorbidities, routine monitoring, infectious complications, nutrition, and treatment recommendations. These guidelines can provide a framework on which to build knowledge of lung disease in sickle cell disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    PubMed

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2015-08-12

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease

  18. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    PubMed

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2018-03-14

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle

  19. Contribution of the TTC21B gene to glomerular and cystic kidney diseases.

    PubMed

    Bullich, Gemma; Vargas, Iván; Trujillano, Daniel; Mendizábal, Santiago; Piñero-Fernández, Juan Alberto; Fraga, Gloria; García-Solano, José; Ballarín, José; Estivill, Xavier; Torra, Roser; Ars, Elisabet

    2017-01-01

    The TTC21B gene was initially described as causative of nephronophthisis (NPHP). Recently, the homozygous TTC21B p.P209L mutation has been identified in families with focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions. Heterozygous TTC21B variants have been proposed as genetic modifiers in ciliopathies. We aimed to study the causative and modifying role of the TTC21B gene in glomerular and cystic kidney diseases. Mutation analysis of the TTC21B gene was performed by massive parallel sequencing. We studied the causative role of the TTC21B gene in 17 patients with primary diagnosis of FSGS or NPHP and its modifying role in 184 patients with inherited glomerular or cystic kidney diseases. Disease-causing TTC21B mutations were identified in three families presenting nephrotic proteinuria with FSGS and tubulointerstitial lesions in which some family members presented hypertension and myopia. Two families carried the homozygous p.P209L and the third was compound heterozygous for the p.P209L and a novel p.H426D mutation. Rare heterozygous TTC21B variants predicted to be pathogenic were found in five patients. These TTC21B variants were significantly more frequent in renal patients compared with controls (P = 0.0349). Two patients with a heterozygous deleterious TTC21B variant in addition to the disease-causing mutation presented a more severe phenotype than expected. Our results confirm the causal role of the homozygous p.P209L TTC21B mutation in two new families with FSGS and tubulointerstitial disease. We identified a novel TTC21B mutation demonstrating that p.P209L is not the unique causative mutation of this nephropathy. Thus, TTC21B mutation analysis should be considered for the genetic diagnosis of families with FSGS and tubulointerstitial lesions. Finally, we provide evidence that heterozygous deleterious TTC21B variants may act as genetic modifiers of the severity of glomerular and cystic kidney diseases. © The Author 2016. Published by

  20. Ursodeoxycholic acid for cystic fibrosis-related liver disease.

    PubMed

    Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

    2014-12-15

    Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies.Date of the most recent search of the Group's trials register: 29 May 2014. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. Ten trials have been identified, of which three trials involving 118 participants were included; the dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few

  1. Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

    PubMed

    Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

    2018-04-01

    Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

  2. A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases.

    PubMed

    Bullich, Gemma; Domingo-Gallego, Andrea; Vargas, Iván; Ruiz, Patricia; Lorente-Grandoso, Laura; Furlano, Mónica; Fraga, Gloria; Madrid, Álvaro; Ariceta, Gema; Borregán, Mar; Piñero-Fernández, Juan Alberto; Rodríguez-Peña, Lidia; Ballesta-Martínez, Maria Juliana; Llano-Rivas, Isabel; Meñica, Mireia Aguirre; Ballarín, José; Torrents, David; Torra, Roser; Ars, Elisabet

    2018-05-22

    Molecular diagnosis of inherited kidney diseases remains a challenge due to their expanding phenotypic spectra as well as the constantly growing list of disease-causing genes. Here we develop a comprehensive approach for genetic diagnosis of inherited cystic and glomerular nephropathies. Targeted next generation sequencing of 140 genes causative of or associated with cystic or glomerular nephropathies was performed in 421 patients, a validation cohort of 116 patients with previously known mutations, and a diagnostic cohort of 207 patients with suspected inherited cystic disease and 98 patients with glomerular disease. In the validation cohort, a sensitivity of 99% was achieved. In the diagnostic cohort, causative mutations were found in 78% of patients with cystic disease and 62% of patients with glomerular disease, mostly familial cases, including copy number variants. Results depict the distribution of different cystic and glomerular inherited diseases showing the most likely diagnosis according to perinatal, pediatric and adult disease onset. Of all the genetically diagnosed patients, 15% were referred with an unspecified clinical diagnosis and in 2% genetic testing changed the clinical diagnosis. Therefore, in 17% of cases our genetic analysis was crucial to establish the correct diagnosis. Complex inheritance patterns in autosomal dominant polycystic kidney disease and Alport syndrome were suspected in seven and six patients, respectively. Thus, our kidney-disease gene panel is a comprehensive, noninvasive, and cost-effective tool for genetic diagnosis of cystic and glomerular inherited kidney diseases. This allows etiologic diagnosis in three-quarters of patients and is especially valuable in patients with unspecific or atypical phenotypes. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  3. Lung function imaging methods in Cystic Fibrosis pulmonary disease.

    PubMed

    Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

    2017-05-17

    Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

  4. Improved diagnostic differentiation of renal cystic lesions with phase-contrast computed tomography (PCCT)

    NASA Astrophysics Data System (ADS)

    Noel, Peter B.; Willner, Marian; Fingerle, Alexander; Herzen, Julia; Münzel, Daniela; Hahn, Dieter; Rummeny, Ernst J.; Pfeiffer, Franz

    2012-03-01

    The diagnostic quality of phase-contrast computed tomography (PCCT) is one the unexplored areas in medical imaging; at the same time, it seems to offer the opportunity as a fast and highly sensitive diagnostic tool. Conventional computed tomography (CT) has had an enormous impact on medicine, while it is limited in soft-tissue contrast. One example that portrays this challenge is the differentiation between benign and malignant renal cysts. In this work we report on a feasibility study to determine the usefulness of PCCT in differentiation of renal cysts. A renal phantom was imaged with a grating-based PCCT system consisting of a standard rotating anode x-ray tube (40 kV, 70 mA) and a Pilatus II photoncounting detector (pixel size: 172 μm). The phantom is composed of a renal equivalent soft-tissue and cystic lesions grouped in non-enhancing cyst and hemorrhage series and an iodine enhancing series. The acquired projection images (absorption and phase-contrast) are reconstructed with a standard filtered backprojection algorithm. For evaluation both reconstructions are compared in respect to contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and subjective image quality. We found that with PCCT a significantly improved differentiation between hemorrhage renal cysts from contrast enhancing malignant cysts is possible. If comparing PCCT and CT with respect to CNR and SNR, PCCT shows significant improvements. In conclusion, PCCT has the potential to improve the diagnostics and characterization of renal cysts without using any contrast agents. These results in combination with a non-synchrotron setup indicate a future paradigm shift in diagnostic computed tomography.

  5. A rare cause of childhood renal cysts: Xp11.2 translocation renal cell carcinoma.

    PubMed

    Taşkınlar, Hakan; Avlan, Dinçer; Çıtak, Çağlar; Polat, Ayşe; Naycı, Ali

    2015-01-01

    Pediatric renal cysts are rare, usually asymptomatic and incidentally detected in children. Cyst associated renal cell carcinoma (RCC) or cystic RCC is extremely rare in children. Bosniak classification system has been accepted for the management of cystic renal masses. Xp11.2 translocation RCC is a recently classified distinct subtype and usually affects children and adolescents. We report the case of a 10-year-old girl with Xp11.2 translocation RCC from a cyst of the right kidney.

  6. A rare cause of childhood renal cysts: Xp11.2 translocation renal cell carcinoma

    PubMed Central

    Taşkınlar, Hakan; Avlan, Dinçer; Çıtak, Çağlar; Polat, Ayşe; Naycı, Ali

    2015-01-01

    Pediatric renal cysts are rare, usually asymptomatic and incidentally detected in children. Cyst associated renal cell carcinoma (RCC) or cystic RCC is extremely rare in children. Bosniak classification system has been accepted for the management of cystic renal masses. Xp11.2 translocation RCC is a recently classified distinct subtype and usually affects children and adolescents. We report the case of a 10-year-old girl with Xp11.2 translocation RCC from a cyst of the right kidney. PMID:25624966

  7. Dose-Dependent Effects of Sirolimus on mTOR Signaling and Polycystic Kidney Disease

    PubMed Central

    Novalic, Zlata; van der Wal, Annemieke M.; Leonhard, Wouter N.; Koehl, Gudrun; Breuning, Martijn H.; Geissler, Edward K.; de Heer, Emile

    2012-01-01

    Inhibition of the mammalian target of rapamycin (mTOR) shows beneficial effects in animal models of polycystic kidney disease (PKD); however, two clinical trials in patients with autosomal dominant PKD failed to demonstrate a short-term benefit in either the early or progressive stages of disease. The stage of disease during treatment and the dose of mTOR inhibitors may account for these differing results. Here, we studied the effects of a conventional low dose and a higher dose of sirolimus (blood levels of 3 ng/ml and 30–60 ng/ml, respectively) on mTOR activity and renal cystic disease in two Pkd1-mutant mouse models at different stages of the disease. When initiated at early but not late stages of disease, high-dose treatment strongly reduced mTOR signaling in renal tissues, inhibited cystogenesis, accelerated cyst regression, and abrogated fibrosis and the infiltration of immune cells. In contrast, low-dose treatment did not significantly reduce renal cystic disease. Levels of p-S6RpSer240/244, which marks mTOR activity, varied between kidneys; severity of the renal cystic phenotype correlated with the level of mTOR activity. Taken together, these data suggest that long-term treatment with conventional doses of sirolimus is insufficient to inhibit mTOR activity in renal cystic tissue. Mechanisms to increase bioavailability or to target mTOR inhibitors more specifically to kidneys, alone or in combination with other compounds, may improve the potential for these therapies in PKD. PMID:22343118

  8. Ursodeoxycholic acid for cystic fibrosis-related liver disease.

    PubMed

    Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

    2017-09-11

    Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. This is an update of a previous review. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies and searched online trial registries.Date of the most recent search of the Group's trials register: 09 April 2017. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. The authors used GRADE to assess the quality of the evidence. Twelve trials have been identified, of which four trials involving 137 participants were included; data were only available from three of the trials (118 participants) since one cross-over trial did not report appropriate data. The dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30

  9. [CT diagnosis of hemorrhagic renal cysts].

    PubMed

    Wu, Y Z; Li, D T; Luo, J G

    2001-06-28

    CT signs of nineteen cases of hemorrhagic renal cysts that surgically and pathologically proved were analyzed. 8 of the 19 cases revealed as high density hemorrhagic lesion. CT signs in those 8 patients include low density rim sign, cyst immerging sign, and perirenal fascia thickening. The other 11 of 19 cases revealed as low density lesion. CT signs include thickened cyst wall and inhomogeneous density of the cystic content. The hounsfield unit of the lesion is correlated with the duration of disease. It is suggested that CT is valuable in diagnosis of high density hemorrhagic renal cysts, and it gives a clue to the diagnosis of low density hemorrhagic renal cysts.

  10. Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease.

    PubMed

    Siano, Maria; De Gregorio, Fabiola; Boggia, Bartolo; Sepe, Angela; Ferri, Pasqualina; Buonpensiero, Paolo; Di Pasqua, Antonio; Raia, Valeria

    2010-06-01

    Meconium ileus has been detected as a risk factor for development of liver disease in cystic fibrosis, with influence on morbidity and mortality. To evaluate the effect of early treatment with ursodeoxycholic acid in patients with cystic fibrosis and meconium ileus to prevent chronic hepatic involvement and to explore the potential role of therapy on clinical outcomes. 26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4 years, range 3,5-9) were assigned to two groups: group 1 (14 patients) treated early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd). Anthropometric data, pulmonary function tests, pancreatic status, complications such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation were compared among groups. A higher prevalence of cystic fibrosis chronic liver disease was observed in the UDCAd group with a statistically significant difference at 9 years of age (p<0.05). Chronic infection by P. aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p<0.05). No differences were observed in nutritional status and other complications. Early treatment with ursodeoxycholic acid may be beneficial in patients at risk of developing cystic fibrosis chronic liver disease such as those with meconium ileus. Multicentre studies should be encouraged to confirm these data. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  11. Renal Involvement in Inflammatory Bowel Diseases.

    PubMed

    Corica, Domenico; Romano, Claudio

    2016-02-01

    The prevalence of extraintestinal manifestations in inflammatory bowel diseases varies from 6% to 46%. The aetiology of extraintestinal manifestations remains unclear. There are theories based on an immunological response influenced by genetic factors. Extraintestinal manifestations can involve almost every organ system. They may originate from the same pathophysiological mechanism of intestinal disease, or as secondary complications of inflammatory bowel diseases, or autoimmune diseases susceptibility. The most frequently involved organs are the joints, skin, eyes, liver and biliary tract. Renal involvement has been considered as an extraintestinal manifestation and has been described in both Crohn's disease and ulcerative colitis. The most frequent renal involvements in patients with inflammatory bowel disease are nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis. The aim of this review is to evaluate and report the most important data in the literature on renal involvement in patients with inflammatory bowel disease. Bibliographical searches were performed of the MEDLINE electronic database from January 1998 to January 2015 with the following key words (all fields): (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (kidney OR renal OR nephrotoxicity OR renal function OR kidney disease OR renal disease OR glomerulonephritis OR interstitial nephritis OR amyloidosis OR kidney failure OR renal failure) AND (5-aminosalicylic acid OR aminosalicylate OR mesalazine OR TNF-α inhibitors OR cyclosporine OR azathioprine OR drugs OR pediatric). Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Genetics Home Reference: medullary cystic kidney disease type 1

    MedlinePlus

    ... They lead to the production of an altered protein. It is unclear how this change causes kidney disease. ... cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat Genet. 2013 Mar;45(3):299-303. ...

  13. Inflammation in renal atherosclerotic disease.

    PubMed

    Udani, Suneel M; Dieter, Robert S

    2008-07-01

    The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

  14. G-protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of autosomal dominant polycystic kidney disease

    PubMed Central

    Kwon, Michelle; Pavlov, Tengis S.; Nozu, Kandai; Rasmussen, Shauna A.; Ilatovskaya, Daria V.; Lerch-Gaggl, Alexandra; North, Lauren M.; Kim, Hyunho; Qian, Feng; Sweeney, William E.; Avner, Ellis D.; Blumer, Joe B.; Staruschenko, Alexander; Park, Frank

    2012-01-01

    Polycystic kidney diseases are the most common genetic diseases that affect the kidney. There remains a paucity of information regarding mechanisms by which G proteins are regulated in the context of polycystic kidney disease to promote abnormal epithelial cell expansion and cystogenesis. In this study, we describe a functional role for the accessory protein, G-protein signaling modulator 1 (GPSM1), also known as activator of G-protein signaling 3, to act as a modulator of cyst progression in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD). A complete loss of Gpsm1 in the Pkd1V/V mouse model of ADPKD, which displays a hypomorphic phenotype of polycystin-1, demonstrated increased cyst progression and reduced renal function compared with age-matched cystic Gpsm1+/+ and Gpsm1+/− mice. Electrophysiological studies identified a role by which GPSM1 increased heteromeric polycystin-1/polycystin-2 ion channel activity via Gβγ subunits. In summary, the present study demonstrates an important role for GPSM1 in controlling the dynamics of cyst progression in an orthologous mouse model of ADPKD and presents a therapeutic target for drug development in the treatment of this costly disease. PMID:23236168

  15. Diagnosis of renal disease in rabbits.

    PubMed

    Harcourt-Brown, Frances Margaret

    2013-01-01

    There are differences in renal anatomy and physiology between rabbits and other domestic species. Neurogenic renal ischemia occurs readily. Reversible prerenal azotemia may be seen in conjunction with gut stasis. Potentially fatal acute renal failure may be due to structural kidney damage or post-renal disease. Chronic renal failure is often associated with encephalitozoonosis. Affected rabbits cannot vomit and often eat well. Weight loss, lethargy, and cachexia are common clinical signs. Polydypsia/polyuria may be present. Derangements in calcium and phosphorus metabolism are features of renal disease. Radiography is always indicated. Urolithiasis, osteosclerosis, aortic and renal calcification are easily seen on radiographs. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Renal disease in patients with celiac disease.

    PubMed

    Boonpheng, Boonphiphop; Cheungpasitporn, Wisit; Wijarnpreecha, Karn

    2018-04-01

    Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.

  17. Longitudinal cystic fibrosis care.

    PubMed

    Antunovic, S S; Lukac, M; Vujovic, D

    2013-01-01

    Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges. Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities. From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy. With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation-specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport. Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease-transforming management options for individuals with cystic fibrosis.

  18. Investigating self-efficacy, disease knowledge and adherence to treatment in adolescents with cystic fibrosis.

    PubMed

    Faint, Nicholas R; Staton, Janelle M; Stick, Stephen M; Foster, Juliet M; Schultz, André

    2017-05-01

    Patient adherence is integral to the effectiveness of prescribed treatment, and is associated with beneficial disease outcomes, yet in adolescents with cystic fibrosis, adherence is often sub-optimal. Multiple factors may contribute to treatment adherence, including disease knowledge and self-efficacy. In adolescents with cystic fibrosis: (i) to compare the disease knowledge of adolescents and their parents before transition to adult care; (ii) to determine the relationship between disease knowledge (adolescent, parent) and adherence; and (iii) to evaluate self-efficacy and its association with disease knowledge and adherence. Adolescents with cystic fibrosis and their parents were recruited from a tertiary children's hospital. Disease knowledge and self-efficacy was assessed using the Knowledge of Disease Management-CF and General Self-Efficacy Scales respectively. Using pharmacy records, medication possession ratio was calculated to measure treatment adherence in the preceding year. Thirty-nine adolescent (aged 12-17 (median 14) years) and parent pairs were recruited. Adherence to hypertonic saline, but not other medications, was significantly associated with disease knowledge in adolescents (r 2  = 0.40, P = 0.029). Mean (SD) adolescent self-efficacy was 30.8 (4.0), and not associated with disease knowledge or adherence. Mean (SD) disease knowledge was less in adolescents than parents (55 (16)% and 72 (14)% respectively, P < 0.001). Disease knowledge is sub-optimal in adolescents with cystic fibrosis, even in the 2 years immediately before transition to adult care. Given that adherence with some treatments has been associated with disease knowledge our results suggest the need for educational interventions in adolescents with cystic fibrosis to optimise self-management and health outcomes. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  19. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene

    PubMed Central

    Sosnay, Patrick R; Siklosi, Karen R; Van Goor, Fredrick; Kaniecki, Kyle; Yu, Haihui; Sharma, Neeraj; Ramalho, Anabela S; Amaral, Margarida D; Dorfman, Ruslan; Zielenski, Julian; Masica, David L; Karchin, Rachel; Millen, Linda; Thomas, Philip J; Patrinos, George P; Corey, Mary; Lewis, Michelle H; Rommens, Johanna M; Castellani, Carlo; Penland, Christopher M; Cutting, Garry R

    2013-01-01

    Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation to clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 cystic fibrosis patients in registries and clinics in North America and Europe. Among these patients, 159 CFTR variants had an allele frequency of ≥0.01%. These variants were evaluated for both clinical severity and functional consequence with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of cystic fibrosis patients enabled assignment of 12 of the remaining 32 variants as neutral while the other 20 variants remained indeterminate. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically-relevant genomic variation. PMID:23974870

  20. Retrospective evaluation of ultrasound-indeterminate renal multilocular cystic masses by using neutrophil-lymphocyte ratio and computed tomography.

    PubMed

    Wang, Hanfeng; Gu, Liangyou; Jia, Rui; Zeng, Jing; Liu, Xiaoxia; Zhang, Dawei; Wu, Yongjie; Luo, Guangda; Zhang, Xu

    2017-01-01

    To evaluate the clinical usefulness of neutrophil-lymphocyte ratio (NLR) in differentiating the ultrasound-indeterminate renal multilocular cystic masses (RMCM) in comparison with computed tomography (CT) and whether NLR has additional benefits to CT on sensitivity of detecting the malignant. Overall, 93 patients who underwent normal ultrasound with a conclusion of indeterminate RMCM were examined by NLR and CT within 30 days before surgery or follow-up from March to September 2014 at PLA General Hospital and enrolled in this retrospective study. Logistic regression model was performed to find independent predictors for differentiating true nature of RMCM; differences in the validity parameters and diagnostic power of CT, NLR, and their combination were compared using McNemar tests and AUC model, respectively. The final diagnoses of the 93 patients consisted of 36 patients with benign complex cysts, 16 with multilocular cystic renal cell carcinoma, 9 with multilocular cystic nephroma, and 32 with clear cell renal cell carcinoma. Higher NLR were strongly associated with malignant masses. Multivariate logistic regression analysis revealed that NLR could be an independent predictor for differentiating true nature of these masses (OR = 3.617; 95% CI: 1.219-10.727; P = 0.020). For detecting the malignant masses, the sensitivity, specificity, and accuracy were 71.9%, 80.6%, and 75.3% for CT and 57.9%, 88.9%, and 69.9% for NLR under cutoff value of 2.31, respectively, whereas those of CT+NLR were 89.5%, 69.4%, and 81.7%. No significant difference was found between CT and NLR in sensitivity (P = 0.185), specificity (P = 0.549), and accuracy (P = 0.428). But the sensitivity of CT+NLR was significantly higher than those of CT (P = 0.002) and NLR (P<0.001), respectively; AUC model analysis indicated that CT+NLR got the largest area of 0.795 (P<0.001, 95% CI: 0.693-0.896) in comparison with those of CT (area = 0.795, P<0.001, 95% CI: 0.661-0.864) and NLR (area = 0.734, P<0

  1. [Caroli's disease: congenital cystic and segmentary dilatation of the intrahepatic bile ducts].

    PubMed

    Serra, C A; Recalde, E B; Martellotto, G I

    1987-01-01

    Congenital cystic segmentary dilatation of the intrahepatic biliary ducts is a rare disease. Although several cases has been described in medical literature, its occurrence such as it was originally referred is exceptional. Some cases coexist with congenital hepatic fibrosis and portal hypertension. A characteristic phenomenon is the formation of stones and canalicular infection. In this article, three cases of Caroli disease (females, 57, 53 and 58 years old) are described. Case n 1 was a complex malformation including: a) cystic and segmentary dilatations of the intrahepatic biliar ducts; b) intra and extrahepatic lithiasis and recurrent infections; c) fusion of the choledocus and gallbladder in a common sac; d) hepatic cavernosus hemangioma and a supernumerarious lobe. Case n 2 showed: a) cystic and segmentary dilatation of the intrahepatic biliar ducts; b) portal fibrosis; c) polycystic kidneys; d) portal hypertension. Case n 3 showed: a) cystic and segmentary dilatation of the intrahepatic biliar ducts; b) portal fibrosis; c) polycystic kidneys and spleen; d) portal hypertension. Prognostic of this patients is variable and depends on the recurrent infections and the coexistence of other malformations which are frequently severe. Surgery is the only treatment for the disease although there are no definite conclusions concerning the long-term results.

  2. Immune and Inflammatory Role in Renal Disease

    PubMed Central

    Ryan, Michael J.

    2013-01-01

    Chronic and acute renal diseases, irrespective of the initiating cause, have inflammation and immune system activation as a common underlying mechanism. The purpose of this review is to provide a broad overview of immune cells and inflammatory proteins that contribute to the pathogenesis of renal disease, and to discuss some of the physiological changes that occur in the kidney as a result of immune system activation. An overview of common forms of acute and chronic renal disease is provided, followed by a discussion of common therapies that have antiinflammatory or immunosuppressive effects in the treatment of renal disease. PMID:23720336

  3. Gender hormones and the progression of experimental polycystic kidney disease.

    PubMed

    Stringer, Kenneth D; Komers, Radko; Osman, Shukri A; Oyama, Terry T; Lindsley, Jessie N; Anderson, Sharon

    2005-10-01

    Male gender is a risk factor for progression of autosomal-dominant polycystic kidney disease (ADPKD), clinically and in the Han:SPRD rat model. Orchiectomy limits progression, but mechanisms of the detrimental effect of androgen, and/or beneficial effects of estrogen, are not known. This protocol tested the hypothesis that male gender (intact androgen status) promotes progression, while female gender (intact estrogen status) is protective; and that these disease-modifying effects are due to changes in expression of known fibrotic mediators. Studies were performed in male and female noncystic control (+/+) and cystic (+/-) rats subjected to orchiectomy, ovariectomy, or sham operation. At 12 weeks of age, renal function was measured. Blood and kidneys were taken for measurement of plasma and renal renin, endothelin (ET-1), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF), using biochemical, protein expression, and immunohistochemical methods. Cystic male rats exhibited significantly reduced glomerular filtration (GFR) and effective renal plasma flow (ERPF) rates, with suppression of plasma and renal renin, up-regulation of renal ET-1 and eNOS, and down-regulation of renal VEGF expression. Orchiectomy attenuated the fall in GFR and ERPF, while numerically limiting changes in eNOS and VEGF. Female rats exhibited less cystic growth, with normal renin status, lesser elevation of renal ET-1, and proportionately lesser changes in VEGF and eNOS. Ovariectomy led to higher blood pressure and reduced GFR and ERPF, with a trend toward upregulation of ET-1, and significant down-regulation of VEGF and eNOS. Female gender is protective, but ovariectomy attenuates the protective effect of female gender, in association with changes in renal expression of ET-1, VEGF, and eNOS. The accelerated disease in male rats can be attenuated by orchiectomy and consequent changes in expression of disease mediators.

  4. Sickle cell disease: renal manifestations and mechanisms

    PubMed Central

    Nath, Karl A.; Hebbel, Robert P.

    2015-01-01

    Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

  5. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by medical...

  6. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by medical...

  7. Pathologic and Radiologic Correlation of Adult Cystic Lung Disease: A Comprehensive Review

    PubMed Central

    Parimi, Vamsi; Taddonio, Michale; Kane, Joshua Robert; Yeldandi, Anjana

    2017-01-01

    The presence of pulmonary parenchymal cysts on computed tomography (CT) imaging presents a significant diagnostic challenge. The diverse range of possible etiologies can usually be differentiated based on the clinical setting and radiologic features. In fact, the advent of high-resolution CT has facilitated making a diagnosis solely on analysis of CT image patterns, thus averting the need for a biopsy. While it is possible to make a fairly specific diagnosis during early stages of disease evolution by its characteristic radiological presentation, distinct features may progress to temporally converge into relatively nonspecific radiologic presentations sometimes necessitating histological examination to make a diagnosis. The aim of this review study is to provide both the pathologist and the radiologist with an overview of the diseases most commonly associated with cystic lung lesions primarily in adults by illustration and description of pathologic and radiologic features of each entity. Brief descriptions and characteristic radiologic features of the various disease entities are included and illustrative examples are provided for the common majority of them. In this article, we also classify pulmonary cystic disease with an emphasis on the pathophysiology behind cyst formation in an attempt to elucidate the characteristics of similar cystic appearances seen in various disease entities. PMID:28270943

  8. Non-proteinuric rather than proteinuric renal diseases are the leading cause of end-stage kidney disease.

    PubMed

    Bolignano, Davide; Zoccali, Carmine

    2017-04-01

    Proteinuria is a distinguishing feature in primary and secondary forms of chronic glomerulonephritis, which contribute to no more than the 20% of the end-stage kidney disease (ESKD) population. The contribution of non-proteinuric nephropathies to the global ESKD burden is still poorly focused and scarce research efforts are dedicated to the elucidation of risk factors and mechanistic pathways triggering ESKD in these diseases. We abstracted information on proteinuria in the main renal diseases other than glomerulonephritides that may evolve into ESKD. In type 2 diabetes, non-proteinuric diabetic kidney disease (DKD) is more frequent than proteinuric DKD, and risk factors for non-proteinuric forms of DKD now receive increasing attention. Similarly, proteinuria is most often inconspicuous or absent in the most frequent cause of ESKD, i.e. hypertension-related chronic kidney disease (CKD), as well as in progressive cystic diseases like autosomal dominant polycystic kidney disease and in pyelonephritis/tubulo-interstitial diseases. Maintaining a high degree of attention in the care of CKD patients with proteinuria is fundamental to effectively retard progression toward kidney failure. However, substantial research efforts are still needed to develop treatment strategies that may help the vast majority of CKD patients who eventually develop ESKD via mechanistic pathways other than proteinuria. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  9. Best practices in the treatment of early cystic fibrosis lung disease.

    PubMed

    Proesmans, Marijke

    2017-02-01

    For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

  10. Technical aspects of renal denervation in end-stage renal disease patients with challenging anatomy.

    PubMed

    Spinelli, Alessio; Da Ros, Valerio; Morosetti, Daniele; Onofrio, Silvia D; Rovella, Valentina; Di Daniele, Nicola; Simonetti, Giovanni

    2014-01-01

    We describe our preliminary experience with percutaneous renal denervation in end-stage renal disease patients with resistant hypertension and challenging anatomy, in terms of the feasibility, safety, and efficacy of this procedure. Four patients with end-stage renal disease patients with resistant hypertension (mean hemodialysis time, 2.3 years) who had been taking at least four antihypertensive medications underwent percutaneous renal denervation. Renal artery eligibility included the absence of prior renal artery interventions, vessel stenosis <70%, or extended calcifications (more than 30% of the vessel circumference). No cut off values of vessel diameter were used. All patients were successfully treated with no intra- or postprocedural complications, and all showed 24-hour ambulatory blood pressure reduction at the 12-month follow-up. Percutaneous renal denervation is a feasible approach for end-stage renal disease patients with resistant hypertension with encouraging short-term preliminary results in terms of procedural efficacy and safety.

  11. Dornase alfa as postoperative therapy in cystic fibrosis sinonasal disease.

    PubMed

    Cimmino, Mariano; Nardone, Massimiliano; Cavaliere, Matteo; Plantulli, Angela; Sepe, Angela; Esposito, Valeria; Mazzarella, Giuseppina; Raia, Valeria

    2005-12-01

    To determine the benefit of nasally inhaled dornase alfa in patients with cystic fibrosis and nasal symptoms. Double-blind placebo-controlled trial. Cystic Fibrosis Regional Center of Campania at the University of Naples "Federico II." A total of 24 patients with cystic fibrosis and chronic sinusitis. Patients underwent sinonasal surgery during a 3-year period and received once-daily doses of either dornase alfa (2.5 mg) or hypotonic saline solution (5 mL) beginning 1 month after surgery and for a 12-month period. Primary outcomes were nasal-related symptoms and nasal endoscopic appearance; secondary outcomes were forced expiratory volume in 1 second, nasal computed tomography findings, and saccharine clearance test results. Patients were evaluated before and after treatment. After surgery, all outcomes were significantly improved for each treatment at 1 month (P<.05); primary outcomes were improved at 24 and 48 weeks in the group receiving dornase alfa (P<.05), and at 12 weeks in the group receiving placebo. Secondary outcomes were better in the dornase alfa group (P<.01) than in the placebo group at 12 months except for the saccharine clearance test results. In particular, median relative difference in forced expiratory volume in 1 second between dornase alfa and placebo was significantly improved in the dornase alfa group (P<.01). Nasally inhaled dornase alfa can be effective in patients with cystic fibrosis and sinonasal disease who do not respond to conventional therapy after surgical treatment. Further studies should be carried out to determine the long-term effect on sinus disease, recurrence of polyps, and quality of life.

  12. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, T; Southern, K W

    2007-04-18

    measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), weighted mean difference 6.86 (95% CI of 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. There is currently no evidence to support the use of CFTR gene transfer reagents as a treatment for lung disease in people with cystic fibrosis. Future studies need to investigate clinically important outcome measures.

  13. The normal and pathologic renal medulla: a comprehensive overview.

    PubMed

    López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

    2015-04-01

    The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the facility...

  15. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the facility...

  16. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the facility...

  17. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the facility...

  18. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the facility...

  19. Cross-Sectional Imaging in a Case of Adventitial Cystic Disease of the Popliteal Artery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ricci, Paolo; Panzetti, Claudio; Mastantuono, Marco

    1999-01-15

    Adventitial cystic disease of the popliteal artery is an unusual condition of uncertain etiology, in which a mucin-containing cyst forms in the wall of the artery and produces lower extremity claudication, typically in young and middle-aged men. A diagnosis of adventitial cystic disease of the popliteal artery was made preoperatively in a 47-year-old man by means of several imaging modalities, including angiography, magnetic resonance imaging, and ultrasound. The pathological findings confirmed the suggested diagnosis.

  20. Cystic fibrosis.

    PubMed

    O'Sullivan, Brian P; Freedman, Steven D

    2009-05-30

    Cystic fibrosis is the most common lethal genetic disease in white populations. The outlook for patients with the disease has improved steadily over many years, largely as a result of earlier diagnosis, more aggressive therapy, and provision of care in specialised centres. Researchers now have a more complete understanding of the molecular-biological defect that underlies cystic fibrosis, which is leading to new approaches to treatment. One of these treatments, hypertonic saline, is already in use, whereas others are in advanced stages of development. We review clinical care for cystic fibrosis and discuss recent advances in the understanding of its pathogenesis, implementation of screening of neonates, and development of therapies aimed at treating the basic defect.

  1. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.57... disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... conclusion that a claimant developed chronic renal disease must be supported by medical documentation. (b) A...

  2. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of chronic renal disease. 79.57... disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... conclusion that a claimant developed chronic renal disease must be supported by medical documentation. (b) A...

  3. Cystic Echinococcosis

    PubMed Central

    Brunetti, Enrico; McCloskey, Cindy

    2015-01-01

    Echinococcosis is one of the 17 neglected tropical diseases (NTDs) recognized by the World Health Organization. The two major species of medical importance are Echinococcus granulosus and Echinococcus multilocularis. E. granulosus affects over 1 million people and is responsible for over $3 billion in expenses every year. In this minireview, we discuss aspects of the epidemiology, clinical manifestations, and diagnosis of cystic echinococcosis or cystic hydatid disease caused by E. granulosus. PMID:26677245

  4. CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.

    PubMed

    Fernandez Fernandez, Elena; de Santi, Chiara; De Rose, Virginia; Greene, Catherine M

    2018-05-11

    Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert Commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

  5. Treatments of various otolaryngological cystic diseases by OK-4321: its indications and limitations.

    PubMed

    Ohta, Nobuo; Fukase, Shigeru; Suzuki, Yusuke; Ishida, Akihiro; Aoyagi, Masaru

    2010-11-01

    The aim of this study was to evaluate the indications for, and outcomes and limitations of, OK-432 therapy in various otolaryngological cystic diseases. A retrospective clinical study at Yamagata University School of Medicine and the Fukase Clinic in Japan. Between April 1996 and November 2009 we tried OK-432 therapy in 148 patients with otolaryngological cystic diseases. In cases of plunging ranulas, lymphangiomas, branchial cleft cysts, thyroglossal duct cysts, thyroid cysts, and cervical lymphocele, we aspirated as much of the fluid content of each cystic lesion as possible, and we then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. Disappearance of the lesion was observed in 119 of 148 patients (80%). Marked reduction was observed in 20 of 148 patients (14%). Partial reduction was observed in four patients (3%), and no response was seen in five patients (3%). Plunging ranula, lymphangioma, thyroglossal duct cyst, thyroid cyst, auricular hematoma, and salivary mucocele showed better responses to OK-432 therapy than did branchial cleft cyst. Serious complications with OK-432 therapy were infrequent, and the therapy seemed to have no influence on future surgery. Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of various otolaryngological cystic diseases.

  6. Cardiovascular Disease in Patients with End-Stage Renal Disease on Hemodialysis

    PubMed Central

    Aoki, Jiro; Ikari, Yuji

    2017-01-01

    Cardiovascular disease is a major concern for patients with end-stage renal disease (ESRD), especially those on hemodialysis. ESRD patients with coronary artery disease often do not have symptoms or present with atypical symptoms. Coronary lesions in ESRD patients are characterized by increased media thickness, infiltration and activation of macrophages, and marked calcification. Several studies showed worsened clinical outcomes after coronary revascularization, which were dependent on the severity of renal dysfunction. ESRD patients on hemodialysis have the most severe renal dysfunction; thus, the clinical outcomes are worse in these patients than in those with other types of renal dysfunction. Medications for primary or secondary cardiovascular prevention are also insufficient in ESRD patients. Efficacy of drug-eluting stents is inferior in ESRD patients, compared to the excellent outcomes observed in patients with normal renal function. Unsatisfactory outcomes with trials targeting cardiovascular disease in patients with ESRD emphasize a large potential to improve outcomes. Thus, optimal strategies for diagnosis, prevention, and management of cardiovascular disease should be modified in ESRD patients. PMID:29515692

  7. Pregnancy in women with renal disease. Yes or no?

    PubMed Central

    Edipidis, K

    2011-01-01

    Women with renal disease who conceive and continue pregnancy, are at significant risk for adverse maternal and fetal outcomes. Although advances in antenatal and neonatal care continue to improve these outcomes, the risks remain proportionate to the degree of underlying renal dysfunction. The aim of this article, is to examine the impact of varying degrees of renal insufficiency on pregnancy outcome, in women with chronic renal disease and to provide if possible, useful conclusions whether and when, a woman with Chronic Kidney Disease (CKD), should decide to get pregnant. This article, reviews briefly the normal physiological changes of renal function during pregnancy, and make an attempt to clarify the nature and severity of the risks, in the settings of chronic renal insufficiency and end stage renal disease, including dialysis patients and transplant recipients. PMID:21897751

  8. Airway disease phenotypes in animal models of cystic fibrosis.

    PubMed

    McCarron, Alexandra; Donnelley, Martin; Parsons, David

    2018-04-02

    In humans, cystic fibrosis (CF) lung disease is characterised by chronic infection, inflammation, airway remodelling, and mucus obstruction. A lack of pulmonary manifestations in CF mouse models has hindered investigations of airway disease pathogenesis, as well as the development and testing of potential therapeutics. However, recently generated CF animal models including rat, ferret and pig models demonstrate a range of well characterised lung disease phenotypes with varying degrees of severity. This review discusses the airway phenotypes of currently available CF animal models and presents potential applications of each model in airway-related CF research.

  9. Genetic Expression in Cystic Fibrosis Related Bone Disease. An Observational, Transversal, Cross-Sectional Study.

    PubMed

    Ciuca, Ioana M; Pop, Liviu L; Rogobete, Alexandru F; Onet, Dan I; Guta-Almajan, Bogdan; Popa, Zoran; Horhat, Florin G

    2016-09-01

    Cystic fibrosis (CF) is the most frequent monogenic genetic disease with autosomal recessive transmission and characterized by important clinical polymorphism and significant lethal prospective. CF related bone disease occurs frequently in adults with CF. Childhood is the period of bone formation, and therefore, children are more susceptible to low bone density. Several factors like pancreatic insufficiency, hormone imbalance, and physical inactivity contribute to CF bone disease development. Revealing this would be important for prophylactic treatment against bone disease occurrence. The study was observational, transversal, with a cross-sectional design. The study included 68 children with cystic fibrosis, genotyped and monitored in the National CF Centre. At the annual assessment, besides clinical examination, biochemical evaluation for pancreatic insufficiency, and diabetes, they were evaluated for bone mineral density using dual energy X-ray absorptiometry (DXA). Twenty-six patients, aged over 10 years were diagnosed with CF bone disease, without significant gender gap. Bone disease was frequent in patients aged over 10 years with exocrine pancreatic insufficiency, carriers of severe mutations, and CF liver disease. CF carriers of a severe genotype which associates pancreatic insufficiency and CF liver disease, are more likely predisposed to low bone mineral density. Further studies should discover other significant influences in order to prevent the development of CF bone disease and an improved quality of life in cystic fibrosis children.

  10. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, Tim W R; Southern, Kevin W

    2013-11-26

    who received the CFTR gene transfer agents in the Alton study, "influenza-like" symptoms were found (risk ratio 7.00 (95% confidence interval 1.10 to 44.61)). There were no other significant increases in adverse events in any of the studies.Alton measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. There is currently no evidence to support the use of CFTR gene transfer agents as a treatment for lung disease in people with cystic fibrosis. Future studies need to investigate clinically important outcome measures.

  11. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, Tim W R; Southern, Kevin W

    2012-10-17

    received the CFTR gene transfer agents in the Alton study, "influenza-like" symptoms were found (risk ratio 7.00 (95% confidence interval 1.10 to 44.61)). There were no other significant increases in adverse events in any of the studies.Alton measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% CI of 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. There is currently no evidence to support the use of CFTR gene transfer reagents as a treatment for lung disease in people with cystic fibrosis. Future studies need to investigate clinically important outcome measures.

  12. Long-term success of combined kidney-lung transplantation in a patient with cystic fibrosis.

    PubMed

    Borro, José M; Rama, Pablo; Rey, Teresa; Fernández-Rivera, Constantino

    2013-06-01

    Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function. Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.

  13. Liver disease in patients with cystic fibrosis.

    PubMed

    Kamal, Natasha; Surana, Pallavi; Koh, Christopher

    2018-05-01

    The aim of this study was to provide an overview of the current understanding of the pathophysiology, diagnosis and management of cystic fibrosis-liver disease (CFLD). CFLD has a variety of manifestations. Previously, it was thought that patients progressed from mild cholestatic disease to cirrhosis to decompensated cirrhosis with portal hypertension. Newer evidence suggests that some patients may develop cirrhosis while others develop noncirrhotic portal hypertension. Advances in our understanding of the pathophysiology of disease necessitate modifications to the current diagnostic criteria. Both fibroscan and noninvasive biomarkers can be used to identify patients with cirrhosis and portal hypertension. Ursodeoxycholic acid remains the mainstay of therapy despite a paucity of rigorous studies supporting its use. Novel therapeutic agents such as CF transmembrane conductance regulator (CFTR) modulators and potentiators are encouraging but need to be evaluated specifically in CFLD. A better understanding of the pathophysiology of disease is critical to developing more disease-specific diagnostics and therapeutics.

  14. Renal cell carcinoma in a cat with polycystic kidney disease undergoing renal transplantation.

    PubMed

    Adams, Daniel J; Demchur, Jolie A; Aronson, Lillian R

    2018-01-01

    A 10-year-old spayed female American Shorthair cat underwent renal transplantation due to worsening chronic kidney disease secondary to polycystic kidney disease. During transplantation, the right kidney grossly appeared to be more diseased than the left and was firmly adhered to the surrounding tissues. An intraoperative fine-needle aspirate of the right native kidney revealed inflammatory cells but no evidence of neoplasia. To create space for the allograft, a right nephrectomy was performed. Following nephrectomy, the right native kidney was submitted for biopsy. Biopsy results revealed a renal cell carcinoma. Although the cat initially recovered well from surgery, delayed graft function was a concern in the early postoperative period. Significant azotemia persisted and the cat began to have diarrhea. Erythematous skin lesions developed in the perineal and inguinal regions, which were suspected to be secondary to thromboembolic disease based on histopathology. The cat's clinical status continued to decline with development of signs of sepsis, followed by marked obtundation with uncontrollable seizures. Given the postoperative diagnosis of renal cell carcinoma and the cat's progressively declining clinical status, humane euthanasia was elected. This case is the first to document renal cell carcinoma in a cat with polycystic kidney disease. An association of the two diseases has been reported in the human literature, but such a link has yet to be described in veterinary medicine. Given the association reported in the human literature, a plausible relationship between polycystic kidney disease and renal cell carcinoma in cats merits further investigation.

  15. Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.

    PubMed

    Hackl, Agnes; Mehler, Katrin; Gottschalk, Ingo; Vierzig, Anne; Eydam, Marcus; Hauke, Jan; Beck, Bodo B; Liebau, Max C; Ensenauer, Regina; Weber, Lutz T; Habbig, Sandra

    2017-05-01

    Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early

  16. Frequency and clinical predictors of coronary artery disease in chronic renal failure renal transplant candidates.

    PubMed

    de Albuquerque Seixas, Emerson; Carmello, Beatriz Leone; Kojima, Christiane Akemi; Contti, Mariana Moraes; Modeli de Andrade, Luiz Gustavo; Maiello, José Roberto; Almeida, Fernando Antonio; Martin, Luis Cuadrado

    2015-05-01

    Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a particular risk; however, risk predictors have been used to diagnose coronary heart disease. This study evaluated the frequency and importance of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, and assessed a previously developed scoring system. Coronary angiographies conducted between March 2008 and April 2013 from 99 candidates for renal transplantation from two transplant centers in São Paulo state were analyzed for associations between significant coronary artery diseases (≥70% stenosis in one or more epicardial coronary arteries or ≥50% in the left main coronary artery) and clinical parameters. Univariate logistic regression analysis identified diabetes, angina, and/or previous infarction, clinical peripheral arterial disease and dyslipidemia as predictors of coronary artery disease. Multiple logistic regression analysis identified only diabetes and angina and/or previous infarction as independent predictors. The results corroborate previous studies demonstrating the importance of these factors when selecting patients for coronary angiography in clinical pretransplant evaluation.

  17. Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

    PubMed

    George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

    2016-01-01

    Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end

  18. Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients.

    PubMed

    Stehling, Florian; Büscher, Rainer; Grosse-Onnebrink, Jörg; Hoyer, Peter F; Mellies, Uwe

    2017-01-01

    Introduction . Antibiotic treatment regimens against Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients often include aminoglycoside antibiotics that may cause chronic renal failure after repeated courses. Aminoaciduria is an early marker of acute aminoglycoside-induced renal tubular dysfunction. We hypothesized that urinary amino acid reabsorption is decreased after repeated once-daily tobramycin therapies. Methods . In this prospective cross-sectional study creatinine clearance was estimated by the Schwartz and the Cockcroft-Gault formula. Tubular amino acid reabsorption was determined by ion exchange chromatography in 46 patients with CF who received multiple tobramycin courses (6.3 ± 10.1 (1-57)) in a once-daily dosing regimen and 10 who did not. Results . Estimated creatinine clearance employing the Cockcroft-Gault was mildly reduced in 17/46 (37%) of the patients who received tobramycin and 5/10 (50%) of the patients who did not but in none using the Schwartz formula. No association with lifetime tobramycin courses was found. Tubular amino acid reabsorption was not influenced by the amount of once-daily tobramycin courses. Conclusion . Clinically not significant reduction of eCCL occurred in a minority of CF patients. However, chronic tubular dysfunction was not present in patients with CF repeatedly treated with tobramycin in the once-daily dosing scheme.

  19. Cystic fibrosis.

    PubMed

    Elborn, J Stuart

    2016-11-19

    Cystic fibrosis is a common life-limiting autosomal recessive genetic disorder, with highest prevalence in Europe, North America, and Australia. The disease is caused by mutation of a gene that encodes a chloride-conducting transmembrane channel called the cystic fibrosis transmembrane conductance regulator (CFTR), which regulates anion transport and mucociliary clearance in the airways. Functional failure of CFTR results in mucus retention and chronic infection and subsequently in local airway inflammation that is harmful to the lungs. CFTR dysfunction mainly affects epithelial cells, although there is evidence of a role in immune cells. Cystic fibrosis affects several body systems, and morbidity and mortality is mostly caused by bronchiectasis, small airways obstruction, and progressive respiratory impairment. Important comorbidities caused by epithelial cell dysfunction occur in the pancreas (malabsorption), liver (biliary cirrhosis), sweat glands (heat shock), and vas deferens (infertility). The development and delivery of drugs that improve the clearance of mucus from the lungs and treat the consequent infection, in combination with correction of pancreatic insufficiency and undernutrition by multidisciplinary teams, have resulted in remarkable improvements in quality of life and clinical outcomes in patients with cystic fibrosis, with median life expectancy now older than 40 years. Innovative and transformational therapies that target the basic defect in cystic fibrosis have recently been developed and are effective in improving lung function and reducing pulmonary exacerbations. Further small molecule and gene-based therapies are being developed to restore CFTR function; these therapies promise to be disease modifying and to improve the lives of people with cystic fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Heart involvement in cystic fibrosis: A specific cystic fibrosis-related myocardial changes?

    PubMed

    Labombarda, Fabien; Saloux, Eric; Brouard, Jacques; Bergot, Emmanuel; Milliez, Paul

    2016-09-01

    Cystic fibrosis is a complex multi-systemic chronic disease characterized by progressive organ dysfunction with development of fibrosis, possibly affecting the heart. Over the last four decades pathological, experimental, and clinical evidence points towards the existence of a specific myocardial involvement in cystic fibrosis. Multi-modality cardiac imaging, especially recent echocardiographic techniques, evidenced diastolic and/or systolic ventricular dysfunction in cystic fibrosis leading to the concept of a cystic fibrosis-related cardiomyopathy. Hypoxemia and inflammation are among the most important factors for heart involvement in cystic fibrosis. Cystic Fibrosis Transmembrane Regulator was found to be involved in the regulation of cardiomyocyte contraction and may also account for cystic fibrosis-related myocardial dysfunction. This review, mainly focused on echocardiographic studies, seeks to synthesize the existing literature for and against the existence of heart involvement in cystic fibrosis, its mechanisms and prognostic implications. Careful investigation of the heart function may be helpful for risk stratification and therapeutic decisions in patients with cystic fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Lung ultrasound has limited diagnostic value in rare cystic lung diseases: a cross-sectional study.

    PubMed

    Davidsen, Jesper Rømhild; Bendstrup, Elisabeth; Henriksen, Daniel P; Graumann, Ole; Laursen, Christian B

    2017-01-01

    Background : Lung ultrasound (LUS) used to identify interstitial syndrome (IS) and pleural thickening related to diffuse parenchymal lung disease (DPLD) has shown significant correlations with ground glass opacity (GGO) on high-resolution computed tomography (HRCT). However, the applicability of LUS in patients with DPLD subtypes as rare cystic lung diseases has not previously been investigated. This study aimed to observe if distinctive LUS findings could be found in patients with lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), and Birt-Hogg-Dubé syndrome (BHDS). Methods : This single centre case-based cross-sectional study of patients diagnosed with LAM, PCLH and BHDS was conducted at a Danish DPLD specialist centre. Patients underwent clinical examination including LUS. LUS findings were compared to findings scored according to a modified Belmaati score on HRCT and reviewed in consensus between two pulmonologists and one radiologist. Results : Twelve patients with HRCT proven cystic lung disease were included, six with LAM, three with PLCH, two with BHDS, and one with uncharacteristic cystic lung disease. The mean age was 48.7 years (SD ± 15.8). In general all had normal LUS findings. IS could not be found in any patients despite GGO presentation on HRCT among 75% of the patients with a Belmaati in the highest category of 0.76-1.00. Pleural thickening on LUS was present in three patients, but with inconsistent findings. Conclusion : This study indicates that LUS has limited value as a diagnostic tool in patients with LAM, PLCH, and BHDS as normal LUS findings did not rule out severe cystic lung disease.

  2. Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease.

    PubMed

    Fujimaru, T; Mori, T; Sekine, A; Mandai, S; Chiga, M; Kikuchi, H; Ando, F; Mori, Y; Nomura, N; Iimori, S; Naito, S; Okado, T; Rai, T; Hoshino, J; Ubara, Y; Uchida, S; Sohara, E

    2018-07-01

    Distinguishing autosomal-dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease-causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Quantitative magnetic resonance imaging assessments of autosomal recessive polycystic kidney disease progression and response to therapy in an animal model.

    PubMed

    Erokwu, Bernadette O; Anderson, Christian E; Flask, Chris A; Dell, Katherine M

    2018-05-01

    BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is associated with significant mortality and morbidity, and currently, there are no disease-specific treatments available for ARPKD patients. One major limitation in establishing new therapies for ARPKD is a lack of sensitive measures of kidney disease progression. Magnetic resonance imaging (MRI) can provide multiple quantitative assessments of the disease.MethodsWe applied quantitative image analysis of high-resolution (noncontrast) T2-weighted MRI techniques to study cystic kidney disease progression and response to therapy in the PCK rat model of ARPKD.ResultsSerial imaging over a 2-month period demonstrated that renal cystic burden (RCB, %)=[total cyst volume (TCV)/total kidney volume (TKV) × 100], TCV, and, to a lesser extent, TKV detected cystic kidney disease progression, as well as the therapeutic effect of octreotide, a clinically available medication shown previously to slow both kidney and liver disease progression in this model. All three MRI measures correlated significantly with histologic measures of renal cystic area, although the correlation of RCB and TCV was stronger than that of TKV.ConclusionThese preclinical MRI results provide a basis for applying these quantitative MRI techniques in clinical studies, to stage and measure progression in human ARPKD kidney disease.

  4. [Managing focal incidental renal lesions].

    PubMed

    Nicolau, C; Paño, B; Sebastià, C

    2016-01-01

    Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  5. Characteristics and survival of patients with end stage renal disease and spina bifida in the United States renal data system.

    PubMed

    Ouyang, Lijing; Bolen, Julie; Valdez, Rodolfo; Joseph, David; Baum, Michelle A; Thibadeau, Judy

    2015-02-01

    We describe the characteristics, treatments and survival of patients with spina bifida in whom end stage renal disease developed from 2004 through 2008 in the United States Renal Data System. We used ICD-9-CM code 741.* to identify individuals with spina bifida using hospital inpatient data from 1977 to 2010, and physician and facility claims from 2004 to 2008. We constructed a 5:1 comparison group of patients with end stage renal disease without spina bifida matched by age at first end stage renal disease service, gender and race/ethnicity. We assessed the risk of mortality and of renal transplantation while on dialysis using multivariate cause specific proportional hazards survival analysis. We also compared survival after the first renal transplant from the first end stage renal disease service to August 2011. We identified 439 patients with end stage renal disease and spina bifida in whom end stage renal disease developed at an average younger age than in patients without spina bifida (41 vs 62 years, p <0.001) and in whom urological issues were the most common primary cause of end stage renal disease. Compared to patients with end stage renal disease without spina bifida those who had spina bifida showed a similar mortality hazard on dialysis and after transplantation. However, patients with end stage renal disease without spina bifida were more likely to undergo renal transplantation than patients with spina bifida (HR 1.51, 95% CI 1.13-2.03). Hospitalizations related to urinary tract infections were positively associated with the risk of death on dialysis in patients with end stage renal disease and spina bifida (HR 1.42, 95% CI 1.33-1.53). Spina bifida was not associated with increased mortality in patients with end stage renal disease on dialysis or after renal transplantation. Proper urological and bladder management is imperative in patients with spina bifida, particularly in adults. Copyright © 2015 American Urological Association Education and

  6. Renal proximal tubule function is preserved in Cftrtm2camΔF508 cystic fibrosis mice

    PubMed Central

    Kibble, J D; Balloch, K J D; Neal, A M; Hill, C; White, S; Robson, L; Green, R; Taylor, C J

    2001-01-01

    Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftrtm2camΔF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. Renal Na+ clearance was similar in wild-type (1.4 ± 0.3 μl min−1, number of animals, N= 12) and CF mice (1.6 ± 0.4 μl min−1, N= 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 ± 0.8 μl min−1, N= 8) and CF mice (9.3 ± 1.4 μl min−1, N= 9); no difference between genotypes was observed. In situ microperfusion revealed that fluid absorptive rate (Jv) was similar under control conditions between wild-type (2.2 ± 0.4 nl mm−1 min−1, n= 10) and CF mice (1.9 ± 0.3 nl mm−1 min−1, n= 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate caused no significant change in Jv in either wild-type (2.6 ± 0.7 nl mm−1 min−1, n= 10) or Cftrtm2camΔF508 mice (2.0 ± 0.5 nl mm−1 min−1, n= 10). CFTR expression was confirmed in samples of outer cortex using RT-PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch clamping. In conclusion, no functional deficit in proximal tubule function was found in Cftrtm2camΔF508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl− conductance in mouse proximal tubule cells. PMID:11306663

  7. Diagnosis, follow-up and treatment of cystic fibrosis-related liver disease.

    PubMed

    van de Peppel, Ivo P; Bertolini, Anna; Jonker, Johan W; Bodewes, Frank A J A; Verkade, Henkjan J

    2017-11-01

    To provide an insight and overview of the challenges in the diagnosis, follow-up and treatment of cystic fibrosis-related liver disease (CFLD). The variable pathophysiology of CFLD complicates its diagnosis and treatment. A 'gold standard' for CFLD diagnosis is lacking. Over the past years, new techniques to diagnose features of CFLD, such as transient elastography, have been investigated. Although most of these tests confirm cystic fibrosis-related liver involvement (CFLI), they are, however, not suitable to distinguish various phenotypical presentations or predict progression to clinically relevant cirrhosis or portal hypertension. A combined initiative from the European and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has been started, aimed to obtain consensus on CFLD criteria and definitions. Currently, only ursodeoxycholic acid is used in CFLD treatment, although it has not been convincingly demonstrated to change the natural course of the disease. Drugs that directly target cystic fibrosis transmembrane conductance regulator protein dysfunction show promising results; however, more long-term follow-up and validation studies are needed. CFLD is an umbrella term referring to a wide variety of liver manifestations with variable clinical needs and consequences. CFLD with portal hypertension is the most severe form of CFLD due to its significant implications on morbidity and mortality. The clinical relevance of other CFLI is uncertain. Consensus on CFLD definitions is essential to validate new diagnostic tools and therapeutic outcome measures.

  8. Disease management improves end-stage renal disease outcomes.

    PubMed

    Sands, Jeffrey J

    2006-01-01

    Renal disease management organizations have reported achieving significant decreases in mortality and hospitalization in conjunction with cost savings, improved patient satisfaction and quality of life. Disease management organizations strive to fill existing gaps in care delivery through the standardized use of risk assessment, predictive modeling, evidence-based guidelines, and process and outcomes measurement. Patient self-management education and the provision of individual nurse care managers are also key program components. As we more fully measure clinical outcomes and total healthcare costs, including payments from all insurance and government entities, pharmacy costs and out of pocket expenditures, the full implications of disease management can be better defined. The results of this analysis will have a profound influence on United States healthcare policy. At present current data suggest that the promise of disease management, improved care at reduced cost, can and is being realized in end-stage renal disease. Copyright 2006 S. Karger AG, Basel.

  9. Gastrointestinal Manifestations of Cystic Fibrosis

    PubMed Central

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  10. [Atheroembolism renal disease: diagnosis and etiologic factors].

    PubMed

    Granata, A; Insalaco, M; Di Pietro, F; Di Rosa, S; Romano, G; Scuderi, R

    2012-07-01

    Atheromatous renal disease is the major cause of renal insufficiency in the elderly, and cholesterol embolism is a manifestation of this disease. Cholesterol embolism occurs in patients suffering from diffuse erosive atherosclerosis, usually after triggering causes, such as aortic surgery, arterial invasive procedures (angiography, left heart catheterization and coronary angioplasty) and anticoagulant or thrombolytic therapy. It is characterized by occlusion of small arteries with cholesterol emboli deriving from eroded atheromatous plaques of the aorta or large feeder arteries. The proximity of the kidneys to the abdominal aorta and the large renal blood supply make the kidney a frequent target organ for cholesterol atheroembolism. The exact incidence of atheroembolic renal disease (AERD) is not known. The reported incidence AERD varied in the literature because of the differences in study design and the different criteria used for making the diagnosis. Retrospective data derived from autopsy or biopsy studies may exaggerate the frequency by including many subclinical cases. Clinical observations that are based on a short duration of follow-up after an invasive vascular procedure and the infrequency of the confirmatory renal biopsies can lead to an underestimation of the true incidence of AERD. The initial signs and symptoms in patients diagnosed with cholesterol embolism were blue toes syndrome, livedo reticularis, gangrene, leg, toe or foot pain, abdominal pain and flank or back pain, gross haematuria, accelerated hypertension and renal failure. Cholesterol embolism may also be associated with fever, increased erythrocyte sedimentation rate and eosinophilia. Thus, in the cases of spontaneous cholesterol embolism, differential diagnosis includes, polyarteritis nodosa, allergic vasculitis and subacute bacterial endocarditis. Skin and renal biopsy specimens are the best sample for histologic diagnosis. There is, at present, no pharmacological treatments shown to be

  11. Sympatho-renal axis in chronic disease.

    PubMed

    Sobotka, Paul A; Mahfoud, Felix; Schlaich, Markus P; Hoppe, Uta C; Böhm, Michael; Krum, Henry

    2011-12-01

    Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney's somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics-insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders.

  12. Serum lipoprotein changes in dogs with renal disease.

    PubMed

    Behling-Kelly, E

    2014-01-01

    People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated. Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high-density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatinine concentration. Prospective study of client-owned dogs presented to the Cornell University Hospital for Animals: 29 dogs with confirmed CKD, 5 dogs with nephrotic syndrome (NS), and 12 healthy control dogs presented for routine vaccinations, dental cleaning, or owned by students. Lipoprotein electrophoresis was used to quantify relative proportions of the 3 main classes of lipoproteins in canine serum: low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), and HDL. Serum cholesterol and creatinine concentrations; urinalysis and urine protein-to-creatinine ratio were measured by standard methods. Dyslipidemia was consistently found in dogs with CKD and NS and was characterized by a decrease in HDL and variable increases in LDL and VLDL. Dogs with NS had a proportionately greater increase in the VLDL fraction, as compared with dogs with CKD. Dyslipidemia similar to that documented in people with renal disease occurs in dogs with CKD, despite serum cholesterol concentrations often being within the reference interval. The contribution of altered lipoproteins to the pathogenesis of renal disease in dogs warrants additional study. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  13. Lung ultrasound has limited diagnostic value in rare cystic lung diseases: a cross-sectional study

    PubMed Central

    Davidsen, Jesper Rømhild; Bendstrup, Elisabeth; Henriksen, Daniel P.; Graumann, Ole; Laursen, Christian B.

    2017-01-01

    ABSTRACT Background: Lung ultrasound (LUS) used to identify interstitial syndrome (IS) and pleural thickening related to diffuse parenchymal lung disease (DPLD) has shown significant correlations with ground glass opacity (GGO) on high-resolution computed tomography (HRCT). However, the applicability of LUS in patients with DPLD subtypes as rare cystic lung diseases has not previously been investigated. This study aimed to observe if distinctive LUS findings could be found in patients with lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), and Birt-Hogg-Dubé syndrome (BHDS). Methods: This single centre case-based cross-sectional study of patients diagnosed with LAM, PCLH and BHDS was conducted at a Danish DPLD specialist centre. Patients underwent clinical examination including LUS. LUS findings were compared to findings scored according to a modified Belmaati score on HRCT and reviewed in consensus between two pulmonologists and one radiologist. Results: Twelve patients with HRCT proven cystic lung disease were included, six with LAM, three with PLCH, two with BHDS, and one with uncharacteristic cystic lung disease. The mean age was 48.7 years (SD ± 15.8). In general all had normal LUS findings. IS could not be found in any patients despite GGO presentation on HRCT among 75% of the patients with a Belmaati in the highest category of 0.76–1.00. Pleural thickening on LUS was present in three patients, but with inconsistent findings. Conclusion: This study indicates that LUS has limited value as a diagnostic tool in patients with LAM, PLCH, and BHDS as normal LUS findings did not rule out severe cystic lung disease. PMID:28649310

  14. Intestinal bile acid malabsorption in cystic fibrosis.

    PubMed

    O'Brien, S; Mulcahy, H; Fenlon, H; O'Broin, A; Casey, M; Burke, A; FitzGerald, M X; Hegarty, J E

    1993-08-01

    This study aimed at examining the mechanisms participating in excessive faecal bile acid loss in cystic fibrosis. The study was designed to define the relation between faecal fat and faecal bile acid loss in patients with and without cystic fibrosis related liver disease; to assess terminal ileal bile acid absorption by a seven day whole body retention of selenium labelled homotaurocholic acid (SeHCAT); and to determine if small intestinal bacterial overgrowth contributes to faecal bile acid loss. The study population comprised 40 patients (27 men; median age 18 years) with cystic fibrosis (n = 8) and without (n = 32) liver disease and eight control subjects. Faecal bile acid excretion was significantly higher in cystic fibrosis patients without liver disease compared with control subjects (mean (SEM) 21.5 (2.4) and 7.3 (1.2) micromoles/kg/24 hours respectively; p < 0.01) and patients with liver disease (7.9 (1.3) micromoles/kg/24 hours; p < 0.01). No correlation was found between faecal fat (g fat/24 hours) and faecal bile acid (micromoles 24 hours) excretion. Eight (33%) of cystic fibrosis patients had seven day SeHCAT retention < 10% (normal retention > 20%). SeHCAT retention in cystic fibrosis patients with liver disease was comparable with control subjects (30.0 (SEM) 8.3% v 36.8 (5.9)%; p = NS) while SeHCAT retention in cystic fibrosis patients who did not have liver disease was significantly reduced (19.9 (3.8); p < 0.05). Although evidence of small bowel bacterial overgrowth was present in 40% of patients no relation was found between breath hydrogen excretion, faecal fat, and faecal bile acid loss. The results are consistent with the presence of an abnormality in terminal ideal function in patients with cystic fibrosis who do not have liver disease and that a defect in the ileal absorption of bile acids may be a contributory factor to excessive faecal bile acid loss. Faecal bile acid loss in cystic fibrosis is unrelated to the presence of intraluminal fat

  15. Intestinal bile acid malabsorption in cystic fibrosis.

    PubMed Central

    O'Brien, S; Mulcahy, H; Fenlon, H; O'Broin, A; Casey, M; Burke, A; FitzGerald, M X; Hegarty, J E

    1993-01-01

    This study aimed at examining the mechanisms participating in excessive faecal bile acid loss in cystic fibrosis. The study was designed to define the relation between faecal fat and faecal bile acid loss in patients with and without cystic fibrosis related liver disease; to assess terminal ileal bile acid absorption by a seven day whole body retention of selenium labelled homotaurocholic acid (SeHCAT); and to determine if small intestinal bacterial overgrowth contributes to faecal bile acid loss. The study population comprised 40 patients (27 men; median age 18 years) with cystic fibrosis (n = 8) and without (n = 32) liver disease and eight control subjects. Faecal bile acid excretion was significantly higher in cystic fibrosis patients without liver disease compared with control subjects (mean (SEM) 21.5 (2.4) and 7.3 (1.2) micromoles/kg/24 hours respectively; p < 0.01) and patients with liver disease (7.9 (1.3) micromoles/kg/24 hours; p < 0.01). No correlation was found between faecal fat (g fat/24 hours) and faecal bile acid (micromoles 24 hours) excretion. Eight (33%) of cystic fibrosis patients had seven day SeHCAT retention < 10% (normal retention > 20%). SeHCAT retention in cystic fibrosis patients with liver disease was comparable with control subjects (30.0 (SEM) 8.3% v 36.8 (5.9)%; p = NS) while SeHCAT retention in cystic fibrosis patients who did not have liver disease was significantly reduced (19.9 (3.8); p < 0.05). Although evidence of small bowel bacterial overgrowth was present in 40% of patients no relation was found between breath hydrogen excretion, faecal fat, and faecal bile acid loss. The results are consistent with the presence of an abnormality in terminal ideal function in patients with cystic fibrosis who do not have liver disease and that a defect in the ileal absorption of bile acids may be a contributory factor to excessive faecal bile acid loss. Faecal bile acid loss in cystic fibrosis is unrelated to the presence of intraluminal fat

  16. Assessment of myocardial mechanics in patients with end-stage renal disease and renal transplant recipients using speckle tracking echocardiography.

    PubMed

    Pirat, Bahar; Bozbas, Huseyin; Simsek, Vahide; Sade, L Elif; Sayin, Burak; Muderrisoglu, Haldun; Haberal, Mehmet

    2015-04-01

    Velocity vector imaging allows quantitation of myocardial strain and strain rate from 2-dimensional images based on speckle tracking echocardiography. The aim of this study was to analyze the changes in myocardial strain and strain rate patterns in patients with end-stage renal disease and renal transplant recipients. We studied 33 patients with end-stage renal disease on hemodialysis (19 men; mean age, 36 ± 8 y), 24 renal transplant recipients with functional grafts (21 men; mean age, 36 ± 7 y) and 26 age- and sex-matched control subjects. Longitudinal peak systolic strain and strain rate for basal, mid, and apical segments of the left ventricular wall were determined by velocity vector imaging from apical 4- and 2-chamber views. The average longitudinal strain and strain rate for the left ventricle were noted. From short-axis views at the level of papillary muscles, average circumferential, and radial strain, and strain rate were assessed. Mean heart rate and systolic and diastolic blood pressure during imaging were similar between the groups. Longitudinal peak systolic strain and strain rate at basal and mid-segments of the lateral wall were significantly higher in renal transplant recipients and control groups than endstage renal disease patients. Average longitudinal systolic strain from the 4-chamber view was highest in control subjects (-14.5% ± 2.9%) and was higher in renal transplant recipients (-12.5% ± 3.0%) than end-stage renal disease patients (-10.2% ± 1.6%; P ≤ .001). Radial and circumferential strain and strain rate at the level of the papillary muscle were lower in patients with end-stage renal disease than other groups. Differences in myocardial function in patients with end-stage renal disease, renal transplant recipients, and normal controls can be quantified by strain imaging. Myocardial function is improved in renal transplant recipients compared with end-stage renal disease patients.

  17. Spectrum of Renal and Urinary Tract Diseases in Kashmiri Children.

    PubMed

    Ashraf, Mohd; Kumar, Virender; Bano, Rifat Ara; Wani, Khursheed Ahmed; Ahmed, Javed; Ahmed, Kaisar

    2016-06-01

    Definite paucity of data pertaining to spectrum of renal and urinary tract diseases in our state and in various parts of India forms the basis of this study. Available data has emphasized more on specific clinical syndromes and chronic renal diseases rather than over all spectrums of renal and urinary tract diseases, that too in adult population. The present study a retrospective analysis, forms one of the basic data of paediatric nephrology and urology related disorders in our state. Retrospective analysis of the case records of all the hospitalized patients with renal and urinary tract diseases between 2012 and 2013 were performed. Case records were analysed and categorized into various groups like; Urinary Tract Infections (UTI), Acute Kidney Injury (AKI), Acute Glomerulonephritis (AGN), Nephrotic Syndrome (NS), haematuria, Polycystic Kidney Disease (PCKD), Posterior Urethral Valve (PUV), Vesicoureteric Reflux (VUR), Chronic Kidney Disease (CKD), Congenital Anomalies of Kidney and Urinary Iract (CAKUT) and others. These groups were divided into subgroups to get more insight about the pattern of these diseases. Out of 28114 patients hospitalized between 2012 and 2013 years, 447 (232 males and 215 females) patients were diagnosed of renal and urinary tract diseases which forms 1.58% the total admitted patients. Among these patients 32.9% (147/447) were diagnosed Acute Kidney Injury (AKI); 24.1% (108/447): Urinary Tract Infection (UTI); 9.6% (43/447): Acute Glomerulonephritis (AGN); 5.6% (25/447): bilateral hydronephrosis with UTI; 4.47% (20/447): nephrotic syndrome (NS); 3.5% (16/447): haematuria; and 4% (18/447) were having CAKUT (Congenital Anomalies Of Kidney And Urinary Tract). In addition to this there were 17 cases of Renal Tubular Acidosis (RTA), 3 cases of Barter syndrome and one case of Liddle syndrome. A substantial number of children are hospitalized with renal and urinary tract diseases with delayed ages of presentation, which at times have suffered

  18. Renal creatinine handling in very old patients with chronic renal disease.

    PubMed

    Musso, Carlos G; Michelángelo, Hernán; Vilas, Manuel; Martinez, Bernardo; Bonetto, Alberto; Jauregui, Ricardo; Algranati, Luis

    2011-09-01

    Renal creatinine handling is basically the result of its glomerular filtration and proximal tubular secretion. However, creatinine reabsorption has been documented in certain conditions, such as premature babies, newborns, and healthy elderly people. Additionally, it is known that there is an increase in the proportion of secreted creatinine in chronic renal disease. In this paper, we report our studies on the characteristic reabsorption pattern of creatinine in the elderly with chronic renal disease. We studied twenty-seven volunteers with chronic kidney disease, eleven of whom were young and the rest were very old (age > 75 years old). We measured creatinine clearance without (Ccr) and with cimetidine (CcrWC) and Ccr/CcrWC ratio from each volunteer, in timed urine samples. Then, Ccr, CcrWC, and Ccr/CcrWC ratio were compared between young and very old people in two chronic kidney disease subgroups: stages II-III and stages IV-V. Statistical analysis was performed applying a non-parametric test (Wilcoxon). We observed a tendency towards a lower Ccr/CcrWC ratio in the very old stage II-III group compared with the young one: 1 (0.96-1.26) (very old) vs 1.3 (1.1-1.5) (young), P = 0.09, on the contrary, there was no significant difference in Ccr/CcrWC ratio between very old and young person with stage IV-V CKD: 1.66 (1.41-2.21) (young) vs 1.77 (1.1-2.7) (young), P = NS. Creatinine secretion pattern in very old patients with advanced chronic renal disease is similar to that observed in young ones with similar level of CKD.

  19. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  20. Chloride impermeability in cystic fibrosis

    NASA Astrophysics Data System (ADS)

    Quinton, Paul M.

    1983-02-01

    Cystic fibrosis is the most common fatal genetic disease affecting Caucasians and is perhaps best characterized as an exocrinopathy involving a disturbance in fluid and electrolyte transport1. A high NaCl concentration in the sweat is characteristic of patients with this disease; the basic physiological reason for this abnormality is unknown. We have microperfused isolated sweat ducts from control subjects and cystic fibrosis patients, and report here results which suggest that abnormally low Cl- permeability in cystic fibrosis leads to poor reabsorption of NaCl in the sweat duct, and hence to a high concentration of NaCl in the sweat.

  1. Calcium Stone Growth in Urine from Cystic Fibrosis Patients and Healthy Controls

    NASA Astrophysics Data System (ADS)

    McSorley, Anita; Jones, Andrew M.; Webb, A. Kevin; Rao, P. Nagaraj; Kavanagh, John P.

    2007-04-01

    Cystic fibrosis patients have an increased risk of renal stone disease. There is some evidence that this may be related to a different excretory pattern of stone risk factors, but an alternative hypothesis, that the urine of cystic fibrosis patients is deficient in urinary inhibitors of crystallization and stone formation has not been tested. Here we have grown calcium stones, in vitro, in the presence of urine from healthy controls and compared this with growth in the presence of urine from cystic fibrosis patients. A stone farm was used to grow twelve calcium stones simultaneously, firstly in artificial urine for about 200 hours and then in 90% whole human urine for another 500 hours. Six of the stones received urine from healthy controls and six received urine from adult cystic fibrosis patients. There were no significant differences in stone mass at any of the key time points or in the overall growth pattern (p>0.05) between stones destined for, or treated with, urine from CF patients and the controls. Human urine greatly inhibited stone growth in vitro but there was no difference in the growth rate in urine from healthy controls and CF patients. This refutes the hypothesis that a tendency for a higher prevalence of urinary stones in CF patients is related to a deficiency in inhibitory activity.

  2. Stenting of the Cystic Duct in Benign Disease: A Definitive Treatment for the Elderly and Unwell

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hersey, N., E-mail: naomi.hersey@sth.nhs.uk; Goode, S. D., E-mail: s.goode@sheffield.sc.uk; Peck, R. J., E-mail: robert.peck@sth.nhs.uk

    PurposeThere have been few case reports describing cystic duct stent insertion in the management of acute cholecystitis secondary to benign disease with no case series published to date. We present our series demonstrating the role of cystic duct stents in managing benign gallbladder disease in those patients unfit for surgery.Materials and MethodsThirty three patients unfit for surgery in our institution underwent cystic duct stent insertion for the management of acute cholecystitis in the period June 2008 to June 2013. Patients underwent a mixture of transperitoneal and transhepatic gallbladder puncture. The cystic duct was cannulated with a hydrophilic guidewire which wasmore » subsequently passed through the common bile duct and into the duodenum. An 8Fr 12-cm double-pigtail stent was placed with the distal end lying within the duodenum and the proximal end within the gallbladder.ResultsTen patients presented with gallbladder perforation, 21 patients with acute cholecystitis, 1 with acute cholangitis and 1 with necrotising pancreatitis. The technical success rate was 91 %. We experienced a 13 % complication rate with 3 % mortality rate at 30 days.ConclusionCystic duct stent insertion can be successfully used to manage acute cholecystitis, gallbladder empyema or gallbladder perforations in those unfit for surgery and should be considered alongside external gallbladder drainage as a definitive mid-term treatment option.« less

  3. The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

    PubMed

    Frayman, Katherine B; Armstrong, David S; Carzino, Rosemary; Ferkol, Thomas W; Grimwood, Keith; Storch, Gregory A; Teo, Shu Mei; Wylie, Kristine M; Ranganathan, Sarath C

    2017-12-01

    In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Update on host-pathogen interactions in cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Frey, Nina; Hartl, Dominik

    2016-12-01

    Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease.

  5. The impact of daily temperature on renal disease incidence: an ecological study.

    PubMed

    Borg, Matthew; Bi, Peng; Nitschke, Monika; Williams, Susan; McDonald, Stephen

    2017-10-27

    Extremely high temperatures over many consecutive days have been linked to an increase in renal disease in several cities. This is becoming increasingly relevant with heatwaves becoming longer, more intense, and more frequent with climate change. This study aimed to extend the known relationship between daily temperature and kidney disease to include the incidence of eight temperature-prone specific renal disease categories - total renal disease, urolithiasis, renal failure, acute kidney injury (AKI), chronic kidney disease (CKD), urinary tract infections (UTIs), lower urinary tract infections (LUTIs) and pyelonephritis. Daily data was acquired for maximum, minimum and average temperature over the period of 1 July 2003 to 31 March 2014 during the warm season (October to March) in Adelaide, South Australia. Data for daily admissions to all metropolitan hospitals for renal disease, including 83,519 emergency department admissions and 42,957 inpatient admissions, was also obtained. Renal outcomes were analyzed using time-stratified negative binomial regression models, with the results aggregated by day. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated for associations between the number of admissions and daily temperature. Increases in daily temperature per 1 °C were associated with an increased incidence for all renal disease categories except for pyelonephritis. Minimum temperature was associated with the greatest increase in renal disease followed by average temperature and then maximum temperature. A 1°C increase in daily minimum temperature was associated with an increase in daily emergency department admissions for AKI (IRR 1.037, 95% CI: 1.026-1.048), renal failure (IRR 1.030, 95% CI: 1.022-1.039), CKD (IRR 1.017, 95% CI: 1.001-1.033) urolithiasis (IRR 1.015, 95% CI: 1.010-1.020), total renal disease (IRR 1.009, 95% CI: 1.006-1.011), UTIs (IRR 1.004, 95% CI: 1.000-1.007) and LUTIs (IRR 1.003, 95% CI: 1.000-1.006). An increased

  6. Renal autotransplantation--a possibility in the treatment of complex renal vascular diseases and ureteric injuries.

    PubMed

    Hau, Hans Michael; Bartels, Michael; Tautenhahn, Hans-Michael; Morgul, Mehmet Haluk; Fellmer, Peter; Ho-Thi, Phuc; Benckert, Christoph; Uhlmann, Dirk; Moche, Michael; Thelen, Armin; Schmelzle, Moritz; Jonas, Sven

    2012-12-31

    We report our contemporary experiences with renal autotransplantation in patients with complicated renal vascular diseases and/or complex ureteral injuries. Since its first performance, renal autotransplantation has been steadily improved and become a safe and effective procedure. Between 1998 and 2006, 6 renal autotransplantations in 6 patients were performed at the University Medical Center of Leipzig. After nephrectomy and renal perfusion ex vivo, the kidney was implanted standardized in the fossa iliaca. The vessels were anastomized to the iliac vessels, the ureter was reimplanted in an extravesical tunneled ureteroneocystostomy technique according to Lich-Gregoir. Demographic, clinical, and laboratory data of the patients were collected and analyzed for pre-, intra-, and postoperative period. Indications for renal autotransplantation were complex renovascular diseases in 2 patients (1 with fibromuscular dysplasia and 1 with Takayasu's arteritis) and in 4 patients with complex ureteral injuries. The median duration of follow-up was 9.7 years (range: 5.6-13.3). The laboratory values of our 6 patients showed improvements of creatinine, urea and blood pressure levels in comparison to the preoperative status at the end of follow-up period. The present study reports excellent results of renal autotransplantation in patients with renovascular disease or complex ureteric injuries. After a median follow-up of 9.7 years all 6 patients present with stable renal function as well as normal blood pressure values. Postoperative complications were observed with a rate comparable to other studies.

  7. MRI appearance of massive renal replacement lipomatosis in the absence of renal calculus disease

    PubMed Central

    Fitzgerald, E; Melamed, J; Taneja, S S; Rosenkrantz, A B

    2011-01-01

    Renal replacement lipomatosis is a rare benign entity in which extensive fibrofatty proliferation of the renal sinus is associated with marked renal atrophy. In this report, we present a case of massive renal replacement lipomatosis demonstrated on MRI. The presentation was atypical given an absence of associated renal calculus disease, and an initial CT scan was interpreted as suspicious for a liposarcoma. The differential diagnosis and key MRI findings that served to establish this specific diagnosis are reviewed. Histopathological correlation is also presented, as the patient underwent nephroureterectomy. PMID:21257835

  8. Histological pattern of paediatric renal diseases in northern Pakistan.

    PubMed

    Ali, Akhtar; Ali, Mohammad Usman; Akhtar, Sultan Zafar

    2011-07-01

    To determine histological spectrum of renal diseases among the paediatric population in the province Khyber Pukhtunkhwa, and to note any change in histological pattern with age and serum creatinine. This is a retrospective analysis of 415 paediatric renal biopsies performed at the department of nephrology, Lady Reading Hospital Peshawar from 1998-2005. Children from 3 to 15 years of age, having renal disease and indications for biopsy, underwent ultrasound guided percutaneous renal biopsy. Indications included nephrotic syndrome, nephritic/nephrotic syndrome with renal insufficiency and nephrotic syndrome with steroid resistance. Patients with acute or chronic renal failure were not included. The specimens were examined without immunoflorescence, under light microscopy using different staining techniques, Results were analyzed for different age groups, serum creatinine levels and for both male and females with renal disease. The overall male to female ratio in the study was 1.6: 1. Nephrotic syndrome was most common indication for renal biopsy in 50% of the cases, followed by renal insufficiency (26%) and steroid resistance (24%). In children with primary glomerulonephritis, minimal change disease (MCD) was found to be the most common histological pattern (24.09%), followed by focal segmental glomerulosclerosis (FSGS), 18.30%; mesangioproliferative glomerulonephritis (GN) (MsePGN), 17.83%; mesangiocapillary GN (MPGN), 11.08%; post streptococcal proliferative GN (Post. strep GN), 10.60%; membranous GN (MGN), 4.82%; crescentic GN (Cres.GN), 4.34%. Among children with secondary GN, chronic sclerosing GN was found to be most common (1.93%), followed by chronic tubulo interstitial nephritis (Chr.TIN), 1.69% and hypertensive nephropathy (H.Neph), 1.69%; Renal Amyloidosis, 0.96% and Lupus Nephritis III, 0.96%; acute tubular necrosis (ATN), 0.72%; Alport's Syndrome (0.48%). Overall, MCD was the most common histological pattern in all age groups and among children with

  9. 42 CFR 406.13 - Individual who has end-stage renal disease.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Individual who has end-stage renal disease. 406.13... Premiums § 406.13 Individual who has end-stage renal disease. (a) Statutory basis and applicability. This... renal disease, and specifies the beginning and end of the period of entitlement. It implements section...

  10. 42 CFR 406.13 - Individual who has end-stage renal disease.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Individual who has end-stage renal disease. 406.13... Premiums § 406.13 Individual who has end-stage renal disease. (a) Statutory basis and applicability. This... renal disease, and specifies the beginning and end of the period of entitlement. It implements section...

  11. 42 CFR 406.13 - Individual who has end-stage renal disease.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Individual who has end-stage renal disease. 406.13... Premiums § 406.13 Individual who has end-stage renal disease. (a) Statutory basis and applicability. This... renal disease, and specifies the beginning and end of the period of entitlement. It implements section...

  12. Burn injury mortality in patients with preexisting and new onset renal disease.

    PubMed

    Knowlin, Laquanda T; Purcell, Laura; Cairns, Bruce A; Charles, Anthony G

    2018-06-01

    We sought to examine the impact of preexisting and new onset renal disease on burn injury mortality. Retrospective analysis of patients admitted to a regional burn center from 2002-2012 was performed. Variables analyzed included demographics, burn mechanism, inhalation injury status, and % TBSA. Poisson regression was performed to estimate risk of in-hospital burn mortality. There were a total of 7640 patients over the study period. The adjusted 60-day risk of in-hospital mortality in patients with preexisting renal disease (PRD was 3 times higher compared to patients with no preexisting renal disease (IRR = 3.22, 95% CI = 1.26-8.25). The adjusted 60-day risk of mortality is 2 times higher for patients with new onset renal disease compared to those without (IRR = 2.11, 95% CI = 1.55-2.87). Preexisting and new onset renal disease results in a significantly higher risk of mortality following burn injury compared to patients without renal disease. Prevention of new onset renal injury and careful management of patients with preexisting renal disease to prevent exacerbation should be pursued. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Pooled analysis of the CONFIRM Registries: outcomes in renal disease patients treated for peripheral arterial disease using orbital atherectomy.

    PubMed

    Lee, Michael S; Yang, Tae; Adams, George L; Mustapha, Jihad; Das, Tony

    2014-08-01

    Patients with renal disease typically have severely calcified peripheral arterial disease. As a result, this population may have worse clinical outcomes following endovascular intervention compared to patients without renal insufficiency. Clinical trials typically exclude this patient population. Analysis of the CONFIRM I-III registries revealed 1105 patients with renal disease (1777 lesions) and 1969 patients without renal disease (2907 lesions) who underwent orbital atherectomy. This subanalysis compared the composite procedural complication rate including dissection, perforation, slow flow, vessel closure, spasm, embolism, and thrombus formation in patients with and without renal disease. Patients with renal disease had a higher prevalence of diabetes (P<.001), hypertension (P<.001), hyperlipidemia (P<.001), and coronary artery disease (P<.001), Rutherford 5 or 6 lesions (P<.001), as well as more lesions treated (P<.001), more vessels treated (P<.001), and more below-the-knee lesions (P<.001). The renal disease and non-renal disease groups had similar composite procedural complication rates (21.3% vs. 22.4%; P=.46), dissection (11.1% vs. 11.5%; P=.83), perforation (0.6% vs. 0.8%; P=.55), slow flow (5.0% vs. 4.2%; P=.19), spasm (6.7% vs. 6.2%; P=.40), embolism (1.7% vs. 2.6%; P=.12), and thrombus formation (1.4% vs. 1.0%; P=.56). The renal disease group had a trend toward decreased vessel closure (1.1% vs. 1.6%; P=.08). Plaque modification with orbital atherectomy resulted in similar low rates of procedural complications in the renal disease group compared with the non-renal disease group despite more unfavorable baseline clinical and lesion characteristics in the renal disease group.

  14. Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

    PubMed

    Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

    2010-11-01

    A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010

  15. Kidney dendritic cells in acute and chronic renal disease.

    PubMed

    Hochheiser, Katharina; Tittel, André; Kurts, Christian

    2011-06-01

    Dendritic cells are not only the master regulators of adaptive immunity, but also participate profoundly in innate immune responses. Much has been learned about their basic immunological functions and their roles in various diseases. Comparatively little is still known about their role in renal disease, despite their obvious potential to affect immune responses in the kidney, and immune responses that are directed against renal components. Kidney dendritic cells form an abundant network in the renal tubulointerstitium and constantly survey the environment for signs of injury or infection, in order to alert the immune system to the need to initiate defensive action. Recent studies have identified a role for dendritic cells in several murine models of acute renal injury and chronic nephritis. Here we summarize the current knowledge on the role of kidney dendritic cells that has been obtained from the study of murine models of renal disease. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

  16. Down syndrome with end-stage renal disease.

    PubMed

    Kute, Vivek B; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Engineer, Divyesh P; Thakkar, Umang G; Trivedi, Hargovind L

    2013-10-01

    Down syndrome is one of the most common genetic causes of learning disabilities in children. Although the incidence of renal and urological involvement in Down syndrome is not very common, monitoring of patients with Down syndrome for renal diseases should be done regularly as patient's age into the second and third decades. With increased survival, it appears that a growing number of these patients present with chronic renal failure. Down syndrome patients are apparently not suited for peritoneal dialysis because of lacking cooperation. This procedure can be prone to failure, mainly because of an increased risk of peritonitis. Handling such patients especially those on peritoneal dialysis is challenging. Here we report a case of Down syndrome with end-stage renal disease treated with hemodialysis for 6 months. To the best of our knowledge and current literature review this is the first case report of a patient with Down syndrome undergoing hemodialysis.

  17. Disease-modifying genetic factors in cystic fibrosis.

    PubMed

    Marson, Fernando A L

    2018-05-01

    To compile data from the past 10 years regarding the role of modifying genes in cystic fibrosis (CF). CF is a model disease for understanding of the action of modifying genes. Although it is a monogenic (CFTR) autosomal recessive disease, CF presents with wide phenotypic variability. In CF, variability occurs with different intensity among patients by each organ, being organ-specific, resulting from the mutual interaction of environmental and genetic factors, including CFTR mutations and various other genes, most of which are associated with inflammatory processes. In individuals, using precision medicine, gene modification studies have revealed individualized responses to drugs depending on particular CFTR mutations and modifying genes, most of which are alternative ion channels. Studies of modifying genes in CF allow: understanding of clinical variability among patients with the same CFTR genotype; evaluation of precision medicine; understanding of environmental and genetic effects at the organ level; understanding the involvement of genetic variants in inflammatory responses; improvements in genetic counseling; understanding the involvement of genetic variants in inflammatory responses in lung diseases, such as asthma; and understanding the individuality of the person with the disease.

  18. Renal involvement in Gaucher's disease.

    PubMed Central

    Siegal, A.; Gutman, A.; Shapiro, M. S.; Griffel, B.

    1981-01-01

    A patient with chronic Gaucher's disease is described who developed glomerulopathy 24 years after splenectomy terminating in renal failure. The pathological changes of this very rare complication of Gaucher's disease are described. The few similar cases reported in the literature are reviewed and the possible pathogenetic pathways discussed. Images Fig. 1 Fig. 2 Fig. 3 PMID:7301691

  19. Management of the Upper Airway in Cystic Fibrosis

    PubMed Central

    Illing, Elisa A.; Woodworth, Bradford A.

    2015-01-01

    Purpose of Review Upper airway disease engenders significant morbidity for patients with cystic fibrosis and is increasingly recognized as having a much greater role in pulmonary outcomes and quality of life than originally believed. Widespread disparate therapeutic strategies for cystic fibrosis chronic rhinosinusitis underscore the absence of a standardized treatment paradigm. This review outlines the most recent evidence-based trends in the management of upper airway disease in cystic fibrosis. Recent Findings The unified airway theory proposes that the sinuses are a focus of initial bacterial colonization which seeds the lower airway and may play a large role in maintaining lung infections. Mounting evidence suggests more aggressive treatment of the sinuses may confer significant improvement in pulmonary disease and quality of life outcomes in cystic fibrosis patients. However, there is a lack of high-level evidence regarding medical and surgical management of cystic fibrosis chronic rhinosinusitis that makes generalizations difficult. Summary Well designed clinical trials with long-term follow-up concerning medical and surgical interventions for cystic fibrosis sinus disease are required to establish standardized treatment protocols, but increased interest in the sinuses as a bacterial reservoir for pulmonary infections has generated considerable attention. PMID:25250804

  20. Percutaneous Image-Guided Aspiration and Sclerosis of Adventitial Cystic Disease of the Femoral Vein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnson, Jason M.; Kiankhooy, Armin; Bertges, Daniel J.

    2009-07-15

    Adventitial cystic disease (ACD), also known as cystic mucoid or myxomatous degeneration, is a rare vascular disease mainly seen in arteries. Seventeen cases have been reported in the world literature. We report the first known case of ACD successfully treated with percutaneous image-guided ethanol sclerosis. Computed tomography showed a cystic mass adherent to the wall of the common femoral vein. An ultrasound examination revealed a deep venous thrombosis of the leg, secondary to extrinsic compression of the common femoral vein. Three years prior to our procedure, the cyst was aspirated, which partially relieved the patient's symptoms. Over the following 3more » years the patient's symptoms worsened and a 10-cm discrepancy in thigh size developed, in addition to the deep venous thrombosis associated with lower-extremity edema. Using ultrasound guidance and fluoroscopic control, the cyst was drained and then sclerosed with absolute ethanol. The patient's symptoms and leg swelling resolved completely within several weeks. Follow-up physical examination and duplex ultrasound 6 months following sclerosis demonstrated resolution of the symptoms and elimination of the extrinsic compression effect of the ACD on the common femoral vein.« less

  1. Twenty-eight-year review of childhood renal diseases from renal biopsy data: A single centre in China.

    PubMed

    Jiang, Mengjie; Xiao, Zizheng; Rong, Liping; Xu, Yuanyuan; Chen, Lizhi; Mo, Ying; Sun, Liangzhong; Sun, Wei; Jiang, Xiaoyun

    2016-12-01

    The aim of the present study was to investigate the clinicopathologic characteristics of biopsy-proven childhood renal diseases and to compare the trends and changes during two different time intervals between 1984 and 2011 at the First Affiliated Hospital of Sun Yat-sen University in China. We retrospectively analyzed kidney biopsy data from children with renal diseases and compared the data during two time intervals, namely 1984-1997 and 1998-2011. A total of 1313 children were enrolled in the present study. There were 921 children with primary glomerular disease (PGD) and 312 children with secondary glomerular disease (SGD), accounting for 70.1% and 23.8% of participants, respectively. The major clinical manifestation of PGD was nephrotic syndrome (NS), which accounted for 31.2% of cases, while the main aetiology of SGD was lupus nephritis (40.7%). The main biopsy patterns of PGD were IgA nephritis (27.6%), minimal change disease (24.0%), and mesangial proliferative glomerulonephritis (16.9%). PGD was the major class of disease in both time intervals, but the ratio of PGD decreased over time, while the ratio of SGD and other glomerular diseases increased. PGD was also the major class of disease in each age group; however, the incidence of PGD decreased with increasing age. The incidence patterns of paediatric renal diseases changed over the 28-year period of this study. Our results show that different renal diseases characterize different age intervals. Furthermore, there are several associations between clinical presentation and biopsy features in childhood renal disease. © 2015 Asian Pacific Society of Nephrology.

  2. New animal models of cystic fibrosis: what are they teaching us?

    PubMed Central

    Keiser, Nicholas W.; Engelhardt, John F.

    2013-01-01

    Purpose of review Cystic fibrosis is the first human genetic disease to benefit from the directed engineering of three different species of animal models (mice, pigs, and ferrets). Recent studies on the cystic fibrosis pig and ferret models are providing new information about the pathophysiology of cystic fibrosis in various organ systems. Additionally, new conditional cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice are teaching unexpected lessons about CFTR function in surprising cellular locations. Comparisons between these animal models and the human condition are key to dissecting the complexities of disease pathophysiology in cystic fibrosis. Recent findings Cystic fibrosis pigs and ferrets have provided new models to study the spontaneous development of disease in the lung and pancreas, two organs that are largely spared overt spontaneous disease in cystic fibrosis mice. New cystic fibrosis mouse models are now interrogating CFTR functions involved in growth and inflammation at an organ-based level using conditional knockout technology. Together, these models are providing new insights on the human condition. Summary Basic and clinical cystic fibrosis research will benefit greatly from the comparative pathophysiology of cystic fibrosis mice, pigs, and ferrets. Both similarities and differences between these three cystic fibrosis models will inform pathophysiologically important mechanisms of CFTR function in humans and aid in the development of both organ-specific and general therapies for cystic fibrosis. PMID:21857224

  3. What's it Like to Have Cystic Fibrosis?

    MedlinePlus

    ... deal with cystic fibrosis. What Is CF? Cystic fibrosis (CF) is a disease that causes the body to make thick, sticky mucus (say: ... special protein. This protein is defective in cystic fibrosis, producing the thick, sticky mucus that causes problems for people with CF. What Causes CF? ...

  4. [Pseudo-Bartter syndrome as manifestation of cystic fibrosis with DF508 mutation].

    PubMed

    Galaviz-Ballesteros, María de Jesús; Acosta-Rodríguez-Bueno, Carlos Patricio; Consuelo-Sánchez, Alejandra; Franco-Álvarez, Isidro; Olalla-Mora, Odilo Iván; Vázquez-Frias, Rodrigo

    Pseudo Bartter syndrome (PBS) is defined as hypokalaemic hypochloraemic metabolic alkalosis in the absence of renal tubular pathology. Children with cystic fibrosis (CF) are at risk of developing electrolyte abnormalities and even PBS may occur. 5 months old female infant with a history of two events of dehydration with vomit, refusal to eat, chronic cough, polyuria, malnutrition, metabolic alkalosis, hypokalemia, hyponatremia, hypochloremia and acute renal failure. Chronic cough study was performed, discarding pulmonary tuberculosis, gastroesophageal reflux disease and impaired swallowing. PBS was diagnosed due to hypokalaemic hypochloraemic metabolic alkalosis in the absence of renal tubular pathology. CF was corroborated by electrolytes in sweat and through molecular analysis of the delta F508 mutation. This is one of the few reported cases linking PBS and this mutation. In patients with hyponatremic dehydration episodes with hypokalaemic hypochloraemic metabolic alkalosis, PBS should be considered as differential diagnosis. CF could be presented as PBS, mainly in patients younger than 2 years. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Bilateral Adventitial Cystic Disease of the Popliteal Artery: A Case Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ortiz M, William R.; Lopera, Jorge E., E-mail: Jorge.lopera@utsouthwestern.edu; Gimenez, Carlos R.

    2006-04-15

    Adventitial cystic disease (ACD) of the popliteal artery is an uncommon vascular condition of unknown etiology. In the present case report, we describe a case of bilateral ACD of the popliteal artery in a 58-year-old male. To the best of our knowledge, this is the first case of bilateral ACD of the popliteal artery reported in the literature.

  6. Brown Nail-bed Arcs and Chronic Renal Disease

    PubMed Central

    Stewart, W. K.; Raffle, E. J.

    1972-01-01

    A brown arc affecting the distal part of the fingernail-bed, just proximal to the point of separation of the nail from its bed, has been found in 12 out of 34 patients with chronic renal disease (35%) compared with an incidence of less than 2% in a series of unselected patients. It represents a distinctive form of pigmentation, possibly due to lipochromes. No decisive association could be found between the presence or absence of the pigmented nail arc and the level of impaired renal function. Nevertheless it seems that renal disease predisposes towards the development of brown nail arcs. Imagesp786-a PMID:5014252

  7. Dosing of antirheumatic drugs in renal disease and dialysis.

    PubMed

    Swarup, Areena; Sachdeva, Namita; Schumacher, H Ralph

    2004-08-01

    Many patients with rheumatic diseases have their management complicated by renal problems. Renal failure modifies the metabolism of many drugs, especially by retention. Questions often arise about the effects of renal failure on the handling of drugs commonly used in rheumatology. For which drugs must we be especially concerned about increased toxicity? Patients on chronic dialysis may also need a variety of drugs for rheumatic disease. How are our drugs dialyzed, and which of these can be safety used and how best to use them?Decisions about dosing of rheumatic drugs are often required for the patients with chronic renal insufficiency or on long-term dialysis, although many drugs have not been formally studied in these settings. Patients with renal insufficiency are excluded from most drug trials. Data for some of these drugs have to be extrapolated based on the information available about the pharmacokinetics of the drug.This review addresses dosing of commonly used drugs in rheumatology in patients with chronic renal insufficiency or failure. It is compiled from a MEDLINE search of papers dealing with renal handling of antirheumatic drugs and suggestions for dose adjustments for these drugs. Drugs reviewed include commonly used disease-modifying antirheumatic drugs (DMARDS), drugs used for treatment of gout, commonly used nonsteroidal antnflammatory drugs (NSAIDS) and the newer COX-2 inhibitors.

  8. Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

    PubMed

    Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

    2017-11-01

    Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  9. Hyponatremia-associated rhabdomyolysis following exercise in an adolescent with cystic fibrosis.

    PubMed

    Kaskavage, Jillian; Sklansky, Daniel

    2012-07-01

    Adolescents with well-controlled cystic fibrosis, including good lung function and appropriate growth, commonly participate in competitive athletic activities. We present the case of an adolescent male with cystic fibrosis, hyponatremia, dehydration, and rhabdomyolysis after participating in football practice on a summer morning. The patient presented with severe myalgia and serum sodium of 129 mmol/L, chloride 90 mmol/L, and creatine phosphokinase 1146 U/L. Aggressive hydration with intravenous 0.9% saline resulted in clinical improvement with no renal or muscular sequelae. Health care providers need to educate patients with cystic fibrosis about maintaining adequate hydration and sodium repletion during exercise. Research is needed regarding the appropriate amount and composition of oral rehydration fluids in exercising individuals with cystic fibrosis, as the physiology encountered in these patients provides a unique challenge to maintaining electrolyte balance and stimulation of thirst.

  10. The airway microbiota in early cystic fibrosis lung disease.

    PubMed

    Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

    2017-11-01

    Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

  11. Leptospirosis Renal Disease: Emerging Culprit of Chronic Kidney Disease Unknown Etiology.

    PubMed

    Yang, Chih-Wei

    2018-01-01

    Leptospirosis is the most prevalent zoonosis affecting more than 1 million populations worldwide. Interestingly, leptospirosis endemic regions coincide with chronic kidney disease (CKD) hotspots largely due to flooding and agricultural overlaps. Acute leptospirosis induces multiple organ dysfunction including acute kidney injury and may predispose to CKD and end-stage renal disease, if not treated timely. Asymptomatic infection may carry the bacteria in the kidney and CKD progresses insidiously. Histologic finding of leptospirosis renal disease includes tubulointerstitial nephritis, interstitial fibrosis, and tubular atrophy. Proximal tubule dysfunction and hypokalemia are observed in adult male workers with leptospirosis, a characteristic similarity to CKD unknown etiology (CKDu). CKDu is a form of CKD that is not attributable to traditional risk factors clustering in agricultural communities affecting young male farmers. Kidney pathology shows a chronic tubulointerstitial disease. CKDu is being reported as an endemic nephropathy across the globe. Recent surveys suggest that asymptomatic leptospira renal colonization is an overlooked risk for renal fibrosis and CKDu. Population with anti-leptospira seropositivity is associated with lower estimated glomerular filtration rate in endemic regions and carrier may progress to CKD. Leptospirosis has been considered as a risk factor for CKDu in Sri Lanka and in Mesoamerican area. Sugarcane workers in Nicaragua showed increased anti-leptospira seropositivity and higher urinary biomarkers for kidney injury. Emerging evidence with signs of infection were reported in these endemic population, indicating that leptospira exposure could play a role in CKDu as a cause of primary kidney disease or a susceptible factor when secondary injury such as heat stress or dehydration aggravates kidney disease. Therefore, leptospirosis as an emerging culprit of CKDu deserves further in-depth investigation. © 2017 S. Karger AG, Basel.

  12. Early detection of cystic fibrosis lung disease: multiple‐breath washout versus raised volume tests

    PubMed Central

    Lum, Sooky; Gustafsson, Per; Ljungberg, Henrik; Hülskamp, Georg; Bush, Andrew; Carr, Siobhán B; Castle, Rosemary; Hoo, Ah‐fong; Price, John; Ranganathan, Sarath; Stroobant, John; Wade, Angie; Wallis, Colin; Wyatt, Hilary; Stocks, Janet

    2007-01-01

    Background Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple‐breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco–abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow‐volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV0.5 and FEF25–75 ) than boys (mean (95% CI girls–boys): –1.2 (–2.1 to −0.3) for FEV0.5 Z score; FEF25–75: –1.2 (–2.2 to −0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC. PMID:17121870

  13. [Acute renal failure: a rare presentation of Addison's disease].

    PubMed

    Salhi, Houda

    2016-01-01

    Addison's disease is a rare condition. Its onset of symptoms most often is nonspecific contributing to a diagnostic and therapeutic delay. Acute renal failure can be the first manifestation of this disease. We report the case of a patient with Addison's disease who was initially treated for acute renal failure due to multiple myeloma and whose diagnosis was adjusted thereafter. Patient's condition dramatically improved after treatment with intravenous rehydration; injectable hydrocortisone.

  14. Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies.

    PubMed

    Jacquot, J; Delion, M; Gangloff, S; Braux, J; Velard, F

    2016-04-01

    Mutations within the gene encoding for the chloride ion channel cystic fibrosis transmembrane conductance regulator (CFTR) results in cystic fibrosis (CF), the most common lethal autosomal recessive genetic disease that causes a number of long-term health problems, as the bone disease. Osteoporosis and increased vertebral fracture risk associated with CF disease are becoming more important as the life expectancy of patients continues to improve. The etiology of low bone density is multifactorial, most probably a combination of inadequate peak bone mass during puberty and increased bone losses in adults. Body mass index, male sex, advanced pulmonary disease, malnutrition and chronic therapies are established additional risk factors for CF-related bone disease (CFBD). Consistently, recent evidence has confirmed that CFTR plays a major role in the osteoprotegerin (OPG) and COX-2 metabolite prostaglandin E2 (PGE2) production, two key regulators in the bone formation and regeneration. Several others mechanisms were also recognized from animal and cell models contributing to malfunctions of osteoblast (cell that form bone) and indirectly of bone-resorpting osteoclasts. Understanding such mechanisms is crucial for the development of therapies in CFBD. Innovative therapeutic approaches using CFTR modulators such as C18 have recently shown in vitro capacity to enhance PGE2 production and normalized the RANKL-to-OPG ratio in human osteoblasts bearing the mutation F508del-CFTR and therefore potential clinical utility in CFBD. This review focuses on the recently identified pathogenic mechanisms leading to CFBD and potential future therapies for treating CFBD.

  15. Non-neoplastic cystic and cystic-like lesions of the pancreas: may mimic pancreatic cystic neoplasms.

    PubMed

    Goh, Brian K P; Tan, Yu-Meng; Chung, Yaw-Fui A; Chow, Pierce K H; Ong, Hock-Soo; Lim, Dennis T H; Wong, Wai-Keong; Ooi, London L P J

    2006-05-01

    epithelial (congenital) cyst (n = 3), retention cyst (n = 1) and mucinous non-neoplastic cyst (n = 1). At a median follow up of 20 months (range, 3-34 months), none of the patients had any evidence of recurrent disease. Non-neoplastic cystic and cystic-like lesions of the pancreas are rare causes of pancreatic cystic lesions that are generally benign and do not require surgery when asymptomatic. However, despite advances in diagnostic investigations such as endoscopic ultrasound with fluid aspirate and magnetic resonance imaging, the preoperative diagnosis remains unreliable. Hence, the challenge for all clinicians is to recognize these lesions preoperatively and to avoid 'unnecessary' surgery.

  16. Revascularization to preserve renal function in patients with atherosclerotic renovascular disease.

    PubMed

    Novick, A C; Textor, S C; Bodie, B; Khauli, R B

    1984-08-01

    There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.

  17. Diagnosis and treatment of endocrine comorbidities in patients with cystic fibrosis.

    PubMed

    Siwamogsatham, Oranan; Alvarez, Jessica A; Tangpricha, Vin

    2014-10-01

    The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis. As life expectancy in cystic fibrosis has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes, cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with cystic fibrosis. This review summarizes the updated screening and management of endocrine diseases in the cystic fibrosis population.

  18. Oxidant Mechanisms in Renal Injury and Disease

    PubMed Central

    Ratliff, Brian B.; Abdulmahdi, Wasan; Pawar, Rahul

    2016-01-01

    Abstract Significance: A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression. Recent Advances: Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes. Critical Issues: The review summarizes the critical sources of oxidative stress in the kidney during injury/disease, including generation of ROS and RNS from mitochondria, NADPH oxidase, and inducible nitric oxide synthase. The review next summarizes the renal antioxidant systems that protect against oxidative stress, including superoxide dismutase and catalase, the glutathione and thioredoxin systems, and others. Next, we describe how oxidative stress affects kidney function and promotes damage in every nephron segment, including the renal vessels, glomeruli, and tubules. Future Directions: Despite the limited success associated with the application of antioxidants for treatment of kidney injury/disease thus far, preventing the generation and accumulation of ROS and RNS provides an ideal target for potential therapeutic treatments. The review discusses the shortcomings of antioxidant treatments previously used and the potential promise of new ones. Antioxid. Redox Signal. 25, 119–146. PMID:26906267

  19. A complex case of congenital cystic renal disease

    PubMed Central

    Cordiner, David S; Evans, Clair A; Brundler, Marie-Anne; McPhillips, Maeve; Murio, Enric; Darling, Mark; Taheri, Sepideh

    2012-01-01

    This case outlines the potential complexity of autosomal recessive polycystic kidney disease (ARPKD). It highlights the challenges involved in managing this condition, some of the complications faced and areas of uncertainty in the decision making process. With a paucity of published paediatric cases on this subject, this should add to the pool of information currently available. PMID:22605879

  20. Histopathological retrospective study of canine renal disease in Korea, 2003~2008

    PubMed Central

    Yhee, Ji-Young; Yu, Chi-Ho; Kim, Jong-Hyuk; Im, Keum-Soon; Chon, Seung-Ki

    2010-01-01

    Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson's trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations. PMID:21113095

  1. Bosniak classification system: a prospective comparison of CT, contrast-enhanced US, and MR for categorizing complex renal cystic masses.

    PubMed

    Graumann, Ole; Osther, Susanne Sloth; Karstoft, Jens; Hørlyck, Arne; Osther, Palle Jörn Sloth

    2016-11-01

    Background The Bosniak classification was originally based on computed tomographic (CT) findings. Magnetic resonance (MR) and contrast-enhanced ultrasonography (CEUS) imaging may demonstrate findings that are not depicted at CT, and there may not always be a clear correlation between the findings at MR and CEUS imaging and those at CT. Purpose To compare diagnostic accuracy of MR, CEUS, and CT when categorizing complex renal cystic masses according to the Bosniak classification. Material and Methods From February 2011 to June 2012, 46 complex renal cysts were prospectively evaluated by three readers. Each mass was categorized according to the Bosniak classification and CT was chosen as gold standard. Kappa was calculated for diagnostic accuracy and data was compared with pathological results. Results CT images found 27 BII, six BIIF, seven BIII, and six BIV. Forty-three cysts could be characterized by CEUS, 79% were in agreement with CT (κ = 0.86). Five BII lesions were upgraded to BIIF and four lesions were categorized lower with CEUS. Forty-one lesions were examined with MR; 78% were in agreement with CT (κ = 0.91). Three BII lesions were upgraded to BIIF and six lesions were categorized one category lower. Pathologic correlation in six lesions revealed four malignant and two benign lesions. Conclusion CEUS and MR both up- and downgraded renal cysts compared to CT, and until these non-radiation modalities have been refined and adjusted, CT should remain the gold standard of the Bosniak classification.

  2. Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

    PubMed Central

    Tullos, Nathan; Stewart, Nicholas J.; Surles, Bret

    2015-01-01

    Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. PMID:25377076

  3. Role of the intrarenal renin-angiotensin system in the progression of renal disease.

    PubMed

    Urushihara, Maki; Kagami, Shoji

    2017-09-01

    The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

  4. Celiac disease or positive tissue transglutaminase antibodies in patients undergoing renal biopsies.

    PubMed

    Nurmi, Rakel; Metso, Martti; Pörsti, Ilkka; Niemelä, Onni; Huhtala, Heini; Mustonen, Jukka; Kaukinen, Katri; Mäkelä, Satu

    2018-01-01

    An association between celiac disease and renal diseases has been suggested, but the results are controversial. To investigate the prevalence of celiac disease autoimmunity among individuals undergoing renal biopsies and to evaluate whether co-existent celiac autoimmunity influences the clinical outcome of the renal disease. The prevalence of celiac autoimmunity (previous diagnosis of celiac disease or positive tissue transglutaminase antibodies) was determined in 827 consecutive patients undergoing kidney biopsies due to clinical indications. Up to 15 years' follow-up data on kidney function and co-morbidities were obtained. Celiac autoimmunity was found in 45 (5.4%) patients. Among the IgA nephropathy patients, 8.2% of had celiac autoimmunity. At the time of kidney biopsy and after a median follow-up of 5 to 6 years, renal function measured by estimated glomerular filtration rate (eGFR) was inferior in IgA nephropathy patients with celiac autoimmunity compared to those without it (P=0.048 and P=0.022, respectively). The prevalence of celiac autoimmunity seems to be high in patients undergoing renal biopsies, especially in patients with IgA nephropathy. Such autoimmunity may be associated with worse renal function in IgA nephropathy. Hence the co-existence of celiac disease should be taken into consideration when treating patients with renal diseases. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  5. Aspergillus and cystic fibrosis: old disease - new classifications.

    PubMed

    Felton, Imogen C; Simmonds, Nicholas J

    2014-11-01

    Aspergillus pulmonary infection has traditionally been recognized as a clinical spectrum of increasing pathogenicity, encompassing saprophytic airways colonization historically regarded of doubtful clinical significance, to allergic bronchopulmonary aspergillosis, chronic cavitatory and life-threatening invasive disease in the immunocompromised host. Whilst the latter two categories are rarely encountered in cystic fibrosis (CF), there is recognition of an extending spectrum of disease yet to be reflected in consensus management guidelines. The purpose of this review is to provide an up-to-date overview of this extending spectrum, with a focus on disease categories and their clinical significance. Conflicting evidence regarding the clinical significance of Aspergillus colonization and sensitization in CF, alongside the emergence of a novel disease category 'Aspergillus bronchitis', has led to proposals for the reclassification of Aspergillus disease. In addition, lack of standardization and poor sensitivity of culture-dependent mycology techniques renders clinical and epidemiological interpretation of these isolates challenging. The role of Aspergillus in the absence of established CF-allergic bronchopulmonary aspergillosis remains unclear. The following review discusses new approaches proposed to categorise the extended spectrum of CF Aspergillus disease, highlighting the need for enhanced microbiological investigation and serological monitoring of patients in light of evidence which differentiates colonization from categories of greater pathogenic potential.

  6. Festival food coma in cystic fibrosis.

    PubMed

    Pandit, Chetan; Graham, Christie; Selvadurai, Hiran; Gaskin, Kevin; Cooper, Peter; van Asperen, Peter

    2013-07-01

    Children with cystic fibrosis liver disease and portal hypertension are at risk of developing acute hepatic encephalopathy. Even in the presence of normal synthetic liver function these children may have porto-systemic shunting. We report a case of an adolosecent who had cystic fibrosis liver disease and presented with life threatening hepatinc encephalopathy. This case illustrates that it is necessary to consider an appropriate dietary regimen in adolosecents with liver disease to prevent hepatic decompensation. Copyright © 2012 Wiley Periodicals, Inc.

  7. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

    PubMed

    Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

    2012-04-15

    Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

  8. Integrin Alpha 8 Recessive Mutations Are Responsible for Bilateral Renal Agenesis in Humans

    PubMed Central

    Humbert, Camille; Silbermann, Flora; Morar, Bharti; Parisot, Mélanie; Zarhrate, Mohammed; Masson, Cécile; Tores, Frédéric; Blanchet, Patricia; Perez, Marie-José; Petrov, Yuliya; Khau Van Kien, Philippe; Roume, Joelle; Leroy, Brigitte; Gribouval, Olivier; Kalaydjieva, Luba; Heidet, Laurence; Salomon, Rémi; Antignac, Corinne; Benmerah, Alexandre; Saunier, Sophie; Jeanpierre, Cécile

    2014-01-01

    Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of kidney development defects including renal agenesis, hypoplasia, and (cystic) dysplasia. Heterozygous mutations of several genes have been identified as genetic causes of RHD with various severity. However, these genes and mutations are not associated with bilateral renal agenesis, except for RET mutations, which could be involved in a few cases. The pathophysiological mechanisms leading to total absence of kidney development thus remain largely elusive. By using a whole-exome sequencing approach in families with several fetuses with bilateral renal agenesis, we identified recessive mutations in the integrin α8-encoding gene ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in absence of kidney development. We provide evidence of a damaging effect of the human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a genetic cause of bilateral renal agenesis and that, at least in some cases, bilateral renal agenesis is an autosomal-recessive disease. PMID:24439109

  9. Renal disease in the acquired immunodeficiency syndrome in north central Nigeria.

    PubMed

    Agaba, E I; Agaba, P A; Sirisena, N D; Anteyi, E A; Idoko, J A

    2003-01-01

    The brunt of the human immunodeficiency virus infection/the acquired immunodeficiency syndrome is largely borne by communities in sub-Saharan Africa. We describe renal disease in Nigerians with the acquired immunodeficiency syndrome. Consecutive patients with the acquired immunodeficiency syndrome (AIDS) seen in the infections unit of the Jos University Teaching Hospital and a similar group of healthy controls were evaluated for renal disease. Subjects with past history of renal disease, hypovolemia, hypertension, diabetes mellitus and/or a documented fever were excluded from the study. Of the 79 patients with the acquired immunodeficiency syndrome and 57 controls studied, renal disease was present in 41 (51.8%) of the patients in the AIDS group and 7 (12.2%) of controls. While 15 (19%) of the AIDS group had azotemia alone and 20 (25.3%) had proteinuria alone, 6 (7.6%) had azotemia and proteinuria. The mean protein excretion/24 hours was significantly higher in the AIDS group compared to controls, (2.99 +/- 54 g and 0.56 +/- 0.12 g respectively, p = 0.001), while the GFR was significantly higher in controls compared to the study group (103.30 +/- 37.78 and 68.03 +/- 37.55 respectively, p = 0.004). Subjects in the AIDS group with renal disease had a significantly longer duration of illness compared to those without (12.33 +/- 8.67 months and 7.28 +/- 7.78 months respectively, p = 0.008). Age and serum CD4+ cell counts were similar in patients with and without renal disease in the AIDS group. Renal disease is a common complication of acquired immunodeficiency syndrome, the duration of illness being strongly associated with its presence.

  10. Nephronophthisis: Disease Mechanisms of a Ciliopathy

    PubMed Central

    Hildebrandt, Friedhelm; Attanasio, Massimo; Otto, Edgar

    2009-01-01

    Nephronophthisis (NPHP), a recessive cystic kidney disease, is the most frequent genetic cause of end-stage kidney disease in children and young adults. Positional cloning of nine genes (NPHP1-9) and functional characterization of their encoded proteins (nephrocystins) has contributed to a unifying theory that defines cystic kidney diseases as “ciliopathies”. The theory is based on the finding that all proteins mutated in cystic kidney diseases of humans or animal models are expressed in primary cilia or centrosomes of renal epithelial cells. Primary cilia are sensory organelles that connect mechanosensory, visual, and other stimuli to mechanisms of epithelial cell polarity and cell cycle control. Mutations in NPHP genes cause defects in signaling mechanisms that involve the non-canonical Wnt signaling pathway and the sonic hedgehog signaling pathway, resulting in defects of planar cell polarity and tissue maintenance. The ciliary theory explains the multiple organ involvement in NPHP, which includes retinal degeneration, cerebellar hypoplasia, liver fibrosis, situs inversus, and mental retardation. Positional cloning of dozens of unknown genes that cause NPHP will elucidate further signaling mechanisms involved. Nephrocystins are highly conserved in evolution, thus allowing the use of animal models to develop future therapeutic approaches. PMID:19118152

  11. Hypertensive renal disease: susceptibility and resistance in inbred hypertensive rat lines.

    PubMed

    Braun, Michael C; Herring, Stacy M; Gokul, Nisha; Monita, Monique; Bell, Rebecca; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

    2013-10-01

    Spontaneously hypertensive rat (SHR) lines differ in their susceptibility to hypertensive end-organ disease and may provide an informative model of genetic risk of disease. Lines derived from the original SHR-B and SHR-C clades are highly resistant to hypertensive end-organ disease, whereas lines derived from the SHR-A clade were selected for stroke susceptibility and experience hypertensive renal disease. Here we characterize the temporal development of progressive renal injury in SHR-A3 animals consuming 0.3% sodium in the diet and drinking water. SHR-A3 rats demonstrate albuminuria, glomerular damage, tubulointerstitial injury, and renal fibrosis that emerge at 18 weeks of age and progress. Mortality of SHR-A3 animals was 50% at 40 weeks of age, and animals surviving to this age had reduced renal function. In contrast SHR-B2, which are 87% genetically identical to SHR-A3, are substantially protected from renal injury and demonstrate only moderate changes in albuminuria and renal histological injury over this time period. At 40 weeks of age, electron microscopy of the renal glomerulus revealed severe podocyte effacement in SHR-A3, but slit diaphragm architecture in SHR-B2 at this age was well preserved. Renal injury traits in the F1 and F2 progeny of an intercross between SHR-A3 and SHR-B2 were measured to determine heritability of renal injury in this model. Heritability of albuminuria, glomerular injury, and tubulointerstitial injury were estimated at 48.9, 66.5 and 58.6%, respectively. We assessed the relationship between blood pressure and renal injury measures in the F2 animals and found some correlation between these variables that explain up to 26% of the trait variation. Quantitative trait locus (QTL) mapping was performed using over 200 single nucleotide polymorphism markers distributed across the 13% of the genome that differs between these two closely related lines. Mapping of albuminuria, tubulointerstitial injury, and renal fibrosis failed to

  12. Case Report of a Hypobaric Chamber Fitness to Fly Test in a Child With Severe Cystic Lung Disease.

    PubMed

    Loo, Sarah; Campbell, Andrew; Vyas, Julian; Pillarisetti, Naveen

    2017-07-01

    Patients with severe cystic lung disease are considered to be at risk for cyst rupture during air travel because of the possibility of increase in cyst size and impaired equilibration of pressure between the cysts and other parts of the lung. This may have clinically devastating consequences for the patient but may also result in significant costs for emergency alteration of flight schedule. We report the use of a hypobaric chamber to simulate cabin pressure changes encountered on a commercial flight to assess the safety to fly of a child with severe cystic lung disease secondary to Langerhans cell histiocytosis. The test did not result in an air leak, and the child subsequently undertook air travel without mishap. This is the first reported use of a hypobaric chamber test in a child with severe cystic lung disease. This test has the potential to be used as a fitness to fly test in children at risk for air leak syndromes who are being considered for air travel. Copyright © 2017 by the American Academy of Pediatrics.

  13. Biomarker for early renal microvascular and diabetic kidney diseases.

    PubMed

    Futrakul, Narisa; Futrakul, Prasit

    2017-11-01

    Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

  14. [Genetic counseling in cystic fibrosis].

    PubMed

    Julia, S; Bieth, E

    2000-08-01

    Genetic counseling is an important part of health care in patients with cystic fibrosis or respiratory diseases associated with the CFTR (cystic fibrosis transmembrane conductance regulator) gene, including certain types of allergic bronchopulmonary aspergilloses or bronchial diseases (diffuse bronchiectasia). The basic goal is to provide patients with information on the transmission of cystic fibrosis and to asses the risk of recurrence. This risk is determined from molecular biology analyses examining the CFTR gene. Genotyping is the only means of screening for the heterozygous state, frequent in the French population (about 1/30). Because of the large number of mutated alleles not covered entirely by the genetic tests, there remains a question of probability expressed as a residual risk of a heterozygous state. A prenatal genotype diagnosis should be proposed to heterozygous couples who have a 25% risk of having a diseased child. Technically, this is almost always possible and the results are highly reliable. Nevertheless, there remains the risks related to sample taking and the ethical issue about which the patients must be informed. Management of these at risk couples who desire a child must be based on a multidisciplinary approach, particularly important when one of the parents has overt cystic fibrosis.

  15. An Approach for Treating the Hepatobiliary Disease of Cystic Fibrosis by Somatic Gene Transfer

    NASA Astrophysics Data System (ADS)

    Yang, Yiping; Raper, Steven E.; Cohn, Jonathan A.; Engelhardt, John F.; Wilson, James M.

    1993-05-01

    Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.

  16. Cocaine-induced renal disease.

    PubMed

    Gitman, Michael D; Singhal, Pravin C

    2004-09-01

    Cocaine has anaesthetic, vasoconstrictive and CNS stimulatory effects. Presently, it is used clinically as a local anaesthetic and abused as a recreational drug. It has been implicated in both acute and chronic renal failure and has been reported to affect every aspect of the nephron. This article will review the spectrum of cocaine-induced kidney disease and attempt to give insight into the pathophysiological mechanisms involved.

  17. Risk factors for end stage renal disease in non-WT1-syndromic Wilms tumor.

    PubMed

    Lange, Jane; Peterson, Susan M; Takashima, Janice R; Grigoriev, Yevgeny; Ritchey, Michael L; Shamberger, Robert C; Beckwith, J Bruce; Perlman, Elizabeth; Green, Daniel M; Breslow, Norman E

    2011-08-01

    We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease. End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions. The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend). Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  18. The large spectrum of renal disease in diabetic patients

    PubMed Central

    Bermejo, Sheila; Pascual, Julio

    2017-01-01

    Abstract The prevalence of diabetic nephropathy (DN) among diabetic patients seems to be overestimated. Recent studies with renal biopsies show that the incidence of non-diabetic nephropathy (NDN) among diabetic patients is higher than expected. Renal impairment of diabetic patients is frequently attributed to DN without meeting the KDOQI criteria or performing renal biopsy to exclude NDN. In this editorial, we update the spectrum of renal disease in diabetic patients and the impact on diagnosis, prognosis and therapy. PMID:28396743

  19. Pregnancy in patients with chronic renal disease.

    PubMed Central

    Bear, R. A.

    1978-01-01

    Pregnancy is not invariably contra-indicated in patients with pre-existing renal disease. Clinical data now exist that permit the clinician to distinguish such patients who are likely to experience difficulty during pregnancy from those in whom pregnancy can be undertaken with high expectation of success. Patients suffering from systemic lupus erythematosus, active or inactive, with or without lupus nephritis, should avoid pregnancy. Patients with other forms of chronic renal disease in whom the serum creatinine concentration prior to pregnancy is less than 1.5 mg/dL are not exposed to increased maternal or fetal risk. On the other hand, patients with serum creatinine values exceeding 1.6 mg/dL experience a high incidence of maternal and fetal complications and should avoid pregnancy. The life expectancy of recipients of a renal transplant is uncertain, and these patients should receive counselling as to the advisability of undertaking pregnancy. The maternal risk in such patients is not inordinately high, but the fetal risk is considerable. PMID:350371

  20. Voice Disorder in Cystic Fibrosis Patients

    PubMed Central

    Lourenço, Bruna Mendes; Costa, Kauê Machado; da Silva Filho, Manoel

    2014-01-01

    Cystic fibrosis is a common autosomal recessive disorder with drastic respiratory symptoms, including shortness of breath and chronic cough. While most of cystic fibrosis treatment is dedicated to mitigating the effects of respiratory dysfunction, the potential effects of this disease on vocal parameters have not been systematically studied. We hypothesized that cystic fibrosis patients, given their characteristic respiratory disorders, would also present dysphonic symptoms. Given that voice disorders can severely impair quality of life, the identification of a potential cystic fibrosis-related dysphonia could be of great value for the clinical evaluation and treatment of this disease. We tested our hypothesis by measuring vocal parameters, using both objective physical measures and the GRBAS subjective evaluation method, in male and female cystic fibrosis patients undergoing conventional treatment and compared them to age and sex matched controls. We found that cystic fibrosis patients had a significantly lower vocal intensity and harmonic to noise ratio, as well as increased levels of jitter and shimmer. In addition, cystic fibrosis patients also showed higher scores of roughness, breathiness and asthenia, as well as a significantly altered general grade of dysphonia. When we segregated the results according to sex, we observed that, as a group, only female cystic fibrosis patients had significantly lower values of harmonic to noise ratio and an abnormal general grade of dysphonia in relation to matched controls, suggesting that cystic fibrosis exerts a more pronounced effect on vocal parameters of women in relation to men. Overall, the dysphonic characteristics of CF patients can be explained by dysfunctions in vocal fold movement and partial upper airway obstruction, potentially caused by the accumulation of mucus and chronic cough characteristic of CF symptomatology. Our results show that CF patients exhibit significant dysphonia and suggest they may

  1. Renal Autoregulation in Health and Disease

    PubMed Central

    Carlström, Mattias; Wilcox, Christopher S.; Arendshorst, William J.

    2015-01-01

    . Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study. PMID:25834230

  2. The End-Stage Renal Disease Program: Basis for the Army Organ Transplant Program

    DTIC Science & Technology

    1985-07-19

    gradually lost, the condition is known as chronic renal failure . End-stage renal disease (ESRD) is the late and terminal phase of chronic renal ...extended Medicare coverage to persons suffering from kidney ( renal ) failure who either were currently or fully insured under the Social Security Act or...NO.NO. 11. TITLE (Include Security Classification) THE END-STAGE RENAL DISEASE PROGRAM: BASIS FOR THE ARMY ORGAN TRANSPLANT PROGRAM 12. PERSONAL

  3. Renovascular disease, microcirculation, and the progression of renal injury: role of angiogenesis

    PubMed Central

    2011-01-01

    Emerging evidence supports the pivotal role of renal microvascular disease as a determinant of tubulo-interstitial and glomerular fibrosis in chronic kidney disease. An intact microcirculation is vital to restore blood flow to the injured tissues, which is a crucial step to achieve a successful repair response. The purpose of this review is to discuss the impact and mechanisms of the functional and structural changes of the renal microvascular network, as well as the role of these changes in the progression and irreversibility of renal injury. Damage of the renal microcirculation and deterioration of the angiogenic response may constitute early steps in the complex pathways involved in progressive renal injury. There is limited but provocative evidence that stimulation of vascular proliferation and repair may stabilize renal function and slow the progression of renal disease. The feasibility of novel potential therapeutic interventions for stabilizing the renal microvasculature is also discussed. Targeted interventions to enhance endogenous renoprotective mechanisms focused on the microcirculation, such as cell-based therapy or the use of angiogenic cytokines have shown promising results in some experimental and clinical settings. PMID:21307362

  4. Diabetic nephropathy. Is end-stage renal disease inevitable?

    PubMed

    Bogusky, R T

    1983-10-01

    The appearance of proteinuria in an insulin-dependent diabetic patient is an ominous sign. Proteinuria heralds the presence of diabetic nephropathy and early death, or chronic renal failure requiring dialysis or transplantation, in 50% of patients. The pathogenesis of diabetic nephropathy is unknown. Adequate insulin administration is the most important preventive measure. Hypertension, if present, should be aggressively treated to delay progression of renal disease. Good nutrition, prompt treatment of urinary tract infections, and caution in the use of radiocontrast agents are other important preventive measures. Hemodialysis, peritoneal dialysis, and transplantation are options for patients with end-stage renal disease. No matter which is selected, the patient may still have multiple amputations, blindness, congestive heart failure, infections, and uncontrolled glycemia. Advancements are being made, however, that promise a better future for insulin-dependent diabetics.

  5. Paraprotein-Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal Significance.

    PubMed

    Rosner, Mitchell H; Edeani, Amaka; Yanagita, Motoko; Glezerman, Ilya G; Leung, Nelson

    2016-12-07

    Paraprotein-related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders. Copyright © 2016 by the American Society of Nephrology.

  6. A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus)

    PubMed Central

    Prozesky, Leon; Lawrence, John

    2018-01-01

    The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

  7. A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus).

    PubMed

    Mitchell, Emily P; Prozesky, Leon; Lawrence, John

    2018-01-01

    The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

  8. Scattered Deletion of PKD1 in Kidneys Causes a Cystic Snowball Effect and Recapitulates Polycystic Kidney Disease

    PubMed Central

    Leonhard, Wouter N.; Zandbergen, Malu; Veraar, Kimberley; van den Berg, Susan; van der Weerd, Louise; Breuning, Martijn; de Heer, Emile

    2015-01-01

    In total, 1 in 1000 individuals carries a germline mutation in the PKD1 or PKD2 gene, which leads to autosomal dominant polycystic kidney disease (ADPKD). Cysts can form early in life and progressively increase in number and size during adulthood. Extensive research has led to the presumption that somatic inactivation of the remaining allele initiates the formation of cysts, and the progression is further accelerated by renal injury. However, this hypothesis is primarily on the basis of animal studies, in which the gene is inactivated simultaneously in large percentages of kidney cells. To mimic human ADPKD in mice more precisely, we reduced the percentage of Pkd1-deficient kidney cells to 8%. Notably, no pathologic changes occurred for 6 months after Pkd1 deletion, and additional renal injury increased the likelihood of cyst formation but never triggered rapid PKD. In mildly affected mice, cysts were not randomly distributed throughout the kidney but formed in clusters, which could be explained by increased PKD-related signaling in not only cystic epithelial cells but also, healthy-appearing tubules near cysts. In the majority of mice, these changes preceded a rapid and massive onset of severe PKD that was remarkably similar to human ADPKD. Our data suggest that initial cysts are the principal trigger for a snowball effect driving the formation of new cysts, leading to the progression of severe PKD. In addition, this approach is a suitable model for mimicking human ADPKD and can be used for preclinical testing. PMID:25361818

  9. Neural control of renal function in health and disease.

    PubMed

    DiBona, G F

    1994-04-01

    The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

  10. Pathophysiology of cystic fibrosis and drugs used in associated digestive tract diseases

    PubMed Central

    Haack, Adriana; Aragão, Giselle Gonçalves; Novaes, Maria Rita Carvalho Garbi

    2013-01-01

    Cystic fibrosis (CF) causes chronic infections in the respiratory tract and alters the digestive tract. This paper reviews the most important aspects of drug treatment and changes in the digestive tract of patients with CF. This is a review of the literature, emphasizing the discoveries made within the last 15 years by analyzing scientific papers published in journals indexed in the Scientific Electronic Library Online, Sciences Information, United States National Library of Medicine and Medical Literature Analysis and Retrieval System Online databases, both in English and Portuguese, using the key words: cystic fibrosis, medication, therapeutic, absorption, digestion. Randomized, observational, experimental, and epidemiological clinical studies were selected, among others, with statistical significance of 5%. This review evaluates the changes found in the digestive tract of CF patients including pancreatic insufficiency, constipation and liver diseases. Changes in nutritional status are also described. Clinical treatment, nutritional supplementation and drug management were classified in this review as essential to the quality of life of CF patients, and became available through public policies for monitoring and treating CF. The information gathered on CF and a multi professional approach to the disease is essential in the treatment of these patients. PMID:24379572

  11. Autosomal dominant polycystic kidney disease in children

    PubMed Central

    Cadnapaphornchai, Melissa A.

    2015-01-01

    Purpose of review Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, affecting one in 500 individuals. The cardinal manifestation of ADPKD is progressive cystic dilatation of renal tubules with kidney enlargement and progression to end-stage renal disease in approximately half of cases by 60 years of age. Although previously considered a condition of adults, it is clear that children and young adults are subject to the complications of ADPKD. Recent findings It has been increasingly recognized that interventions early in life are necessary in order to confer the best long-term outcome in this common condition. Therefore, it is imperative for pediatricians to recognize the manifestations and complications of this disease. Until recently ADPKD management focused on general principles of chronic kidney disease. However, several recent clinical trials in children and adults with ADPKD have focused on disease-specific therapies. Summary This review will highlight the clinical manifestations, diagnosis, and appropriate management of ADPKD in childhood and will review recent relevant clinical trials in children and adults with this condition. PMID:25635587

  12. Liesegang rings in renal cyst fluid.

    PubMed

    Katz, L B; Ehya, H

    1990-01-01

    Peculiar ring-like structures identified as Liesegang rings (LRs) were found in renal cyst fluid from three patients with benign renal cysts. They ranged in size from 5 to 820 mu. Most had a double-layer outer wall with equally spaced radial cross-striations and an amorphous central nidus. Special stains were performed in one case, and the results are discussed. Reports of LRs in cystic or inflamed tissues have recently appeared in the literature. Some LRs have been mistaken for eggs or mature components of the giant kidney worm, Dioctophyma renale. We propose that cytologic assessment of renal cyst fluid in conjunction with histologic examination decreases the likelihood of misdiagnosis of LRs.

  13. Coexistent findings of renal glomerular disease with Hashimoto's thyroiditis.

    PubMed

    Koçak, Gülay; Huddam, Bülent; Azak, Alper; Ortabozkoyun, Levent; Duranay, Murat

    2012-05-01

    Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disease with a female preponderance. Renal involvement in HT is not uncommon. In the present study, we aimed to define the frequency and characteristics of the glomerular diseases associated with HT and further the understanding of any common pathogenesis between HT and glomerular disease. We reviewed retrospectively 28 patients with HT who were referred to our Department because of unexplained haematuria, proteinuria or renal impairment from 2007 to 2011. Routine laboratory investigations including blood count, serum biochemistry, urinalysis and 24-h urinary protein excretion were performed on all patients. Renal biopsy was performed in 20 patients with HT, and the specimens were examined by light microscopy and immunofluorescence staining. We detected four cases of focal segmental glomerulosclerosis (FSGS), four membranous glomerulonephritis (MGN), two minimal-change disease (MCD), three immunoglobulin A nephritis (IgAN), three chronic glomerulonephritis (CGN) and one amyloidosis. In three patients, the renal biopsy findings were nonspecific. Daily urinary protein excretion and glomerular filtration rates were found to be independent of the level of thyroid hormone and thyroid-specific autoantibodies. Glomerular pathologies associated with HT are similar to those in the general population, the most common lesions being MGN, FSGS and IgA nephritis. © 2012 Blackwell Publishing Ltd.

  14. RON kinase inhibition reduces renal endothelial injury in sickle cell disease mice

    PubMed Central

    Khaibullina, Alfia; Adjei, Elena A.; Afangbedji, Nowah; Ivanov, Andrey; Kumari, Namita; Almeida, Luis E.F.; Quezado, Zenaide M.N.; Nekhai, Sergei; Jerebtsova, Marina

    2018-01-01

    Sickle cell disease patients are at increased risk of developing a chronic kidney disease. Endothelial dysfunction and inflammation associated with hemolysis lead to vasculopathy and contribute to the development of renal disease. Here we used a Townes sickle cell disease mouse model to examine renal endothelial injury. Renal disease in Townes mice was associated with glomerular hypertrophy, capillary dilation and congestion, and significant endothelial injury. We also detected substantial renal macrophage infiltration, and accumulation of macrophage stimulating protein 1 in glomerular capillary. Treatment of human cultured macrophages with hemin or red blood cell lysates significantly increased expression of macrophage membrane-associated protease that might cleave and activate circulating macrophage stimulating protein 1 precursor. Macrophage stimulating protein 1 binds to and activates RON kinase, a cell surface receptor tyrosine kinase. In cultured human renal glomerular endothelial cells, macrophage stimulating protein 1 induced RON downstream signaling, resulting in increased phosphorylation of ERK and AKT kinases, expression of Von Willebrand factor, increased cell motility, and re-organization of F-actin. Specificity of macrophage stimulating protein 1 function was confirmed by treatment with RON kinase inhibitor BMS-777607 that significantly reduced downstream signaling. Moreover, treatment of sickle cell mice with BMS-777607 significantly reduced glomerular hypertrophy, capillary dilation and congestion, and endothelial injury. Taken together, our findings demonstrated that RON kinase is involved in the induction of renal endothelial injury in sickle cell mice. Inhibition of RON kinase activation may provide a novel approach for prevention of the development of renal disease in sickle cell disease. PMID:29519868

  15. The Renal Histopathology Spectrum of Elderly Patients with Kidney Diseases

    PubMed Central

    Zhu, Ping; Zhou, Fu-de; Zhao, Ming-hui

    2014-01-01

    Abstract The elderly population has significantly increased in China. However, data regarding renal histopathology in this population is lacking. The present study retrospectively analyzed renal disease spectrum of 430 elderly patients who had received renal biopsy at Peking University First Hospital between January 2003 and December 2012. Among 6049 patients receiving renal biopsies during the same period, 430 (7.10%) were elderly (≥65 years). The ratio of male (263 patients) to female (167 patients) was 1.57:1, with an age of 70.29 ± 3.99 (range 65–82) years at the time of biopsy. The most common indication for renal biopsy was nephrotic syndrome (59.53%), followed by acute kidney injury (AKI, 19.53%) and chronic glomerulonephritis (CGN, 16.05%). The most common renal histopathology in primary glomerular disease was idiopathic membranous nephropathy (iMN, 61.02%), followed by IgA nephropathy (18.22%), minimal change disease (MCD, 9.32%) and focal segmental glomerulosclerosis (6.78%). ANCA-associated vasculitis (AAV, 43.95%) was the leading secondary glomerular disease, followed by HBV-related glomerulonephritis (HBV-GN, 24.2%), and amyloidosis (14.01%). In patients with nephrotic syndrome, iMN (50%) was the leading cause, followed by HBV-GN (16.02%), MCD (7.81%), and amyloidosis (7.81%). In patients with iMN, 89.5% presented as nephrotic syndrome, 8.39% as CGN. In patients with AKI, the leading cause was AAV (48.12%), followed by acute interstitial nephritis (20.48%) and acute tubular necrosis (8.43%). In conclusion, in elderly Chinese patients, the most common renal histopathology pattern was iMN in patients with nephrotic syndrome, and AAV in patients with AKI. PMID:25526441

  16. Baclofen Toxicity in a Patient with Hemodialysis-Dependent End-Stage Renal Disease.

    PubMed

    Porter, Lauren M; Merrick, Stephanie S; Katz, Kenneth D

    2017-04-01

    Oral baclofen toxicity is extremely rare, but can affect patients with renal disease due to the drug's predominant renal clearance of approximately 69-85%. Patients with severely impaired renal function typically develop symptoms soon after initiating baclofen therapy, even at relatively low doses. A 69-year-old woman with a history of hemodialysis-dependent end-stage renal disease presented to the Emergency Department with encephalopathy, ataxia, and dystonia after the addition of a recent baclofen prescription for back pain (10 mg twice daily). She had been taking baclofen as prescribed for approximately 1 week when, the day prior to admission, she had increased her dose to a total of 40 mg. Diagnostic studies demonstrated the patient had chronic, end-stage renal disease and a supratherapeutic concentration of baclofen. Signs and symptoms resolved with hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is of critical importance for emergency physicians to appreciate impaired baclofen clearance in those with underlying renal disease to obviate the potential for significant drug toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Comparative study on the National Renal Disease Registry in America, England and Iran.

    PubMed

    Ajami, Sima; Askarianzadeh, Mahdi; Saghaeiannejad-Isfahani, Sakineh; Mortazavi, Mojgan; Ehteshami, Asghar

    2014-01-01

    A disease registry is a database that includes information about people diagnosed with specific types of diseases. The registry collects information that can be used for capturing, managing, and organizing specific information for patients. The aim of this study was to identify and compare the National Renal Disease Registry (NRDR) in selected countries including the United States, United Kingdom, and Iran. Retrieval of data of the NRDR performed through scholars responsible in related agencies, including the Ministry of Health and Medical Education, and Renal Disease charity, and data registries in the United States, United Kingdom, and Iran. This research was an applied and descriptive, comparative study. The study population consisted of the National Renal Disease Registry of the selected countries including the United States, United Kingdom, and Iran, from which data were collected using forms that were designed according to the study objectives. Sources of data were researchers, scholars responsible in related agencies, including the Ministry of Health and Medical Education, and Renal Disease charity, data registries, articles, books, journals, databases, websites, and related documents. Data were gathered through phone, e-mail, study, observation, and interview. The researchers collected data for each country based on the study objectives and then put them in comparative tables. Data were analyzed by descriptive, comparative, and theoretical methods. There is no NRDR in Iran to report the short- and long-term results of renal disease. Most of the renal transplant teams report their own results as single-center experiences. America and Britain have pre-eminent national registry of renal disease, compared to other countries. The Iranian Society of Nephrology should be actively involved to create a National Renal Registry in Iran. The registry should have representatives from the universities, government, armed forces, and private sectors. Researchers proposed

  18. History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

    PubMed

    Calderon-Margalit, Ronit; Golan, Eliezer; Twig, Gilad; Leiba, Adi; Tzur, Dorit; Afek, Arnon; Skorecki, Karl; Vivante, Asaf

    2018-02-01

    The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

  19. Advances in the Urinary Exosomes in Renal Diseases.

    PubMed

    Chen, Pei-Pei; Qin, Yan; Li, Xue-Mei

    2016-08-01

    Cells secrete around 30- 100 nm membrane-enclosed vesicles that are released into the extracellular spaceis termed exosomes(EXs). EXs widely present in body fluids and incorporated proteins,nucleic acids that reflect the physiological state of their cells of origin and they may play an important role in cell-to-cell communication in various physiological and disease processes. In this article we review the recent basic and clinical studies in urinary EXs in renal diseases,focusing on their biological characteristics and potential roles as new biological markers,intervention treatment goals,and targeted therapy vectors in renal diseases.However,some issues still exist;in particular,the clinical application of EXs as a liquid biopsy technique warrants further investigations.

  20. Discrepancy between Medical Evidence Form 2728 and Renal Biopsy for Glomerular Diseases

    PubMed Central

    Hogan, Susan L.; Jennette, Caroline E.; Kenderes, Barbara; Krisher, Jenna; Jennette, J. Charles; McClellan, William M.

    2010-01-01

    Background and objectives: The United States Renal Data System (USRDS) is a commonly utilized database for epidemiologic research of ESRD patients. USRDS uses Medical Evidence Form 2728 to collect medical information about ESRD patients. The validity of the Form 2728 “primary cause of renal failure” field for glomerular diseases has not been evaluated, although inconsistencies between Form 2728 information and medical records have been documented previously with respect to comorbidities. Design, setting, participants, & measurements: Form 2728 information was linked with renal biopsy results from the Glomerular Disease Collaborative Network (GDCN) for 217 patients with biopsy-confirmed glomerular diseases who had reached ESRD. Biopsy results were compared with the Form 2728 “primary cause of renal failure” field. Diseases were considered individually, and also categorized into commonly used disease groups. Percentage of agreement and disease-specific measures of validity were calculated. Results: Overall agreement between renal biopsy and Form 2728 was low (14.8% overall, 23.0% when categorized). Agreement was better after Form 2728 was revised in 1995 (10.0% before versus 23.2% after overall). The cause of ESRD field was left blank in 57% of the forms submitted for glomerular disease patients. Individual glomerular diseases had very low specificities, but tended to have high positive predictive values. Conclusions: Form 2728 does not accurately reflect the renal pathology diagnosis as captured by biopsy. The large degree of missing data and misclassification should be of concern to those performing epidemiologic research using Form 2728 information on glomerular diseases. PMID:20688886

  1. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.

    PubMed

    Srigley, John R; Delahunt, Brett; Eble, John N; Egevad, Lars; Epstein, Jonathan I; Grignon, David; Hes, Ondrej; Moch, Holger; Montironi, Rodolfo; Tickoo, Satish K; Zhou, Ming; Argani, Pedram

    2013-10-01

    The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC

  2. Renal Failure in Sickle Cell Disease: Prevalence, Predictors of Disease, Mortality and Effect on Length of Hospital Stay.

    PubMed

    Yeruva, Sri L H; Paul, Yonette; Oneal, Patricia; Nouraie, Mehdi

    2016-09-01

    Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk of developing renal dysfunction is not known. We used the Truven Health MarketScan ® Medicaid Databases from 2007 to 2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.

  3. Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

    PubMed

    Berg, Ulla B; Németh, Antal

    2018-04-01

    On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

  4. [Chronic renal disease as cardiovascular risk factor].

    PubMed

    Hermans, M M H; Kooman, J P; Stehouwer, C D A

    2008-07-19

    A lowering of the glomerular filtration rate (GFR) and/or the presence of albuminuria are signs of chronic renal disease. Both variables are for the most part independently associated with an increased risk of cardiovascular morbidity and mortality. Albuminuria is a marker of endothelial dysfunction. A decrease of the GFR is associated with non-traditional risk factors, e.g. renal anaemia, uraemic toxins due to a decrease of the renal clearance, hyperhomocysteinaemia caused by a diminished homocysteine metabolism, excessive activation of the sympathetic nervous system which is related to sleep apnoea syndrome, oxidative stress and dyslipidaemia associated with the formation of vasotoxic, oxidised LDL cholesterol. These non-traditional risk factors may, alone or in combination with traditional atherogenic risk factors (e.g. age, male gender, smoking, hypercholesterolaemia, hypertension, obesity, positive family history and diabetes mellitus), partially via endothelial dysfunction, result in harmful effects on arterial function, increasing cardiovascular morbidity and mortality. Different stages of chronic kidney disease are associated with specific risk factors, making a specific therapeutic approach essential.

  5. Odour perception in chronic renal disease.

    PubMed

    Griep, M I; Van der Niepen, P; Sennesael, J J; Mets, T F; Massart, D L; Verbeelen, D L

    1997-10-01

    The sense of smell plays an important role in the quality of life. Many studies have shown a declining odour perception in the elderly, as well as in subjects in poor health or nutritional state. Considering the high prevalence of poor nutritional state in renal disease and the importance of odour perception in nutrition and health, the relationship between renal function, nutritional state, and odour perception is explored in this study. A total of 101 patients with chronic renal failure participated in the study. Thirty-eight haemodialysis patients (mean age = 64.3 years) were evaluated both before and after dialysis. Sixteen patients on peritoneal dialysis treatment (mean age = 64.0 years), 28 transplanted patients (mean age = 53.5 years, mean creatinine clearance = 64.0 ml/min) and 19 patients with varying degrees of renal insufficiency were also included (mean age = 63.7 years, mean creatinine clearance = 29.5 ml/min). Patients with cognitive deficits or upper respiratory airway diseases were excluded. A validated objective procedure was used to measure odour perception, by determining the detection threshold for isoamyl acetate (banana odour) as the lowest detectable odour concentration. Healthy control persons had significantly lower odour thresholds compared to patients on peritoneal (P = 0.001) and haemodialysis (P = 0.002). No significant difference was observed in odour perception between patients on peritoneal and haemodialysis (P = 0.779) and for patients on haemodialysis before and after a dialysis session. Transplanted patients had significantly better odour perception compared to matched patients on dialysis (P < 0.001). Odour perception of transplanted patients and matched healthy control persons was similar (P = 0.81). In patients with varying degrees of renal insufficiency, including healthy controls and transplanted patients, a significant positive correlation was found between odour perception and creatinine clearance (P = 0.02). A significant

  6. Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

    PubMed

    Falkevall, Annelie; Mehlem, Annika; Palombo, Isolde; Heller Sahlgren, Benjamin; Ebarasi, Lwaki; He, Liqun; Ytterberg, A Jimmy; Olauson, Hannes; Axelsson, Jonas; Sundelin, Birgitta; Patrakka, Jaakko; Scotney, Pierre; Nash, Andrew; Eriksson, Ulf

    2017-03-07

    Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Changes in Renal Function and Blood Pressure in Patients with Stone Disease

    NASA Astrophysics Data System (ADS)

    Worcester, Elaine M.

    2007-04-01

    Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

  8. Diseases causing end-stage renal failure in New South Wales.

    PubMed Central

    Stewart, J H; McCarthy, S W; Storey, B G; Roberts, B A; Gallery, E; Mahony, J F

    1975-01-01

    The nature of the original renal disease was determined in 403 consecutive cases of end-stage renal failure, in 317 of which the clinical diagnosis was corroborated by histological examination of the kidney. Five diseases accounted for 20 or more cases--glomerulonephritis (31% of the total), analgesic nephropathy (29%), primary vesicoureteral reflux (8%), essential hypertension (6%), and polycystic kidneys (5%). In only four cases did renal failure result from chronic pyelonephritis without a demonstrable primary cause. Greater use of micturating cystography and cystoscopy and routine urine testing for salicylate are advocated for earlier diagnosis of the major causes of "pyelonephritis". The incidence of end-stage renal failure in people aged 15-55 in New South Wales was estimated to be at least 34 new cases per million of total population each year. PMID:1090338

  9. Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

    PubMed

    Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

    2018-03-01

    Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall

  10. Dissecting the roles of aquaporins in renal pathophysiology using transgenic mice

    PubMed Central

    Verkman, A. S.

    2008-01-01

    Transgenic mice lacking renal aquaporins (AQPs), or containing mutated AQPs, have been useful in confirming anticipated AQP functions in renal physiology and in discovering new functions. Mice lacking AQPs 1–4 manifest defects in urinary concentrating ability to different extents. Mechanistic studies have confirmed the involvement of AQP1 in near-isosmolar fluid absorption in proximal tubule, and in countercurrent multiplication and exchange mechanisms that produce medullary hypertonicity in the antidiuretic kidney. Deletion of AQPs 2–4 impairs urinary concentrating ability by reduction of transcellular water permeability in collecting duct. Recently created transgenic mouse models of nephrogenic diabetes insipidus produced by AQP2 gene mutation offer exciting possibilities to test new drug therapies. Several unanticipated AQP functions in kidney have been discovered recently that are unrelated to their role in transcellular water transport. There is evidence for involvement of AQP1 in kidney cell migration following renal injury, of AQP7 in renal glycerol clearance, of AQP11 in prevention of renal cystic disease, and possibly of AQP3 in regulation of collecting duct cell proliferation. Future work in renal AQPs will focus on mechanisms responsible for these non-fluid-transporting functions, and on the development of small-molecule AQP inhibitors for use as aquaretic-type diuretics. PMID:18519083

  11. Early bronchiectasis in cystic fibrosis detected by surveillance CT.

    PubMed

    Pillarisetti, Naveen; Linnane, Barry; Ranganathan, Sarath

    2010-08-01

    There is emerging evidence that cystic fibrosis lung disease begins early in infancy. Newborn screening allows early detection and surveillance of pulmonary disease and the possibility of early intervention in this life-shortening condition. We report two children with cystic fibrosis who underwent a comprehensive assessment from diagnosis that included measurement of lung function, limited-slice high-resolution CT and BAL performed annually. Early aggressive surveillance enabled significant lung disease and bronchiectasis to be detected during the first few years of life and led to a change in management, highlighting a clinical role for CT scanning during the preschool years in children with cystic fibrosis.

  12. Clinical course of dengue fever and its impact on renal function in renal transplant recipients and patients with chronic kidney disease.

    PubMed

    Arun Thomas, E T; George, Jacob; Sruthi, Devi; Vineetha, N S; Gracious, Noble

    2018-04-01

    Dengue fever is a mosquito-borne viral disease endemic in many tropical and sub-tropical countries. There is only limited data in the literature about dengue fever in renal transplant recipients and patients with chronic kidney disease. This study compares the clinical course of dengue fever and its impact on renal function in renal transplant recipients, patients with chronic kidney disease and patients with normal base line renal function. An observational study was conducted from 1 st May to 31 st July 2017, at a tertiary care centre of South India. A major epidemic of dengue had occurred during the study period. Twelve renal transplant recipients, 22 patients with CKD and 58 patients with normal baseline renal function (control group) admitted with dengue fever were prospectively studied. Nadir WBC count was lowest in renal transplant recipients (2575 + 1187/mm 3 ), [P<0.001]. Renal transplant recipients took more time for normalisation of platelet count (6 + 4.5 days), [P<0.001]. All 22 patients with CKD and 11 of 12 renal transplant recipients had worsening of renal function where as only 17 of 58 patients in the control group had worsening [P<0.001]. Sixteen patients with CKD, one renal transplant recipient and none among control group required hemodialysis [P<0.001]. Dialysis requiring patients had more hemoconcentration (52.5+ 19.9% increase in haemoglobin), [P<0.001]. Seven patients with CKD were dialysis dependent at the end of 2 weeks. Clinical features of dengue fever were different in renal transplant recipients and patients with CKD. Severe worsening of renal function was common in CKD patients. Worsening of renal function in renal transplant recipients was less severe and transient. This article is protected by copyright. All rights reserved.

  13. Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

    PubMed

    Bozbas, Huseyin; Pirat, Bahar; Demirtas, Saadet; Simşek, Vahide; Yildirir, Aylin; Sade, Elif; Sayin, Burak; Sezer, Siren; Karakayali, Hamdi; Muderrisoglu, Haldun

    2009-02-01

    Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

  14. Intravenous Renal Cell Transplantation for Polycystic Kidney Disease

    DTIC Science & Technology

    2013-10-01

    extend the utility of organs available for transplant. Data obtained to date demonstrate markedly lower renal cyst volume and fibrosis and better...Nephrology in November, 2013. 15. SUBJECT TERMS polycystic kidney diseases; renal insufficiency, chronic; kidney failure, chronic; fibrosis 16. SECURITY...reflect better diagnosis and reporting, they illustrate that ESRD from PKD is a huge health problem. The main goal of this proposal is the development

  15. Cardiovascular disease in live related renal transplantation.

    PubMed

    Kaul, A; Sharm, R K; Gupta, A; Sinha, N; Singh, U

    2011-11-01

    Cardiovascular disease has become the leading cause of morbidity and mortality in renal transplant recipients, although its pathogenesis and treatment are poorly understood. Modifiable cardiovascular risk factors and graft dysfunction both play an important role in development of post transplant cardiovascular events. Prevalence of cardiovascular disease was studied in stable kidney transplant patients on cyclosporine based triple immunosuppression in relation to the various risk factors and post transplant cardiovascular events. Analysis of 562 post transplant patients with stable graft function for 6 months, the patients were evaluated for cardiovascular events in post transplant period. Pre and post transplant risk factors were analyzed using the COX proportional hazard model. 174 patients had undergone pre transplant coronary angiography, 15 of these patients underwent coronary revascularization (angioplasty in 12, CABG in 3). The prevalence of CAD was 7.2% in transplant recipients. Of 42 patients with CAD 31 (73.8%) had cardiovascular event in post transplant period. Age > or = 40 yrs, male sex, graft dysfunction, diabetes as primary renal disease, pre transplant cardiovascular event, chronic rejection showed significant correlation in univariate analysis and there was significant between age > or = 40 years (OR = 2.16 with 95% CI, 0.977-4.78) S creatinine > or = 1.4 mg % (OR = 2.40 with 95% CI, 1.20 - 4.82), diabetes as primary disease (OR with 95% CI 3.67, 3.2-14.82), PTDM (OR 3.67, 95% CI 1.45-9.40), pre-transplant cardiovascular disease (OR 4.14, 95% CI .38-13.15) with post transplant cardiovascular event on multivariate analysis. There was poor patient and graft survival among those who suffered post transplant cardiovascular event. The incidence of cardiovascular disease continues to be high after renal transplantation and modifiable risk factors should be identified to prevent occurrence of events in post transplant period.

  16. Immune response, diagnosis and treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis lung disease.

    PubMed

    Eickmeier, Olaf; Rieber, Nikolaus; Eckrich, Jonas; Hector, Andreas; Graeppler-Mainka, Ute; Hartl, Dominik

    2013-01-01

    Patients with cystic fibrosis (CF) suffer from chronic infective lung disease, which determines morbidity and mortality. While bacteria, such as Pseudomonas aeruginosa, are well-known to contribute to pulmonary pathology, the relevance of fungi in CF airways remains poorly understood. The best studied fungus in CF is Aspergillus fumigatus, which frequently colonizes CF airways and causes a disease condition termed allergic bronchopulmonary aspergillosis. This review aims to provide an update on the immunological mechanisms, diagnostic approaches and therapeutic strategies for allergic bronchopulmonary aspergillosis and other Aspergillus fumigatusmediated phenotypes in CF lung disease.

  17. Molecular mechanisms in lithium-associated renal disease: a systematic review.

    PubMed

    Rej, Soham; Pira, Shamira; Marshe, Victoria; Do, André; Elie, Dominique; Looper, Karl J; Herrmann, Nathan; Müller, Daniel J

    2016-11-01

    Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease. We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium's effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers. From a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD. Future studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium's biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events.

  18. Panniculectomy Outcomes in Patients with End-Stage Renal Disease in Preparation for Renal Transplant.

    PubMed

    Mundra, Leela S; Rubio, Gustavo A; AlQattan, Husain T; Thaller, Seth R

    2018-06-01

    End-stage renal disease (ESRD) is associated with increased cardiovascular risk factors, electrolyte imbalances, and iron deficiency anemia. These factors may increase the risk of adverse outcomes in patients undergoing panniculectomy. There is a paucity of data regarding outcomes in patients with ESRD undergoing panniculectomy. The purpose of this study is to investigate whether ESRD is associated with increased rate of complications following a panniculectomy. The Nationwide Inpatient Sample database (2006-2011) was used to identify patients who underwent a panniculectomy. Among this cohort, patients diagnosed with end-stage renal disease were identified. Patients excluded from the study were emergency admissions, pregnant women, patients less than 18 years old, and patients with concurrent nephrectomy or kidney transplants. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-squared and risk-adjusted multivariate logistic regression analyses were performed to determine whether end-stage renal disease was associated with increased rate of postoperative complications. A total of 34,779 panniculectomies were performed during the study period. Of these, 613 (1.8%) were diagnosed with ESRD. Patients with ESRD were older (mean age 58.9 vs. 49.3, p < 0.01) and more likely to have Medicare (63.5 vs. 18.4%, p < 0.01). They had higher rates of comorbidities, including diabetes, hypertension, congestive heart failure, chronic lung disease, chronic anemia, liver disease, peripheral artery disease, obesity, and coagulopathies (p < 0.01). The procedure was more likely to occur at a large, teaching hospital (p < 0.01). Postoperatively, patients with ESRD had a higher rate of death (3.3 vs. 0.2%, p < 0.01), wound complications (10.6 vs. 6.2%, p < 0.01), venous thromboembolism (4.9 vs. 0.8%, p < 0.01), blood transfusions (25.3% vs. 7.0%, p < 0.01), non-renal major medical complications (40.0% vs. 8.4%), and longer hospital

  19. Role of L-arginine in the pathogenesis and treatment of renal disease.

    PubMed

    Cherla, Gautam; Jaimes, Edgar A

    2004-10-01

    L-arginine is a semi essential amino acid and also a substrate for the synthesis of nitric oxide (NO), polyamines, and agmatine. These L-arginine metabolites may participate in the pathogenesis of renal disease and constitute the rationale for manipulating L-arginine metabolism as a strategy to ameliorate kidney disease. Modification of dietary L-arginine intake in experimental models of kidney diseases has been shown to have both beneficial as well as deleterious effects depending on the specific model studied. L-arginine supplementation in animal models of glomerulonephritis has been shown to be detrimental, probably by increasing the production of NO from increased local expression of inducible NO synthase (iNOS). L-arginine supplementation does not modify the course of renal disease in humans with chronic glomerular diseases. However, beneficial effects of L-arginine supplementation have been reported in several models of chronic kidney disease including renal ablation, ureteral obstruction, nephropathy secondary to diabetes, and salt-sensitive hypertension. L-arginine is reduced in preeclampsia and recent experimental studies indicate that L-arginine supplementation may be beneficial in attenuating the symptoms of preeclampsia. Administration of exogenous L-arginine has been shown to be protective in ischemic acute renal failure. In summary, the role of L-arginine in the pathogenesis and treatment of renal disease is not completely understood and remains to be established.

  20. Renal Complex Cystic Masses: Usefulness of Contrast-Enhanced Ultrasound (CEUS) in Their Assessment and Its Agreement with Computed Tomography.

    PubMed

    Sanz, Enrique; Hevia, Vital; Gómez, Victoria; Álvarez, Sara; Fabuel, Jose-Javier; Martínez, Laura; Rodriguez-Patrón, Rafael; González-Gordaliza, Cristina; Burgos, Francisco-Javier

    2016-12-01

    Around 10 % of renal cell carcinomas (RCC) are cystic, while some benign cysts have complex appearance in conventional diagnostic tests such as computed tomography (CT) or magnetic resonance imaging (MRI). These renal complex cystic masses (RCCMs) are a challenging entity in urological practice and sometimes have a difficult management, requiring surgical removal. Contrast-enhanced ultrasound (CEUS) is a very sensitive test detecting microvascularization in real time, and it has been used in the diagnostic workup of these kinds of lesions. The aim of our study was to assess the diagnostic power of CEUS in the evaluation of RCCM. This is a prospective observational study between April 2011 and July 2014. A total of 66 patients with 67 RCCMs were enrolled (Bosniak 2-4). Twenty-four patients underwent surgical removal of the RCCM. All participants underwent CEUS (experimental) and CT (control). All CEUS procedures were performed by a single high-experienced observer (urologist). Benign lesions were defined as those Bosniak 2-2F, and malignant were Bosniak 3-4. Statistical analysis was made measuring consistency (kappa index and Landis-Koch scale) and validity (sensitivity, specificity, positive and negative predictive values) of the study. Median size of RCCM measured by CEUS and CT was 3.8 cm (interquartile range (AIQ) 3.2-4.6) and 3.9 cm (AIQ 3.2-4.5), respectively. Kappa index shows good agreement between both tests (0.71; 95 % CI 0.57-0.85), both overall and stratified by categories according to Bosniak classification. CEUS has a sensitivity 100 %, specificity 81.4 %, positive predictive value 70.4 %, and negative predictive value 100 %. A total of eight RCCMs were discordant, and seven of eight classified as malignant by CEUS and not by CT. Of those seven lesions classified as malignant by CEUS, six (six of seven, 85.7 %) were malignant in the pathological exam. CEUS is a very useful tool for assessing RCCM, with good results in terms of consistency

  1. The role of anaerobic bacteria in the cystic fibrosis airway.

    PubMed

    Sherrard, Laura J; Bell, Scott C; Tunney, Michael M

    2016-11-01

    Anaerobic bacteria are not only normal commensals, but are also considered opportunistic pathogens and have been identified as persistent members of the lower airway community in people with cystic fibrosis of all ages and stages of disease. Currently, the role of anaerobic bacteria in cystic fibrosis lower airway disease is not well understood. Therefore, this review describes the recent studies relating to the potential pathophysiological role(s) of anaerobes within the cystic fibrosis lungs. The most frequently identified anaerobic bacteria in the lower airways are common to both cystic fibrosis and healthy lungs. Studies have shown that in cystic fibrosis, the relative abundance of anaerobes fluctuates in the lower airways with reduced lung function and increased inflammation associated with a decreased anaerobic load. However, anaerobes found within the lower airways also produce virulence factors, may cause a host inflammatory response and interact synergistically with recognized pathogens. Anaerobic bacteria are potentially members of the airway microbiota in health but could also contribute to the pathogenesis of lower airway disease in cystic fibrosis via both direct and indirect mechanisms. A personalized treatment strategy that maintains a normal microbial community may be possible in the future.

  2. Management of pain in autosomal dominant polycystic kidney disease and anatomy of renal innervation.

    PubMed

    Tellman, Matthew W; Bahler, Clinton D; Shumate, Ashley M; Bacallao, Robert L; Sundaram, Chandru P

    2015-05-01

    Chronic pain is a prominent feature of autosomal dominant polycystic kidney disease that is difficult to treat and manage, often resulting in a decrease in quality of life. Understanding the underlying anatomy of renal innervation and the various etiologies of pain that occur in autosomal dominant polycystic kidney disease can help guide proper treatments to manage pain. Reviewing previously studied treatments for pain in autosomal dominant polycystic kidney disease can help characterize treatment in a stepwise fashion. We performed a literature search of the etiology and management of pain in autosomal dominant polycystic kidney disease and the anatomy of renal innervation using PubMed® and Embase® from January 1985 to April 2014 with limitations to human studies and English language. Pain occurs in the majority of patients with autosomal dominant polycystic kidney disease due to renal, hepatic and mechanical origins. Patients may experience different types of pain which can make it difficult to clinically confirm its etiology. An anatomical and histological evaluation of the complex renal innervation helps in understanding the mechanisms that can lead to renal pain. Understanding the complex nature of renal innervation is essential for surgeons to perform renal denervation. The management of pain in autosomal dominant polycystic kidney disease should be approached in a stepwise fashion. Acute causes of renal pain must first be ruled out due to the high incidence in autosomal dominant polycystic kidney disease. For chronic pain, nonopioid analgesics and conservative interventions can be used first, before opioid analgesics are considered. If pain continues there are surgical interventions such as renal cyst decortication, renal denervation and nephrectomy that can target pain produced by renal or hepatic cysts. Chronic pain in patients with autosomal dominant polycystic kidney disease is often refractory to conservative, medical and other noninvasive treatments

  3. Recurrent renal cancer in Birt-Hogg-Dubé syndrome: A case report.

    PubMed

    Ather, Hammad; Zahid, Nida

    2018-01-01

    Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant disease. It is caused by constitutional mutations in the FLCN gene. Since BHDS is a rare syndrome therefore it is unknown to many physicians. However, it is important to identify this rare syndrome at early stages because incidence of renal cancer in BHD patients is very high and its detection at early stages can prevent its metastasis. Hence, we want to present a case of BHDS and draw the attention of the treating physician to this rare inherited disorder and discuss its appropriate diagnosis and management. We present a case of a 50-year old male presented to the consulting clinics of a University Hospital with right flank pain since the last 2 months. The Computed Tomography (CT) and biopsy on the right renal mass indicated clear cell type renal cell carcinoma with significant lymphadenopathy. Past history of cystic lung disease and pneumothorax along with positive finding of renal cell carcinoma on CT and biopsy suggested Birt-Hogg-Dub́e (BHD) syndrome. The patient underwent right radical nephrectomy and lymph node dissection. His 3 months post- surgery follow up CT scan indicated disease recurrence. In conclusion, it is important to identify this rare syndrome at early stages. Diagnosis for the patients with a positive family history for renal cell cancer and pneumothorax should be considered. FLCN sequencing should also be taken into account in patients and their families because incidence of renal cancer in BHD patients is very high and detection at early stages can prevent its metastasis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Effects of TORC1 Inhibition during the Early and Established Phases of Polycystic Kidney Disease

    PubMed Central

    Ta, Michelle H. T.; Schwensen, Kristina G.; Foster, Sheryl; Korgaonkar, Mayuresh; Ozimek-Kulik, Justyna E.; Phillips, Jacqueline K.; Peduto, Anthony; Rangan, Gopala K.

    2016-01-01

    The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs. PMID:27723777

  5. A Case of New Familiar Genetic Variant of Autosomal Dominant Polycystic Kidney Disease-2: A Case Study.

    PubMed

    Litvinchuk, Tetiana; Tao, Yunxia; Singh, Ruchi; Vasylyeva, Tetyana L

    2015-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation due to mutations in genes coding for polycystin-1 [PKD1 (85-90% of cases), on ch 16p13.3] and polycystin-2 [PKD2 (10-15% of cases), on ch 4q13-23] and PKD3 gene (gene unmapped). It is also associated with TSC2/PKD1 contiguous gene syndrome. ADPKD is usually inherited, but new mutations without a family history occur in approximately 10% of the cases. A 17-year-old boy was followed up for bilateral cystic kidney disease, hypertension, and obesity since he was 13 years old. The diagnosis was an accidental finding during abdominal CT at age 13 to rule out appendicitis. A renal ultrasonogram also demonstrated a multiple bilateral cysts. Because of parental history of bilateral renal cysts, PKD1 and PKD2, genetic testing was ordered. Results showed, PKD2 variant 1:3 bp deletion of TGT; nucleotide position: 1602-1604; codon position: 512-513; mRNA reading frame maintained. The same mutation was later identified in his father. A smaller number of patients have a defect in the PKD2 locus on chromosome 4 (resulting in PKD2 disease). There are no known published cases on this familiar genetic variant of ADPKD-2 cystic kidney disease. In this case, the disease is present unusually early in life.

  6. Aging-associated renal disease in mice is fructokinase dependent.

    PubMed

    Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J

    2016-10-01

    Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (<5%) fructose content. At the end of 2 yr, wild-type mice showed elevations in systolic blood pressure, mild albuminuria, and glomerular changes with mesangial matrix expansion, variable mesangiolysis, and segmental thrombi. The renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.

  7. Misdiagnosis of Addison's disease in a patient with end-stage renal disease.

    PubMed

    Kocyigit, Ismail; Unal, Aydin; Tanriverdi, Fatih; Hayri Sipahioglu, Murat; Tokgoz, Bulent; Oymak, Oktay; Utas, Cengiz

    2011-01-01

    Addison's disease is a rare disorder in patients with end-stage renal disease (ESRD). In patients, the diagnosis of Addison's disease is difficult in clinical practice because most of the clinical findings of this disease are similar to those of the renal failure. We present a 51-year-old male patient, who underwent hemodialysis therapy for 8 years, diagnosed with Addison's disease after having myalgia, skin hyperpigmentation, weight loss, sweating, and nausea for the past few weeks. The physical examination was completely normal except for muscle weakness, hyperpigmentation on labial mucosa and skin in a patient. The laboratory tests revealed anemia and hypoglycemia. Serum cortisol, adrenocorticotropic hormone (ACTH) levels, and ACTH stimulation test results were consistent with Addison's disease. Adrenal computerized tomography revealed bilateral atrophic glands. Additionally, it was found that elevated serum thyroid stimulating hormone levels and antithyroid peroxidase antibody titer were positive. Our purpose is to emphasize that physicians should be alert to the potential for additional different conditions particularly in terms of adrenal failure in patients with ESRD.

  8. Sodium intake, RAAS-blockade and progressive renal disease.

    PubMed

    de Borst, Martin H; Navis, Gerjan

    2016-05-01

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the renal protective effect of RAAS-blockade is incomplete. Short-term clinical studies have demonstrated that dietary sodium restriction potentiates the antiproteinuric effect of RAAS-blockade. More recently, it was shown that this effect is accompanied by a lower risk of end-stage renal disease and adverse cardiovascular outcomes. The modulation of RAAS-blockade efficacy by sodium intake is likely multifactorial, and is mediated by effects of sodium on local tissue RAAS in kidney, vasculature and brain, and by effects on the immune system. Despite the evidence showing the beneficial effects of even a moderate sodium restriction (∼2.5g/d), it remains difficult to realize in clinical practice. In an analysis based on 24-h urinary sodium excretion data from more than 10,000 CKD patients and renal transplant recipients, we found that sodium intake in these patients is on average 3.8g/d, closely resembling the global general population (3.95g/d). Behavioral approaches including the use of online dietary coaching (ehealth) and feedback using data from 24-h urine collections may be useful to successfully lower dietary sodium intake, aiming to improve cardio-renal outcomes in patients with CKD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity.

    PubMed

    Brunel, Shan F; Willment, Janet A; Brown, Gordon D; Devereux, Graham; Warris, Adilia

    2018-04-01

    Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro . Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms. CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity.

  10. Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity

    PubMed Central

    Brunel, Shan F.; Brown, Gordon D.; Devereux, Graham; Warris, Adilia

    2018-01-01

    Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro. Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms. CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity. PMID:29651422

  11. "Cystic fibrotics could survive cholera, choleraics could survive cystic fibrosis"; hypothesis that explores new horizons in treatment of cystic fibrosis.

    PubMed

    Azimi, Arsalan

    2015-12-01

    Cystic fibrosis, the most common inherited disease of white population, is a disease of CFTR channels, in which mucosal function of many organs especially respiratory tract is impaired. Decreased mucociliary clearance and accumulation of mucus in airways facilitates colonization of infectious microorganisms, followed by infection. Following chronic infection, persistent inflammation ensues, which results in airway remodeling and deterioration of mucociliary clearance and result in a vicious cycle. Here, it is hypothesized that cholera toxin (CT) could ameliorate symptoms of cystic fibrosis as CT could dilute the thickened mucus, improve mucociliary clearance and alleviate airway obstruction. CT strengthens immunity of airway mucosa and it could attenuates bacterial growth and reduce persistency of infection. CT also modulates cellular immune response and it could decrease airway inflammation, hinder airway remodeling and prevent respiratory deterioration. Thereby it is hypothesized that CT could target and ameliorate many of pathophysiologic steps of the disease and it explores new horizons in treatment of CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Living with Cystic Fibrosis: A Guide for the Young Adult.

    ERIC Educational Resources Information Center

    Cystic Fibrosis Foundation, Atlanta, GA.

    Intended for the young adult with cystic fibrosis, the booklet provides information on dealing with problems and on advances in treatment and detection related to the disease. Addressed are the following topics: description of cystic fibrosis; inheritance of cystic fibrosis; early diagnosis; friends, careers, and other matters; treatment;…

  13. Barriers to exercise for patients with renal disease: an integrative review.

    PubMed

    Hannan, Mary; Bronas, Ulf G

    2017-12-01

    Renal disease is a common health condition that leads to loss of physical function, frailty, and premature loss of independence in addition to other severe comorbidities and increased mortality. Increased levels of physical activity and initiation of exercise training is recommended in the current guidelines for all patients with renal disease, but participation and adherence rates are low. The barriers to exercise and physical activity in patients with renal disease are not well defined and currently based on patient provider perception and opinion. There have been no published reviews that have synthesized published findings on patient reported barriers to exercise. This integrative literature review therefore aimed to identify the current understanding of patient reported barriers to regular exercise. This integrative review found that patient perceived barriers to exercise are not consistent with the barriers that have been identified by renal disease specialists and healthcare providers, which were disinterest, lack of motivation, and being incapable of exercise. The patient reported barriers identified through this review were complex and diverse, and the most frequently reported patient perceived barrier to exercise was low energy levels and fatigue. It is clear that additional research to identify patient perceived barriers to exercise is needed and that patient directed interventions to address these barriers should be developed. This integrative review provides information to the interdisciplinary nephrology team that can be used to tailor their assessment of barriers to exercise and provide exercise education for patients with renal disease.

  14. Chest Computed Tomographic Image Screening for Cystic Lung Diseases in Patients with Spontaneous Pneumothorax Is Cost Effective.

    PubMed

    Gupta, Nishant; Langenderfer, Dale; McCormack, Francis X; Schauer, Daniel P; Eckman, Mark H

    2017-01-01

    Patients without a known history of lung disease presenting with a spontaneous pneumothorax are generally diagnosed as having primary spontaneous pneumothorax. However, occult diffuse cystic lung diseases such as Birt-Hogg-Dubé syndrome (BHD), lymphangioleiomyomatosis (LAM), and pulmonary Langerhans cell histiocytosis (PLCH) can also first present with a spontaneous pneumothorax, and their early identification by high-resolution computed tomographic (HRCT) chest imaging has implications for subsequent management. The objective of our study was to evaluate the cost-effectiveness of HRCT chest imaging to facilitate early diagnosis of LAM, BHD, and PLCH. We constructed a Markov state-transition model to assess the cost-effectiveness of screening HRCT to facilitate early diagnosis of diffuse cystic lung diseases in patients presenting with an apparent primary spontaneous pneumothorax. Baseline data for prevalence of BHD, LAM, and PLCH and rates of recurrent pneumothoraces in each of these diseases were derived from the literature. Costs were extracted from 2014 Medicare data. We compared a strategy of HRCT screening followed by pleurodesis in patients with LAM, BHD, or PLCH versus conventional management with no HRCT screening. In our base case analysis, screening for the presence of BHD, LAM, or PLCH in patients presenting with a spontaneous pneumothorax was cost effective, with a marginal cost-effectiveness ratio of $1,427 per quality-adjusted life-year gained. Sensitivity analysis showed that screening HRCT remained cost effective for diffuse cystic lung diseases prevalence as low as 0.01%. HRCT image screening for BHD, LAM, and PLCH in patients with apparent primary spontaneous pneumothorax is cost effective. Clinicians should consider performing a screening HRCT in patients presenting with apparent primary spontaneous pneumothorax.

  15. Parent knowledge of disease management in cystic fibrosis: Assessing behavioral treatment management.

    PubMed

    Nicolais, Christina J; Bernstein, Ruth; Riekert, Kristin A; Quittner, Alexandra L

    2018-02-01

    Cystic fibrosis (CF) is a life-shortening, burdensome disease requiring complex knowledge to manage the disease. Significant gaps in knowledge have been documented for parents, which may lead to unintentionally poor adherence and insufficient transfer of treatment responsibility from parents to adolescents. There are no current, validated measures of parent knowledge for this population and there are no measures that assess the knowledge required for day-to-day behavioral management of CF. We assessed the psychometric properties of the parent version of the Knowledge of Disease Management-Cystic Fibrosis measure (KDM-CF-P) using data from iCARE (I Change Adherence and Raise Expectations), a randomized control adherence intervention trial. A total of 196 parents in the iCARE standard care/control arm completed 35 items assessing their knowledge of disease management at their 12-month study visit, prior to beginning the intervention. Items were eliminated from the measure if they met the threshold for ceiling effects, were deemed clinically irrelevant, or did not correlate well with their intended scale. Item-to-total correlations, confirmatory factor analysis, discriminant function, reliability, and convergent validity were calculated. The KDM-CF-P (19 items) demonstrated internal consistency of KR20 = 0.60 on each scale and a two-scale structure. Convergent validity for knowledge scores was found with maternal education, family income, and type of medical insurance. Parents correctly answered approximately 85% of items on the KDM-CF-P. The KDM-CF-P psychometrics support a two-scale measure with clinical utility. It is useful for assessing gaps in knowledge that can be remediated through individualized, tailored interventions. © 2017 Wiley Periodicals, Inc.

  16. Relationship between renal function and renal volume in autosomal dominant polycystic kidney disease: cross-sectional study.

    PubMed

    Torres-Sánchez, M J; Ávila-Barranco, E; Esteban de la Rosa, R J; Fernández-Castillo, R; Esteban, M A; Carrero, J J; García-Valverde, M; Bravo-Soto, J A

    2016-03-01

    To determine in patients with autosomal dominant polycystic kidney disease the relationship between total renal volume (the sum of both kidneys, TRV) as measured by magnetic resonance and renal function; and its behaviour according to sex and the presence of arterial hypertension, hypercholesterolaemia and hyperglycemia. Cross-sectional study including patients with autosomal dominant polycystic kidney disease who underwent periodic reviews at Nephrology external consultations at Hospital de las Nieves de Granada, and who underwent an magnetic resonance to estimate renal volume between January 2008 and March 2011. We evaluated 67 patients (59.7% women, average age of 48±14.4 years) and found a significant positive association between TRV and serum creatinine or urea, which was reversed compared with estimated glomerular filtration by MDRD-4 and Cockcroft-Gault. Women showed an average serum creatinine level and a significantly lower TRV level compared with males. Subgroups affected by arterial hypertension and hyperuricemia presented average values for serum creatinine and urea, higher for TRV and lower for estimated glomerular filtration. The hypercholesterolaemia subgroup showed higher average values for urea and lower for estimated glomerular filtration, without detecting significant differences compared with TRV. The volume of polycystic kidneys measured by magnetic resonance is associated with renal function, and can be useful as a complementary study to monitor disease progression. The presence of arterial hypertension, hyperuricemia or hypercholesterolaemia is associated with a poorer renal function. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  17. Exploring the pathways leading from disadvantage to end-stage renal disease for indigenous Australians.

    PubMed

    Cass, Alan; Cunningham, Joan; Snelling, Paul; Wang, Zhiqiang; Hoy, Wendy

    2004-02-01

    Indigenous Australians are disadvantaged, relative to other Australians, over a range of socio-economic and health measures. The age- and sex-adjusted incidence of end-stage renal disease (ESRD)--the irreversible preterminal phase of chronic renal failure--is almost nine times higher amongst Indigenous than it is amongst non-indigenous Australians. A striking gradient exists from urban to remote regions, where the standardised ESRD incidence is from 20 to more than 30 times the national incidence. We discuss the profound impact of renal disease on Indigenous Australians and their communities. We explore the linkages between disadvantage, often accompanied by geographic isolation, and both the initiation of renal disease, and its progression to ESRD. Purported explanations for the excess burden of renal disease in indigenous populations can be categorised as: primary renal disease explanations;genetic explanations;early development explanations; and socio-economic explanations. We discuss the strengths and weaknesses of these explanations and suggest a new hypothesis which integrates the existing evidence. We use this hypothesis to illuminate the pathways between disadvantage and the human biological processes which culminate in ESRD, and to propose prevention strategies across the life-course of Indigenous Australians to reduce their ESRD risk. Our hypothesis is likely to be relevant to an understanding of patterns of renal disease in other high-risk populations, particularly indigenous people in the developed world and people in developing countries. Furthermore, analogous pathways might be relevant to other chronic diseases, such as diabetes and cardiovascular disease. If we are able to confirm the various pathways from disadvantage to human biology, we will be better placed to advocate evidence-based interventions, both within and beyond the scope of the health-care system, to address the excess burden of renal and other chronic diseases among affected

  18. Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

    PubMed Central

    Collaco, J. Michael; Vanscoy, Lori; Bremer, Lindsay; McDougal, Kathryn; Blackman, Scott M.; Bowers, Amanda; Naughton, Kathleen; Jennings, Jacky; Ellen, Jonathan; Cutting, Garry R.

    2011-01-01

    Context Disease variation can be substantial even in conditions with a single gene etiology such as cystic fibrosis (CF). Simultaneously studying the effects of genes and environment may provide insight into the causes of variation. Objective To determine whether secondhand smoke exposure is associated with lung function and other outcomes in individuals with CF, whether socioeconomic status affects the relationship between secondhand smoke exposure and lung disease severity, and whether specific gene-environment interactions influence the effect of secondhand smoke exposure on lung function. Design, Setting, and Participants Retrospective assessment of lung function, stratified by environmental and genetic factors. Data were collected by the US Cystic Fibrosis Twin and Sibling Study with missing data supplemented by the Cystic Fibrosis Foundation Data Registry. All participants were diagnosed with CF, were recruited between October 2000 and October 2006, and were primarily from the United States. Main Outcome Measures Disease-specific cross-sectional and longitudinal measures of lung function. Results Of 812 participants with data on secondhand smoke in the home, 188 (23.2%) were exposed. Of 780 participants with data on active maternal smoking during gestation, 129 (16.5%) were exposed. Secondhand smoke exposure in the home was associated with significantly lower cross-sectional (9.8 percentile point decrease; P<.001) and longitudinal lung function (6.1 percentile point decrease; P=.007) compared with those not exposed. Regression analysis demonstrated that socioeconomic status did not confound the adverse effect of secondhand smoke exposure on lung function. Interaction between gene variants and secondhand smoke exposure resulted in significant percentile point decreases in lung function, namely in CFTR non-ΔF508 homozygotes (12.8 percentile point decrease; P=.001), TGFβ1-509 TT homozygotes (22.7 percentile point decrease; P=.006), and TGFβ1 codon 10 CC

  19. Relative risk of renal disease among people living with HIV: a systematic review and meta-analysis

    PubMed Central

    2012-01-01

    Background Antiretroviral therapy (ART) has substantially decreased mortality and HIV-related morbidity. However, other morbidities appear to be more common among PLHIV than in the general population. This study aimed to estimate the relative risk of renal disease among people living with HIV (PLHIV) compared to the HIV-uninfected population. Methods We conducted a systematic review and meta-analysis of relative risks of renal disease among populations of PLHIV reported in studies from the peer-reviewed literature. We searched Medline for relevant journal articles published before September 2010, yielding papers published during or after 2002. We also searched conference proceedings of the International AIDS Society (IAS) and Conference on Retroviruses and Opportunistic Infections (CROI) prior to and including 2010. Eligible studies were observational studies reporting renal disease defined as acute or chronic reduced renal function with glomerular filtration rate less than or equal to 60 ml/min/1.73 m2 among HIV-positive adults. Pooled relative risks were calculated for various groupings, including class of ART drugs administered. Results The overall relative risk of renal disease was 3.87 (95% CI: 2.85-6.85) among HIV-infected people compared to HIV-uninfected people. The relative risk of renal disease among people with late-stage HIV infection (AIDS) was 3.32 (1.86-5.93) compared to other PLHIV. The relative risk of renal disease among PLHIV who were receiving antiretroviral therapy (ART) was 0.54 (0.29-0.99) compared to treatment-naïve PLHIV; the relative risk of renal disease among PLHIV who were treated with tenofovir was 1.56 (0.83-2.93) compared to PLHIV who were treated with non-tenofovir therapy. The risk of renal disease was also found to significantly increase with age. Conclusion PLHIV are at increased risk of renal disease, with greater risk at later stages of infection and at older ages. ART prolongs survival and decreases the risk of renal disease

  20. Disease disclosure in individuals with cystic fibrosis: Association with psychosocial and health outcomes.

    PubMed

    Borschuk, Adrienne P; Everhart, Robin S; Eakin, Michelle N; Rand-Giovannetti, Devin; Borrelli, Belinda; Riekert, Kristin A

    2016-09-01

    This study aimed to quantify cystic fibrosis (CF) disclosure and examine associations between disclosure and psychosocial and health outcomes. Participants completed measures assessing disease disclosure and psychosocial outcomes. Data from chart reviews and pharmacy records were obtained. Participants (N=128; ages 16-63) were more likely to disclose to romantic partners (97%) and close friends (94%) than to casual friends (79%), bosses (71%), or co-workers (53%). Participants reported more comfort discussing CF with and doing treatments in front of romantic partners and close friends than other groups. Disclosure was associated with higher social support, social functioning, and medication adherence self-efficacy. Lower lung-function was associated with disclosure to bosses and co-workers. Clinicians should consider discussing disclosure with patients, as limited disclosure may have a negative impact on psychosocial outcomes. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. The lectin pathway in renal disease: old concept and new insights.

    PubMed

    Gaya da Costa, Mariana; Poppelaars, Felix; Berger, Stefan P; Daha, Mohamed R; Seelen, Marc A

    2018-04-26

    The complement system is composed of a network of at least 40 proteins, which significantly contributes to health and disease. The lectin pathway (LP) is one of three pathways that can activate the complement system. Next to protection of the host against pathogens, the LP has been shown to play a crucial role in multiple renal diseases as well as during renal replacement therapy. Therefore, several complement-targeted drugs are currently being explored in clinical trials. Among these complement inhibitors, specific LP inhibitors are also being tested in renal abnormalities such as in immunoglobulin A nephropathy and lupus nephritis. Using various in vitro models, Yaseen et al. (Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement component 3 (C3) in absence of C4 and/or C2. FASEB J 2017; 31: 2210-2219) showed that Mannan-associated serine protease2 can directly activate C3 thereby bypassing C2 and C4 in the activation of the LP. These new findings broaden our understanding of the mechanisms of complement activation and could potentially impact our strategies to inhibit the LP in renal diseases. In support of these findings, we present data of human renal biopsies, demonstrating the occurrence of the LP bypass mechanism in vivo. In conclusion, this review provides a detailed overview of the LP and clarifies the recently described bypass mechanism and its relevance. Finally, we speculate on the role of the C4 bypass mechanism in other renal diseases.

  2. Cystic adventitial degeneration: ectopic ganglia from adjacent joint capsules.

    PubMed

    Ortmann, J; Widmer, M K; Gretener, S; Do, D D; Willenberg, T; Daliri, A; Baumgartner, I

    2009-11-01

    Cystic adventitial degeneration is a rare non-atherosclerotic cause of peripheral arterial occlusive disease, mainly seen in young men without other evidence of vascular disease. Diagnosis will be established by clinical findings and by ultrasound or angiography and can be treated by excision or enucleation of the affected arterial segment or by percutaneous ultrasound-guided aspiration. However, the etiology of adventitial cysts remains unknown. We report a case of cystic adventitial degeneration showing a connection between the joint capsule and the adventitial cyst, supporting the theory that cystic adventitial degeneration may represent ectopic ganglia from adjacent joint capsules.

  3. Cystic pulmonary hydatidosis

    PubMed Central

    Sarkar, Malay; Pathania, Rajnish; Jhobta, Anupam; Thakur, Babu Ram; Chopra, Rajesh

    2016-01-01

    Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by the larval stages of the cestode Echinococcus granulosus. Worldwide, pulmonary hydatid cyst is a significant problem medically, socially, and economically. Surgery is the definitive therapy of pulmonary hydatidosis. Benzimidazoles may be considered in patients with a surgical contraindication. This review will focus on pathogenesis, lifecycle, clinical features, and management of pulmonary hydatid disease. PMID:27051107

  4. Diabetes mellitus and renal involvement in chronic viral liver disease.

    PubMed

    Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

    2015-01-01

    Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with

  5. Dental treatment for people with cystic fibrosis.

    PubMed

    Harrington, N; Barry, P J; Barry, S M

    2016-06-01

    To describe the nature and consequences of the multi-system genetic condition cystic fibrosis with a view to ensuring optimal dental treatment planning for these patients. A literature search was conducted to identify the key medical and dental manifestations of cystic fibrosis. These findings are discussed and utilised to create recommendations for treatment planning in patients with cystic fibrosis for the practising dental practitioner. Cystic fibrosis is a complex, lethal, multisystem autosomal recessive disorder resulting from mutations on chromosome 7 which result in dysfunction of an ion channel that sits on epithelial surfaces. Respiratory disease remains the leading cause of mortality. Survival has greatly increased in recent decades secondary to improved treatment and specialist care. Specific dental manifestations of the disease may result from the condition itself or complications of treatment. Modification of patient management may be necessary to provide optimum patient care. The pathophysiology and clinical manifestations are relevant to practicing dental practitioners and inform recommendations to be utilised to ensure optimal treatment planning for these patients.

  6. Regression of Crizotinib-Associated Complex Cystic Lesions after Switching to Alectinib.

    PubMed

    Taima, Kageaki; Tanaka, Hisashi; Tanaka, Yoshihito; Itoga, Masamichi; Takanashi, Shingo; Tasaka, Sadatomo

    2017-09-01

    Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation. Switching to alectinib may be beneficial in patients demonstrating crizotinib-associated complex renal cysts with systemic inflammation and exhaustion.

  7. Regression of Crizotinib-Associated Complex Cystic Lesions after Switching to Alectinib

    PubMed Central

    Taima, Kageaki; Tanaka, Hisashi; Tanaka, Yoshihito; Itoga, Masamichi; Takanashi, Shingo; Tasaka, Sadatomo

    2017-01-01

    Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation. Switching to alectinib may be beneficial in patients demonstrating crizotinib-associated complex renal cysts with systemic inflammation and exhaustion. PMID:28794366

  8. An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

    PubMed Central

    Kuang, Ye Min; Gan, Gary C. H.; Burgess, David; Denniss, Alan Robert

    2015-01-01

    Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials. PMID:26495305

  9. Could Notch signaling pathway be a potential therapeutic option in renal diseases?

    PubMed

    Marquez-Exposito, Laura; Cantero-Navarro, Elena; Lavoz, Carolina; Fierro-Fernández, Marta; Poveda, Jonay; Rayego-Mateos, Sandra; Rodrigues-Diez, Raúl R; Morgado-Pascual, José Luis; Orejudo, Macarena; Mezzano, Sergio; Ruiz-Ortega, Marta

    2018-02-10

    Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells. Recent studies suggest an interaction between Notch and NF-κB pathway involved in the regulation of renal inflammatory process. On the other hand, there are some miRNAs that could regulate Notch components and down-stream responses. All these data suggest that Notch blockade could be a novel therapeutic option for renal diseases. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  10. MDCT findings of renal cell carcinoma associated with Xp11.2 translocation and TFE3 gene fusion and papillary renal cell carcinoma.

    PubMed

    Woo, Sungmin; Kim, Sang Youn; Lee, Myoung Seok; Moon, Kyung Chul; Kim, See Hyung; Cho, Jeong Yeon; Kim, Seung Hyup

    2015-03-01

    OBJECTIVE. The purpose of this study was to compare the MDCT features of renal cell carcinoma (RCC) associated with Xp11.2 translocation and TFE3 gene fusion (Xp11 RCC) and papillary RCC. MATERIALS AND METHODS. The study included 19 and 39 patients with histologically proven Xp11 RCC and papillary RCC, respectively, who underwent multiphase renal MDCT before nephrectomy. CT findings were compared between Xp11 RCC and papillary RCC using the Student t test and chi-square test. Subgroup analyses of small (< 4 cm) renal masses for these features were performed. RESULTS. Patients with Xp11 RCC were younger (p < 0.001), and it was more prevalent in women (p = 0.007). Tumor size was greater in Xp11 RCC (p = 0.004) and more common in cystic change (p < 0.001). Calcification and unenhanced high-attenuating areas were more frequent in Xp11 RCC (p = 0.001 and 0.026, respectively). Xp11 RCCs were more prevalent in lymph node and distant metastasis (p < 0.001 and p = 0.031, respectively). Xp11 RCC and papillary RCC showed no significant difference in epicenter, margin, and venous and collecting duct invasion (p = 0.403-1.000). Although Xp11 RCC and papillary RCC had lower attenuation than the renal cortex on corticomedullary and early excretory phases (p < 0.001), only Xp11 RCCs were hyperattenuating to the cortex on the unenhanced phase (p < 0.001). Xp11 RCCs had significantly higher attenuation compared with papillary RCCs on all phases (p ≤ 0.02). Regarding small masses, cystic change, calcification, and lymph node metastasis were still more frequent in Xp11 RCCs (p ≤ 0.016). CONCLUSION. Greater size, more cystic change, calcification, high-attenuating areas on unenhanced imaging, and lymph node and distant metastasis were helpful for differentiating Xp11 RCC from papillary RCC.

  11. Chest Computed Tomographic Image Screening for Cystic Lung Diseases in Patients with Spontaneous Pneumothorax Is Cost Effective

    PubMed Central

    Langenderfer, Dale; McCormack, Francis X.; Schauer, Daniel P.; Eckman, Mark H.

    2017-01-01

    Rationale: Patients without a known history of lung disease presenting with a spontaneous pneumothorax are generally diagnosed as having primary spontaneous pneumothorax. However, occult diffuse cystic lung diseases such as Birt-Hogg-Dubé syndrome (BHD), lymphangioleiomyomatosis (LAM), and pulmonary Langerhans cell histiocytosis (PLCH) can also first present with a spontaneous pneumothorax, and their early identification by high-resolution computed tomographic (HRCT) chest imaging has implications for subsequent management. Objectives: The objective of our study was to evaluate the cost-effectiveness of HRCT chest imaging to facilitate early diagnosis of LAM, BHD, and PLCH. Methods: We constructed a Markov state-transition model to assess the cost-effectiveness of screening HRCT to facilitate early diagnosis of diffuse cystic lung diseases in patients presenting with an apparent primary spontaneous pneumothorax. Baseline data for prevalence of BHD, LAM, and PLCH and rates of recurrent pneumothoraces in each of these diseases were derived from the literature. Costs were extracted from 2014 Medicare data. We compared a strategy of HRCT screening followed by pleurodesis in patients with LAM, BHD, or PLCH versus conventional management with no HRCT screening. Measurements and Main Results: In our base case analysis, screening for the presence of BHD, LAM, or PLCH in patients presenting with a spontaneous pneumothorax was cost effective, with a marginal cost-effectiveness ratio of $1,427 per quality-adjusted life-year gained. Sensitivity analysis showed that screening HRCT remained cost effective for diffuse cystic lung diseases prevalence as low as 0.01%. Conclusions: HRCT image screening for BHD, LAM, and PLCH in patients with apparent primary spontaneous pneumothorax is cost effective. Clinicians should consider performing a screening HRCT in patients presenting with apparent primary spontaneous pneumothorax. PMID:27737563

  12. Salt, hypertension and renal disease: comparative medicine, models and real diseases.

    PubMed Central

    Michell, A. R.

    1994-01-01

    Dogs are well established as experimental animals for the study of both renal disease and hypertension, but most work is based on surgical or pharmacological models and relatively little on spontaneous diseases. This review argues for the latter as an underexploited aspect of comparative medicine. The most important feature of canine hypertension may not be the ease with which models can be produced but the fact that dogs are actually rather resistant to hypertension, and perhaps to its effects, even when they have chronic renal failure. The importance of natural models of chronic renal failure is strengthened by the evidence that self-sustaining progression is a consequence of extreme nephron loss, that is, a late event, rather than the dominant feature of the course of the disease. The role of salt in hypertension is discussed and emphasis given to the importance of understanding the physiological basis of nutritional requirement and recognizing that it is unlikely to exceed 0.6 mmol/kg/day for most healthy adult mammals except during pregnancy or lactation. Such a perspective is essential to the evaluation of experiments, whether in animals or humans, in order to avoid arbitrary definitions of 'high' or 'low' sodium intake, and the serious misinterpretations of data which result. An age-related rise in arterial pressure may well be a warning of excess salt intake, rather than a normal occurrence. Problems of defining hypertension in the face of variability of arterial pressure are also discussed. PMID:7831161

  13. (131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease.

    PubMed

    Ortega, A J M; Vázquez, R G; Cuenca, J I C; Brocca, M A M; Castilla, J; Martínez, J M M; González, E N

    2016-01-01

    Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short-term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. DTC and radioiodine treatment while on haemodialysis. peritoneal dialysis. Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  14. Recent advances in understanding and managing cystic fibrosis transmembrane conductance regulator dysfunction

    PubMed Central

    Alton, Eric W.F.W.

    2015-01-01

    Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians and has been extensively studied for many decades. The cystic fibrosis transmembrane conductance regulator gene was identified in 1989. It encodes a complex protein which has numerous cellular functions. Our understanding of cystic fibrosis pathophysiology and genetics is constantly expanding and being refined, leading to improved management of the disease and increased life expectancy in affected individuals. PMID:26097737

  15. Improved survival with renal transplantation for end-stage renal disease due to granulomatosis with polyangiitis: data from the United States Renal Data System.

    PubMed

    Wallace, Zachary S; Wallwork, Rachel; Zhang, Yuqing; Lu, Na; Cortazar, Frank; Niles, John L; Heher, Eliot; Stone, John H; Choi, Hyon K

    2018-05-14

    Renal transplantation is the optimal treatment for selected patients with end-stage renal disease (ESRD). However, the survival benefit of renal transplantation among patients with ESRD attributed to granulomatosis with polyangiitis (GPA) is unknown. We identified patients from the United States Renal Data System with ESRD due to GPA (ESRD-GPA) between 1995 and 2014. We restricted our analysis to waitlisted subjects to evaluate the impact of transplantation on mortality. We followed patients until death or the end of follow-up. We compared the relative risk (RR) of all-cause and cause-specific mortality in patients who received a transplant versus non-transplanted patients using a pooled logistic regression model with transplantation as a time-varying exposure. During the study period, 1525 patients were waitlisted and 946 received a renal transplant. Receiving a renal transplant was associated with a 70% reduction in the risk of all-cause mortality in multivariable-adjusted analyses (RR=0.30, 95% CI 0.25 to 0.37), largely attributed to a 90% reduction in the risk of death due to cardiovascular disease (CVD) (RR=0.10, 95% 0.06-0.16). Renal transplantation is associated with a significant decrease in all-cause mortality among patients with ESRD attributed to GPA, largely due to a decrease in the risk of death to CVD. Prompt referral for transplantation is critical to optimise outcomes for this patient population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Presentation, pathology and prognosis of renal disease in type 2 diabetes

    PubMed Central

    Tan, Jasmine; Zwi, L Jonathan; Collins, John F; Marshall, Mark R; Cundy, Tim

    2017-01-01

    Objective Non-diabetic renal disease (NDRD) is common in patients with type 2 diabetes (T2D), but the relationship between its presentation and prognosis is unknown. Research design and methods In a retrospective cohort study, we compared renal and patient survival among 263 patients with T2D who had native renal biopsies between 2002 and 2008 from three Auckland hospitals in New Zealand. The presence of diabetic nephropathy (DN), NDRD or mixed (DN and NDRD) was determined from biopsy. We examined clinical associations according to NDRD etiologies and mode of presentation—acute (defined by acute kidney injury (AKI)) or non-acute. Patients were followed until end-stage renal disease, death or December 2015. Survival was compared using Log-rank test. Results 94 (36%) patients had DN, 72 (27%) had NDRD, and 97 (37%) had mixed pathologies. Obesity-related focal segmental glomerulosclerosis was the most common NDRD (46%) in patients with non-acute presentations, whereas interstitial nephritis or immune-complex glomerulonephritides were the most prevalent in those with acute presentations (60%). DN was commonly associated with AKI (p<0.001). The prevalence of DN increased with diabetes duration (p<0.001), but NDRD was still found in 55% of subjects with ≥14 years T2D. NDRD was strongly associated with the absence of retinopathy (p<0.001). Renal survival was best in the NDRD group (p<0.001). Among those with DN, renal prognosis was worse in those with more advanced DN lesions and those with an acute presentation (p<0.001). The proportion of all-cause mortality was similar in all three groups, but overall survival was poorest in the DN group (p=0.025). Conclusions Renal disease in patients with T2D is heterogeneous. The renal prognosis differs markedly according to histopathological diagnosis and mode of presentation. PMID:28878938

  17. Impact of feline AIM on the susceptibility of cats to renal disease

    PubMed Central

    Sugisawa, Ryoichi; Hiramoto, Emiri; Matsuoka, Shigeru; Iwai, Satomi; Takai, Ryosuke; Yamazaki, Tomoko; Mori, Nobuko; Okada, Yuki; Takeda, Naoki; Yamamura, Ken-ichi; Arai, Toshiro; Arai, Satoko; Miyazaki, Toru

    2016-01-01

    Renal failure is one of the most important social problems for its incurability and high costs for patients’ health care. Through clarification of the underlying mechanism for the high susceptibility of cats to renal disease, we here demonstrates that the effective dissociation of serum AIM protein from IgM is necessary for the recovery from acute kidney injury (AKI). In cats, the AIM-IgM binding affinity is 1000-fold higher than that in mice, which is caused by the unique positively-charged amino-acid cluster present in feline AIM. Hence, feline AIM does not dissociate from IgM during AKI, abolishing its translocation into urine. This results in inefficient clearance of lumen-obstructing necrotic cell debris at proximal tubules, thereby impairing AKI recovery. Accordingly, mice whose AIM is replaced by feline AIM exhibit higher mortality by AKI than in wild-type mice. Recombinant AIM administration into the mice improves their renal function and survival. As insufficient recovery from AKI predisposes patients to chronic, end-stage renal disease, feline AIM may be involved crucially in the high mortality of cats due to renal disease. Our findings could be the basis of the development of novel AKI therapies targeting AIM-IgM dissociation, and may support renal function in cats and prolong their lives. PMID:27731392

  18. Impact of feline AIM on the susceptibility of cats to renal disease.

    PubMed

    Sugisawa, Ryoichi; Hiramoto, Emiri; Matsuoka, Shigeru; Iwai, Satomi; Takai, Ryosuke; Yamazaki, Tomoko; Mori, Nobuko; Okada, Yuki; Takeda, Naoki; Yamamura, Ken-Ichi; Arai, Toshiro; Arai, Satoko; Miyazaki, Toru

    2016-10-12

    Renal failure is one of the most important social problems for its incurability and high costs for patients' health care. Through clarification of the underlying mechanism for the high susceptibility of cats to renal disease, we here demonstrates that the effective dissociation of serum AIM protein from IgM is necessary for the recovery from acute kidney injury (AKI). In cats, the AIM-IgM binding affinity is 1000-fold higher than that in mice, which is caused by the unique positively-charged amino-acid cluster present in feline AIM. Hence, feline AIM does not dissociate from IgM during AKI, abolishing its translocation into urine. This results in inefficient clearance of lumen-obstructing necrotic cell debris at proximal tubules, thereby impairing AKI recovery. Accordingly, mice whose AIM is replaced by feline AIM exhibit higher mortality by AKI than in wild-type mice. Recombinant AIM administration into the mice improves their renal function and survival. As insufficient recovery from AKI predisposes patients to chronic, end-stage renal disease, feline AIM may be involved crucially in the high mortality of cats due to renal disease. Our findings could be the basis of the development of novel AKI therapies targeting AIM-IgM dissociation, and may support renal function in cats and prolong their lives.

  19. Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

    PubMed

    Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

    2018-05-22

    Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

  20. Lung transplantation in patients with cystic fibrosis.

    PubMed

    Morton, Judith; Glanville, Allan R

    2009-10-01

    Cystic fibrosis is one of the most common indications for lung transplantation worldwide and certainly the most common indication for all pediatric lung transplants and for bilateral lung transplantation irrespective of age. Outcomes are outstanding when compared with other indications for lung transplantation, and an increasing number of centers now report mean survival of greater than 10 years posttransplant. Hence it is important to concentrate on the broad panoply of potential systemic complications of cystic fibrosis and address proactively issues that may be associated with adverse outcomes. Optimum management of infectious, nutritional, diabetic, renal, bone, and gut complications is critical to long-term success so that recipients may realize their full potential. Timing of referral for consideration of active listing should allow sufficient time for the patient and lung transplant team to develop a productive working relationship based on best available evidence and mutual trust, which will culminate in a long-term successful outcome. Copyright Thieme Medical Publishers.

  1. Outcomes of kidney transplantation in Alport syndrome compared with other forms of renal disease.

    PubMed

    Kelly, Yvelynne P; Patil, Anish; Wallis, Luke; Murray, Susan; Kant, Saumitra; Kaballo, Mohammed A; Casserly, Liam; Doyle, Brendan; Dorman, Anthony; O'Kelly, Patrick; Conlon, Peter J

    2017-11-01

    Alport syndrome is an inherited renal disease characterized by hematuria, renal failure, hearing loss and a lamellated glomerular basement membrane. Patients with Alport syndrome who undergo renal transplantation have been shown to have patient and graft survival rates similar to or better than those of patients with other renal diseases. In this national case series, based in Beaumont Hospital Dublin, we studied the cohort of patients who underwent renal transplantation over the past 33 years, recorded prospectively in the Irish Renal Transplant Registry, and categorized them according to the presence or absence of Alport syndrome. The main outcomes assessed were patient and renal allograft survival. Fifty-one patients diagnosed with Alport syndrome in Beaumont Hospital received 62 transplants between 1982 and 2014. The comparison group of non-Alport patients comprised 3430 patients for 3865 transplants. Twenty-year Alport patient survival rate was 70.2%, compared to 44.8% for patients with other renal diseases (p = .01). Factors associated with patient survival included younger age at transplantation as well as differences in recipient sex, donor age, cold ischemia time, and episodes of acute rejection. Twenty-year graft survival was 46.8% for patients with Alport syndrome compared to 30.2% for those with non-Alport disease (p = .11). Adjusting for baseline differences between the groups, patients with end-stage kidney disease (ESKD) due to Alport syndrome have similar patient and graft survival to those with other causes of ESKD. This indicates that early diagnosis and management can lead to favorable outcomes for this patient cohort.

  2. The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

    PubMed Central

    Maltese, Giuseppe; Karalliedde, Janaka

    2012-01-01

    Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s). Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease. PMID:22121479

  3. Renal disease in cats infected with feline immunodeficiency virus.

    PubMed

    Baxter, K J; Levy, J K; Edinboro, C H; Vaden, S L; Tompkins, M B

    2012-01-01

    Feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) infection cause similar clinical syndromes of immune dysregulation, opportunistic infections, inflammatory diseases, and neoplasia. Renal disease is the 4th most common cause of death associated with HIV infection. To investigate the association between FIV infection and renal disease in cats. Client-owned cats (153 FIV-infected, 306 FIV-noninfected) and specific-pathogen-free (SPF) research colony cats (95 FIV-infected, 98 FIV-noninfected). A mixed retrospective/prospective cross-sectional study. Blood urea nitrogen (BUN), serum creatinine, urine specific gravity (USG), and urine protein:creatinine ratio (UPC) data were compared between FIV-infected and FIV-noninfected cats. In FIV-infected cats, total CD4+ and CD8+ T lymphocytes were measured using flow cytometry, and CD4+:CD8+ T lymphocyte ratio was calculated. Renal azotemia was defined as a serum creatinine ≥ 1.9 mg/dL with USG ≤ 1.035. Proteinuria was defined as a UPC > 0.4 with an inactive urine sediment. Among the client-owned cats, no association was detected between FIV infection and renal azotemia (P = .24); however, a greater proportion of FIV-infected cats were proteinuric (25.0%, 16 of 64 cats) compared to FIV-noninfected cats (10.3%, 20 of 195 cats) (P < .01). Neither neuter status nor health status were risk factors for proteinuria in FIV-infected cats, but UPC was positively correlated with the CD4+:CD8+ T lymphocyte ratio (Spearman's rho = 0.37, P = .01). Among the SPF research colony cats, no association was detected between FIV infection and renal azotemia (P = .21) or proteinuria (P = .25). Proteinuria but not azotemia was associated with natural FIV infection. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  4. Elevated plasma TGF-beta1 in renal diseases: cause or consequence?

    PubMed

    Junker, U; Haufe, C C; Nuske, K; Rebstock, K; Steiner, T; Wunderlich, H; Junker, K; Reinhold, D

    2000-07-01

    We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer. Copyright 2000 Academic Press.

  5. A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis

    ClinicalTrials.gov

    2017-10-12

    Lung Diseases; Pulmonary Disease; Cystic Fibrosis; Cystic Fibrosis Lung; Cystic Fibrosis Pulmonary Exacerbation; Cystic Fibrosis With Exacerbation; Respiratory Tract Disease; Pulmonary Inflammation; Multi-antibiotic Resistance; Antibiotic Resistant Infection; Lung Infection; Lung Infection Pseudomonal; Lung; Infection, Atypical Mycobacterium; Burkholderia Infections; Burkholderia Cepacia Infection; Lung Inflammation

  6. Nutritional state and lung disease in cystic fibrosis.

    PubMed

    Bakker, W

    1992-10-01

    The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

  7. [Insights into cystic fibrosis-related bone disease].

    PubMed

    Braun, C; Bacchetta, J; Reix, P

    2016-08-01

    With the increasing life expectancy of patients with cystic fibrosis (CF), prevalence of late complications such as CF-related bone disease (CFBD) has increased. It was initially described in 24% of the adult population with CF and has also been reported in the pediatric population. CFBD is multifactorial and progresses in different steps. Both decreased bone formation and increased bone resorption (in different amounts) are observed. CFBD is likely primitive (directly related to the CFTR defect itself), but is also worsened by acquired secondary factors such as lung infections, chronic inflammation, denutrition, vitamin deficiency, and decreased physical activity. CFBD may be clinically apparent (i.e., mainly vertebral and costal fractures), or clinically asymptomatic (therefore corresponding to abnormalities in bone density and architecture). CFBD management mainly aims to prevent the occurrence of fractures. Prevention and regular monitoring of bone disease as early as 8 years of age is of the utmost importance, as is the control of possible secondary deleterious CFBD factors. New radiological tools, such as high-resolution peripheral quantitative computed tomography, allow an accurate evaluation of cortical and trabecular bone micro-architecture in addition to compartmental density; as such, they will likely improve the assessment of the bone fracture threat in CF patients in the near future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Special procedures for approving end stage renal disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease...

  9. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Special procedures for approving end stage renal disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease...

  10. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Special procedures for approving end stage renal disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease...

  11. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Special procedures for approving end stage renal disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease...

  12. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Special procedures for approving end stage renal disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease...

  13. Medicare Program; End-Stage Renal Disease Prospective Payment System, Payment for Renal Dialysis Services Furnished to Individuals With Acute Kidney Injury, and End-Stage Renal Disease Quality Incentive Program. Final rule.

    PubMed

    2017-11-01

    This rule updates and makes revisions to the end-stage renal disease (ESRD) prospective payment system (PPS) for calendar year (CY) 2018. It also updates the payment rate for renal dialysis services furnished by an ESRD facility to individuals with acute kidney injury (AKI). This rule also sets forth requirements for the ESRD Quality Incentive Program (QIP), including for payment years (PYs) 2019 through 2021.

  14. Personalized Medicine: New Perspectives for the Diagnosis and the Treatment of Renal Diseases.

    PubMed

    Gluba-Brzózka, Anna; Franczyk, Beata; Olszewski, Robert; Banach, Maciej; Rysz, Jacek

    2017-06-10

    The prevalence of renal diseases is rising and reaching 5-15% of the adult population. Renal damage is associated with disturbances of body homeostasis and the loss of equilibrium between exogenous and endogenous elements including drugs and metabolites. Studies indicate that renal diseases are influenced not only by environmental but also by genetic factors. In some cases the disease is caused by mutation in a single gene and at that time severity depends on the presence of one or two mutated alleles. In other cases, renal disease is associated with the presence of alteration within a gene or genes, but environmental factors are also necessary for the development of disease. Therefore, it seems that the analysis of genetic aspects should be a natural component of clinical and experimental studies. The goal of personalized medicine is to determine the right drug, for the right patient, at the right time. Whole-genome examinations may help to change the approach to the disease and the patient resulting in the creation of "personalized medicine" with new diagnostic and treatment strategies designed on the basis of genetic background of each individual. The identification of high-risk patients in pharmacogenomics analyses will help to avoid many unwarranted side effects while optimizing treatment efficacy for individual patients. Personalized therapies for kidney diseases are still at the preliminary stage mainly due to high costs of such analyses and the complex nature of human genome. This review will focus on several areas of interest: renal disease pathogenesis, diagnosis, treatment, rate of progression and the prediction of prognosis.

  15. Cystic fibrosis-related diabetes: a distinct condition.

    PubMed

    Cano Megías, Marta; González Albarrán, Olga

    2015-01-01

    Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  16. Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease.

    PubMed

    Hein, G J; Panzani, C G; Rodríguez, F M; Salvetti, N R; Díaz, P U; Gareis, N C; Benítez, G A; Ortega, H H; Rey, F

    2015-05-01

    Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. Follicular cell steroidogenesis and proliferation in ovulatory follicles is stimulated by hormones such as insulin and its necessary post-receptor response. The aim of this study was to determine the expression of insulin receptor (IR), IR substrate-1 (IRS1) and phosphatidylinositol 3-kinase (PI3K), key intermediates in the insulin pathway, in control cows and cows with spontaneous COD and ACTH-induced COD. IR and IRS1 mRNA levels were greater in granulosa cells and lower in follicular cysts than in control tertiary follicles. PI3K mRNA levels were similar in all follicles evaluated, whereas the expression of IR, IRS1 and PI3K was similar in theca cells. Protein expression of IR was higher in control tertiary follicles than in the same structures in animals with COD and with cysts. IRS1 and PI3K protein expression showed the same pattern in tertiary and cystic follicles. However, the protein expression of subunit alpha p85 of PI3K was greater in theca cells from tertiary follicles than in cystic follicles. These results provide new insights into the insulin response in cows with COD. The lower gene and protein expressions of some insulin downstream effectors at an early stage of the signaling pathway could negatively influence the functionality of ovaries and contribute to follicle persistence. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Ramadan fasting and patients with renal diseases: A mini review of the literature

    PubMed Central

    Emami-Naini, Afsoon; Roomizadeh, Peyman; Baradaran, Azar; Abedini, Amin; Abtahi, Mohammad

    2013-01-01

    Fasting during the month of Ramadan is one of the five pillars of Islam. During this month, adult Muslims are obligated to refrain from eating and drinking from dawn to dusk. Although based on Islamic principles patients are exempted from fasting, each year, many Muslim patients express their willingness to observe the fast in Ramadan month to respect the cultural customs. There are concerns about the impact of fluid restriction and dehydration during Ramadan fasting for patients with renal diseases. In this study, we reviewed the PubMed, Google Scholar, EBSCO, SCIRUS, Embase, and DOAJ data sources to identify the published studies on the impact of Ramadan fasting on patients with renal diseases. Our review on published reports on renal transplant recipients revealed no injurious effect of Ramadan fasting for the renal graft function. Nearly all studies on this topic suggest that Ramadan fasting is safe when the function of the renal graft is acceptable and stable. Regarding the impact of Ramadan fasting on patients with chronic kidney disease, there is concern about the role of renal hypoperfusion in developing tubular cell injury. Finally, there is controversy between studies about the risk of dehydration in Ramadan in developing renal stones. There are uncertainties about the change in the incidence of renal colic in Ramadan month compared with the other periods of the year. Despite such discrepancies, nearly all studies are in agreement on consuming adequate amounts of water from dusk to dawn to reduce the risk of renal stone formation. PMID:24379850

  18. Ramadan fasting and patients with renal diseases: A mini review of the literature.

    PubMed

    Emami-Naini, Afsoon; Roomizadeh, Peyman; Baradaran, Azar; Abedini, Amin; Abtahi, Mohammad

    2013-08-01

    Fasting during the month of Ramadan is one of the five pillars of Islam. During this month, adult Muslims are obligated to refrain from eating and drinking from dawn to dusk. Although based on Islamic principles patients are exempted from fasting, each year, many Muslim patients express their willingness to observe the fast in Ramadan month to respect the cultural customs. There are concerns about the impact of fluid restriction and dehydration during Ramadan fasting for patients with renal diseases. In this study, we reviewed the PubMed, Google Scholar, EBSCO, SCIRUS, Embase, and DOAJ data sources to identify the published studies on the impact of Ramadan fasting on patients with renal diseases. Our review on published reports on renal transplant recipients revealed no injurious effect of Ramadan fasting for the renal graft function. Nearly all studies on this topic suggest that Ramadan fasting is safe when the function of the renal graft is acceptable and stable. Regarding the impact of Ramadan fasting on patients with chronic kidney disease, there is concern about the role of renal hypoperfusion in developing tubular cell injury. Finally, there is controversy between studies about the risk of dehydration in Ramadan in developing renal stones. There are uncertainties about the change in the incidence of renal colic in Ramadan month compared with the other periods of the year. Despite such discrepancies, nearly all studies are in agreement on consuming adequate amounts of water from dusk to dawn to reduce the risk of renal stone formation.

  19. Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients.

    PubMed

    Chen, Xiao; Zhu, Qingqiang; Li, Baoxin; Cui, Wenjing; Zhou, Hao; Duan, Na; Liu, Yongkang; Kundra, Vikas; Wang, Zhongqiu

    2017-02-01

    To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. • Xp11.2/TFE RCC was more prevalent in young women. • On unenhanced CT, Xp11.2/TFE RCC attenuation was greater than in renal parenchyma. • Xp111/2TFE RCC arises primarily from the renal medulla. • Xp11.2/TFE RCC enhancement was less than in the cortex on all phases. • Enhancement was greater than in the medulla in arterial and corticomedullary phase.

  20. Caring for Children with Cystic Fibrosis: A Collaborative Clinical and School Approach

    ERIC Educational Resources Information Center

    Strawhacker, MaryAnn Tapper; Wellendorf, Joyce

    2004-01-01

    Earlier diagnosis and more effective treatments have improved both morbidity and mortality associated with cystic fibrosis, making regular school attendance a reality. School nurses have a unique opportunity to assist students with cystic fibrosis successfully manage their disease. Medical treatment for cystic fibrosis can be complex, leaving…

  1. ABCG8 polymorphisms and renal disease in type 2 diabetic patients.

    PubMed

    Nicolas, Anthony; Fatima, Sehrish; Lamri, Amel; Bellili-Muñoz, Naima; Halimi, Jean-Michel; Saulnier, Pierre-Jean; Hadjadj, Samy; Velho, Gilberto; Marre, Michel; Roussel, Ronan; Fumeron, Frédéric

    2015-06-01

    Sterols, bile acids and their receptors have been involved in diabetic nephropathy. The ATP-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) play an important role in intestinal sterol absorption and bile acid secretion. The aim of our study was to assess the associations between two ABCG8 coding polymorphisms, T400K and D19H, and the incidence of renal events in type 2 diabetic subjects. Participants were the 3137 French type 2 diabetic subjects with micro- or macro-albuminuria from the genetic substudy of the DIABHYCAR trial. The mean duration of follow-up was 4years. Renal events were defined as a doubling of serum creatinine concentration or end-stage renal disease at follow-up. We then used a second population (DIAB2NEPHROGENE) of 2140 type 2 diabetic patients for the purpose of validation. In DIABHYCAR, the 400K allele was significantly associated with a higher risk of incident renal events in a multiple adjusted model (HR: 1.75 [95% CI 1.20-2.56], P=0.003). This association was still significant after further adjustments for baseline values of estimated glomerular filtration rate and urinary albumin excretion. In the validation population, the 400K allele was associated with the prevalence of end-stage renal disease (OR=2.01 [95% CI 1.15-3.54], P=0.015). No significant association was found between the D19H polymorphism and the risk of diabetic nephropathy. A polymorphism of the sterol transporter ABCG8 has been associated with the prevalence of end-stage renal disease and with the incidence of new renal events in type 2 diabetic patients. Copyright © 2015. Published by Elsevier Inc.

  2. Whole exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies

    PubMed Central

    Gee, Heon Yung; Otto, Edgar A.; Hurd, Toby W.; Ashraf, Shazia; Chaki, Moumita; Cluckey, Andrew; Vega-Warner, Virginia; Saisawat, Pawaree; Diaz, Katrina A.; Fang, Humphrey; Kohl, Stefan; Allen, Susan J.; Airik, Rannar; Zhou, Weibin; Ramaswami, Gokul; Janssen, Sabine; Fu, Clementine; Innis, Jamie L.; Weber, Stefanie; Vester, Udo; Davis, Erica E.; Katsanis, Nicholas; Fathy, Hanan M.; Jeck, Nikola; Klaus, Gunther; Nayir, Ahmet; Rahim, Khawla A.; Attrach, Ibrahim Al; Hassoun, Ibrahim Al; Ozturk, Savas; Drozdz, Dorota; Helmchen, Udo; O’Toole, John F.; Attanasio, Massimo; Nürnberg, Gudrun; Nürnberg, Peter; Washburn, Joseph; MacDonald, James; James, Jeffrey W.; Levy, Shawn; Hildebrandt, Friedhelm

    2013-01-01

    Rare single-gene disorders cause chronic disease. However, half of the 6,000 recessive single gene causes of disease are still unknown. Because recessive disease genes can illuminate, at least in part, disease pathomechanism, their identification offers direct opportunities for improved clinical management and potentially treatment. Rare diseases comprise the majority of chronic kidney disease (CKD) in children but are notoriously difficult to diagnose. Whole exome resequencing facilitates identification of recessive disease genes. However, its utility is impeded by the large number of genetic variants detected. We here overcome this limitation by combining homozygosity mapping with whole exome resequencing in 10 sib pairs with a nephronophthisis-related ciliopathy, which represents the most frequent genetic cause of CKD in the first three decades of life. In 7 of 10 sib-ships with a histologic or ultrasonographic diagnosis of nephronophthisis-related ciliopathy we detect the causative gene. In six sib-ships we identify mutations of known nephronophthisis-related ciliopathy genes, while in two additional sib-ships we found mutations in the known CKD-causing genes SLC4A1 and AGXT as phenocopies of nephronophthisis-related ciliopathy. Thus whole exome resequencing establishes an efficient, non-invasive approach towards early detection and causation-based diagnosis of rare kidney diseases. This approach can be extended to other rare recessive disorders, thereby providing accurate diagnosis and facilitating the study of disease mechanisms. PMID:24257694

  3. Whole-exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies.

    PubMed

    Gee, Heon Yung; Otto, Edgar A; Hurd, Toby W; Ashraf, Shazia; Chaki, Moumita; Cluckey, Andrew; Vega-Warner, Virginia; Saisawat, Pawaree; Diaz, Katrina A; Fang, Humphrey; Kohl, Stefan; Allen, Susan J; Airik, Rannar; Zhou, Weibin; Ramaswami, Gokul; Janssen, Sabine; Fu, Clementine; Innis, Jamie L; Weber, Stefanie; Vester, Udo; Davis, Erica E; Katsanis, Nicholas; Fathy, Hanan M; Jeck, Nikola; Klaus, Gunther; Nayir, Ahmet; Rahim, Khawla A; Al Attrach, Ibrahim; Al Hassoun, Ibrahim; Ozturk, Savas; Drozdz, Dorota; Helmchen, Udo; O'Toole, John F; Attanasio, Massimo; Lewis, Richard A; Nürnberg, Gudrun; Nürnberg, Peter; Washburn, Joseph; MacDonald, James; Innis, Jeffrey W; Levy, Shawn; Hildebrandt, Friedhelm

    2014-04-01

    Rare single-gene disorders cause chronic disease. However, half of the 6000 recessive single gene causes of disease are still unknown. Because recessive disease genes can illuminate, at least in part, disease pathomechanism, their identification offers direct opportunities for improved clinical management and potentially treatment. Rare diseases comprise the majority of chronic kidney disease (CKD) in children but are notoriously difficult to diagnose. Whole-exome resequencing facilitates identification of recessive disease genes. However, its utility is impeded by the large number of genetic variants detected. We here overcome this limitation by combining homozygosity mapping with whole-exome resequencing in 10 sib pairs with a nephronophthisis-related ciliopathy, which represents the most frequent genetic cause of CKD in the first three decades of life. In 7 of 10 sibships with a histologic or ultrasonographic diagnosis of nephronophthisis-related ciliopathy, we detect the causative gene. In six sibships, we identify mutations of known nephronophthisis-related ciliopathy genes, while in two additional sibships we found mutations in the known CKD-causing genes SLC4A1 and AGXT as phenocopies of nephronophthisis-related ciliopathy. Thus, whole-exome resequencing establishes an efficient, noninvasive approach towards early detection and causation-based diagnosis of rare kidney diseases. This approach can be extended to other rare recessive disorders, thereby providing accurate diagnosis and facilitating the study of disease mechanisms.

  4. [Epidemiology and systematics of cystic and alveolar hydatid disease].

    PubMed

    Gottstein, B

    2000-01-01

    Echinococcus multilocularis, a small tapeworm in foxes, has gained considerable public attention owing to its wide distribution in central Europe. Conversely, diagnosis and treatment of the disease have been significantly improved in recent years. Consequently, the incidence among human populations has remained stable and relatively low for many decades. In southern Germany, France (Franche Comté and Doubs), Austria and Switzerland, the annual incidence ranges between 0.02 and 1.4 new cases per 100,000 inhabitants. The relevance of human AE refers to the high lethality of the untreated disease. Therapy consists predominantly of radical surgery followed by continuous, long-term chemotherapy using albendazole (or mebendazole). The action of chemotherapy alone is parasitostatic rather than parasitocidal; nevertheless, clinical improvement is observed in > 80 % of such cases, including a significantly improved prognosis. Diagnosis relies predominantly on imaging procedures and serology. Immunodiagnosis must be performed early, especially when a preclinical diagnosis is desired upon exposure to infection. Thus, in the framework of seroepidemiological studies, first-time evidence was obtained about the phenomenon of natural resistance in non-diseased persons. This raised the question of a potential immunogenetic predisposition in certain infected persons. E. granulosus (cystic hydatid disease) is practically non-existent as autochthonous infection in central Europe now. Most clinical cases of E. granulosus infections are thus observed among persons who have immigrated from - predominantly - the mediterranean basin.

  5. Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

    PubMed

    Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

    2017-09-25

    von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

  6. Deaths from occlusive arterial disease in renal allograft recipients.

    PubMed

    Ibels, L S; Stewart, J H; Mahony, J F; Sheil, A G

    1974-08-31

    In a series of 325 recipients of cadaveric renal transplants sudden occlusive arterial disease was found to be responsible for 12% of deaths. Acute myocardial infarction (9%) occurred 25 times more than expected in the normal population and cerebral thrombosis (3%) 300 times more. The greatest loss was in the initial three-month period after transplantation. Patients with renal failure due to essential hypertension were especially at risk, accounting for six of the 12 deaths.

  7. Zinc restriction during different periods of life: influence in renal and cardiovascular diseases.

    PubMed

    Tomat, Analía Lorena; Costa, María de los Ángeles; Arranz, Cristina Teresa

    2011-04-01

    Micronutrient undernutrition during critical periods of growth has become an important health issue in developing and developed countries, particularly among pregnant women and children having an imbalanced diet. Zinc is a widely studied microelement in infant feeding because it is a component of several enzymes involved in intermediary metabolism ranging from growth to cell differentiation and metabolism of proteins, carbohydrates, and lipids. Human and experimental studies have reported an association between zinc deficiency and the etiopathogenesis of cardiovascular and renal diseases like hypertension, atherosclerosis, congestive heart failure, coronary heart disease, and diabetes. The main links between the development of these pathologies and zinc deficiency are multiple mechanisms involving oxidative stress damage, apoptosis, and inflammation. A substantial body of evidence suggests that a poor in utero environment elicited by maternal dietary or placental insufficiency may "programme" susceptibility in the fetus to later development of cardiovascular, renal, metabolic, and endocrine diseases. Zinc deficiency in rats during intrauterine and postnatal growth can also be considered a model of fetal programming of cardiovascular and renal diseases in adult life. Dietary zinc restriction during fetal life, lactation, and/or postweaning induces an increase in arterial blood pressure and impairs renal function in adult life. This review focuses on the contributions of experimental and clinical studies to current knowledge of the physiologic role of zinc in the cardiovascular and renal systems. Moreover, this review examines the relationship between zinc deficiency during different periods of life and the development of cardiovascular and renal diseases in adult life. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Heritability of Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

    2007-01-01

    Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

  9. Cystic fibrosis - resources

    MedlinePlus

    Resources - cystic fibrosis ... The following organizations are good resources for information on cystic fibrosis : Cystic Fibrosis Foundation -- www.cff.org March of Dimes -- www.marchofdimes.org/baby/cystic-fibrosis-and- ...

  10. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease.

    PubMed

    Collins, Allan J; Foley, Robert N; Gilbertson, David T; Chen, Shu-Cheng

    2015-06-01

    The United States Renal Data System (USRDS) began in 1989 through US Congressional authorization under National Institutes of Health competitive contracting. Its history includes five contract periods, two of 5 years, two of 7.5 years, and the fifth, awarded in February 2014, of 5 years. Over these 25 years, USRDS reporting transitioned from basic incidence and prevalence of end-stage renal disease (ESRD), modalities, and overall survival, as well as focused special studies on dialysis, in the first two contract periods to a comprehensive assessment of aspects of care that affect morbidity and mortality in the second two periods. Beginning in 1999, the Minneapolis Medical Research Foundation investigative team transformed the USRDS into a total care reporting system including disease severity, hospitalizations, pediatric populations, prescription drug use, and chronic kidney disease and the transition to ESRD. Areas of focus included issues related to death rates in the first 4 months of treatment, sudden cardiac death, ischemic and valvular heart disease, congestive heart failure, atrial fibrillation, and infectious complications (particularly related to dialysis catheters) in hemodialysis and peritoneal dialysis patients; the burden of congestive heart failure and infectious complications in pediatric dialysis and transplant populations; and morbidity and access to care. The team documented a plateau and decline in incidence rates, a 28% decline in death rates since 2001, and changes under the 2011 Prospective Payment System with expanded bundled payments for each dialysis treatment. The team reported on Bayesian methods to calculate mortality ratios, which reduce the challenges of traditional methods, and introduced objectives under the Health People 2010 and 2020 national health care goals for kidney disease.

  11. Scleroderma renal crisis in a case of mixed connective tissue disease.

    PubMed

    Vij, Mukul; Agrawal, Vinita; Jain, Manoj

    2014-07-01

    Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

  12. Antimicrobial resistance in the respiratory microbiota of people with cystic fibrosis.

    PubMed

    Sherrard, Laura J; Tunney, Michael M; Elborn, J Stuart

    2014-08-23

    Cystic fibrosis is characterised by chronic polymicrobial infection and inflammation in the airways of patients. Antibiotic treatment regimens, targeting recognised pathogens, have substantially contributed to increased life expectancy of patients with this disease. Although the emergence of antimicrobial resistance and selection of highly antibiotic-resistant bacterial strains is of major concern, the clinical relevance in cystic fibrosis is yet to be defined. Resistance has been identified in recognised cystic fibrosis pathogens and in other bacteria (eg, Prevotella and Streptococcus spp) detected in the airway microbiota, but their role in the pathophysiology of infection and inflammation in chronic lung disease is unclear. Increased antibiotic resistance in cystic fibrosis might be attributed to a range of complex factors including horizontal gene transfer, hypoxia, and biofilm formation. Strategies to manage antimicrobial resistance consist of new antibiotics or localised delivery of antimicrobial agents, iron sequestration, inhibition of quorum-sensing, and resistome analysis. Determination of the contributions of every bacterial species to lung health or disease in cystic fibrosis might also have an important role in the management of antibiotic resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease

    PubMed Central

    2012-01-01

    Background Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome. Methods RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson’s correlation, Mann–Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis. Results Most patients had glomerulonephritis (82%). Median age was 46 years [21–87], eGFR 59 mL/min/ 1.73m2 [5–130], percentage of interstitial fibrosis 10% [0–90], glomerulosclerosis 13% [0–96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = −0.275, p = 0.038) and renal dysfunction (r = −0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic

  14. Association between renal iron accumulation and renal interstitial fibrosis in a rat model of chronic kidney disease.

    PubMed

    Naito, Yoshiro; Fujii, Aya; Sawada, Hisashi; Oboshi, Makiko; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Hirotani, Shinichi; Masuyama, Tohru

    2015-07-01

    Iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD). Renal fibrosis is a final common feature that contributes to the progression of CKD; however, little is known about the association between renal iron accumulation and renal interstitial fibrosis in CKD. Here we investigate the effects of iron chelation on renal interstitial fibrosis in a rat model of CKD. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. At 8 weeks after operation, 5/6 nephrectomized rats were administered an oral iron chelator, deferasirox (DFX), in chow for 8 weeks. Other CKD rats were given a normal diet. Sham-operative rats given a normal diet served as a control. CKD rats exhibited hypertension, glomerulosclerosis and renal interstitial fibrosis. Iron chelation with DFX did not change hypertension and glomerulosclerosis; however, renal interstitial fibrosis was attenuated in CKD rats. Consistent with these findings, renal gene expression of collagen type III and transforming growth factor-β was increased in CKD rats compared with the controls, while iron chelation suppressed these increments. In addition, a decrease in vimentin along an increase in E-cadherin in renal gene expression was observed in CKD rats with iron chelation. CKD rats also showed increased CD68-positive cells in the kidney, whereas its increase was attenuated by iron deprivation. Similarly, increased renal gene expression of CD68, tumor necrosis factor-α and monocyte chemoattractant protein-1 was suppressed in CKD rats with iron chelation. Renal iron accumulation seems to be associated with renal interstitial fibrosis in a rat model of CKD.

  15. [Cystic echinococcosis mimicking tuberculosis in childhood].

    PubMed

    Pekcan, Sevgi; Kiper, Nural; Köse, Mehmet; Cobanoğlu, Nazan; Yalçın, Ebru; Doğru, Deniz; Ozçelik, Uğur

    2011-01-01

    Both cystic echinococcosis (CE) and tuberculosis (Tbc) are important health problems in developing countries. Pulmonary CE and Tbc have to be differentiated from other diseases as they have increased the risk of morbidity and mortality. Besides, these two diseases can mimic each other. Here, we discuss a 7 year-old patient admitted with fever, cough who was unresponsive to nonspecific antibiotic treatment given for pneumonia, had Tbc treatment due to a positive tuberculin skin test and radiologic appearance consistent with Tbc and on follow-up. He was eventually diagnosed as CE based on a cystic lesion consistent with CE in the liver and echinococcosis specific IgE positivity and was succesfully treated with anti-parasitic therapy.

  16. Preimplantation genetic diagnosis for cystic fibrosis: a case report.

    PubMed

    Biazotti, Maria Cristina Santoro; Pinto Junior, Walter; Albuquerque, Maria Cecília Romano Maciel de; Fujihara, Litsuko Shimabukuro; Suganuma, Cláudia Haru; Reigota, Renata Bednar; Bertuzzo, Carmen Sílvia

    2015-01-01

    Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This disorder produces a variable phenotype including lung disease, pancreatic insufficiency, and meconium ileus plus bilateral agenesis of the vas deferens causing obstructive azoospermia and male infertility. Preimplantation genetic diagnosis is an alternative that allows identification of embryos affected by this or other genetic diseases. We report a case of couple with cystic fibrosis; the woman had the I148 T mutation and the man had the Delta F508 gene mutation. The couple underwent in vitro fertilization, associated with preimplantation genetic diagnosis, and with subsequent selection of healthy embryos for uterine transfer. The result was an uneventful pregnancy and delivery of a healthy male baby.

  17. Preimplantation genetic diagnosis for cystic fibrosis: a case report

    PubMed Central

    Biazotti, Maria Cristina Santoro; Pinto, Walter; de Albuquerque, Maria Cecília Romano Maciel; Fujihara, Litsuko Shimabukuro; Suganuma, Cláudia Haru; Reigota, Renata Bednar; Bertuzzo, Carmen Sílvia

    2015-01-01

    Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This disorder produces a variable phenotype including lung disease, pancreatic insufficiency, and meconium ileus plus bilateral agenesis of the vas deferens causing obstructive azoospermia and male infertility. Preimplantation genetic diagnosis is an alternative that allows identification of embryos affected by this or other genetic diseases. We report a case of couple with cystic fibrosis; the woman had the I148 T mutation and the man had the Delta F508 gene mutation. The couple underwent in vitro fertilization, associated with preimplantation genetic diagnosis, and with subsequent selection of healthy embryos for uterine transfer. The result was an uneventful pregnancy and delivery of a healthy male baby. PMID:25993078

  18. Endovascular treatment of cerebral aneurysm after renal transplantation in polycystic kidney disease.

    PubMed

    Demartini, Zeferino; Galdino, Jennyfer; Koppe, Gelson L; Bignelli, Alexandre T; Francisco, Alexandre N; Gatto, Luana Am

    2018-06-01

    Background Patients with polycystic kidney disease have a higher prevalence of intracranial aneurysms and may progress to renal failure requiring transplantation. The endovascular treatment of intracranial aneurysms may improve prognosis, since rupture often causes premature death or disability, but the nephrotoxicity risk associated with contrast medium must be always considered in cases of renal impairment. Methods A 55-year-old female patient with polycystic kidney disease and grafted kidney associated with anterior communicant artery aneurysm was successfully treated by embolization. Results The renal function remained normal after the procedure. To the authors' knowledge, this is the first case of endovascular treatment of brain aneurysm in a transplanted patient reported in the medical literature. Conclusions The endovascular procedure in renal transplant patients is feasible and can be considered to treat this population. Further studies and cases are needed to confirm its safety.

  19. The European Cystic Fibrosis Society Patient Registry: valuable lessons learned on how to sustain a disease registry.

    PubMed

    Viviani, Laura; Zolin, Anna; Mehta, Anil; Olesen, Hanne Vebert

    2014-06-07

    Disease registries have the invaluable potential to provide an insight into the natural history of the disease under investigation, to provide useful information (e.g. through health indicators) for planning health care services and to identify suitable groups of patients for clinical trials enrolment. However, the establishment and maintenance of disease registries is a burdensome initiative from economical and organisational points of view and experience sharing on registries management is important to avoid waste of resources. The aim of this paper is to discuss the problems embedded in the institution and management of an international disease registry to warn against common mistakes that can derail the best of intentions: we share the experience of the European Cystic Fibrosis Society Patient Registry, which collects data on almost 30,000 patients from 23 countries. We discuss the major problems that researchers often encounter in the creation and management of disease registries: definition of the aims the registry has to reach, definition of the criteria for patients referral to the registry, definition of the information to record, set up of a data quality process, handling of missing data, maintenance of data confidentiality, regulation of data use and dissemination of research results. We give examples on how many crucial aspects were solved by the European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion criteria and variables definition, data management, data quality controls, missing data handling, confidentiality maintenance, data use and results dissemination. We suggest an extensive literature research and discussions in working groups with different stake holders, including patient representatives, on the objectives, inclusion criteria and the information to record. We propose to pilot the recording of few variables and test the applicability of their definition first. The use of a shared electronic platform for data

  20. The European Cystic Fibrosis Society Patient Registry: valuable lessons learned on how to sustain a disease registry

    PubMed Central

    2014-01-01

    Background Disease registries have the invaluable potential to provide an insight into the natural history of the disease under investigation, to provide useful information (e.g. through health indicators) for planning health care services and to identify suitable groups of patients for clinical trials enrolment. However, the establishment and maintenance of disease registries is a burdensome initiative from economical and organisational points of view and experience sharing on registries management is important to avoid waste of resources. The aim of this paper is to discuss the problems embedded in the institution and management of an international disease registry to warn against common mistakes that can derail the best of intentions: we share the experience of the European Cystic Fibrosis Society Patient Registry, which collects data on almost 30,000 patients from 23 countries. Methods We discuss the major problems that researchers often encounter in the creation and management of disease registries: definition of the aims the registry has to reach, definition of the criteria for patients referral to the registry, definition of the information to record, set up of a data quality process, handling of missing data, maintenance of data confidentiality, regulation of data use and dissemination of research results. Results We give examples on how many crucial aspects were solved by the European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion criteria and variables definition, data management, data quality controls, missing data handling, confidentiality maintenance, data use and results dissemination. Conclusions We suggest an extensive literature research and discussions in working groups with different stake holders, including patient representatives, on the objectives, inclusion criteria and the information to record. We propose to pilot the recording of few variables and test the applicability of their definition first. The use of a

  1. What is the importance of classifying Aspergillus disease in cystic fibrosis patients?

    PubMed

    Jones, Andrew M; Horsley, Alex; Denning, David W

    2014-08-01

    Aspergillus species are commonly isolated from lower respiratory tract samples of patients with cystic fibrosis (CF) and markers of immunological sensation to Aspergillus are frequently encountered in this group of patients; however, the contribution of Aspergillus to CF lung disease outside of the typical complications of ABPA and aspergilloma formation remains largely unclear. Patients with CF show discretely different responses to Aspergillus, though the underlying reasons for this variation are unknown. Recent work has begun to allow us to categorize patient responses to Aspergillus based upon molecular markers of infection and immune sensitization. Aspergillus sensitization and/or airway infection is associated with worse FEV1, in CF and other patients (asthma, chronic obstructive pulmonary disease, bronchiectasis). Classification of different clinical phenotypes of Aspergillus will enable future studies to determine the natural history of different manifestations of Aspergillus disease and evaluate the effects of intervention with antifungal therapy.

  2. Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis.

    PubMed

    Elborn, J Stuart; Bell, Scott C; Madge, Susan L; Burgel, Pierre-Regis; Castellani, Carlo; Conway, Steven; De Rijcke, Karleen; Dembski, Birgit; Drevinek, Pavel; Heijerman, Harry G M; Innes, J Alistair; Lindblad, Anders; Marshall, Bruce; Olesen, Hanne V; Reimann, Andreas L; Solé, Ampara; Viviani, Laura; Wagner, Thomas O F; Welte, Tobias; Blasi, Francesco

    2016-02-01

    The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme. Copyright ©ERS 2016.

  3. Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group.

    PubMed

    Harms, H K; Matouk, E; Tournier, G; von der Hardt, H; Weller, P H; Romano, L; Heijerman, H G; FitzGerald, M X; Richard, D; Strandvik, B; Kolbe, J; Kraemer, R; Michalsen, H

    1998-09-01

    Cystic fibrosis is characterized by the accumulation of thick viscous purulent secretions. Recombinant human deoxyribonuclease I (rhDNase) breaks down extracellular DNA, which contributes to the increased viscosity of sputum. A multinational, open-label study was conducted in 974 cystic fibrosis patients with moderate lung disease [forced vital capacity (FVC) 40-70% of predicted values] to examine the safety and efficacy of aerosolized rhDNase, 2.5 mg, once daily over a period of at least 12 weeks. Patients were assessed under conditions reflecting routine clinical practice. During rhDNase therapy, at least one respiratory tract infection (RTI) requiring intravenous antibiotics was experienced by 29.5% of patients. Forced expiratory volume in 1 second (FEV1) and FVC were significantly improved from baseline by a mean of 10.5% and 7.2%, respectively. Voice alteration and pharyngitis were the most frequent rhDNase-related adverse events, but only 2% of all patients discontinued treatment due to adverse events. The results obtained were similar to a subanalysis of data from the first 3 months of a placebo-controlled U.S. study. The patients in the present study had a similar frequency of RTIs and improvement in pulmonary function, and reported fewer rhDNase-related and cystic fibrosis-related adverse events than patients in the U.S. study. We conclude that administration of rhDNase is safe, well tolerated, and effective under conditions reflecting routine clinical practice in patients with cystic fibrosis and moderate lung disease.

  4. Health-related quality of life in end-stage renal disease patients: the effects of renal rehabilitation.

    PubMed

    Kouidi, E

    2004-05-01

    Health-related quality of life (HRQoL) consists of a number of components like functional status, psychological and social functioning, cognition and disease and treatment-related symptoms. End-stage renal disease (ESRD) patients display emotional disturbances, as well as non-adherence to treatment and fluid and food intake, depression, anxiety, social withdrawal and cardiovascular and other co-existing disease morbidity. They have very low functional capacity and physical limitations in their daily activities that affect their mortality and morbidity. Exercise training in ESRD patients is effective in increasing work related activities and important components of their daily life and improving physical functioning. A physical rehabilitation program also leads to a reduction in depression and improvement in family and social interactions. Therefore, renal rehabilitation should be considered as an important therapeutic method for improving physical fitness, social function, well-being and thus health-adjusted quality of life in ESRD patients.

  5. [Effect of a modified low protein and low fat diet on histologic changes and metabolism in kidneys in an experimental model of polycystic kidney disease].

    PubMed

    Banković-Calić, Neda; Ogbori, Malkom R; Nicman, Evin

    2002-01-01

    Dietary protein restriction slows progression in numerous animal models of renal diseases. Flax seed has also demonstrated useful anti-inflammatory properties in a number of animal models and human diseases. We undertook several studies to determine if feeding with low protein casein, soy diet and flax seed diet would ameliorate renal injury in Han:SPRD-cy rat model of polycystic kidney disease. Male offspring of Han:SPRD-cy heterozygotes received protein modified diet: ad libidum LP 8% casein in test or 20% casein in control group for 8 weeks; 20% heat treated soy protein or 20% casein in control group two separate studies for 8 weeks ad libidum and pair feeding in 6 weeks; and 10% flax seed diet or control rat chow for 8 weeks from weaning. Tissue was harvested for histological assessment and metabolic changes in lipids, citric acid metabolites and osmolytes. Morphometrically after histochemical and immunohistochemical staining cystic changes, renal tubular proliferation and apoptosis, number of interstitial cells/macrophages infiltration and interstitial fibrosis were measured. Gas chromatography was used for lipid analysis in renal and liver tissue. 1-HNMR spectroscopy was used for urine and tissue organic anion and osmolytes content analysis. RESULTS IN PROTEIN MODIFIED DIET: Casein low protein as well as soy protein fed animals demonstrated reduced PKD pathology: significant reduction in cystic changes, interstitial inflammation and fibrosis and also reduction in tubular cells proliferation and apoptosis. Pair feeding protocol in second soy diet study confirmed that significant effect on renal histology was not because of protein deprivation and growth retardation. 1-H NMR spectroscopy revealed that progression of chronic renal failure in Han:SPRD-cy rat PKD is associated with renal depletion of citric acid cycle metabolite and betaine. Amelioration of PKD by soy protein diet is associated with renal retention of citric acid cycle anions, despite increased

  6. Serum cystatin C concentration measured routinely is a prognostic marker for renal disease in dogs.

    PubMed

    Iwasa, Naoki; Takashima, Satoshi; Iwasa, Tatsuo; Iwasa, Kazuko; Suzuki, Tomomi; Kobatake, Yui; Kitagawa, Hitoshi; Nishii, Naohito

    2018-06-14

    This study examined the predictive value of serum cystatin C (Cys-C) concentration, measured during routine periodic health examinations, in the renal prognosis of dogs. A cohort of 140 dogs weighing <15 kg whose serum Cys-C concentrations were measured during periodic health examinations from December 2013 to March 2016 were prospectively studied, with renal disease-related death the predicted end point. Of the 140 dogs, nine died from renal diseases during the follow-up period (539 ± 249 days). Serum Cys-C concentrations were higher in the dogs that subsequently died of renal disease than in the censored group (0.8 ± 0.25 vs. 0.3 ± 0.1 mg/dl, respectively; P < .01). Dogs with high serum Cys-C concentrations (>0.55 mg/dl) had a shorter (P < .01) renal disease-specific survival period than those with low serum Cys-C concentrations (≤0.55 mg/dl). In conclusion, high serum Cys-C concentrations in periodic health examinations in dogs <15 kg predicted poorer prognosis for renal function. Copyright © 2018. Published by Elsevier Ltd.

  7. Prevalence of Sexually Transmitted Diseases in Asymptomatic Renal Transplant Recipients.

    PubMed

    Sarier, Mehmet; Sepin Ozen, Nevgun; Guler, Hicran; Duman, Ibrahim; Yüksel, Yücel; Tekin, Sabri; Yavuz, Asuman Havva; Yucetin, Levent; Erdogan Yilmaz, Mine

    2018-04-04

    Sexually transmitted diseases, which may be asymptomatic, have the potential to cause serious health problems in renal transplant recipients. The aim of this study was to determine the prevalence of sexually transmitted diseases in sexually active asymptomatic renal transplant patients by using real-time multiplex polymerase chain reaction assays. This prospective controlled study was conducted between November 2016 and January 2017 in our hospital. Our study group included 80 consecutive, sexually active asymptomatic patients (40 men and 40 women) who had undergone renal transplant in our hospital and who presented to our outpatient clinic for routine follow-up. We also included a control group of 80 consecutive, sexually active nontransplant patients (40 men and 40 women). All patient samples were tested for Gardnerella vaginalis and obligate anaerobes (Prevotella bivia, Porphyromonas species), Candida species, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma species, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2, and Cytomegalovirus by real-time multiplex polymerase chain reaction. The prevalences of infection with Gardnerella vaginalis and obligate anaerobes (P = .043), Ureaplasma species (P = .02), and Cytomegalovirus (P = .016) were found to be significantly higher in the study group versus the control group. However, there was no difference between the 2 groups regarding the prevalence of Mycoplasma infection (P = .70). Sexually transmitted diseases may occur more frequently in sexually active asymptomatic renal transplant recipients than in nontransplanted individuals. Real-time multiplex polymerase chain reaction analysis may be a suitable method for determining these pathogens.

  8. Pancreatitis with normal lipase and amylase in setting of end-stage renal disease.

    PubMed

    Sharma, Anuj; Masood, Umair; Khan, Babar; Chawla, Kunal; Manocha, Divey

    2017-09-01

    Pancreatitis with normal lipase and amylase level is a rare phenomenon. This is especially true in patient with end-stage renal disease as lipase and amylase are renally excreted. Literature review reveals previous case report of pancreatitis with normal lipase and amylase level, however, none of them occurred in the setting of end-stage renal disease. Our case is the first such reported case of pancreatitis in such setting. Here we report a 30year old male with past medical history of end-stage renal disease who presented in emergency department with acute abdominal pain. Laboratory work up revealed normal lipase and amylase level. However, radiological work up was consistent with pancreatitis. This case report highlight the importance of taking the overall clinical picture rather than laboratory work up to rule in or rule out the diagnosis of pancreatitis. Furthermore, this should also serve an important reminder for clinicians to further investigate where clinical suspicion for pancreatitis is high. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. NEK8 Links the ATR-regulated Replication Stress Response and S-phase CDK Activity to Renal Ciliopathies

    PubMed Central

    Choi, Hyo Jei Claudia; Lin, Jia-Ren; Vannier, Jean-Baptiste; Slaats, Gisela G.; Kile, Andrew C.; Paulsen, Renee D.; Manning, Danielle K.; Beier, David R.; Giles, Rachel H.; Boulton, Simon J.; Cimprich, Karlene A.

    2013-01-01

    Summary Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) which further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders. PMID:23973373

  10. Microvascular disease precedes the decline in renal function in the streptozotocin-induced diabetic rat

    PubMed Central

    Maric-Bilkan, Christine; Flynn, Elizabeth R.

    2012-01-01

    Diabetic nephropathy is a progressive and generalized vasculopathic condition associated with abnormal angiogenesis. We aim to determine whether changes in renal microvascular (MV) density correlate with and play a role in the progressive deterioration of renal function in diabetes. We hypothesize that MV changes represent the early steps of renal injury that worsen as diabetes progresses, initiating a vicious circle that leads to irreversible renal injury. Male nondiabetic (ND) or streptozotocin-induced diabetic (D) Sprague-Dawley rats were followed for 4 or 12 wk. Renal blood flow and glomerular filtration rate (GFR) were measured by PAH and 125I-[iothalamate], respectively. Renal MV density was quantified ex vivo using three-dimensional micro computed tomography and JG-12 immunoreactivity. Vascular endothelial growth factor (VEGF) levels (ELISA) and expression of VEGF receptors and factors involved in MV remodeling were quantified in renal tissue by Western blotting. Finally, renal morphology was investigated by histology. Four weeks of diabetes was associated with increased GFR, accompanied by a 34% reduction in renal MV density and augmented renal VEGF levels. However, at 12 wk, while GFR remained similarly elevated, reduction of MV density was more pronounced (75%) and associated with increased MV remodeling, renal fibrosis, but unchanged renal VEGF compared with ND at 12 wk. The damage, loss, and subsequent remodeling of the renal MV architecture in the diabetic kidney may represent the initiating events of progressive renal injury. This study suggests a novel concept of MV disease as an early instigator of diabetic kidney disease that may precede and likely promote the decline in renal function. PMID:22031855

  11. Increased Sympathetic Renal Innervation in Hemodialysis Patients Is the Anatomical Substrate of Sympathetic Hyperactivity in End-Stage Renal Disease.

    PubMed

    Mauriello, Alessandro; Rovella, Valentina; Anemona, Lucia; Servadei, Francesca; Giannini, Elena; Bove, Pierluigi; Anselmo, Alessandro; Melino, Gerry; Di Daniele, Nicola

    2015-11-26

    Renal denervation represents an emerging treatment for resistant hypertension in patients with end-stage renal disease, but data about the anatomic substrate of this treatment are lacking. Therefore, the aim of this study was to investigate the morphological basis of sympathetic hyperactivity in the setting of hemodialysis patients to identify an anatomical substrate that could warrant the use of this new therapeutic approach. The distribution of sympathetic nerves was evaluated in the adventitia of 38 renal arteries that were collected at autopsy or during surgery from 25 patients: 9 with end-stage renal disease on dialysis (DIAL group) and 16 age-matched control nondialysis patients (CTRL group). Patients in the DIAL group showed a significant increase in nerve density in the internal area of the peri-adventitial tissue (within the first 0.5 mm of the beginning of the adventitia) compared with the CTRL group (4.01±0.30 versus 2.87±0.28×mm(2), P=0.01). Regardless of dialysis, hypertensive patients with signs of severe arteriolar damage had a greater number of nerve endings in the most internal adventitia, and this number was significantly higher than in patients without hypertensive arteriolar damage (3.90±0.36 versus 2.87±0.41×mm(2), P=0.04), showing a correlation with hypertensive arteriolar damage rather than with hypertensive clinical history. The findings from this study provide a morphological basis underlying sympathetic hyperactivity in patients with end-stage renal disease and might offer useful information to improve the use of renal denervation in this group of patients. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  12. Impact of lung disease on respiratory impedance in young children with cystic fibrosis.

    PubMed

    Ramsey, Kathryn A; Ranganathan, Sarath C; Gangell, Catherine L; Turkovic, Lidija; Park, Judy; Skoric, Billy; Stick, Stephen M; Sly, Peter D; Hall, Graham L

    2015-12-01

    This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease. Copyright ©ERS 2015.

  13. Pattern of biopsy proven renal diseases at PNS SHIFA, Karachi: A cross-sectional survey

    PubMed Central

    Sabir, Sohail; Mubarak, Muhammed; Ul-Haq, Irfan; Bibi, Aisha

    2013-01-01

    Introduction: Percutaneous renal biopsy (RB) is an invaluable diagnostic procedure in patients with medical renal diseases.Objectives: To determine the pattern of biopsy proven renal disease (BPRD) from a tertiary care naval hospital in Karachi, Pakistan. Methods and Materials: All the renal biopsies in adult patients (≥18 years) performed at our hospital from 2008 to 2012 were retrospectively reviewed. The biopsies were evaluated by light microscopy and immunofluorescence. Results: A total 60 cases were analyzed. The mean age was 33.3±12.9 years (range: 18 to 72 years).The male to female ratio was 3:1. The most common indication of renal biopsy was nephrotic syndrome (43.3%), followed by renal failure (26.6%) and non-nephrotic proteinuria (23.3%). Primary glomerulonephritides (PGN) were predominant overall lesions, found in 46 (76.6%) of the total biopsies. Among PGN, the most common lesion was focal segmental glomerulosclerosis (FSGS), followed by membranous glomerulonephritis (MGN), IgA nephropathy (IgAN) and chronic sclerosing glomerulonephritis (CSGN) and a variety of rare lesions. Secondary glomerulonephritides (SGN) were found in only three (5%) cases. There were two cases of amyloidosis and one of lupus nephritis (LN). Tubulointerstitial disease (TID) and vascular disease were rare. Conclusion: This study provides information about the epidemiology of BPRD in a large tertiary care naval center in Southern Pakistan. PMID:25340152

  14. Renal function assessment in atrial fibrillation: Usefulness of chronic kidney disease epidemiology collaboration vs re-expressed 4 variable modification of diet in renal disease.

    PubMed

    Abumuaileq, Rami Riziq-Yousef; Abu-Assi, Emad; López-López, Andrea; Raposeiras-Roubin, Sergio; Rodríguez-Mañero, Moisés; Martínez-Sande, Luis; García-Seara, Francisco Javier; Fernandez-López, Xesus Alberte; González-Juanatey, Jose Ramón

    2015-10-26

    To compare the performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation. We studied 911 consecutive patients with non-valvular atrial fibrillation on vitamin-K antagonist. The performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation with respect to either a composite endpoint of major bleeding, thromboembolic events and all-cause mortality or each individual component of the composite endpoint was assessed using continuous and categorical ≥ 60, 59-30, and < 30 mL/min per 1.73 m(2) estimated glomerular filtration rate. During 10 ± 3 mo, the composite endpoint occurred in 98 (10.8%) patients: 30 patients developed major bleeding, 18 had thromboembolic events, and 60 died. The new equation provided lower prevalence of renal dysfunction < 60 mL/min per 1.73 m(2) (32.9%), compared with the re-expressed equation (34.1%). Estimated glomerular filtration rate from both equations was independent predictor of composite endpoint (HR = 0.98 and 0.97 for the re-expressed and the new equation, respectively; P < 0.0001) and all-cause mortality (HR = 0.98 for both equations, P < 0.01). Strong association with thromboembolic events was observed only when estimated glomerular filtration rate was < 30 mL/min per 1.73 m(2): HR is 5.1 for the re-expressed equation, and HR = 5.0 for the new equation. No significant association with major bleeding was observed for both equations. The new equation reduced the prevalence of renal dysfunction. Both equations performed similarly in predicting major adverse outcomes.

  15. Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells

    NASA Astrophysics Data System (ADS)

    Rich, Devra P.; Anderson, Matthew P.; Gregory, Richard J.; Cheng, Seng H.; Paul, Sucharita; Jefferson, Douglas M.; McCann, John D.; Klinger, Katherine W.; Smith, Alan E.; Welsh, Michael J.

    1990-09-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (ΔF508), corrected the Cl- channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease.

  16. Care of the Patient with Renal Disease: Peritoneal Dialysis and Transplants, Nursing 321A.

    ERIC Educational Resources Information Center

    Hulburd, Kimberly

    A description is provided of a course, "Care of the Patient with Renal Disease," offered at the community college level to prepare licensed registered nurses to care for patients with renal disease, including instruction in performing the treatments of peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD). The first…

  17. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    PubMed

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  18. Transcatheter embolization of renal artery aneurysm in Behçet's disease.

    PubMed

    Planer, D; Verstandig, A; Chajek-Shaul, T

    2001-01-01

    A 20-year-old man with Behçet's disease presented with a ruptured renal artery aneurysm. This patient had previously had aneurysms of the coronary arteries and coronary vein thrombosis that were treated with immunosuppression. A selective transcatheter embolization of the renal artery branch was done successfully and treatment with corticosteroids and methotrexate was added. Presented here is a rare complication of Behçet's disease, with discussion on the pathophysiology, differential diagnosis, and the advantages and disadvantages of the angiographic treatment. This paper is supplemented with a comprehensive review of the literature.

  19. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation

    PubMed Central

    Ortiz, Alberto; Mauer, Michael; Linthorst, Gabor E.; Oliveira, João P.; Serra, Andreas L.; Maródi, László; Mignani, Renzo; Vujkovac, Bojan; Beitner-Johnson, Dana; Lemay, Roberta; Cole, J.Alexander; Svarstad, Einar; Waldek, Stephen; Germain, Dominique P.; Wanner, Christoph

    2012-01-01

    Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. Results. Men within the first quartile had a mean eGFR slope of –0.1 mL/min/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of –6.7 mL/min/1.73m2/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4–3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2–184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope –4.4 mL/min/1.73m2/year). Conclusions. Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes. PMID:21804088

  20. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation.

    PubMed

    Warnock, David G; Ortiz, Alberto; Mauer, Michael; Linthorst, Gabor E; Oliveira, João P; Serra, Andreas L; Maródi, László; Mignani, Renzo; Vujkovac, Bojan; Beitner-Johnson, Dana; Lemay, Roberta; Cole, J Alexander; Svarstad, Einar; Waldek, Stephen; Germain, Dominique P; Wanner, Christoph

    2012-03-01

    The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m(2)/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m(2)/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4-3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2-184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m(2)/year). Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.

  1. New and emerging targeted therapies for cystic fibrosis

    PubMed Central

    Rowe, Steven M

    2016-01-01

    Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70 000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development. PMID:27030675

  2. Hospital admissions for neurological and renal diseases among dentists and dental assistants occupationally exposed to mercury.

    PubMed

    Thygesen, Lau Caspar; Flachs, Esben Meulengracht; Hanehøj, Kirsten; Kjuus, Helge; Juel, Knud

    2011-12-01

    For many years an amalgam containing metallic mercury, which has been associated with neurological and renal diseases, has been used in dentistry. In this nationwide study we compared hospital admissions due to neurological and renal diseases among dentists and dental assistants to admissions in controls. This register-based cohort study included all Danish workers employed in dental clinics, general practitioners' clinics or lawyers' offices between 1964 and 2006. We compared dentists with general practitioners and lawyers, and dental assistants with medical secretaries, nurses and legal secretaries. We also compared dentists and dental assistants employed during periods with high occupational mercury exposure with dentists and dental assistants employed during periods with less mercury exposure. We followed all subjects in a nationwide register of hospital admissions. We analysed risk of neurological diseases, Parkinson's disease and renal diseases using a Cox regression model. The cohort consisted of 122,481 workers including 5371 dentists and 33,858 dental assistants. For neurological diseases, no association was observed for dental assistants, while for dentists an increasing risk for periods with less mercury exposure was observed. Among dental assistants, a negative association between employment length and risk of neurological disease was observed. Admissions for renal disease among dental assistants were increased during periods with less mercury exposure compared with controls. For dentists a non-significant increased risk was observed between employment length and renal disease risk. Our nationwide study does not indicate that occupational exposure to mercury increases the risk of hospital admissions for neurological, Parkinson's or renal diseases.

  3. Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota.

    PubMed

    Miragoli, Francesco; Federici, Sara; Ferrari, Susanna; Minuti, Andrea; Rebecchi, Annalisa; Bruzzese, Eugenia; Buccigrossi, Vittoria; Guarino, Alfredo; Callegari, Maria Luisa

    2017-02-01

    Cystic fibrosis is often associated with intestinal inflammation due to several factors, including altered gut microbiota composition. In this study, we analyzed the fecal microbiota among patients with cystic fibrosis of 10-22 years of age, and compared the findings with age-matched healthy subjects. The participating patients included 14 homozygotes and 14 heterozygotes with the delF508 mutation, and 2 heterozygotes presenting non-delF508 mutations. We used PCR-DGGE and qPCR to analyze the presence of bacteria, archaea and sulfate-reducing bacteria. Overall, our findings confirmed disruption of the cystic fibrosis gut microbiota. Principal component analysis of the qPCR data revealed no differences between homozygotes and heterozygotes, while both groups were distinct from healthy subjects who showed higher biodiversity. Archaea were under the detection limit in all homozygotes subjects, whereas methanogens were detected in 62% of both cystic fibrosis heterozygotes and healthy subjects. Our qPCR results revealed a low frequency of sulfate-reducing bacteria in the homozygote (13%) and heterozygote (13%) patients with cystic fibrosis compared with healthy subjects (87.5%). This is a pioneer study showing that patients with cystic fibrosis exhibit significant reduction of H 2 -consuming microorganisms, which could increase hydrogen accumulation in the colon and the expulsion of this gas through non-microbial routes. © FEMS 2016.

  4. Impact of Renal Disease on Patients with Hepatitis C: A Retrospective Analysis of Disease Burden, Clinical Outcomes, and Health Care Utilization and Cost.

    PubMed

    Solid, Craig A; Peter, Senaka A; Natwick, Tanya; Guo, Haifeng; Collins, Allan J; Arduino, Jean Marie

    2017-01-01

    Few studies explore the magnitude of the disease burden and health care utilization imposed by renal disease among patients with hepatitis C virus (HCV). We aimed to describe the characteristics, outcomes, and health care utilization and costs of patients with HCV with and without renal impairment. This retrospective analysis used 2 administrative claims databases: the US commercially insured population in Truven Health MarketScan® data (aged 20-64 years), and the US Medicare fee-for-service population in the Medicare 20% sample (aged ≥65 years). Baseline characteristics and comorbid conditions were identified from claims during 2011; patients were followed for up to 1 year (beginning January 1, 2012) to identify health outcomes of interest and health care utilization and costs. In the MarketScan and Medicare databases, 35,965 and 10,608 patients with HCV were identified, 8.5 and 26.5% with evidence of renal disease (chronic kidney disease [CKD] or end-stage renal disease [ESRD]). Most comorbid conditions and unadjusted outcome rates increased across groups from patients with no evidence of renal disease to non-ESRD CKD to ESRD. Health care utilization followed a similar pattern, as did the costs. Our findings suggest that HCV patients with concurrent renal disease have significantly more comorbidity, a higher likelihood of negative health outcomes, and higher health care utilization and costs. © 2017 S. Karger AG, Basel.

  5. Retroperitoneal dedifferentiated liposarcoma with huge cystic degeneration: A case report.

    PubMed

    Uchihashi, Kazuyoshi; Matsuyama, Atsuji; Shiba, Eisuke; Kimura, Yoshizo; Ogata, Toshiro; Yabuki, Kei; Harada, Hiroshi; Kubo, Chisachi; Tsuda, Yojiro; Jotatsu, Mao; Hisaoka, Masanori

    2017-05-01

    Prominent cyst formation is an unusual feature of liposarcoma. We report here a case of dedifferentiated liposarcoma with huge cystic change without preoperative chemo- or radiation therapy. The lesion arose in the retroperitoneum juxtaposed to the right kidney of a 67-year-old woman. She underwent a surgical removal of the retroperitoneal cyst. The cystic tumor contained 1600 mL of old bloody fluid, and its wall was composed of edematous, inflamed or sclerosing fibrous tissue with fatty tissue containing abundant atypical stromal cells, which were immunohistochemically positive for MDM2 and CDK4, and demonstrated MDM2 gene amplification by fluorescence in situ hybridization. The wall was contiguous to an atypical lipomatous nodule located in the mesentery. The following surgical specimens of the right hemicolectomy and right nephrectomy revealed atypical cells infiltrating into the subserosa of the colon and the perirenal fat tissue or that in the renal sinus. This case indicates that well differentiated or dedifferentiated liposarcoma should be also considered as a differential diagnosis of perirenal cystic mass. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  6. Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants

    PubMed Central

    Sullivan-Brown, Jessica; Schottenfeld, Jodi; Okabe, Noriko; Hostetter, Christine L.; Serluca, Fabrizio C.; Thiberge, Stephan Y.; Burdine, Rebecca D.

    2008-01-01

    Zebrafish are an attractive model for studying the earliest cellular defects occurring during renal cyst formation because its kidney (the pronephros) is simple and genes that cause cystic kidney diseases (CKD) in humans, cause pronephric dilations in zebrafish. By comparing phenotypes in three different mutants, locke, swt and kurly, we find that dilations occur prior to 48 hpf in the medial tubules, a location similar to where cysts form in some mammalian diseases. We demonstrate that the first observeable phenotypes associated with dilation include cilia motility and luminal remodeling defects. Importantly, we show that some phenotypes common to human CKD, such as an increased number of cells, are secondary consequences of dilation. Despite having differences in cilia motility, locke, swt and kurly share similar cystic phenotypes, suggesting that they function in a common pathway. To begin to understand the molecular mechanisms involved in cyst formation, we have cloned the swt mutation and find that it encodes a novel leucine rich repeat containing protein (LRRC50), which is thought to function in correct dynein assembly in cilia. Finally, we show that knockdown of polycystic kidney disease 2 (pkd2) specifically causes glomerular cysts and does not affect cilia motility, suggesting multiple mechanisms exist for cyst formation. PMID:18178183

  7. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis

    PubMed Central

    Olivier, Kenneth N; Saiman, Lisa; Daley, Charles L; Herrmann, Jean-Louis; Nick, Jerry A; Noone, Peadar G; Bilton, Diana; Corris, Paul; Gibson, Ronald L; Hempstead, Sarah E; Koetz, Karsten; Sabadosa, Kathryn A; Sermet-Gaudelus, Isabelle; Smyth, Alan R; van Ingen, Jakko; Wallace, Richard J; Winthrop, Kevin L; Marshall, Bruce C; Haworth, Charles S

    2016-01-01

    Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered ‘good’ agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition. PMID:26666259

  8. Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease.

    PubMed

    Cornec-Le Gall, Emilie; Olson, Rory J; Besse, Whitney; Heyer, Christina M; Gainullin, Vladimir G; Smith, Jessica M; Audrézet, Marie-Pierre; Hopp, Katharina; Porath, Binu; Shi, Beili; Baheti, Saurabh; Senum, Sarah R; Arroyo, Jennifer; Madsen, Charles D; Férec, Claude; Joly, Dominique; Jouret, François; Fikri-Benbrahim, Oussamah; Charasse, Christophe; Coulibaly, Jean-Marie; Yu, Alan S; Khalili, Korosh; Pei, York; Somlo, Stefan; Le Meur, Yannick; Torres, Vicente E; Harris, Peter C

    2018-05-03

    Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes. WES identified a DNAJB11 missense variant (p.Pro54Arg) in two family members presenting with non-enlarged polycystic kidneys and a frameshifting change (c.166_167insTT) in a second family with small renal and liver cysts. DNAJB11 is a co-factor of BiP, a key chaperone in the endoplasmic reticulum controlling folding, trafficking, and degradation of secreted and membrane proteins. Five additional multigenerational families carrying DNAJB11 mutations were identified by the targeted analysis. The clinical phenotype was consistent in the 23 affected members, with non-enlarged cystic kidneys that often evolved to kidney atrophy; 7 subjects reached ESRD from 59 to 89 years. The lack of kidney enlargement, histologically evident interstitial fibrosis in non-cystic parenchyma, and recurring episodes of gout (one family) suggested partial phenotypic overlap with autosomal-dominant tubulointerstitial diseases (ADTKD). Characterization of DNAJB11-null cells and kidney samples from affected individuals revealed a pathogenesis associated with maturation and trafficking defects involving the ADPKD protein, PC1, and ADTKD proteins, such as UMOD. DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. [Four Cases Report on Primary Lung Adenoid Cystic Carcinoma].

    PubMed

    He, Xilan; Chen, Jianhua

    2017-11-20

    Lung adenoid cystic carcinoma is a kind of rare lung cancer. Diagnosis and treatment is not enough understandable for them. We collected and analyzed 4 cases of lung adenoid cystic carcinoma for broadening the sight of this disease. Retrospectively analysed the 4 cases we collected from Hunan Cancer Hospital Between January 2012 and December 2016. We depicted the pathology, immunohistochemical, epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) arrangement in these cases. And the methods of the diagnosis and treatment were analyzed. Lung adenoid cystic carcinoma is usually located in the airway, EGFR mutation and ALK arrangement is rare in this disease. Generally the metastasis of the lung cancer occurred in the advanced stage. The prognosis is good if the mass could be resected completely. Diagnosis of the lung adenoid cystic carcinoma depends on pathological experiments, surgery is the main treatment in the early stage, radiotherapy and chemotherapy is an advisable therapy in the advanced stage. And the prognosis of this kind of lung cancer is better than small cell lung cancer and non-small cell lung cancer.

  10. Epidemiology of skin diseases in renal transplant recipients in a tertiary hospital.

    PubMed

    Chen, Qi Ping; Aw, Derrick C W

    2010-12-01

    There is no published epidemiological data on skin diseases in kidney transplant recipients in this tropical country, which has multi-ethnic groups with the Chinese as the predominant ethnic group. Skin diseases of 143 renal transplant recipients were studied in a skin clinic of a tertiary institution during annual surveillance visits from June 2006 to March 2009. Our study showed that except the common drug specific skin manifestations, sebaceous hyperplasia (56.6%), seborrheic keratosis (60.8%), melanocytic naevi (76.9%), skin tags (37.1%) and viral (29.4%) and fungal (20.3%) infections were the most prevalent skin diseases among renal transplant recipients living in Singapore. The prevalence of pre-malignant and malignant tumours was very low (11.2% actinic keratosis, 1.4% Bowen's disease, 1.4% squamous cell carcinoma, 0.7% basal cell carcinoma, 0.7% keratoacanthoma). Male predominance was seen in sebaceous hyperplasia (72.4% vs 32.1%), actinic keratosis (17.2% vs 1.8%), viral (36.8% vs 19.6%) and fungal (27.6% vs 8.9%) infections. Our study also showed increased prevalence of sebaceous hyperplasia with increased age but its prevalence was significantly higher than that reported in the age matched general population. The prevalence of seborrheic keratosis, actinic keratosis and viral infection correlated positively with post-transplant duration. Our study provides epidemiological data for the prevalence of skin diseases in renal transplant recipients. It emphasises the importance of dermatologic follow-up for renal transplant patients in order to obtain a diagnosis and manage treatable skin diseases.

  11. A Novel Lung Disease Phenotype Adjusted for Mortality Attrition for Cystic Fibrosis Genetic Modifier Studies

    PubMed Central

    Taylor, Chelsea; Commander, Clayton W.; Collaco, Joseph M.; Strug, Lisa J.; Li, Weili; Wright, Fred A.; Webel, Aaron D.; Pace, Rhonda G.; Stonebraker, Jaclyn R.; Naughton, Kathleen; Dorfman, Ruslan; Sandford, Andrew; Blackman, Scott M.; Berthiaume, Yves; Paré, Peter; Drumm, Mitchell L.; Zielenski, Julian; Durie, Peter; Cutting, Garry R.; Knowles, Michael R.; Corey, Mary

    2011-01-01

    SUMMARY Genetic studies of lung disease in Cystic Fibrosis are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age-specific CF percentile values of FEV1 which were adjusted for CF age-specific mortality data. The phenotype was computed for 2061 patients representing the Canadian CF population, 1137 extreme phenotype patients in the UNC/Case Western study, and 1323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow-up and for extreme ages. A disease progression and mortality adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power and avoiding possible distortions. This approach will facilitate large scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF. PMID:21462361

  12. Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history.

    PubMed

    Green, M R; Weaver, L T; Heeley, A F; Nicholson, K; Kuzemko, J A; Barton, D E; McMahon, R; Payne, S J; Austin, S; Yates, J R

    1993-04-01

    The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.

  13. Role for transforming growth factor-beta1 in alport renal disease progression.

    PubMed

    Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D

    1999-11-01

    Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.

  14. Hormonal abnormalities of the pancreas and gut in cystic fibrosis.

    PubMed

    Adrian, T E; McKiernan, J; Johnstone, D I; Hiller, E J; Vyas, H; Sarson, D L; Bloom, S R

    1980-09-01

    We have investigated the effect of cystic fibrosis on alimentary hormones in 10 children by measuring the pancreatic and gut hormone rsponse to a milk drink. Plasma insulin and gastric inhibitory peptide were both significantly reduced (P < 0.05 and P < 0.005, respectively, at 15 min) in the patients with cystic fibrosis, compared with controls, even though the early glucose rise was greater in the former group (P < 0.05 at 15 min). Fasting levels of pancreatic polypeptide were significantly lower in the fibrocystic children (P < 0.01), and the normal response to milk was completely abolished in these patients (P < 0.001). Fasting plasma enteroglucagon concentrations were grossly abolished in the cystic fibrosis patients (P < 0.001) and these remained elevated throughout the test. No significant differences were seen in basal or postmilk responses of plasma glucagon, gastrin, secretin, vasoactive intestinal peptide, or motilin in cystic fibrosis. It would thus appear that the pancreatic polypeptide cell is more susceptible to the effects of the disease process than the beta or alpha cell in cystic fibrosis. Some aspects of the abnormalities in the gastrointestinal endocrine system were similar to those seen in celiac disease and tropical sprue and may, therefore, effect a similar hormonal response in these patients with cystic fibrosis to those with mucosal damage.

  15. Effects of fenoldopam on renal blood flow in hypertensive chronic kidney disease.

    PubMed

    Rovella, Valentina; Ferrannini, Michele; Tesauro, Manfredi; Marrone, Giulia; Busca, Andrea; Sorge, Roberto; Manca di Villahermosa, Simone; Casasco, Maurizio; Di Daniele, Nicola; Noce, Annalisa

    2018-05-15

    The synthetic drug fenoldopam mesylate (FM) may have a renoprotective role, and a "renal dose" of 0.1 µg/kg/min intravenous (IV) infusion of FM has been reported as able to increase renal blood flow without affecting systemic blood pressure. But conclusive data are still lacking. We aimed to investigate by color-Doppler ultrasonography the effects of IV administration of FM at this dosage in hypertensive chronic kidney disease (CKD) patients, and verify whether it may induce any systemic hemodynamic alteration. In 60 hypertensive CKD patients, we measured by duplex Doppler ultrasonography, at baseline and during infusion of 0.1 µg/kg/min of FM, the systolic and diastolic flow velocity (sampled at the renal hilum, intermediate section and origin of both renal arteries) and the intra-parenchymal renal resistive index (RRI) sampled on interlobular arteries of both kidneys. Patients were divided into four subgroups (I-IV) according to classification of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-DOQI). Infusion of 0.1 µg/kg/min FM significantly decreased the RRI (0.73 ± 0.05 vs. 0.65 ± 0.06; p < 0.0001) and increased the systolic and diastolic flow velocities in all renal artery tracts examined. No single episode of systemic hypotension was observed. Very low-dose FM may significantly increase renal blood flow and exert a renal protective effect in hypertensive CKD patients. Infusion of FM at such low dosage appears also to be quite safe, even in CKD and hypertensive patients.

  16. Severe hyperkalaemia complicating parathyroidectomy in patients with end-stage renal disease.

    PubMed

    Pauling, M; Lee, J C; Serpell, J W; Wilson, S

    2017-05-01

    We evaluated the incidence of perioperative hyperkalaemia in end-stage renal disease (ESRD) patients undergoing parathyroidectomy and investigated possible contributors to this phenomenon. This was a retrospective cohort study looking at patients who had undergone parathyroidectomy for chronic kidney disease-associated mineral bone disease (CKD-MBD) at The Alfred Hospital, Melbourne, since 2001. Baseline demographics including age, gender, aetiology of renal failure and mode of renal replacement therapy as well as anaesthetic technique and duration of surgery were studied as possible contributors. Perioperative potassium values were compared to preoperative baseline. Following stratification into normokalaemic and hyperkalaemic groups, demographic and operative data were compared. Twenty-two patients met the inclusion criteria with a median (interquartile range, IQR) age of 48.5 (42-59) years. There was a male predominance of 68%. The median (IQR) surgical time was 131 (115-164) minutes. Potassium levels rose perioperatively, with a 27.3% incidence of perioperative hyperkalaemia. Median duration of surgery was longer in the hyperkalaemic patients (167 minutes versus 125 minutes). Following the withdrawal of cinacalcet, parathyroidectomy is increasingly required in ESRD patients with CKD-MBD. Potentially life-threatening hyperkalaemia poses a significant risk in the perioperative period. Serial electrolyte monitoring is crucial to safety in this patient group. A multidisciplinary approach to perioperative management is required to ensure optimal timing of renal replacement therapy and appropriate means of serial blood sampling.

  17. Neocytolysis Contributes to the Anemia of Renal Disease

    NASA Technical Reports Server (NTRS)

    Rice, Lawrence; Alfrey, Clarence P.; Driscoll, Theda; Whitley, Carl E.; Hachey, David; Suki, Wadi

    1997-01-01

    Neocytolysis is a recently described physiologic process effecting selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin depression appears to initiate the process, providing rationale to investigate its contributions to the anemia of renal disease. When erythropoietin therapy was withheld, four of five stable hemodialysis patients demonstrated Cr-51 red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these patients received oral (13)C-glycine and (15)N-glycine and showed pathologic enrichment of stool porphyrins by the most recently ingested isotope when EPO therapy was held. This confirms selective hemolysis of newly-released red cells. (One patient had chronic hemolysis by isotope studies of blood and stool.) Thus, neocytolysis can contribute to the anemia of renal disease and explains some unresolved issues about such anemia. One implication is the prediction that intravenous bolus erythropoietin therapy is metabolically and economically inefficient compared to lower doses given more frequently subcutaneously.

  18. The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort.

    PubMed

    Korten, Insa; Kieninger, Elisabeth; Yammine, Sophie; Regamey, Nicolas; Nyilas, Sylvia; Ramsey, Kathryn; Casaulta, Carmen; Latzin, Philipp; For The Scild Study Group

    2018-04-26

    The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort is a prospective birth cohort study investigating the initiating events of cystic fibrosis lung disease during infancy, and their influence on the trajectory of disease progression throughout early childhood. Infants with cystic fibrosis are recruited throughout Switzerland after diagnosis by new-born screening. It is the first European population-based prospective cohort study of infants with cystic fibrosis taking advantage of a nationwide new-born screening programme. The study was established in 2011 and recruitment is ongoing. The cohort study is currently divided into three study phases (phase 1: diagnosis to age 1 year; phase 2: age 1 to 3 years; and phase 3: age 3 to 6 years). Study participants have weekly telephone interviews, weekly anterior nasal swab collection and two study visits in the first year of life. They also complete follow-up study visits at 3 and 6 years of age. Data for this study are derived from questionnaires, lung function measurements, telephone interviews, nasal swab material and magnetic resonance imaging. To date, 70 infants have been recruited into the study and 56 have completed phase 1, including a baseline study visit at 6 weeks of age, weekly surveillance and a study visit at one year of age. More than 2500 data points on respiratory health and almost 2000 nasal samples have been collected. Phases 2 and 3 will commence in 2018. The dataset of the SCILD cohort combines lung function data, the collection of environmental and sociodemographic factors, documentation of respiratory symptoms, and microbiological analyses. The design not only allows tracking of the cystic fibrosis lung disease independent of clinical status, but also surveillance of early disease prior to severe clinical symptoms. This cohort profile provides details on the study design and summarizes the first published results of the SCILD cohort.

  19. [Endocrine complications of cystic fibrosis in childhood].

    PubMed

    Castanet, M; Wieliczko, M-C

    2012-05-01

    Since the 20 last years, the median age of survival has dramatically improved in children suffering from cystic fibrosis and complications such as growth retardation, pubertal delay and low bone mineral density are now more often than not observed in affected adolescents. The severity of the disease and the poor nutritional status due to pancreatic insufficiency and malabsorption are commonly implicated but recent data suggest that the disease could also play a role though the alteration of the chlore chanel (CFTR). Furthermore an increase prevalence of glucose intolerance and diabetes due to the progressive β cells destruction is observed in these children that make the life sometimes difficult for these adolescents already affected by an heavy chronic disease. The monitoring of the children should thus now become pluridisciplinary and include regular clinical evaluation of height and pubertal status, mineral bone density by DEXA and OGTT every two years since 10 years of age. Therefore, in addition to the standard treatment of cystic fibrosis is now added the vitamin D supplementation, the subcutaneous insulin therapy and may be the growth hormone that could be a new therapeutic demonstrating beneficial effects in these chronic disease. However further studies need to be performed to improve the management of these new endocrine complications more and more frequent in children and adolescents suffering from cystic fibrosis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  20. Progression of structural lung disease on CT scans in children with cystic fibrosis related diabetes.

    PubMed

    Widger, John; Ranganathan, Sarath; Robinson, Philip J

    2013-05-01

    Diabetes has a deleterious effect on clinical status in children with Cystic Fibrosis (CF). We hypothesized that children with CF Related Diabetes (CFRD) or Impaired Glucose Tolerance (IGT) would have more rapidly progressive lung disease based on chest computed tomography (CT) than those with normal glucose tolerance (NGT). In a retrospective study we compared lung structure changes over time, as assessed by CT, in 34 CF children with CFRD, IGT or NGT. We then compared CT findings with changes in lung function. Percentage forced expiratory volume in 1s (%FEV1) remained stable over time with a mean (±SD) yearly change of -0.5% (±3.9), -0.4% (±2.3) and -0.85% (±2.8) (p=0.92) for the CFRD, IGT and NGT groups respectively. However, there was a mean (95%CI) increase in % CT score of 3.86%/year (1.77-5.95%), 1.59%/year (0.6-2.58%) and 1.09%/year (0.07-2.11%) (p=0.023). In patients with CFRD, there was a more rapid progression of structural lung disease, compared to those who had NGT that was not reflected by change in lung function. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shoshani, T.; Bashan, N.; Seret, H.

    1992-01-01

    Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis patient populations carry the major CF mutation ({Delta}F508). Since different Jewish ethnic groups tended to live as closed isolates until recent times, high frequencies of specific mutations are expected among the remainder cystic fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence the severity of the disease. It is therefore expected that different mutations will be associated with either severe or mild phenotype. Direct genomic sequencing of exons included in the two nucleotide-binding folds of the putative CFTR protein was performed on 119 Israeli cysticmore » fibrosis patients from 97 families. One sequence alteration which is expected to create a termination at residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57(60%) are of Ashkenazi origin. In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in the Ashkenazi Jewish patient population in Israel. This nonsense mutation is associated with presentation of severe disease.« less

  2. Elevated serum concentrations of HE4 as a novel biomarker of disease severity and renal fibrosis in kidney disease

    PubMed Central

    Liang, Jianbo; Yue, Caifeng; Wang, Fen; Song, Junli; Wang, Jianfeng; Liu, Min; Luo, Jinmei; Li, Laisheng

    2016-01-01

    Background Human epididymis protein 4 (HE4), has recently been reported as a mediator of renal fibrosis. However, serum HE4 levels appear in a large number of patient samples with chronic kidney disease (CKD), and the relationship of these levels to disease severity and renal fibrosis is unknown. Methods In 427 patients at different stages of CKD excluding gynecologic cancer and 173 healthy subjects, serum HE4 concentrations were tested by chemiluminescent microparticle immunoassay. Renal biopsy was performed on 259 of 427 subjects. Histological findings were evaluated using standard immunohistochemistry. Results The levels of serum HE4 were higher in CKD patients than in healthy subjects, and higher levels were associated with more severe CKD stages. Patients with more severe renal fibrosis tended to have higher HE4 levels, and correlation analysis showed a significant correlation between HE4 and degree of renal fibrosis (r = 0.938, P < 0.0001). HE4 can be a predictor of renal fibrosis in CKD patients; the area under the receiver-operating characteristic curve (AUC-ROC) was 0.99, higher than the AUC-ROC of serum creatinine (0.89). Conclusion Elevated levels of serum HE4 are associated with decreased kidney function, and also with an advanced stage of renal fibrosis, suggesting that HE4 may serve as a valuable clinical biomarker for renal fibrosis of CKD. PMID:27589683

  3. Cystic fibrosis genetics: from molecular understanding to clinical application

    PubMed Central

    Cutting, Garry R.

    2015-01-01

    The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethalautosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the d iscove1y of the disease-causing gene. PMID:25404111

  4. Cystic fibrosis genetics: from molecular understanding to clinical application.

    PubMed

    Cutting, Garry R

    2015-01-01

    The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethal autosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the discovery of the disease-causing gene.

  5. Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

    PubMed

    Ramsey, Kathryn A; Ranganathan, Sarath; Park, Judy; Skoric, Billy; Adams, Anne-Marie; Simpson, Shannon J; Robins-Browne, Roy M; Franklin, Peter J; de Klerk, Nick H; Sly, Peter D; Stick, Steve M; Hall, Graham L

    2014-11-15

    Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

  6. Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis

    PubMed Central

    Sun, Xingshen; Sui, Hongshu; Fisher, John T.; Yan, Ziying; Liu, Xiaoming; Cho, Hyung-Ju; Joo, Nam Soo; Zhang, Yulong; Zhou, Weihong; Yi, Yaling; Kinyon, Joann M.; Lei-Butters, Diana C.; Griffin, Michelle A.; Naumann, Paul; Luo, Meihui; Ascher, Jill; Wang, Kai; Frana, Timothy; Wine, Jeffrey J.; Meyerholz, David K.; Engelhardt, John F.

    2010-01-01

    Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments. PMID:20739752

  7. Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis.

    PubMed

    Sun, Xingshen; Sui, Hongshu; Fisher, John T; Yan, Ziying; Liu, Xiaoming; Cho, Hyung-Ju; Joo, Nam Soo; Zhang, Yulong; Zhou, Weihong; Yi, Yaling; Kinyon, Joann M; Lei-Butters, Diana C; Griffin, Michelle A; Naumann, Paul; Luo, Meihui; Ascher, Jill; Wang, Kai; Frana, Timothy; Wine, Jeffrey J; Meyerholz, David K; Engelhardt, John F

    2010-09-01

    Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments.

  8. The epidemiology of end-stage renal disease in Nigeria: the way forward.

    PubMed

    Odubanjo, M O; Oluwasola, A O; Kadiri, S

    2011-09-01

    The incidence of CKD (Chronic kidney disease) in Nigeria has been shown by various studies to range between 1.6 and 12.4%. We have shown that the burden of renal disease in Nigeria is probably significantly higher than any previous study on end-stage renal disease (ESRD) has documented, as most studies are hospital-based and fail to include the many patients who do not have access to hospital care. The increased prevalence of ESRD among blacks in the United States and South Africa compared with other races also suggests that ESRD may be more prevalent in Africa than in the United States and other developed nations. Common causes of CKD in Nigerian adults are glomerulonephritis and hypertension, while common causes in children are glomerulonephritis and posterior urethral valves. In the United States, diabetes and hypertension are the commonest causes of CKD and glomerulonephritis plays a less important role. Access to renal replacement therapy (RRT) in Nigeria is limited, and mortality rates are very high, ranging between 40 and 50%. Important steps towards improving the situation are the development of prevention programmes and increased funding to ensure increased availability of RRT. To achieve this, health policies concerning CKD must be formulated, and the lack of a renal registry makes it difficult for this to be done. There is need for the development of a functional organizational structure for the reporting of CKD in Nigeria, the Nigerian Renal Registry.

  9. Aspergillus infections in cystic fibrosis.

    PubMed

    King, Jill; Brunel, Shan F; Warris, Adilia

    2016-07-05

    Patients with cystic fibrosis (CF) suffer from chronic lung infection and airway inflammation. Respiratory failure secondary to chronic or recurrent infection remains the commonest cause of death and accounts for over 90% of mortality. Bacteria as Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex have been regarded the main CF pathogens and their role in progressive lung decline has been studied extensively. Little attention has been paid to the role of Aspergillus spp. and other filamentous fungi in the pathogenesis of non-ABPA (allergic bronchopulmonary aspergillosis) respiratory disease in CF, despite their frequent recovery in respiratory samples. It has become more apparent however, that Aspergillus spp. may play an important role in chronic lung disease in CF. Research delineating the underlying mechanisms of Aspergillus persistence and infection in the CF lung and its link to lung deterioration is lacking. This review summarizes the Aspergillus disease phenotypes observed in CF, discusses the role of CFTR (cystic fibrosis transmembrane conductance regulator)-protein in innate immune responses and new treatment modalities. Copyright © 2016. Published by Elsevier Ltd.

  10. Diagnosis and Treatment of Endocrine Co-Morbidities in Patients with Cystic Fibrosis

    PubMed Central

    Siwamogsatham, Oranan; Alvarez, Jessica

    2015-01-01

    Purpose of review The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis (CF). Recent findings As life expectancy in CF has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes (CFRD), cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Summary Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with CF. This review summarizes the updated screening and management of endocrine diseases in the CF population. PMID:25105995

  11. End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen.

    PubMed

    Sell, D R; Monnier, V M

    1990-02-01

    Structure elucidation of a specific fluorophore from the aging extracellular matrix revealed the presence of a protein crosslink formed through nonenzymatic glycosylation of lysine and arginine residues. The unexpected finding that a pentose instead of a hexose is involved in the crosslinking process suggested that the crosslink, named pentosidine, might provide insight into abnormalities of pentose metabolism in aging and disease. This hypothesis was investigated by quantitating pentosidine in hydrolysates of 103 human skin specimens obtained randomly at autopsy. Pentosidine level was found to increase exponentially from 5 to 75 pmol/mg collagen over lifespan (r = 0.86, P less than 0.001). A three- to tenfold increase was noted in insulin-dependent diabetic and nondiabetic subjects with severe end-stage renal disease requiring hemodialysis (P less than 0.001). Moderately elevated levels were also noted in some very old subjects, some subjects with non-insulin dependent diabetes, and two subjects with cystic fibrosis and diabetes. The cause of the abnormal pentose metabolism in these conditions is unknown but may relate to hemolysis, impaired pentose excretion, cellular stress, and accelerated breakdown of ribonucleotides. Thus, pentosidine emerges as a useful tool for assessment of previously unrecognized disorders of pentose metabolism in aging and disease. Its presence in red blood cells and plasma proteins suggests that it might be used as a measure of integrated pentosemia in analogy to glycohemoglobin for the assessment of cumulative glycemia.

  12. Chloride and potassium channels in cystic fibrosis airway epithelia

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.; Liedtke, Carole M.

    1986-07-01

    Cystic fibrosis, the most common lethal genetic disease in Caucasians, is characterized by a decreased permeability in sweat gland duct and airway epithelia. In sweat duct epithelium, a decreased Cl- permeability accounts for the abnormally increased salt content of sweat1. In airway epithelia a decreased Cl- permeability, and possibly increased sodium absorption, may account for the abnormal respiratory tract fluid2,3. The Cl- impermeability has been localized to the apical membrane of cystic fibrosis airway epithelial cells4. The finding that hormonally regulated Cl- channels make the apical membrane Cl- permeable in normal airway epithelial cells5 suggested abnormal Cl- channel function in cystic fibrosis. Here we report that excised, cell-free patches of membrane from cystic fibrosis epithelial cells contain Cl- channels that have the same conductive properties as Cl- channels from normal cells. However, Cl- channels from cystic fibrosis cells did not open when they were attached to the cell. These findings suggest defective regulation of Cl- channels in cystic fibrosis epithelia; to begin to address this issue, we performed two studies. First, we found that isoprenaline, which stimulates Cl- secretion, increases cellular levels of cyclic AMP in a similar manner in cystic fibrosis and non-cystic fibrosis epithelial cells. Second, we show that adrenergic agonists open calcium-activated potassium channels, indirectly suggesting that calcium-dependent stimulus-response coupling is intact in cystic fibrosis. These data suggest defective regulation of Cl- channels at a site distal to cAMP accumulation.

  13. Lung Cancers Associated with Cystic Airspaces: Underrecognized Features of Early Disease.

    PubMed

    Sheard, Sarah; Moser, Joanna; Sayer, Charlie; Stefanidis, Konstantinos; Devaraj, Anand; Vlahos, Ioannis

    2018-01-01

    Early lung cancers associated with cystic airspaces are increasingly being recognized as a cause of delayed diagnoses-owing to data gathered from screening trials and encounters in routine clinical practice as more patients undergo serial imaging. Several morphologic subtypes of cancers associated with cystic airspaces exist and can exhibit variable patterns of progression as the solid elements of the tumor grow. Current understanding of the pathogenesis of these malignancies is limited, and the numbers of cases reported in the literature are small. However, several tumor cell types are represented in these lesions, with adenocarcinoma predominating. The features of cystic airspaces differ among cases and include emphysematous bullae, congenital or fibrotic cysts, subpleural blebs, bronchiectatic airways, and distended distal airspaces. Once identified, these cystic lesions pose management challenges to radiologists in terms of distinguishing them from benign mimics of cancer that are commonly seen in patients who also are at increased risk of lung cancer. Rendering a definitive tissue-based diagnosis can be difficult when the lesions are small, and affected patients tend to be in groups that are at higher risk of requiring biopsy or resection. In addition, the decision to monitor these cases can add to patient anxiety and cause the additional burden of strained departmental resources. The authors have drawn from their experience, emerging evidence from international lung cancer screening trials, and large databases of lung cancer cases from other groups to analyze the prevalence and evolution of lung cancers associated with cystic airspaces and provide guidance for managing these lesions. Although there are insufficient data to support specific management guidelines similar to those for managing small solid and ground-glass lung nodules, these data and guidelines should be the direction for ongoing research on early detection of lung cancer. © RSNA, 2018.

  14. Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens.

    PubMed

    Luan, Xiaojie; Belev, George; Tam, Julian S; Jagadeeshan, Santosh; Hassan, Noman; Gioino, Paula; Grishchenko, Nikolay; Huang, Yanyun; Carmalt, James L; Duke, Tanya; Jones, Teela; Monson, Bev; Burmester, Monique; Simovich, Tomer; Yilmaz, Orhan; Campanucci, Veronica A; Machen, Terry E; Chapman, L Dean; Ianowski, Juan P

    2017-10-05

    Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR -/- swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.Cystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface liquid secretion. Here the authors show that exposure to bacteria triggers secretion in wild-type but not in pig models of cystic fibrosis, suggesting an impaired response to pathogens contributes to infection.

  15. Why and how to measure renal function in patients with liver disease.

    PubMed

    Piano, Salvatore; Romano, Antonietta; Di Pascoli, Marco; Angeli, Paolo

    2017-01-01

    Patients with advanced liver disease frequently have impaired renal function. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are quite common in patients with cirrhosis and both are associated with a worse prognosis in these patients. A careful assessment of renal function is highly important in these patients to help physicians determine their diagnosis, prognosis and therapeutic management and to define transplantation strategies (liver transplantation alone vs simultaneous liver and kidney transplantation). Although they are still widely used in clinical practice, conventional biomarkers of renal function such as serum creatinine have several limitations in these patients. Recent progress has been made in the evaluation of renal function and new diagnostic criteria for AKI have been proposed. However, certain issues such as the noninvasive assessment of the glomerular filtration rate and/or improvement in the differential diagnosis between hepatorenal syndrome and acute tubular necrosis must still be addressed. The purposes of this paper are: (i) to highlight the importance of the evaluation of renal function in patients with cirrhosis; (ii) to review the state of the art in the assessment of renal function in these patients as well as advances that we expect will be made to improve the accuracy of available tools. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Vascular toxicity of urea, a new "old player" in the pathogenesis of chronic renal failure induced cardiovascular diseases.

    PubMed

    Giardino, Ida; D'Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

    2017-12-01

    Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure.

  17. Marriage and End-Stage Renal Disease: Implications for African Americans

    ERIC Educational Resources Information Center

    Shortridge, Emily F.; James, Cara V.

    2010-01-01

    African Americans are disproportionately represented among patients with end-stage renal disease (ESRD). ESRD is managed with a strict routine that might include regular dialysis as well as dietary, fluid intake, and other lifestyle changes. In a disease such as this, with such disruptive treatment modalities, marriage, specifically, and its ties…

  18. [Chronic renal disease--a global problem in the XXI century].

    PubMed

    Shutov, A M

    2014-01-01

    In 2002, it was proposed to consider functional renal disorders 3 and more months in duration under the general name chronic renal disease (CRD) bearing in mind the common mechanism behind progressive nephropathy and high cardiovascular mortality of such patients. The prevalence of CRD in Russia is unknown; it is supposed that every tenth adult in the world has CRD. Diagnostics of CRD requires at least measurement of serum creatinine, calculation of the glomerular filtration rate by CKD-EPI formula, and determination of albuminuria. A main cause of CRD is cardiovascular disorders. Complicated relationships between cardiac insufficiency and CRD account for 5 types of cardiorenal syndrome. CRD patients are at risk of terminal renal insufficiency requiring replacement therapy; moreover, CRD enhances cardiovascular morbidity and predisposes to acute renal lesion that in turn accelerates progress of CRD. Taken together these events account for the global character of the CRD problem.

  19. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model

    PubMed Central

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

    The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet–fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms

  20. Renal replacement therapy in Latin American end-stage renal disease

    PubMed Central

    Rosa-Diez, Guillermo; Gonzalez-Bedat, Maria; Pecoits-Filho, Roberto; Marinovich, Sergio; Fernandez, Sdenka; Lugon, Jocemir; Poblete-Badal, Hugo; Elgueta-Miranda, Susana; Gomez, Rafael; Cerdas-Calderon, Manuel; Almaguer-Lopez, Miguel; Freire, Nelly; Leiva-Merino, Ricardo; Rodriguez, Gaspar; Luna-Guerra, Jorge; Bochicchio, Tomasso; Garcia-Garcia, Guillermo; Cano, Nuria; Iron, Norman; Cuero, Cesar; Cuevas, Dario; Tapia, Carlos; Cangiano, Jose; Rodriguez, Sandra; Gonzalez, Haydee; Duro-Garcia, Valter

    2014-01-01

    The Latin American Dialysis and Renal Transplant Registry (RLADTR) was founded in 1991; it collects data from 20 countries which are members of Sociedad Latinoamericana de Nefrología e Hipertension. This paper presents the results corresponding to the year 2010. This study is an annual survey requesting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities: hemodialysis (HD), peritoneal dialysis (PD) and living with a functioning graft (LFG), etc. Prevalence and incidence were compared with previous years. The type of renal replacement therapy was analyzed, with special emphasis on PD and transplant (Tx). These variables were correlated with the gross national income (GNI) and the life expectancy at birth. Twenty countries participed in the surveys, covering 99% of the Latin American. The prevalence of end stage renal disease (ESRD) under RRT in Latin America (LA) increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (HD 413 pmp, PD 135 pmp and LFG 111 pmp). HD proportionally increased more than PD, and Tx HD continues to be the treatment of choice in the region (75%). The kidney Tx rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of Tx's in 2010 was 10 397, with 58% deceased donors. The total RRT prevalence correlated positively with GNI (r2 0.86; P < 0.05) and life expectancy at birth (r2 0.58; P < 0.05). The HD prevalence and the kidney Tx rate correlated significantly with the same indexes, whereas the PD rate showed no correlation with these variables. A tendency to rate stabilization/little growth was reported in the most regional countries. As in previous reports, the global incidence rate correlated significantly only with GNI (r2 0.63; P < 0.05). Diabetes remained the leading cause of ESRD. The most frequent causes of death were cardiovascular (45%) and infections (22%). Neoplasms accounted for 10% of the causes of death. The

  1. Respiratory infections in patients with cystic fibrosis undergoing lung transplantation.

    PubMed

    Lobo, Leonard J; Noone, Peadar G

    2014-01-01

    Cystic fibrosis is an inherited disease characterised by chronic respiratory infections associated with bronchiectasis. Lung transplantation has helped to extend the lives of patients with cystic fibrosis who have advanced lung disease. However, persistent, recurrent, and newly acquired infections can be problematic. Classic cystic fibrosis-associated organisms, such as Staphylococcus aureus and Pseudomonas aeruginosa, are generally manageable post-transplantation, and are associated with favourable outcomes. Burkholderia cenocepacia poses particular challenges, although other Burkholderia species are less problematic. Despite concerns about non-tuberculous mycobacteria, especially Mycobacterium abscessus, post-transplantation survival has not been definitively shown to be less than average in patients with these infections. Fungal species can be prevalent before and after transplantation and are associated with high morbidity, so should be treated aggressively. Appropriate viral screening and antiviral prophylaxis are necessary to prevent infection with and reactivation of Epstein-Barr virus and cytomegalovirus and their associated complications. Awareness of drug pharmacokinetics and interactions in cystic fibrosis is crucial to prevent toxic effects and subtherapeutic or supratherapeutic drug dosing. With the large range of potential infectious organisms in patients with cystic fibrosis, infection control in hospital and outpatient settings is important. Despite its complexity, lung transplantation in the cystic fibrosis population is safe, with good outcomes if the clinician is aware of all the potential pathogens and remains vigilant by means of surveillance and proactive treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease.

    PubMed

    Ma, Lijun; Langefeld, Carl D; Comeau, Mary E; Bonomo, Jason A; Rocco, Michael V; Burkart, John M; Divers, Jasmin; Palmer, Nicholette D; Hicks, Pamela J; Bowden, Donald W; Lea, Janice P; Krisher, Jenna O; Clay, Margo J; Freedman, Barry I

    2016-08-01

    Relative to European Americans, evidence supports that African Americans with end-stage renal disease (ESRD) survive longer on dialysis. Renal-risk variants in the apolipoprotein L1 gene (APOL1), associated with nondiabetic nephropathy and less subclinical atherosclerosis, may contribute to dialysis outcomes. Here, APOL1 renal-risk variants were assessed for association with dialytic survival in 450 diabetic and 275 nondiabetic African American hemodialysis patients from Wake Forest and Emory School of Medicine outpatient facilities. Outcomes were provided by the ESRD Network 6-Southeastern Kidney Council Standardized Information Management System. Dates of death, receipt of a kidney transplant, and loss to follow-up were recorded. Outcomes were censored at the date of transplantation or through 1 July 2015. Multivariable Cox proportional hazards models were computed separately in patients with nondiabetic and diabetic ESRD, adjusting for the covariates age, gender, comorbidities, ancestry, and presence of an arteriovenous fistula or graft at dialysis initiation. In nondiabetic ESRD, patients with 2 (vs. 0/1) APOL1 renal-risk variants had significantly longer dialysis survival (hazard ratio 0.57), a pattern not observed in patients with diabetes-associated ESRD (hazard ratio 1.29). Thus, 2 APOL1 renal-risk variants are associated with longer dialysis survival in African Americans without diabetes, potentially relating to presence of renal-limited disease or less atherosclerosis. Copyright © 2016 International Society of Nephrology. All rights reserved.

  3. APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease

    PubMed Central

    Ma, Lijun; Langefeld, Carl D.; Comeau, Mary E.; Bonomo, Jason A.; Rocco, Michael V.; Burkart, John M.; Divers, Jasmin; Palmer, Nicholette D.; Hicks, Pamela J.; Bowden, Donald W.; Lea, Janice P.; Krisher, Jenna O.; Clay, Margo J.; Freedman, Barry I.

    2016-01-01

    Relative to European Americans, evidence supports that African Americans with end-stage renal disease (ESRD) survive longer on dialysis. Renal-risk variants in the apolipoprotein L1 gene (APOL1), associated with non-diabetic nephropathy and less subclinical atherosclerosis, may contribute to dialysis outcomes. Here, APOL1 renal-risk variants were assessed for association with dialytic survival in 450 diabetic and 275 non-diabetic African American hemodialysis patients from Wake Forest and Emory School of Medicine outpatient facilities. Outcomes were provided by the ESRD Network 6-Southeastern Kidney Council Standardized Information Management System. Dates of death, receipt of a kidney transplant, and loss to follow-up were recorded. Outcomes were censored at the date of transplantation or through July 1, 2015. Multivariable Cox proportional hazards models were computed separately in patients with non-diabetic and diabetic ESRD, adjusting for the covariates age, gender, comorbidities, ancestry, and presence of an arteriovenous fistula or graft at dialysis initiation. In non-diabetic ESRD, patients with two (vs. zero/one) APOL1 renal-risk variants had significantly longer dialysis survival (hazard ratio 0.57); a pattern not observed in patients with diabetes-associated ESRD (hazard ratio 1.29). Thus, two APOL1 renal-risk variants are associated with longer dialysis survival in African Americans without diabetes, potentially relating to presence of renal-limited disease or less atherosclerosis. PMID:27157696

  4. Renal disease disparities in Asian and Pacific-based populations in Hawai'i.

    PubMed Central

    Mau, Marjorie K.; West, Margaret; Sugihara, Jared; Kamaka, Martina; Mikami, Judy; Cheng, Shiuh-Feng

    2003-01-01

    The prevalence of end-stage renal disease (ESRD) in the United States is expected to double over the next 10 years. The identification of ethnic differences in the prevalence, treatment, morbidity, and mortality related to chronic kidney disease (CKD) is of great concern. Asian Americans comprise a rapidly expanding sector of the U.S. population and are reported to have ESRD growth rates that are approximately 50% higher than caucasians. Hawai'i has a large, well-established Asian and Pacific-based population that facilitates the examination of disparities in renal disease among the state's diverse ethnic groups. The prevalence of ESRD in Hawai'i has continued to rise due, in part, to high rates of diabetes, glomerulonephritis, and hypertension reported in Asian Americans and Pacific-based populations. ESRD patients in Hawai'i have a two-fold higher prevalence of glomerulonephritis, compared with the general ESRD population in the United States. Other potential sources of renal disparities-such as cultural factors, language barriers, and health access factors-among Hawaii's major ethnic groups are assessed. However, few studies have examined the relative contribution of these potential factors. Consequently, efforts to reduce and eventually eliminate renal disease disparities will require a better understanding of the major sources of health disparities, such as timely medical care, a diverse health workforce, and cultural/social barriers, that affect optimal health care practices in Asian and Pacific-based populations. PMID:14620708

  5. Lung transplantation for cystic fibrosis.

    PubMed

    Coloni, G F; Venuta, F; Ciccone, A M; Rendina, E A; De Giacomo, T; Filice, M J; Diso, D; Anile, M; Andreetti, C; Aratari, M T; Mercadante, E; Moretti, M; Ibrahim, M

    2004-04-01

    Lung transplantation is a robust therapeutic option to treat patients with cystic fibrosis. Since 1996, 109 patients with cystic fibrosis were accepted onto our waiting list with 58 bilateral sequential lung transplants performed in 56 patients and two patients retransplanted for obliterative bronchiolitis syndrome. Preoperative mean FEV(1) was 0.64 L/s, mean PaO(2) with supplemental oxygen was 56 mm Hg, and the mean 6-minute walking test was 320 m. Transplantation was performed through a "clam shell incision" in the first 29 patients and via bilateral anterolateral thoracotomies without sternal division in the remaining patients. Cardiopulmonary bypass was required in 14 patients. In 21 patients the donor lungs had to be trimmed by wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Eleven patients were extubated in the operating room immediately after the procedure. Hospital mortality of 13.8% was related to infection (n = 5), primary graft failure (n = 2), and myocardial infarction (n = 1). Acute rejection episodes occurred 1.6 times per patient/year; lower respiratory tract infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV(1) increased to 82% at 1 year after operation. The 5-year survival rate was 61%. A cyclosporine-based immunosuppressive regimen was initially employed in all patients; 24 were subsequently switched to tacrolimus because of central nervous system toxicity, cyclosporine-related myopathy, or renal failure, obliterative bronchiolitis syndrome, gingival hyperplasia, or hypertrichosis. Ten patients were subsequently switched to sirolimus. Freedom from bronchiolitis obliterans at 5 years was 60%. Our results confirm that bilateral sequential lung transplantation is a robust therapeutic option for patients with cystic fibrosis.

  6. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

    PubMed Central

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

  7. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

    PubMed

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

  8. Spontaneous pneumothorax in diffuse cystic lung diseases.

    PubMed

    Cooley, Joseph; Lee, Yun Chor Gary; Gupta, Nishant

    2017-07-01

    Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders with varying pathophysiologic mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In this article, we review the epidemiology, clinical features, and management DCLD-associated spontaneous pneumothorax, with a focus on lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, and pulmonary Langerhans cell histiocytosis. DCLDs are responsible for approximately 10% of apparent primary spontaneous pneumothoraces. Computed tomography screening for DCLDs (Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis) following the first spontaneous pneumothorax has recently been shown to be cost-effective and can help facilitate early diagnosis of the underlying disorders. Patients with DCLD-associated spontaneous pneumothorax have a very high rate of recurrence, and thus pleurodesis should be considered following the first episode of spontaneous pneumothorax in these patients, rather than waiting for a recurrent episode. Prior pleurodesis is not a contraindication to future lung transplant. Although DCLDs are uncommon, spontaneous pneumothorax is often the sentinel event that provides an opportunity for diagnosis. By understanding the burden and implications of pneumothoraces in DCLDs, clinicians can facilitate early diagnosis and appropriate management of the underlying disorders.

  9. Episodic seasonal Pseudo-Bartter syndrome in cystic fibrosis.

    PubMed

    Kintu, Brett; Brightwell, Alex

    2014-06-01

    Pseudo-Bartter syndrome (PBS) describes an uncommon but well recognised complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. Pseudo-Bartter syndrome is usually seen at initial presentation or within the first two years of life in children with cystic fibrosis. Risk factors for development of PBS include warm weather conditions, severe respiratory or pancreatic disease and gastrointestinal losses (e.g. vomiting and diarrhoea). PBS is rare in older children and adolescents although epidemics have been associated with heat wave conditions in warmer climates. In this era of climate change, it is crucial that clinicians consider Pseudo-Bartter syndrome when patients with cystic fibrosis present unwell during summer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Progression of pulmonary disease after disappearance of Pseudomonas in cystic fibrosis.

    PubMed

    Sharma, G D; Tosi, M F; Stern, R C; Davis, P B

    1995-07-01

    Once cystic fibrosis (CF) patients become chronically colonized, eradication of Pseudomonas aeruginosa (PA) is rare. We report five patients, each colonized for at least 6 yr, whose subsequent cultures did not reveal PA or any other gram-negative pathogen for at least 2 yr. Two patients harbored yeast, normal throat flora, and occasional colonies of Aspergillus fumigatus, but no PA, Haemophilus influenzae, or other gram-negative pathogens. In two patients, sputum cultures revealed Staphylococcus aureus. Sputum smear showed no gram-negative organisms in any patient. Antipseudomonal antibody titers in all patients decreased during the noncolonized period. However, titers increased in four other CF patients who had continued PA colonization. Despite disappearance of PA, four of five patients had clinical progression of lung disease with deterioration of FEV1. We conclude that (1) PA, even after it has chronically colonized the airways of CF patients, can occasionally disappear; and (2) lung disease can progress despite the disappearance of PA. Thus, the elimination of a milieu favorable to PA, such as might be anticipated with therapy directed at the basic defect, may not be sufficient to halt the pulmonary disease progression in CF.

  11. The modern spectrum of biopsy-proven renal disease in Chinese diabetic patients-a retrospective descriptive study.

    PubMed

    Liu, Diankun; Huang, Ting; Chen, Nan; Xu, Gang; Zhang, Ping; Luo, Yang; Wang, Yongping; Lu, Tao; Wang, Long; Xiong, Mengqi; Geng, Jian; Nie, Sheng

    2018-01-01

    Renal biopsies performed in diabetic patients are increasing and becoming more complex. Comprehensive data on modern spectrum of biopsy-proven renal disease in Chinese diabetic patients are lacking. In a nationwide renal biopsy survey including 71,151 native biopsies from 2004 to 2014, diabetic patients were identified according to the clinical diagnosis from referral records. The clinical data were extracted from referral records and pathological reports. A total of 1,604 diabetic patients, including 61 patients with T1DM, were analyzed in this study. The median age is 51.39 ± 11.37 years. Male patients accounted for 58% of the population. We found that only 44.7% of diabetic patients had the isolated pathological diagnosis of diabetic nephropathy (DN), while 49.1% had non-diabetic renal disease (NDRD) alone, and 6.2% had NDRD superimposed on DN. Nephrotic syndrome ( n  = 824, 51.4%) was the most common clinical indication for renal biopsy. Among 887 patients with NDRD, membranous nephropathy ( n  = 357) was the leading diagnosis, followed by IgA nephropathy ( n  = 179). Hypertensive renal disease ( n  = 32), tubulointerstitial nephropathy ( n  = 27) and acute tubular necrosis ( n  = 16) accounted for 3.5%, 2.9%, 1.7% of the NDRD cases respectively. Nearly a half (49.2%) of patients with T1DM had NDRD. Over 55% diabetic patients with kidney disease were diagnosed as non-diabetic renal disease, among which MN and IgAN were the most common two pathological types.

  12. Effect of renal replacement therapy on viscosity in end-stage renal disease patients.

    PubMed

    Feriani, M; Kimmel, P L; Kurantsin-Mills, J; Bosch, J P

    1992-02-01

    Viscosity, an important determinant of microcirculatory hemodynamics, is related to hematocrit (HCT), and may be altered by renal failure or its treatment. To assess these factors, we studied the effect of dialysis on the viscosity of whole blood, plasma, and reconstituted 70% HCT blood of eight continuous ambulatory peritoneal dialysis (CAPD) and nine hemodialysis (HD) patients under steady shear flow conditions at different shear rates, before and after dialysis, compared with nine normal subjects. The density of the red blood cells (RBCs), a marker of cell hydration, was measured in HD patients by a nonaqueous differential floatation technique. Whole blood viscosity was higher in controls than patients, and correlated with HCT before treatment (P less than 0.05) at shear rates of 11.5 to 230 s-1) in HD patients, and 23 to 230 s-1 in all end-stage renal disease (ESRD) patients. In contrast, whole blood viscosity correlated with HCT in CAPD patients only at the lowest shear rates (2.3 and 5.75 s-1, P less than 0.05). Plasma viscosity was higher in CAPD patients than both HD patients before treatment and controls (P less than 0.05, analysis of variance [ANOVA]), despite lower plasma total protein, albumin, and similar fibrinogen concentration compared with HD patients. When all samples were reconstituted to 70% HCT, CAPD patients had higher whole blood viscosity than control subjects'. The high HCT blood viscosity of the ESRD patients was higher than control subjects' at capillary shear rates, suggesting increased RBC aggregation and decreased RBC deformability in patients with renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. UAB HRFD Core Center: Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource

    ClinicalTrials.gov

    2017-09-15

    Hepato/Renal Fibrocystic Disease; Autosomal Recessive Polycystic Kidney Disease; Joubert Syndrome; Bardet Biedl Syndrome; Meckel-Gruber Syndrome; Congenital Hepatic Fibrosis; Caroli Syndrome; Oro-Facial-Digital Syndrome Type I; Nephronophthisis; Glomerulocystic Kidney Disease

  14. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement Costs...

  15. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement Costs...

  16. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement Costs...

  17. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement Costs...

  18. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement Costs...

  19. Distinguishing the histological and radiological features of cystic lung disease in Birt-Hogg-Dubé syndrome from those of tobacco-related spontaneous pneumothorax.

    PubMed

    Fabre, Aurelie; Borie, Raphael; Debray, Marie Pierre; Crestani, Bruno; Danel, Claire

    2014-04-01

    Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominantly inherited genodermatosis that predisposes to cystic lung disease, leading to spontaneous pneumothoraces. This retrospective analysis of five BHD cases (two men, three women) compared lung histology and computed tomography (CT) imaging to a matched cohort of non-BHD patients with spontaneous pneumothoraces (SPN). Lung was sampled during pleurodesis to resect bullae. Recurrent pneumothoraces was seen in two patients. Fourteen sets of histological slides (seven in each group) and 10 CT scans (five in each group) were reviewed. CT scans in BHD showed multiple cysts with a basal predominance and intraparenchymal/peribronchial distribution. On histological examination, BHD lungs showed punch-out cysts with no inflammation, and lacked subpleural fibroelastotic scars and smoking changes. In contrast, all SPN cases showed respiratory bronchiolitis and subpleural fibroelastotic scars. This study emphasizes the importance of smoking history and topography of the lesions in assessing cystic lung disease. Pathologists need to remain alert to the possibility of BHD in the setting of recurrent pneumothoraces in a non-smoker, in particular in a woman, at any age, and should take part in a multidisciplinary approach to the diagnosis of cystic lung disease to obtain clinical and CT scan details. © 2013 John Wiley & Sons Ltd.

  20. Renal hemodynamic effects of the HMG-CoA reductase inhibitors in autosomal dominant polycystic kidney disease

    PubMed Central

    Zand, Ladan; Torres, Vicente E.; Larson, Timothy S.; King, Bernard F.; Sethi, Sanjeev; Bergstralh, Eric J.; Angioi, Andrea; Fervenza, Fernando C.

    2016-01-01

    Background To determine the effect of statins on renal hemodynamics in normal volunteers and those with autosomal dominant polycystic kidney disease either with mild or moderate renal dysfunction. Methods Thirty-two study subjects were enrolled in this study: 11 normal volunteers, 11 study subjects with autosomal dominant polycystic kidney disease (ADPKD) and mild kidney disease and 10 study subjects with ADPKD and moderate kidney disease. Subjects in each group received simvastatin 40 mg once daily for a period of 4 weeks. Renal blood flow was measured based on para-amino-hippurate (PAH) clearance and with the use of a magnetic resonance (MR) scanner at the beginning and following 4 weeks of therapy with statins. Results At the end of the study, except for the lipid profile, which was significantly lower in all groups, other laboratory results showed no change. Four weeks of therapy with simvastatin resulted in no change in serum creatinine, 24-h urinary protein, sodium, iothalamate clearance, PAH clearance or renal blood flow as measured by MRI or based on PAH clearance. Conclusions Four weeks of therapy with simvastatin did not change renal blood flow in the study subjects with ADPKD with mild-to-moderate renal dysfunction or in healthy volunteers. Clinical Trial Registration Number NCT02511418. PMID:26614268

  1. [Historical compilation of cystic fibrosis].

    PubMed

    Navarro, Salvador

    2016-01-01

    Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  2. Preoperative Renal Volume: A Surrogate Measure for Radical Nephrectomy-Induced Chronic Kidney Disease.

    PubMed

    Wu, Fiona Mei Wen; Tay, Melissa Hui Wen; Tai, Bee Choo; Chen, Zhaojin; Tan, Lincoln; Goh, Benjamin Yen Seow; Raman, Lata; Tiong, Ho Yee

    2015-12-01

    Surgically induced chronic kidney disease (CKD) has been found to have less impact on survival as well as function when compared to medical causes for CKD. The aim of this study is to evaluate whether preoperative remaining kidney volume correlates with renal function after nephrectomy, which represents an individual's renal reserve before surgically induced CKD. A retrospective review of 75 consecutive patients (29.3% females) who underwent radical nephrectomy (RN) (2000-2010) was performed. Normal side kidney parenchyma, excluding renal vessels and central sinus fat, was manually outlined in each transverse slice of CT image and multiplied by slice thickness to calculate volume. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. CKD is defined as eGFR < 60 mL/min/1.73 m(2). Mean preoperative normal kidney parenchymal volume (mean age 55 [SD 13] years) is 150.7 (SD 36.4) mL. Over median follow-up of 36 months postsurgery, progression to CKD occurred in 42.6% (n = 32) of patients. On multivariable analysis, preoperative eGFR and preoperative renal volume <144 mL are independent predictors for postoperative CKD. On Kaplan-Meier analysis, median time to reach CKD postnephrectomy is 12.7 (range 0.03-43.66) months for renal volume <144 mL but not achieved if renal volume is >144 mL. Normal kidney parenchymal volume and preoperative eGFR are independent predictive factors for postoperative CKD after RN and may represent renal reserve for both surgically and medically induced CKD, respectively. Preoperative remaining kidney volume may be an adjunct representation of renal reserve postsurgery and predict later renal function decline due to perioperative loss of nephrons.

  3. Neocytolysis contributes to the anemia of renal disease

    NASA Technical Reports Server (NTRS)

    Rice, L.; Alfrey, C. P.; Driscoll, T.; Whitley, C. E.; Hachey, D. L.; Suki, W.

    1999-01-01

    Neocytolysis is a recently described physiological process affecting the selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin (EPO) depression appears to initiate the process, providing the rationale to investigate its contributions to the anemia of renal disease. When EPO therapy was withheld, four of five stable hemodialysis patients showed chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these four patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of pathological isotope enrichment of stool porphyrins when EPO therapy was held, again supporting selective hemolysis of newly released red cells that take up the isotope (one patient had chronic hemolysis indicated by isotope studies of blood and stool). Thus, neocytolysis can contribute to the anemia of renal disease and explain some unresolved issues about such anemia. One implication is the prediction that intravenous bolus EPO therapy is metabolically and economically inefficient compared with lower doses administered more frequently subcutaneously.

  4. Early Renal Involvement in a Girl with Classic Fabry Disease.

    PubMed

    Perretta, Fernando; Antongiovanni, Norberto; Jaurretche, Sebastián

    2017-01-01

    Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the enzyme alpha galactosidase A; this defect leads to the systemic accumulation of globotriaosylceramide and its metabolites. Organic involvement in men is well known, but in women it is controversial, mainly due to the random X-chromosome inactivation in each of their cells (Lyon hypothesis). This would explain why women (heterozygotes) present a wide variability in the severity of their phenotype. The manifestations are multisystemic and begin in early childhood, reaching a severe compromise in adulthood. Typical acroparesthesia in hands and feet, gastrointestinal symptoms, angiokeratomas, dyshidrosis, hearing loss, arrhythmias, hypertrophic cardiomyopathy, cerebrovascular accidents, and renal failure can be observed. Nephropathy is one of the major complications of Fabry disease. Glomerular and vascular changes are present before progression to overt proteinuria and decreased glomerular filtration rate, even in pediatric patients. A case of incipient renal involvement in a girl with classic Fabry disease is reported.

  5. Assessing disease disclosure in adults with cystic fibrosis: the Adult Data for Understanding Lifestyle and Transitions (ADULT) survey Disclosure of disease in adults with cystic fibrosis

    PubMed Central

    2010-01-01

    Background As more patients with cystic fibrosis (CF) reach adulthood and participate in age-appropriate activities (e.g. employment, dating), disclosure of medical status becomes more important. This study assessed rates of disclosure and its perceived impact on relationships using the Adult Data for Understanding Lifestyle and Transitions (ADULT) online survey. Methods Adults with CF participated in the survey via the United States national network of CF Centers. Descriptive and inferential statistics were utilized. Results Participants (n = 865) were more likely to disclose to relatives (94%) and close friends (81%) than to dating partners (73%), bosses/supervisors/teachers (51%) or co-workers (39%). Respondents generally reported a neutral/positive effect on relationships following disclosure. Negative effects of disclosure were infrequent, but more likely with dating partners or bosses/supervisors/teachers. Results also indicated that disclosure may be influenced by severity of lung disease and gender, with those having normal/mild lung disease less likely to disclose their diagnosis to both co-workers (p < 0.01) and bosses/supervisors/teachers (p < 0.01), and women being more likely to disclose to close friends (p < 0.0001) and dating partners (p < 0.05) than men. Conclusions Most adults with CF disclosed their disease to relatives and close friends. Individuals with severe CF lung disease were more likely to disclose their diagnosis to coworkers and supervisors/teachers. It may be helpful to provide support for disclosure of disease in situations such as employment and dating. PMID:20831811

  6. Assessing disease disclosure in adults with cystic fibrosis: the Adult Data for Understanding Lifestyle and Transitions (ADULT) survey Disclosure of disease in adults with cystic fibrosis.

    PubMed

    Modi, Avani C; Quittner, Alexandra L; Boyle, Michael P

    2010-09-10

    As more patients with cystic fibrosis (CF) reach adulthood and participate in age-appropriate activities (e.g. employment, dating), disclosure of medical status becomes more important. This study assessed rates of disclosure and its perceived impact on relationships using the Adult Data for Understanding Lifestyle and Transitions (ADULT) online survey. Adults with CF participated in the survey via the United States national network of CF Centers. Descriptive and inferential statistics were utilized. Participants (n = 865) were more likely to disclose to relatives (94%) and close friends (81%) than to dating partners (73%), bosses/supervisors/teachers (51%) or co-workers (39%). Respondents generally reported a neutral/positive effect on relationships following disclosure. Negative effects of disclosure were infrequent, but more likely with dating partners or bosses/supervisors/teachers. Results also indicated that disclosure may be influenced by severity of lung disease and gender, with those having normal/mild lung disease less likely to disclose their diagnosis to both co-workers (p < 0.01) and bosses/supervisors/teachers (p < 0.01), and women being more likely to disclose to close friends (p < 0.0001) and dating partners (p < 0.05) than men. Most adults with CF disclosed their disease to relatives and close friends. Individuals with severe CF lung disease were more likely to disclose their diagnosis to coworkers and supervisors/teachers. It may be helpful to provide support for disclosure of disease in situations such as employment and dating.

  7. Biophysical properties of normal and diseased renal glomeruli.

    PubMed

    Wyss, Hans M; Henderson, Joel M; Byfield, Fitzroy J; Bruggeman, Leslie A; Ding, Yaxian; Huang, Chunfa; Suh, Jung Hee; Franke, Thomas; Mele, Elisa; Pollak, Martin R; Miner, Jeffrey H; Janmey, Paul A; Weitz, David A; Miller, R Tyler

    2011-03-01

    The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3(-/-) mice (Alport model) and Tg26(HIV/nl) mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3(-/-) mice express abnormal glomerular basement membrane proteins, and Tg26(HIV/nl) mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.

  8. Vascular toxicity of urea, a new “old player” in the pathogenesis of chronic renal failure induced cardiovascular diseases

    PubMed Central

    D’Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

    2017-01-01

    Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure. PMID:29483797

  9. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis.

    PubMed

    Floto, R Andres; Olivier, Kenneth N; Saiman, Lisa; Daley, Charles L; Herrmann, Jean-Louis; Nick, Jerry A; Noone, Peadar G; Bilton, Diana; Corris, Paul; Gibson, Ronald L; Hempstead, Sarah E; Koetz, Karsten; Sabadosa, Kathryn A; Sermet-Gaudelus, Isabelle; Smyth, Alan R; van Ingen, Jakko; Wallace, Richard J; Winthrop, Kevin L; Marshall, Bruce C; Haworth, Charles S

    2016-01-01

    Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

    PubMed Central

    Wolf, Michael S.; Chadha, Ashley D.; Carroll, Clinton M.; Borinstein, Scott C.

    2014-01-01

    Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. PMID:25434733

  11. Abdominal Cystic Echinococcosis Treated with Albendazole. A Pediatric Cohort Study.

    PubMed

    Moroni, Samanta; Moscatelli, Guillermo; Bournissen, Facundo García; González, Nicolás; Ballering, Griselda; Freilij, Héctor; Salgueiro, Fabián; Altcheh, Jaime

    2016-01-01

    Cystic echinococcosis is endemic in Argentina. The standard pharmacological treatment for the disease is albendazole, but surgery is a common alternative. Even though primary infection occurs mainly in the pediatric population, the optimal therapeutic option in pediatrics is not clearly defined and few pediatric cohorts with cystic echinococcosis treated with albendazole have been described to date. To describe therapeutic response to albendazole in a cohort of pediatric patients with abdominal cystic echinococcosis. Patients (0-18 years old) with abdominal cystic echinococcosis who were treated with albendazole between January 1998 and August 2013. Diagnosis of abdominal cystic echinococcosis was made by ultrasound. All patients received albendazole, 10-15 mg/kg/day. Epidemiological data, symptoms, number, location and outcome of the cysts, serology and treatment received were analyzed. The parameter used to assess treatment response was cyst changes evaluated by ultrasound follow up using the WHO-IWGE classification. A total of 28 patients (with 46 abdominal cysts) were included in the cohort. Mean age at enrolment was 9.4 years and mean duration of follow-up, 23.8 months. All patients resided in rural areas and had had contact with dogs. The asymptomatic form of the disease was the most common presentation. All patients received albendazole (mean duration: 142.5 days), with low incidence of adverse events. Albendazole had a positive effect on most of the cysts. Surgery was performed in 13 patients. Treatment with albendazole for uncomplicated cystic echinococcosis cysts is safe and effective, and can potentially reduce the need for surgical intervention.

  12. New and emerging targeted therapies for cystic fibrosis.

    PubMed

    Quon, Bradley S; Rowe, Steven M

    2016-03-30

    Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70,000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Chronic Colovesical Fistula Leading to Chronic Urinary Tract Infection Resulting in End-Stage Renal Disease in a Chronic Granulomatous Disease Patient.

    PubMed

    Siddiqui, M R; Sanford, T; Nair, A; Zerbe, C S; Hughes, M S; Folio, L; Agarwal, Piyush K; Brancato, S J

    2017-02-01

    A 46-year old man with X-linked chronic granulomatous disease (CGD) being followed at the National Institute of Health with uncontrolled CGD colitis who developed chronic colovesical fistula, and end-stage renal disease (ESRD). Despite aggressive medical management of symptoms with immunomodulators and antibiotic prophylaxis, the chronic colovesical fistula led to chronic pyelonephritis, recurrent urinary tract infections, persistent air in the collecting system and bladder, and post-renal obstruction resulting in renal failure. Patient is now hemodialysis dependent and required diverting loop ileostomy placement. This report highlights multiple potential etiologies of rising serum creatinine in patients with CGD.

  14. Survival of patients treated for end-stage renal disease by dialysis and transplantation.

    PubMed Central

    Higgins, M. R.; Grace, M.; Dossetor, J. B.

    1977-01-01

    The results of treatment in 213 patients with end-stage renal disease who underwent hemodialysis, peritoneal dialysis or transplantation, or a combination, between 1962 and 1975 were analysed. Comparison by censored survival analysis showed significantly better (P less than 0.01) patient survival with the integrated therapy of dialysis and transplantation than with either form of dialysis alone. There was no significant difference in survival of males and females but survival at the extremes of age was poorer. Analysis of survival by major cause of renal failure indicated best survival in patients with congenital renal disease. Graft and patient survival rates at 1 year after the first transplantation were 42% and 69%. The major cause of death in this series was vascular disease but infection was responsible for 50% of deaths after transplantation. While integration of dialysis with transplantation produces best patient survival, this course is possible only when sufficient cadaver kidneys are available. PMID:334354

  15. Relationship of MTHFR gene polymorphisms with renal and cardiac disease

    PubMed Central

    Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

    2015-01-01

    AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255

  16. Heterogeneity of the cystic fibrosis phenotype in a large kindred family in Qatar with cystic fibrosis mutation (I1234V).

    PubMed

    Abdul Wahab, A; Al Thani, G; Dawod, S T; Kambouris, M; Al Hamed, M

    2001-04-01

    Twenty-nine subjects (17 families) with cystic fibrosis belonging to the same Bedouin tribe were screened for cystic fibrosis transmembrane regulator gene mutations (CFTR). Homozygous I1234V mutation in exon 19 was identified in all families with a relatively high rate of consanguinity (96.6 per cent). The homozygous I1234V mutation tended to present with a variable degree of pulmonary disease, pancreatic insufficiency and electrolyte imbalance. Homozygous I1234V was found to be a common mutation in the studied Bedouin tribe in Qatar.

  17. Protocols for treating patients with end-stage renal disease: a survey of undergraduate dental programs.

    PubMed

    Sturgill, Jeremiah; Howell, Scott; Perry, Maureen Munnelly; Kothari, Hemali

    2016-11-01

    Approximately 14% of Americans are living with chronic kidney disease (CKD). The prevalence of end-stage renal disease (ESRD), the result of progressing CKD continues to rise by 21,000 per year. There are no updated, evidence-based antibiotic prophylaxis guidelines for patients with renal disease undergoing dental treatment. The most recent was a scientific statement from the American Heart Association (AHA) in 2003. Presented in three parts, the goal of the first part of this study is to determine the current protocol being used to treat renal patients at U.S. dental schools. A 21 multiple-choice question survey was e-mailed to 58 clinic deans of accredited dental schools in the United States regarding renal treatment protocol details including antibiotic prophylaxis. Fifty-two percent of programs report having no established renal patient treatment protocol. For programs with a protocol, when using prophylactic antibiotics, 54% followed AHA protocol, whereas 62% used a modified protocol. There is a lack of consistent, established protocols among undergraduate dental programs. It is suggested that evidence-based guidelines for the safe treatment of patients be developed. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

  18. Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

    2016-10-01

    Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Occupational exposure to respirable crystalline silica and chronic non-malignant renal disease: systematic review and meta-analysis.

    PubMed

    Möhner, Matthias; Pohrt, Anne; Gellissen, Johannes

    2017-10-01

    While occupational exposure to respirable silica is known to lead to lung disease, most notably silicosis, its association with chronic kidney disease is unclear. This review explores the association between occupational exposure to respirable silica and chronic non-malignant renal disease such as glomerulonephritis. The evidence has been collected and compiled. Possible sources of bias are thoroughly discussed. Cohort studies with silica exposure and case-control studies of renal disease were searched in PubMed until January 2015. Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. A meta-analysis was performed to evaluate the association to silica exposure. A total of 23 cohort and four case-control studies were included in the analysis. The meta-analysis of cohort studies yielded elevated overall SMRs for renal disease. Some studies, however, included dose-response analyses, most of which did not show a positive trend. The approaches and results of the case-control studies were very heterogeneous. While the studies of cohorts exposed to silica found elevated SMRs for renal disease, no clear evidence of a dose-response relationship emerged. The elevated risk may be attributed to diagnostic and methodological issues. In order to permit a reliable estimation of a possible causal link, exposed cohorts should be monitored for renal disease, as the information from mortality studies is hardly reliable in this field.

  20. Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction.

    PubMed

    Chakrabarti, S; Syme, H M; Brown, C A; Elliott, J

    2013-01-01

    Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression (P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis.

  1. CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis.

    PubMed

    Tarique, Abdullah A; Sly, Peter D; Holt, Patrick G; Bosco, Anthony; Ware, Robert S; Logan, Jayden; Bell, Scott C; Wainwright, Claire E; Fantino, Emmanuelle

    2017-07-01

    The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. Blood samples were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  2. Pharmacogenetics of cystic fibrosis treatment.

    PubMed

    Carter, Suzanne C; McKone, Edward F

    2016-08-01

    Cystic fibrosis (CF) is genetic autosomal recessive disease caused by reduced or absent function of CFTR protein. Treatments for patients with CF have primarily focused on the downstream end-organ consequences of defective CFTR. Since the discovery of the CFTR gene that causes CF in 1989 there have been tremendous advances in our understanding of the genetics and pathophysiology of CF. This has recently led to the development of new CFTR mutation-specific targeted therapies for select patients with CF. This review will discuss the characteristics of the CFTR gene, the CFTR mutations that cause CF and the new mutation specific pharmacological treatments including gene therapy that are contributing to the dawning of a new era in cystic fibrosis care.

  3. Evaluation of factors related to bone disease in Polish children and adolescents with cystic fibrosis.

    PubMed

    Sands, Dorota; Mielus, Monika; Umławska, Wioleta; Lipowicz, Anna; Oralewska, Beata; Walkowiak, Jarosław

    2015-09-01

    The aim of the study was to evaluate factors related to bone formation and resorption in Polish children and adolescents with cystic fibrosis and to examine the effect of nutritional status, biochemical parameters and clinical status on bone mineral density. The study group consisted of 100 children and adolescents with cystic fibrosis with a mean age 13.4 years old. Anthropometric measurements, included body height, body mass and body mass index (BMI); bone mineral densitometry and biochemical testing were performed. Bone mineral density was measured using a dual-energy X-ray absorption densitometer. Biochemical tests included serum calcium, phosphorus, parathyroid hormone and vitamin D concentrations, as well as 24-h urine calcium and phosphorus excretion. Pulmonary function was evaluated using FEV1%, and clinical status was estimated using the Shwachman-Kulczycki score. Standardized body height, body mass and BMI were significantly lower than in the reference population. Mean serum vitamin D concentration was decreased. Pulmonary disease was generally mild, with a mean FEV1% of 81%. Multivariate linear regression revealed that the only factors that had a significant effect on bone marrow density were BMI and FEV1%. There were no significant correlations between bone mineral density and the results of any of the biochemical tests performed. Nutritional status and bone mineral density were significantly decreased in children and adolescents with cystic fibrosis. In spite of abnormalities in biochemical testing, the factors that were found to have the strongest effect on bone mineral density were standardized BMI and clinical status. Copyright © 2015. Published by Elsevier Urban & Partner Sp. z o.o.

  4. Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases

    PubMed Central

    Hershberger, Kathleen A.; Martin, Angelical S.; Hirschey, Matthew D.

    2017-01-01

    The coenzyme nicotinamide adenine dinucleotide (NAD+) has key roles in the regulation of redox status and energy metabolism. NAD+ depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD+ repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD+ enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD+ functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD+-dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD+ supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD+ metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD+-boosting therapies in preclinical animal models. We surmise that modulating the NAD+–sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases. PMID:28163307

  5. Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases.

    PubMed

    Hershberger, Kathleen A; Martin, Angelical S; Hirschey, Matthew D

    2017-04-01

    The coenzyme nicotinamide adenine dinucleotide (NAD + ) has key roles in the regulation of redox status and energy metabolism. NAD + depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD + repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD + enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD + functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD + -dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD + supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD + metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD + -boosting therapies in preclinical animal models. We surmise that modulating the NAD + -sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases.

  6. Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology

    PubMed Central

    Olivier, Alicia K.; Gibson-Corley, Katherine N.

    2015-01-01

    Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF. PMID:25591863

  7. Spectrum of magnetic resonance imaging findings in pancreatic and other abdominal manifestations of Von Hippel-Lindau disease in a series of 23 patients: a pictorial review.

    PubMed

    Graziani, Rossella; Mautone, Simona; Vigo, Mario; Manfredi, Riccardo; Opocher, Giuseppe; Falconi, Massimo

    2014-01-10

    Von Hippel Lindau disease is a rare autosomal dominantly inherited multisystem disorder characterized by development of benign and malignant tumors. The abdominal manifestation of the syndrome are protean. Magnetic resonance plays an important role in identification of abdominal abnormalities and follow-up of lesions. To describe magnetic resonance imaging findings and patterns of pancreatic and other principal abdominal manifestations in a series of von Hippel-Lindau (VHL) disease patients and to review literature. We retrospectively reviewed abdominal magnetic resonance studies performed in 23 patients (10 males, 13 females) diagnosed of VHL. In all examined patients abdominal involvement was present. The pancreatic imaging findings detected were: unilocular cystic lesions (6/23: 26.1%); serous cystadenomas (11/23: 47.8%), including diffuse lesions (8/23: 34.8%); solid neuroendocrine tumors (8/23: 34.8%); cystic neuroendocrine tumors (1/23: 4.3%). The renal findings detected were: simple renal cysts (18/23: 78.3%); complex renal cysts (13/23: 56.5%), including benign lesions (10/23: 43.5%) and malignant lesions (3/23: 13.0%); renal carcinomas (11/23: 47.8%) and 5 of these (45.5%) were multiple and bilateral. Five patients (21.7%) presented pheochromocytoma (4 of these were bilateral; 80.0%) and 1 patient (4.3%) presented cystadenoma of the epididymis. In VHL disease patients, magnetic resonance imaging plays an essential role in the identification of pancreatic and other abdominal lesions, in their follow-up, in the screening of asymptomatic gene carriers, and in their long-term surveillance.

  8. Apparent renal disease due to elevated creatinine levels associated with the use of boldenone.

    PubMed

    Winnett, Georgia; Cranfield, Lesley; Almond, Michael

    2011-02-01

    The widespread use of reporting estimated glomerular filtration rate (eGFR) alongside serum creatinine has led to a heightened appreciation of renal disease. However, creatinine is recognized as an insensitive marker of true GFR and therefore can lead to misdiagnosis of renal dysfunction in the absence of true pathology. We report the case of a 37-year-old male referred due to abnormal eGFR and creatinine in the absence of clinical signs, symptoms or other biochemical abnormalities of renal disease. Subsequent investigations based on a high index of suspicion for exogenous substance abuse led to a novel observation of significantly raised creatinine due to the presence of boldenone, an equine anabolic steroid commonly abused in body building.

  9. Association Between the Use of Proton Pump Inhibitors and the Risk of ESRD in Renal Diseases: A Population-Based, Case-Control Study

    PubMed Central

    Peng, Yen-Chun; Lin, Cheng-Li; Yeh, Hong-Zen; Chang, Chi-Sen; Wu, Yu-Lin; Kao, Chia-Hung

    2016-01-01

    Abstract Proton pump inhibitors (PPIs) use may be associated with nephritis and acute renal injury. The risk of PPIs and deterioration of renal function, in patients with renal diseases, needs to be investigated. A case-control study was conducted in a nation-wide data setting from the Taiwan National Health Insurance Research Database (NHIRD). This case-control study used data extracted from NHIRD between the years 2006 and 2011. We used propensity scores to match 3808 patients suffering from renal diseases (ICD-9-CM codes 580–589), with patients (aged ≥20 years) who had had a recent diagnosis of end-stage renal diseases (ESRDs) and had undertaken renal replacement therapy during the period of 2006 to 2011. The 3808 control subjects were selected from people who had a history of renal diseases, but no ESRD. The risk of ESRD in patients with renal diseases and PPIs use was estimated by using odds ratios (ORs) and 95% confidence intervals (CI). The use of a PPIs was associated with a significantly higher risk of ESRD (adjusted OR = 1.88, 95% CI = 1.71–2.06) in renal disease patients. Of all the types of PPI combined, the adjusted OR was 1.92 (95% CI = 1.74–2.13) for those on <100 cumulative DDD and was 1.74-fold (95% CI = 1.52–2.00) for those on ≥100 cumulative DDD. PPIs use is associated with the risk of ESRD in patients with renal diseases. It is necessary that appropriate prescription of PPIs coordinated with the close monitoring renal function of patients diagnosed with renal disease. PMID:27082596

  10. Hypertension, End-Stage Renal Disease and Rehabilitation: A Look at Black Americans.

    ERIC Educational Resources Information Center

    Livingston, Ivor Lensworth; Ackah, Samuel

    1992-01-01

    Reviews the important relationship between end-stage renal disease (ESRD) and hypertension for African Americans; and considers issues associated with ESRD and the subsequent need for kidney transplants, including organ availability. Individual and societal implications of these diseases are discussed. (SLD)

  11. The porcine lung as a potential model for cystic fibrosis

    PubMed Central

    Rogers, Christopher S.; Abraham, William M.; Brogden, Kim A.; Engelhardt, John F.; Fisher, John T.; McCray, Paul B.; McLennan, Geoffrey; Meyerholz, David K.; Namati, Eman; Ostedgaard, Lynda S.; Prather, Randall S.; Sabater, Juan R.; Stoltz, David Anthony; Zabner, Joseph; Welsh, Michael J.

    2008-01-01

    Airway disease currently causes most of the morbidity and mortality in patients with cystic fibrosis (CF). However, understanding the pathogenesis of CF lung disease and developing novel therapeutic strategies have been hampered by the limitations of current models. Although the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) has been targeted in mice, CF mice fail to develop lung or pancreatic disease like that in humans. In many respects, the anatomy, biochemistry, physiology, size, and genetics of pigs resemble those of humans. Thus pigs with a targeted CFTR gene might provide a good model for CF. Here, we review aspects of porcine airways and lung that are relevant to CF. PMID:18487356

  12. Febuxostat-induced agranulocytosis in an end-stage renal disease patient

    PubMed Central

    Poh, Xue Er; Lee, Chien-Te; Pei, Sung-Nan

    2017-01-01

    Abstract Introduction: Febuxostat, a nonpurine xanthine oxidase inhibitor, is approved as the first-line urate-lowering therapy in gout patients with normal renal function or mild to moderate renal impairment. The most common adverse effects of febuxostat are liver function test abnormalities, diarrhea, and skin rash. However, there is insufficient data in patients with severe renal impairment and end-stage renal disease (ESRD). We report the first case, to our knowledge, in which agranulocytosis developed after febuxostat treatment in an ESRD patient. Clinical presentation: A 67-year-old woman with gout and ESRD received febuxostat 40 mg a day for 2.5 months. She subsequently complicated with febrile neutropenia and the absolute neutrophil count was only 14/μL. After broad-spectrum antibiotics treatment and no more exposure to febuxostat for 17 days, her infection and neutrophil count recovered. Bone marrow study during neutropenic period showed myeloid hypoplasia without evidence of hematologic neoplasms. Conclusion: As febuxostat use may become more common in the population of advanced renal failure, clinicians should be aware of this rare but potentially life-threatening adverse effect. Based on our experience, close monitoring hemogram and immediate discontinuation of this medication may prevent serious consequences. PMID:28079821

  13. Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

    PubMed

    Akinci, Baris; Unlu, Sadiye Mehtat; Celik, Ali; Simsir, Ilgin Yildirim; Sen, Sait; Nur, Banu; Keskin, Fatma Ela; Ozgen Saydam, Basak; Kutbay Ozdemir, Nilufer; Sarer Yurekli, Banu; Ergur, Bekir Ugur; Sonmez, Melda; Atik, Tahir; Arslan, Atakan; Demir, Tevfik; Altay, Canan; Tunc, Ulku Aybuke; Arkan, Tugba; Gen, Ramazan; Eren, Erdal; Akinci, Gulcin; Yilmaz, Aslihan Arasli; Bilen, Habib; Ozen, Samim; Celtik, Aygul; Savas Erdeve, Senay; Cetinkaya, Semra; Onay, Huseyin; Sarioglu, Sulen; Oral, Elif Arioglu

    2018-07-01

    Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease. © 2018 John Wiley & Sons Ltd.

  14. Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease.

    PubMed

    Dancey, D R; Tullis, E D; Heslegrave, R; Thornley, K; Hanly, P J

    2002-03-01

    It was hypothesized that adult cystic fibrosis (CF) patients with severe lung disease have impaired daytime function related to nocturnal hypoxaemia and sleep disruption. Nineteen CF patients (forced expiratory volume in one second 28+/-7% predicted) and 10 healthy subjects completed sleep diaries, overnight polysomnography (PSG), and assessment of daytime sleepiness and neurocognitive function. CF patients tended to report more awakenings (0.7+/-0.5 versus 0.3+/-0.2 x h(-1), p=0.08), and PSG revealed reduced sleep efficiency (71+/-25 versus 93+/-4%, p=0.004) and a higher frequency of awakenings (4.2+/-2.7 versus 2.4+/-1.4 x h(-1), p=0.06). Mean arterial oxygen saturation during sleep was lower in CF patients (84.4+/-6.8 versus 94.3+/-1.5%, p<0.0001) and was associated with reduced sleep efficiency (regression coefficient (r)=0.57, p=0.014). CF patients had short sleep latency on the multiple sleep latency test (6.7+/-3 min). The CF group reported lower levels of activation and happiness and greater levels of fatigue (p<0.01), which correlated with indices of sleep loss, such as sleep efficiency (r=0.47, p=10.05). Objective neurocognitive performance was also impaired in CF patients, reflected by lower throughput for simple addition/subtraction, serial reaction and colour-word conflict. The authors concluded that adult cystic fibrosis patients with severe lung disease have impaired neurocognitive function and daytime sleepiness, which is partly related to chronic sleep loss and nocturnal hypoxaemia.

  15. Characteristics and Outcomes of In-Hospital Palliative Care Consultation among Patients with Renal Disease Versus Other Serious Illnesses.

    PubMed

    Grubbs, Vanessa; O'Riordan, David; Pantilat, Steve

    2017-07-07

    Despite significant morbidity and mortality associated with ESRD, these patients receive palliative care services much less often than patients with other serious illnesses, perhaps because they are perceived as having less need for such services. We compared characteristics and outcomes of hospitalized patients in the United States who had a palliative care consultation for renal disease versus other serious illnesses. In this observational study, we used data collected by the Palliative Care Quality Network, a national palliative care quality improvement collaborative. The 23-item Palliative Care Quality Network core dataset includes demographics, processes of care, and clinical outcomes of all hospitalized patients who received a palliative care consultation between December of 2012 and March of 2016. The cohort included 33,183 patients, of whom 1057 (3.2%) had renal disease as the primary reason for palliative care consultation. Mean age was 71.9 (SD=16.8) or 72.8 (SD=15.2) years old for those with renal disease or other illnesses, respectively. At the time of consultation, patients with renal disease or other illnesses had similarly low mean Palliative Performance Scale scores (36.0% versus 34.9%, respectively; P =0.08) and reported similar moderate to severe anxiety (14.9% versus 15.3%, respectively; P =0.90) and nausea (5.9% versus 5.9%, respectively; P >0.99). Symptoms improved similarly after consultation regardless of diagnosis ( P ≥0.50), except anxiety, which improved more often among those with renal disease (92.0% versus 66.0%, respectively; P =0.002). Although change in code status was similar among patients with renal disease versus other illnesses, from over 60% full code initially to 30% full code after palliative care consultation, fewer patients with renal disease were referred to hospice than those with other illnesses (30.7% versus 37.6%, respectively; P <0.001). Hospitalized patients with renal disease referred for palliative care

  16. Analysis of the New Zealand Black contribution to lupus-like renal disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Drake, C.G.; Rozzo, S.J.; Hirschfeld, H.F.

    1995-03-01

    F{sub 1} progeny of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop an autoimmune process remarkably similar to human systemic lupus erythematosus. Previous studies have implicated major genetic contributions from the NZW MHC and from a dominant NZB gene on chromosome 4. To identify additional NZB contributions to lupus-like disease, (NZB x SM/J)F{sub 1} x NZW backcross mice were followed for the development of severe renal disease and were comprehensively genotyped. Despite a 50% incidence of disease significant associations between the presence of the NZB genotype and disease were noted on chromosomes 1, 4, 7, 10,more » 13, and 19. The data indicated that multiple NZB genes, in different combinations, contribute to severe renal disease, and that no single gene is required. To further investigate this NZB contribution, NZB x SM/J (NXSM) recombinant inbred (RI) strains were crossed with NZW mice, and F{sub 1} progeny were analyzed for the presence of lupus-like renal disease. Interestingly, nearly all of the (RI x NZW)F{sub 1} cohorts studies expressed some level of disease. Five RI strains generated a high incidence of disease, similar to (NZB x NZW)F{sub 1} mice, and nearly one-half of the cohorts developed disease at intermediate levels. Only two cohorts demonstrated very little disease, supporting the conclusion that multiple genes are capable of disease induction. Experiments correlating the genotypes of these RI strains with their ability to generate disease revealed that none of the disease-associated loci defined by the backcross analysis were present in all five RI strains that generated disease at high levels. Overall, both the backcross data and RI analysis provide additional support for the genetic complexity of lupus nephritis and uphold the conclusion that heterogeneous combinations of contributing NZB genes seem to operate in a threshold manner to generate the disease phenotype. 31 refs., 3 figs., 2 tabs.« less

  17. Disease-causing Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator Determine the Functional Responses of Alveolar Macrophages*

    PubMed Central

    Deriy, Ludmila V.; Gomez, Erwin A.; Zhang, Guangping; Beacham, Daniel W.; Hopson, Jessika A.; Gallan, Alexander J.; Shevchenko, Pavel D.; Bindokas, Vytautas P.; Nelson, Deborah J.

    2009-01-01

    Alveolar macrophages (AMs) play a major role in host defense against microbial infections in the lung. To perform this function, these cells must ingest and destroy pathogens, generally in phagosomes, as well as secrete a number of products that signal other immune cells to respond. Recently, we demonstrated that murine alveolar macrophages employ the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel as a determinant in lysosomal acidification (Di, A., Brown, M. E., Deriy, L. V., Li, C., Szeto, F. L., Chen, Y., Huang, P., Tong, J., Naren, A. P., Bindokas, V., Palfrey, H. C., and Nelson, D. J. (2006) Nat. Cell Biol. 8, 933–944). Lysosomes and phagosomes in murine cftr−/− AMs failed to acidify, and the cells were deficient in bacterial killing compared with wild type controls. Cystic fibrosis is caused by mutations in CFTR and is characterized by chronic lung infections. The information about relationships between the CFTR genotype and the disease phenotype is scarce both on the organismal and cellular level. The most common disease-causing mutation, ΔF508, is found in 70% of patients with cystic fibrosis. The mutant protein fails to fold properly and is targeted for proteosomal degradation. G551D, the second most common mutation, causes loss of function of the protein at the plasma membrane. In this study, we have investigated the impact of CFTR ΔF508 and G551D on a set of core intracellular functions, including organellar acidification, granule secretion, and microbicidal activity in the AM. Utilizing primary AMs from wild type, cftr−/−, as well as mutant mice, we show a tight correlation between CFTR genotype and levels of lysosomal acidification, bacterial killing, and agonist-induced secretory responses, all of which would be expected to contribute to a significant impact on microbial clearance in the lung. PMID:19837664

  18. Renal manifestations of human brucellosis: First report of minimal change disease.

    PubMed

    Sabanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Tsotsiou, Eleni; Kalaitzoglou, Asterios; Kavlakoudis, Christos; Vasileiou, Sotirios

    2016-05-01

    Human brucellosis is considered a great example of the complexity of clinical manifestations possibly affecting multiple organs or systems. Renal manifestations of human brucellosis have been documented in few case reports and one case series. Herein, we present a case of Nephrotic syndrome (NS) due to minimal change disease in the course of acute brucellosis. A 53-year-old male farmer was admitted to our department with acute brucellosis and NS. Renal biopsy revealed minimal change disease. Combined treatment with prednisone (1 mg/kg), rifampicin (600 mg/day), and doxycycline (200 mg/day) was initiated. Complete remission of NS was achieved at the end of the fourth week. One year later, the patient remained in complete remission of NS without any sign of relapse of brucellosis.

  19. Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease

    PubMed Central

    El Machhour, Fala; Keuylian, Zela; Kavvadas, Panagiotis; Dussaule, Jean-Claude

    2015-01-01

    Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. PMID:25421557

  20. Cystic Fibrosis Revisited - a Review Study.

    PubMed

    Klimova, Blanka; Kuca, Kamil; Novotny, Michal; Maresova, Petra

    2017-01-01

    Cystic fibrosis (CF) is an incurable, chronic disease, which causes severe damages to respiratory and digestive tracts. It is the most common genetically inherited disease among caucasians. This disease is caused by defects in CF genes, the so-called mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene population. At present over 100,000 people suffer from this disease worldwide. The purpose of this review study is to describe the pathophysiology of CF and provide the latest information on its diagnosis and treatment therapies with respect to the improvement of patient's quality of life and emphasis on targeted specialized care. The methodological approaches include a method of literature review of available sources exploring the issue of cystic fibrosis both from a global and specific perspective point of view. A search was performed in the databases PubMed, MEDLINE, Web of Science, Scopus, Springer and ScienceDirect. Furthermore, other sources cited in the analyzed studies were also examined. On the basis of evaluation of these literature sources, the research issue was explored. The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of narcolepsy are highlighted. CF requires an integrated treatment approach in specialized CF centers, involving various factors contributing to a better patient's state of health in the form of relevant and well-balanced non-pharmacological and pharmacological therapies. In addition, further large scale clinical trials are needed in order to develop compounds that are aimed at the most common classes of CFTR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Current management of autosomal dominant polycystic kidney disease.

    PubMed

    Akoh, Jacob A

    2015-09-06

    Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging (MRI) were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the financial impact on society of the disease. Current treatment strategies include reducing: cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials (RCT) including mammalian target of rapamycin inhibitors, somatostatin analogues and a vasopressin V2 receptor antagonist have been performed to study the effect of diverse drugs on growth of renal and hepatic cysts, and on deterioration of renal function. Prophylactic native nephrectomy is indicated in patients with a history of cyst infection or recurrent haemorrhage or to those in whom space must be made to implant the graft. The absence of large RCT on various aspects of the disease and its treatment leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease (ESRD). The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a first step towards trying newer interventions so as to develop updated clinical management guidelines.

  2. How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions: implications for airway hyper-responsiveness and asthma in cystic fibrosis.

    PubMed

    McCuaig, Sarah; Martin, James G

    2013-04-01

    Among patients with cystic fibrosis there is a high prevalence (40-70%) of asthma signs and symptoms such as cough and wheezing and airway hyper-responsiveness to inhaled histamine or methacholine. Whether these abnormal airway responses are due to a primary deficiency in the cystic fibrosis transmembrane conductance regulator (CFTR) or are secondary to the inflammatory environment in the cystic fibrosis lungs is not clear. A role for the CFTR in smooth muscle function is emerging, and alterations in contractile signalling have been reported in CFTR-deficient airway smooth muscle. Persistent bacterial infection, especially with Pseudomonas aeruginosa, stimulates interleukin-8 release from the airway epithelium, resulting in neutrophilic inflammation. Increased neutrophilia and skewing of CFTR-deficient T-helper cells to type 2 helper T cells creates an inflammatory environment characterised by high concentrations of tumour necrosis factor α, interleukin-8, and interleukin-13, which might all contribute to increased contractility of airway smooth muscle in cystic fibrosis. An emerging role of interleukin-17, which is raised in patients with cystic fibrosis, in airway smooth muscle proliferation and hyper-responsiveness is apparent. Increased understanding of the molecular mechanisms responsible for the altered smooth muscle physiology in patients with cystic fibrosis might provide insight into airway dysfunction in this disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in older adults: an analysis of Medicare claims data.

    PubMed

    Singh, Jasvinder A; Cleveland, John D

    2017-10-01

    To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly. In a retrospective cohort study using 2006-2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference). Sensitivity analyses included multivariable-adjusted regression models. There were 31 465 new allopurinol or febuxostat treatment episodes in 26 443 patients; 8570 ended in incident renal disease. Crude rates of incident renal disease per 1000 person-years were 192 with allopurinol versus 338 with febuxostat. Crude rates of incident renal disease per 1000 person-years were lower with higher daily dose: allopurinol <200, 200-299 and ≥300 mg/day with 238, 176 and 155; and febuxostat 40 and 80 mg/day with 341 and 326, respectively. In propensity-matched analyses, compared with febuxostat, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% CI 0.49 to 0.77). Compared with febuxostat 40 mg/day, allopurinol doses <200, 200-299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI 0.65 to 0.86), 0.61 (95% CI 0.52 to 0.73) and 0.48 (95% CI 0.41 to 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings. Allopurinol was associated with a lower risk of incident renal disease in elderly patients than febuxostat. Future studies need to examine the mechanism of this potential renal benefit of allopurinol. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Acceptance and effects of a therapeutic renal food in pet cats with chronic kidney disease

    PubMed Central

    Fritsch, Dale A; Jewell, Dennis E

    2015-01-01

    Introduction Renal foods are used to manage chronic kidney disease (CKD) in dogs and cats, but their effectiveness may be limited by the ability to transition animals to them. Material and Methods In a prospective study, pet cats with previously undiagnosed kidney disease (20 International Renal Interest Society (IRIS) 1, 61 IRIS 2, 14 IRIS 3/4, 33 at risk for CKD) were transitioned to a renal food. Markers of renal function were measured and owners answered questionnaires about their pet over one year. Results All but eight cats (120/128; 94 per cent) successfully transitioned to the renal food. Most of the time, cats moderately or extremely liked the food (89 per cent), ate at least half (73 per cent) and were moderately or extremely enthusiastic while eating (68 per cent). Cats rarely disliked the food (2 per cent) or refused to eat it (1 per cent). Markers of renal function were unchanged in IRIS 1 and 2 cats and changed little in IRIS 3/4 cats. In all groups, owner-assessed quality of life improved initially and then remained stable. Mean bodyweight did not change in cats with CKD. Conclusions Most cats with CKD successfully transitioned to the renal food. The results also support previous studies that the renal food can help stabilise cats with CKD. PMID:26587240

  5. CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

    PubMed Central

    Blaisdell, Carol J; Howard, Timothy D; Stern, Augustus; Bamford, Penelope; Bleecker, Eugene R; Stine, O Colin

    2004-01-01

    Background Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity. PMID:15507145

  6. Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

    PubMed

    Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

    2016-07-01

    Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. © 2016 Royal Australasian College of Physicians.

  7. Increased Blood Pressure Variability Prior to Chronic Kidney Disease Exacerbates Renal Dysfunction in Rats

    PubMed Central

    Freitas, Frederico F. C. T.; Araujo, Gilberto; Porto, Marcella L.; Freitas, Flavia P. S.; Graceli, Jones B.; Balarini, Camille M.; Vasquez, Elisardo C.; Meyrelles, Silvana S.; Gava, Agata L.

    2016-01-01

    Increased blood pressure variability (BPV), which can be experimentally induced by sinoaortic denervation (SAD), has emerged as a new marker of the prognosis of cardiovascular and renal outcomes. Considering that increased BPV can lead to organ-damage, the goal of the present study was to evaluate the effects of SAD on renal function in an experimental model of chronic kidney disease (CKD). SAD was performed in male Wistar rats 2 weeks before 5/6 nephrectomy and the animals were evaluated 4 weeks after the induction of CKD. Our data demonstrated that BPV was increased in SAD and CKD animals and that the combination of both conditions (SAD+CKD) exacerbated BPV. The baroreflex sensitivity index was diminished in the SAD and CKD groups; this reduction was more pronounced when SAD and CKD were performed together. 5/6 nephrectomy led to hypertension, which was higher in SAD+CKD animals. Regarding renal function, the combination of SAD and CKD resulted in reduced renal plasma and blood flow, increased renal vascular resistance and augmented uraemia when compared to CKD animals. Glomerular filtration rate and BPV were negatively correlated in SAD, CKD, and SAD+CKD animals. Moreover, SAD+CKD animals presented a higher level of glomerulosclerosis when compared to all other groups. Cardiac and renal hypertrophy, as well as oxidative stress, was also further increased when SAD and CKD were combined. These results show that SAD prior to 5/6 nephrectomy exacerbates renal dysfunction, suggesting that previous augmented BPV should be considered as an important factor to the progression of renal diseases. PMID:27721797

  8. Excisional treatment of renal hydatid cyst mimicking renal tumor with diode laser technique: A case report.

    PubMed

    Uçar, Murat; Karagözlü Akgül, Ahsen; Çelik, Fatih; Kılıç, Nizamettin

    2016-08-01

    Cystic echinococcosis, which is one of the most important helminthic infestations, is a serious life-threatening health problem in developing countries. Hydatid cyst of the kidney is a rare condition in children that can be treated with medical therapy or surgical treatment in some resistant cases. Here, we present a case of renal hydatid cyst that was treated with laparoscopic excision with diode laser. A 15-year-old female patient was admitted with abdominal pain. Abdominal ultrasonography revealed a 32 × 23 × 19-mm solid mass with cystic component at lower pole of right kidney. An indirect hemagglutination (IHA) test for echinococcosis granulosus was positive at a 1:320 titer. Other laboratory tests were within normal limits. The patient received albendazole therapy for 3 months. The follow-up magnetic resonance imaging showed a solitary lesion with exophytic extensions that contained large separations. No contrast enhancement could be detected after gadolinium injection. As no regression could be detected radiologically, surgical treatment was planned. Laparoscopic renal lower pole mass cyst excision with diode laser was performed (Figure). The patient was hospitalized for 1 day without any blood transfusion. Histopathological examination was consistent with hydatid cyst of the kidney. Diagnosis of hydatid cyst of the kidney is generally made incidentally and can be misdiagnosed as a primary kidney tumor. Radiological studies may be insufficient for accurate diagnosis. In our case, laparoscopic excision of cyst and histopathological examination confirmed the diagnosis of cyst hydatid. At the postoperative second month the ultrasonography of kidneys were normal. For patients from endemic areas, hydatid cyst should always be included in the differential diagnosis. Laparoscopic excision of renal hydatid cysts with diode laser is a feasible and safe technique for resistant cases. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier

  9. Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review.

    PubMed

    Mauch, Renan Marrichi; Kmit, Arthur Henrique Pezzo; Marson, Fernando Augusto de Lima; Levy, Carlos Emilio; Barros-Filho, Antonio de Azevedo; Ribeiro, José Dirceu

    2016-12-01

    To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis. A collection of articles published in the last 15 years in English, Portuguese and Spanish was made by research in electronic databases - PubMed, Cochrane, Medline, Lilacs and Scielo - using the keywords cystic fibrosis, growth, nutrition, pulmonary function in varied combinations. Articles that addressed the long term association of growth and nutritional parameters, with an emphasis on growth, with pulmonary disease in cystic fibrosis, were included, and we excluded those that addressing only the relationship between nutritional parameters and cystic fibrosis and those in which the aim was to describe the disease. Seven studies were included, with a total of 12,455 patients. Six studies reported relationship between growth parameters and lung function, including one study addressing the association of growth parameters, solely, with lung function, and all the seven studies reported relationship between nutritional parameters and lung function. The review suggests that the severity of the lung disease, determined by spirometry, is associated with body growth and nutritional status in cystic fibrosis. Thus, the intervention in these parameters can lead to the better prognosis and life expectancy for cystic fibrosis patients. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Evolution of Cardiovascular Disease During the Transition to End-Stage Renal Disease.

    PubMed

    Bansal, Nisha

    2017-03-01

    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The rate of death in incident dialysis patients remains high. This has led to interest in the study of the evolution of CVD during the critical transition period from CKD to ESRD. Understanding the natural history and risk factors of clinical and subclinical CVD during this transition may help guide the timing of appropriate CVD therapies to improve outcomes in patients with kidney disease. This review provides an overview of the epidemiology of subclinical and clinical CVD during the transition from CKD to ESRD and discusses clinical trials of CVD therapies to mitigate risk of CVD in CKD and ESRD patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Mitochondrial tRNAPhe mutation as a cause of end-stage renal disease in childhood

    PubMed Central

    D’Aco, Kristin E; Manno, Megan; Clarke, Colleen; Ganesh, Jaya; Meyers, Kevin EC; Sondheimer, Neal

    2012-01-01

    Background We identified a mitochondrial tRNA mutation (m.586G>A) in a patient with renal failure and symptoms consistent with a mitochondrial cytopathy. This mutation was of unclear significance because there were neither consistent reports of linkage to specific disease phenotypes nor an existing analysis of effects upon mitochondrial function. Case-Diagnosis/Treatment A 16-month-old girl with failure-to-thrive, developmental regression, persistent lactic acidosis, hypotonia, GI dysmotility, adrenal insufficiency and hematologic abnormalities developed hypertension and renal impairment with chronic tubulointerstitial fibrosis, progressing to renal failure with need for peritoneal dialysis. Evaluation of her muscle and blood identified a mutation of the mitochondrial tRNA for phenylalanine, m.586G>A. Conclusions The m.586G>A mutation is pathogenic and is a cause of end-stage renal disease in childhood. The mutation interferes with the stability of tRNAPhe and affects the translation of mitochondrial proteins and the stability of the electron transport chain. PMID:23135609

  12. Different renal phenotypes in related adult males with Fabry disease with the same classic genotype.

    PubMed

    Mignani, Renzo; Moschella, Mariarita; Cenacchi, Giovanna; Donati, Ilaria; Flachi, Marta; Grimaldi, Daniela; Cerretani, Davide; Giovanni, Paola De; Montevecchi, Marcello; Rigotti, Angelo; Ravasio, Alessandro

    2017-07-01

    Fabry disease related patients with classical mutation usually exhibit similar severe phenotype especially concerning renal manifestation. A dry blood spot screening (DBS) and the DNA analysis has been performed in a 48-year-old man (Patient 1) because of paresthesia. The DBS revealed absent leukocyte α -Gal A enzyme activity while DNA analysis identified the I354K mutation. Serum creatinine and e-GFR were in normal range and also albuminuria and proteinuria were absent. The brain MRI showed ischemic lesions and a diffuse focus of gliosis in the white matter, while the echocardiogram showed a left ventricular hypertrophy. The renal biopsy performed in the case index showed a massive deposition of zebra bodies. By a familiar investigation, it was recognized that his brother (Patient 2) died 2 years before from sudden death syndrome at the age of 49. He had suffered sporadic and undiagnosed pain at the extremities, a prior cataract, bilateral neurosensorial hearing loss and left ventricular hypertrophy on Echocardiogram. His previous laboratory examinations revealed a normal serum creatinine and the absence of proteinuria. Pedigree analysis of the brothers revealed a high disease burden among family members, with an affected cousin (Patient 3) who progressed early to end-stage renal disease (ESRD) that required renal transplantation. Here we describe the clinical history of three adult male members of the same family with the same genotype who manifested different presentation and progression of the disease, particularly concerning the renal involvement.

  13. [Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

    PubMed

    Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

    2014-12-08

    A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

  14. Diabetes mellitus as a risk factor for incident chronic kidney disease and end-stage renal disease in women compared with men: a systematic review and meta-analysis.

    PubMed

    Shen, Yanjue; Cai, Rongrong; Sun, Jie; Dong, Xue; Huang, Rong; Tian, Sai; Wang, Shaohua

    2017-01-01

    Diabetes mellitus is a strong risk factor for chronic kidney disease and end-stage renal disease. Whether sex differences in chronic kidney disease and end-stage renal disease incidence exist among diabetic patients remains unclear. This systematic review and meta-analysis was conducted to evaluate the relative effect of diabetes on chronic kidney disease and end-stage renal disease risk in women compared with men. We systematically searched Embase, PubMed, and the Cochrane Library for both cohort and case-control studies until October 2015. Studies were selected if they reported a sex-specific relationship between diabetes mellitus and chronic kidney disease or end-stage renal disease. We generated pooled estimates across studies using random-effects meta-analysis after log transformation with inverse variance weighting. Ten studies with data from more than 5 million participants were included. The pooled adjusted risk ratio of chronic kidney disease associated with diabetes mellitus was 3.34 (95 % CI 2.27, 4.93) in women and 2.84 (95 % CI 1.73, 4.68) in men. The data showed no difference in diabetes-related chronic kidney disease risk between the sexes (pooled adjusted women-to-men relative risk ratio was 1.14 [95 % CI 0.97, 1.34]) except for end-stage renal disease-the pooled adjusted women-to men relative risk ratio was 1.38 (95 % CI 1.22, 1.55; p = 0.114, I² = 38.1 %). The study found no evidence of a sex difference in the association between diabetes mellitus and chronic kidney disease. However, the excess risk for end-stage renal disease was higher in women with diabetes than in men with the same condition, from which we assume that the female gender could accelerate the disease progression. Further studies are needed to support this notion and elucidate the underlying mechanisms.

  15. ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis.

    PubMed

    Pankow, Sandra; Bamberger, Casimir; Calzolari, Diego; Martínez-Bartolomé, Salvador; Lavallée-Adam, Mathieu; Balch, William E; Yates, John R

    2015-12-24

    Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (∆F508 CFTR) is the major cause of cystic fibrosis, one of the most common inherited childhood diseases. The mutated CFTR anion channel is not fully glycosylated and shows minimal activity in bronchial epithelial cells of patients with cystic fibrosis. Low temperature or inhibition of histone deacetylases can partly rescue ∆F508 CFTR cellular processing defects and function. A favourable change of ∆F508 CFTR protein-protein interactions was proposed as a mechanism of rescue; however, CFTR interactome dynamics during temperature shift and inhibition of histone deacetylases are unknown. Here we report the first comprehensive analysis of the CFTR and ∆F508 CFTR interactome and its dynamics during temperature shift and inhibition of histone deacetylases. By using a novel deep proteomic analysis method, we identify 638 individual high-confidence CFTR interactors and discover a ∆F508 deletion-specific interactome, which is extensively remodelled upon rescue. Detailed analysis of the interactome remodelling identifies key novel interactors, whose loss promote ∆F508 CFTR channel function in primary cystic fibrosis epithelia or which are critical for CFTR biogenesis. Our results demonstrate that global remodelling of ∆F508 CFTR interactions is crucial for rescue, and provide comprehensive insight into the molecular disease mechanisms of cystic fibrosis caused by deletion of F508.

  16. The value of ultrasonography alone in screening surveys of cystic echinococcosis in children in Turkey.

    PubMed

    Kilimcioğlu, Ali A; Ozkol, Mine; Bayindir, Petek; Girginkardeşler, Nogay; Ostan, Ipek; Ok, Ulgen Z

    2006-12-01

    A total of 1,205 primary school children were examined for cystic echinococcosis in five villages of Manisa, Turkey, to evaluate the efficacy of diagnostic methods of this infection in community-based screening surveys. Six hundred and thirty children from three villages, examined by a portable ultrasound scanner, chest microfilm and serological methods (ELISA, indirect hemagglutination) in our previous study, were designated as Study Group 1; and 575 children, from two adjacent villages, examined by ultrasonography alone in the present study, were designated as Study Group 2. In Study Group 1, hepatic cystic echinococcosis was detected in two cases (0.3%) by ultrasonography, while 43 (8.9%) and 49 (10.1%) cases were found to be positive for cystic echinococcosis by ELISA and indirect hemagglutination, respectively. Three of 575 children (0.5%) were diagnosed with cystic echinococcosis (two hepatic and one renal involvement) by ultrasonography alone in Study Group 2; and lung lesions were later detected in both cases with liver involvement by chest radiography. Our results suggested that serological tests may be beneficial in suspected cases for confirmation and differential diagnosis, but have some drawbacks, such as discrepancy in results and high false seropositivity rates. Chest microfilm is not easy in field studies and exposure to X-ray is undesirable. As a reliable, simple, inexpensive and rapid technique, ultrasonography alone is recommended to be used in community-based screening surveys for cystic echinococcosis with confirmatory tests for suspected cases found during the screening program.

  17. Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verhaeghe, Catherine; Tabruyn, Sebastien P.; Oury, Cecile

    Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been suggested, probably caused by the process of inflammation, as similarly described in asthma and chronic bronchitis. The present study demonstrates an intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. Microarray experiments showed that CF airway epithelial cells expressed several angiogenic factors such as VEGF-A, VEGF-C, bFGF, and PLGF at higher levels than control cells. These data were confirmed by real-time quantitative PCR and, at the protein level, by ELISA. Conditionedmore » media of these cystic fibrosis cells were able to induce proliferation, migration and sprouting of cultured primary endothelial cells. This report describes for the first time that cystic fibrosis epithelial cells have an intrinsic angiogenic activity. Since excess of angiogenesis is correlated with more severe pulmonary disease, our results could lead to the development of new therapeutic applications.« less

  18. GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

    PubMed Central

    Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

    2013-01-01

    Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

  19. A service evaluation of an integrated model of palliative care of cystic fibrosis.

    PubMed

    Bourke, Stephen J; Booth, Zoe; Doe, Simon; Anderson, Alan; Rice, Sarah; Gascoigne, Alistair; Quibell, Rachel

    2016-07-01

    Patients with advanced cystic fibrosis have severe symptoms with a complex trajectory of exacerbations and recovery. They are often awaiting lung transplantation, and many die without receiving specialist palliative care. We introduced an integrated model whereby palliative specialists joined the cystic fibrosis team to provide palliative care in parallel with standard care. A service evaluation of this model of care was undertaken in a prospective case series documenting symptoms and outcomes, the views of the cystic fibrosis team and the experience of the palliative specialists. Over 3 years, 28 (10%) of 282 patients attending the cystic fibrosis centre had specialist palliative care. They had advanced lung disease (mean forced expiratory volume in 1 s (FEV1) = 0.86 L (25% predicted)), and 17 died: 6 were on a transplant waiting list at death; 10 were unsuitable and 1 died post transplantation. All who died over these 3 years had specialist palliative care. Four patients had successful transplants. Assessment showed a high prevalence of breathlessness, cough, pain, vomiting and fatigue, with a significant impact on daily life. The cystic fibrosis team rated this model of care highly, felt that palliative care should be members of the team, and thought that patients had found it helpful. The palliative specialists gained knowledge of cystic fibrosis, found it beneficial to meet patients earlier in the disease, and identified unmet needs in managing bereavement and the effects of deaths on other patients with cystic fibrosis. This model has been successful in overcoming the difficulties in access to specialist palliative care for patients with cystic fibrosis. © The Author(s) 2016.

  20. Parental care and overprotection of children with cystic fibrosis.

    PubMed

    Cappelli, M; McGrath, P J; MacDonald, N E; Katsanis, J; Lascelles, M

    1989-09-01

    Parental overprotection has often been clinically associated with the psychological maladjustment of children with a chronic disease. The purpose of this study was to examine parental care and overprotection in children with cystic fibrosis compared to healthy controls. Results indicated no differences in the level of parental care or overprotection between controls and children with cystic fibrosis. However, a number of significant correlations were found between parental care and overprotection and children's psychosocial functioning. In particular, positive correlations were found between parental overprotection and poor psychosocial functioning in children with cystic fibrosis, whereas, poor psychosocial functioning in healthy children was associated with lack of parental care. Parental overprotection and care appear to play important roles in the emotional and psychological functioning of healthy and chronically ill children.

  1. CT imaging spectrum of infiltrative renal diseases.

    PubMed

    Ballard, David H; De Alba, Luis; Migliaro, Matias; Previgliano, Carlos H; Sangster, Guillermo P

    2017-11-01

    Most renal lesions replace the renal parenchyma as a focal space-occupying mass with borders distinguishing the mass from normal parenchyma. However, some renal lesions exhibit interstitial infiltration-a process that permeates the renal parenchyma by using the normal renal architecture for growth. These infiltrative lesions frequently show nonspecific patterns that lead to little or no contour deformity and have ill-defined borders on CT, making detection and diagnosis challenging. The purpose of this pictorial essay is to describe the CT imaging findings of various conditions that may manifest as infiltrative renal lesions.

  2. Adult Henoch-Schönlein purpura: Clinical and histopathological predictors of systemic disease and profound renal disease.

    PubMed

    Cao, Ruoxi; Lau, Sandra; Tan, Virlynn; Tey, Hong Liang

    2017-01-01

    A major challenge in the management of adult Henoch-Schönlein purpura is the difficulty in assessing the risk of systemic involvement. There is currently a paucity of data in this area. This study sought to determine specific clinical and histopathological features associated with systemic involvement in adult Henoch-Schönlein purpura. We reviewed the records of 99 adult Henoch-Schönlein purpura patients who presented at the National Skin Centre, Singapore, between January 2008 and May 2015. Renal involvement was found in 56 (56.6%) patients, joint involvement in 21 (21.2%) and gastrointestinal involvement in 13 (13.1%). Age > 30 years was an independent predictor of renal involvement with an adjusted odds ratio of 2.97 (95% confidence interval, 1.08-8.16; P = 0.04). Risk factors for significant renal involvement necessitating nephrology referral were further evaluated: the odds were approximately 60% higher for every 10-year increase in age (95% confidence interval, 1.02-2.57; P = 0.04) and patients with cutaneous bullae and/or necrosis had an almost six times higher risk (95% confidence interval, 1.43-25.00; P = 0.01). This study was limited by its retrospective design. We also lacked long-term data to examine how clinical and histopathological characteristics correlated with long-term disease outcomes. Adult Henoch-Schönlein purpura patients older than 30 years have a threefold increased risk of renal involvement. The risk of profound renal disease necessitating nephrology referral rose significantly with age and the presence of cutaneous bullae and/or necrosis.

  3. End-Stage Renal Disease Models in the Americas: Optimizing Resources to Achieve Better Health Outcomes.

    PubMed

    Gilardino, Ramiro E; González-Pier, Eduardo; Brabata, Claudia

    2018-05-21

    End-stage renal disease, the last and most severe stage of chronic kidney disease, represents a major and rising concern for countries in Latin America, driven in large part by aging populations and the near-epidemic rises in diabetes, obesity, and hypertension. This places a great clinical, economic, and social burden on the region's health systems. During the ISPOR 6th Latin America Conference held in Sao Paulo, Brazil, in September 2017, an educational forum debated on value-based decision making in the treatment of end-stage renal disease in Latin America. We summarize the current state and how to build strategies and implement actions to move to a more patient-centered, outcomes-based approach for renal care in the region, taken from the discussions in the conference and also from a literature review. Models of renal care used in Ontario (Canada), Colombia, and a Chilean hospital stress the importance of empowering and supporting patients and their families, allowing for a better coordination between primary care providers and specialists, providing financial incentives to health units, and establishing an entity that holds insurers and providers accountable for health outcomes and costs of treatment. The study uses the framework of value-based health care for the evaluation of different dialysis options-peritoneal dialysis, hemodialysis, home dialysis, and so forth-and calls for the countries to adopt an integrated care model. We emphasize that countries in Latin America need to recognize the chronic kidney disease challenge and develop health systems and efficient renal care models to be able to reduce the burden of the disease. Copyright © 2018. Published by Elsevier Inc.

  4. Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease.

    PubMed

    El Machhour, Fala; Keuylian, Zela; Kavvadas, Panagiotis; Dussaule, Jean-Claude; Chatziantoniou, Christos

    2015-07-01

    Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. Copyright © 2015 by the American Society of Nephrology.

  5. CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease.

    PubMed

    Bonadia, Luciana Cardoso; de Lima Marson, Fernando Augusto; Ribeiro, Jose Dirceu; Paschoal, Ilma Aparecida; Pereira, Monica Corso; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia

    2014-05-01

    There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics. Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I). There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF

  6. Protocols for treating patients with end-stage renal disease: a survey of nephrology fellowships.

    PubMed

    Perry, Maureen Munnelly; Howell, Scott; Patel, Nipa

    2017-03-01

    Approximately 14% of Americans are living with chronic kidney disease (CKD). The prevalence of end-stage renal disease (ESRD), the result of progressing CKD continues to rise by 21,000 per year. Currently, the only antibiotic prophylaxis guidelines for patients with ESRD undergoing dental treatment were published by the AHA in 2003. Presented in three parts, the first and second parts of this study found no consistent protocols amongst U.S. dental schools and U.S. GPRs and AEGDs, respectively. The goal of the third part of the project was to determine the current protocol being used to treat ESRD patients at U.S. nephrology fellowship programs. An 18 multiple-choice question survey was e-mailed to 130 directors of nephrology fellowships within the U.S. regarding renal treatment protocol details and antibiotic prophylaxis for patients with renal disease. Note that, 34.6% of respondents reported having an established renal treatment protocol. For programs with a protocol, 69% of programs reported following AHA guidelines. There is a lack of consistent, established protocols amongst U.S. nephrology fellowships. It is suggested that updated and evidence based guidelines for the safe treatment of patients be developed. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

  7. Predictors of renal and patient outcomes in anti-GBM disease: clinicopathologic analysis of a two-centre cohort.

    PubMed

    Alchi, Bassam; Griffiths, Meryl; Sivalingam, Murugan; Jayne, David; Farrington, Ken

    2015-05-01

    Patients with anti-glomerular basement membrane (GBM) disease are at increased risk of morbidity and mortality from renal failure, pulmonary haemorrhage or complications of treatment. One-third also have circulating anti-neutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine the clinicopathologic predictors of patient and renal outcomes in anti-GBM disease with or without ANCA. Retrospective review of 43 patients diagnosed with anti-GBM disease over 20 years in two centres, including nine with dual anti-GBM and ANCA positivity. Renal biopsies from 27 patients were scored for the presence of active and chronic lesions. Dual-positive patients were almost 20 years older than those with anti-GBM positivity alone (P = 0.003). The overall 1-year patient and renal survivals were 88 and 16%, respectively. Oligoanuria at diagnosis was the strongest predictor of mortality; none of the 16 patients without oligoanuria died. In a Cox regression model excluding oligoanuria, age was the only other independent predictor of survival. Pulmonary haemorrhage and dialysis dependence did not influence mortality. Thirty-five of the forty-three (81%) patients required dialysis at presentation, including all nine dual-positive patients. Of them, only two (5.7%) regained renal function at 1 year. By logistic regression, oligoanuria at diagnosis and percentage of crescents were independent predictors of dialysis independence at 3 months. However, in biopsied patients, the presence of crescents (>75%) added little to the presence of oligoanuria in predicting dialysis independence. Histological activity and chronicity indices did not predict renal outcome. Two of the nine (22%) dual-positive patients relapsed compared with none of the anti-GBM alone patients. Seven patients received kidney transplants without disease recurrence. Oligoanuria is the strongest predictor of patient and renal survival while percentage of glomerular crescents is the only pathologic

  8. Inadequate erythroid response to hypoxia in cystic fibrosis.

    PubMed

    Vichinsky, E P; Pennathur-Das, R; Nickerson, B; Minor, M; Kleman, K; Higashino, S; Lubin, B

    1984-07-01

    An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.

  9. Does overall environmental quality affect end-stage renal disease survival?

    EPA Science Inventory

    Prevalence of end-stage renal disease (ESRD) in the U.S. increased by 74% from 2000 to 2013, with a 5-year survival of only 42%. To investigate associations between environmental quality and ESRD survival time, we used the Environmental Quality Index (EQI), an aggregate measure o...

  10. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    PubMed Central

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  11. Change in Lactate Levels After Hemodialysis in Patients With End-Stage Renal Disease.

    PubMed

    Hourmozdi, Justin J; Gill, Jasreen; Miller, Joseph B; Markin, Abraham; Adams, Beth; Soi, Vivek; Jaehne, Anja K; Taylor, Andrew R; Langberg, Sam; Rodriguez, Lauren; Fox, Carynne; Uduman, Junior; Yessayan, Lenar T; Rivers, Emanuel P

    2018-06-01

    Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels. This was a prospective observational cohort study performed at an outpatient dialysis facility at an urban tertiary care hospital. The study consisted of 226 patients with end-stage renal disease who were receiving long-term hemodialysis and were enrolled during a 2-day period at the beginning of December 2015. Blood drawn for lactate levels was immediately analyzed before and after hemodialysis sessions. All patients completed their hemodialysis sessions. The prevalence of an abnormal lactate level (greater than 1.8 mmol/L) before hemodialysis was 17.7% (n=40). Overall, lactate levels decreased by 27% (SD 35%) after hemodialysis, with a decrease of 37% (SD 31%) for subgroups with a lactate level of 1.9 to 2.4 mmol/L, and 62% (SD 14%) with a lactate of 2.5 to 3.9 mmol/L. The data presented help providers understand the prevalence of abnormal lactate values in an outpatient end-stage renal disease population. After hemodialysis, lactate levels decreased significantly. This information may help medical providers interpret lactate values when patients with end-stage renal disease present to the ED. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  12. End-Stage Renal Disease From Cast Nephropathy in a Teenager With Neuroendocrine Carcinoma.

    PubMed

    Butani, Lavjay; Ducore, Jonathan

    2016-07-01

    Cast nephropathy is the most common manifestation of renal injury in patients with multiple myeloma but is rarely reported in other conditions. We are reporting our experience in caring for a teenager with a metastatic neuroendocrine carcinoma who developed rapidly progressive kidney injury that advanced to end-stage renal disease. On renal biopsy extensive tubular necrosis and intratubular eosinophilic casts were noted. This previously unreported finding should prompt oncologists to closely monitor for such a complication in patients with secretory tumors. Whether early plasmapheresis could be of benefit, as has been tried in multiple myeloma, remains to be determined.

  13. Albumin modification and fragmentation in renal disease.

    PubMed

    Donadio, Carlo; Tognotti, Danika; Donadio, Elena

    2012-02-18

    Albumin is the most important antioxidant substance in plasma and performs many physiological functions. Furthermore, albumin is the major carrier of endogenous molecules and exogenous ligands. This paper reviews the importance of post-translational modifications of albumin and fragments thereof in patients with renal disease. First, current views and controversies on renal handling of proteins, mainly albumin, will be discussed. Post-translational modifications, namely the fragmentation of albumin found with proteomic techniques in nephrotic patients, diabetics, and ESRD patients will be presented and discussed. It is reasonable to hypothesize that proteolytic fragmentation of serum albumin is due to a higher susceptibility to proteases, induced by oxidative stress. The clinical relevance of the fragmentation of albumin has not yet been established. These modifications could affect some physiological functions of albumin and have a patho-physiological role in uremic syndrome. Proteomic analysis of serum allows the identification of over-expressed proteins and can detect post-translational modifications of serum proteins, hitherto hidden, using standard laboratory techniques. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, Tim W R; Southern, Kevin W; Perry, Luke A; Penny-Dimri, Jahan C; Aslam, Aisha A

    2016-06-17

    Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 05 May 2016.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015.Date of most recent search: 20 April 2016. Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over.Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were

  15. Twelve shifting paradigms in diabetic renal disease and hypertension.

    PubMed

    Mogensen, Carl Erik

    2008-11-13

    In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. . Significant renal involvement and albuminuria is rare in patients with essential hypertension. 2. High GFR is good for prognosis. 3. Only proteinuric diabetic patients have a poor prognosis. 4. Microalbuminuria only predicts renal disease. 5. Reducing blood pressure may cause low perfusion in the kidney and other organs with long-term negative effect, especially on the glomerular filtration rate. 6. Only in the presence of high blood pressure, should microalbuminuric patients receive anti-hypertensive treatment, including blockade of the RAS. 7. Only reducing blood pressure by blocking RAS in diabetes is relevant and justified. 8. Normoalbuminuria as indicated in the present definition is 'normal'. 9. ACE-I or ARB can only be used separately. 10. Diastolic blood pressure and later systolic pulse pressure are the best parameters for blood pressure recording. 11. Microalbuminuria is the strongest risk marker in patients with type 1 diabetes. 12. Screening for microalbuminuria is relevant, but follow-up was not proposed (also regarding microalbuminuria). In the present situation, it is well-known that patients with essential hypertension may sometimes have microalbuminuria, and it is known that it predicts a poor prognosis. Interestingly, in type 1 diabetes, hyperfiltration is a marker for poor prognosis related to metabolic control. Thus hyperfiltration is a marker for bad development, but microalbuminuria (below the proteinuric level) is also associated with a poor prognosis. It was originally believed that microalbuminuria only predicts renal disease. However, surprisingly it predicts as well cardiovascular disease and early mortality. The story about blood pressure and progression of renal disease

  16. Cystic echinococcosis of the liver: A primer for hepatologists

    PubMed Central

    Rinaldi, Francesca; Brunetti, Enrico; Neumayr, Andreas; Maestri, Marcello; Goblirsch, Samuel; Tamarozzi, Francesca

    2014-01-01

    Cystic echinococcosis (CE) is a complex, chronic and neglected disease with a worldwide distribution. The liver is the most frequent location of parasitic cysts. In humans, its clinical spectrum ranges from asymptomatic infection to severe, potentially fatal disease. Four approaches exist in the clinical management of CE: surgery, percutaneous techniques and drug treatment for active cysts, and the ”watch and wait” approach for inactive cysts. Allocation of patients to these treatments should be based on cyst stage, size and location, available clinical expertise, and comorbidities. However, clinical decision algorithms, efficacy, relapse rates, and costs have never been properly evaluated. This paper reviews recent advances in classification and diagnosis and the currently available evidence for clinical decision-making in cystic echinococcosis of the liver. PMID:24868323

  17. Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

    PubMed

    Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

    2017-06-15

    Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

  18. The burden of disease in pediatric non-cystic fibrosis bronchiectasis.

    PubMed

    Kapur, Nitin; Masters, I Brent; Newcombe, Peter; Chang, Anne B

    2012-04-01

    The burden of disease in children with non-cystic fibrosis (non-CF) bronchiectasis is unknown. Our study aimed to identify the determinants of quality of life (QOL) and parental mental health in this group of patients and their parents and to evaluate the effect of exacerbations on these parameters. Parents of 69 children (median age 7 years) with non-CF bronchiectasis prospectively completed two questionnaires (parent-proxy cough-specific quality of life [PC-QOL] and the Depression, Anxiety, and Stress Scale [DASS]) at stable and exacerbation states. Data on clinical, investigational, and lung function parameters were also collected. During the stable state, the median interquartile range (IQR) PC-QOL score was 6.5 (5.3-6.9) and the DASS 21-item questionnaire score was 6 (0-20). Being of a young age correlated with a worse QOL (r(5) = 0.242, P = .04) but radiologic extent, lung function, underlying cause, environmental tobacco smoke exposure, and chronic upper-airway disease did not influence these scores. Exacerbations caused significant worsening in the PC-QOL scores (median [IQR], 4.6 [3.8-5.4]; P = .001) and DASS scores (median [IQR], 22 [9-42]; P < .001; 38% with elevated anxiety, 54% with abnormal depression/stress scores during exacerbation). The presence of viral infection, hypoxia, and hospitalization did not influence the exacerbation PC-QOL and DASS scores. There is a significant burden of disease, especially during exacerbation, on parents of children with bronchiectasis. Prevention, early detection, and appropriate treatment of exacerbations are likely to reduce psychologic morbidity in this group.

  19. [Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients].

    PubMed

    Gorriz, José L; Gutiérrez, Félix; Trullàs, Joan C; Arazo, Piedad; Arribas, Jose R; Barril, Guillermina; Cervero, Miguel; Cofán, Frederic; Domingo, Pere; Estrada, Vicente; Fulladosa, Xavier; Galindo, María J; Gràcia, Sílvia; Iribarren, José A; Knobel, Hernando; López-Aldeguer, José; Lozano, Fernando; Martínez-Castelao, Alberto; Martínez, Esteban; Mazuecos, Maria A; Miralles, Celia; Montañés, Rosario; Negredo, Eugenia; Palacios, Rosario; Pérez-Elías, María J; Portilla, Joaquín; Praga, Manuel; Quereda, Carlos; Rivero, Antonio; Santamaría, Juan M; Sanz, José; Sanz, Jesús; Miró, José M

    2014-11-01

    The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Technological advances shed light on left ventricular cardiac disturbances in cystic fibrosis.

    PubMed

    Sayyid, Zahra N; Sellers, Zachary M

    2017-07-01

    Cystic fibrosis (CF), the most common autosomal recessive lethal disease in Caucasians, causes chronic pulmonary disease and can lead to cor pulmonale with right ventricular dysfunction. The presence of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiac myocardia has prompted debate regarding possible defective ion channel-induced cardiomyopathy. Clinical heart disease in CF is considered rare and is restricted to case reports. It has been unclear if this is due to the lack of physiological importance of CFTR in the heart, the relatively short lifespan of those with CF, or a technical inability to detect subclinical disease. Extensive echocardiographic investigations have yielded contradictory results, leading to the dogma that left ventricular defects in CF occur secondary to lung disease. In this review, we consider why studies examining heart function in CF have not provided clarity on this topic. We then focus on data from new echocardiographic and magnetic resonance imaging technology, which are providing greater insight into cardiac function in CF and demonstrating that, in addition to secondary effects from pulmonary disease, there may be an intrinsic primary defect in the CF heart. With advancing lifespans and activity levels, understanding the risk of cardiac disease is vital to minimizing morbidity in adults with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

    PubMed Central

    Simons, Matias; Gloy, Joachim; Ganner, Athina; Bullerkotte, Axel; Bashkurov, Mikhail; Krönig, Corinna; Schermer, Bernhard; Benzing, Thomas; Cabello, Olga A; Jenny, Andreas; Mlodzik, Marek; Polok, Bozena; Driever, Wolfgang; Obara, Tomoko; Walz, Gerd

    2013-01-01

    Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells1. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure2. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development. PMID:15852005

  2. Complementary and alternative medicine use in children with cystic fibrosis.

    PubMed

    Giangioppo, Sandra; Kalaci, Odion; Radhakrishnan, Arun; Fleischer, Erin; Itterman, Jennifer; Lyttle, Brian; Price, April; Radhakrishnan, Dhenuka

    2016-11-01

    To estimate the overall prevalence of complementary and alternative medicine use among children with cystic fibrosis, determine specific modalities used, predictors of use and subjective helpfulness or harm from individual modalities. Of 53 children attending the cystic fibrosis clinic in London, Ontario (100% recruitment), 79% had used complementary and alternative medicine. The most commonly used modalities were air purifiers, humidifiers, probiotics, and omega-3 fatty acids. Family complementary and alternative medicine use was the only independent predictor of overall use. The majority of patients perceived benefit from specific modalities for cystic fibrosis symptoms. Given the high frequency and number of modalities used and lack of patient and disease characteristics predicting use, we recommend that health care providers should routinely ask about complementary and alternative medicine among all pediatric cystic fibrosis patients and assist patients in understanding the potential benefits and risks to make informed decisions about its use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. [Decline in renal function in old age : Part of physiological aging versus age-related disease].

    PubMed

    Braun, F; Brinkkötter, P T

    2016-08-01

    The incidence and prevalence of chronic renal disease (CKD) in elderly patients are continuously increasing worldwide. Loss of renal function is not only considered to be part of the aging process itself but also reflects the multimorbidity of many geriatric patients. Calculating the glomerular filtration rate using specific algorithms validated for the elderly population and measuring the amount of proteinuria allow an estimation of renal function in elderly patients with high accuracy. Chronic renal failure has many clinical consequences and not only results in a delayed excretion of toxins cleared by the kidneys but also affects hematogenesis, water and electrolyte balance as well as mineral bone metabolism. Furthermore, CKD directly leads to and aggravates geriatric syndromes and in particular the onset of frailty. Therapeutic strategies to halt progression of CKD not only comprise treatment of the underlying disease but also efficient blood pressure and diabetic control and the avoidance of nephrotoxic medications.

  4. Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

    PubMed

    Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

    2015-10-01

    We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular

  5. Cystic echinococcosis: A neglected disease at usual and unusual locations.

    PubMed

    Sarkar, Soma; Roy, Himansu; Saha, Puranjay; Sengupta, Mallika; Sarder, Krisnendu; Sengupta, Manideepa

    2017-01-01

    Echinococcus granulosus causes a zoonotic infection called cystic echinococcosis (CE) or more commonly known as hydatid disease. Although the two most common locations of hydatid cyst are liver and lung, it may also appear in other parts of the body. Clinical presentation of the hydatid disease depends on the site and size of the lesion. A retrospective study was done in Medical College and Hospital, Kolkata, from January 2012 to June 2014, to find the site of involvement, distribution, clinical features, history of contact, mode of presentation, laboratory diagnosis, and treatment modalities of the cases of hydatid cyst. The cases were identified by radiological and laboratory methods, the data were entered in Excel spreadsheet, and analysis was done. Among the 21 cases of hydatid cyst included in the study, solitary hepatic involvement was seen in 11 (52.38%), pulmonary involvement in 4 (19%), and 6 (28.71%) were in unusual locations such as liver cyst extending as retroperitoneal, omental cyst, choledochal cyst, splenic cyst, and in hepatorenal pouch. History of contact with dog was seen in 15 (71.43%). All the patients were treated with surgery and albendazole and were discharged in healthy condition. CE may be present in usual and unusual locations with a lot of variations in the clinical features. Hence, proper radiological and laboratory diagnosis is required for accurate diagnosis and appropriate management of these cases.

  6. Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis.

    PubMed

    Vic, P; Ategbo, S; Turck, D; Husson, M O; Launay, V; Loeuille, G A; Sardet, A; Deschildre, A; Druon, D; Arrouet-Lagande, C

    1998-06-01

    To compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. 22 patients with cystic fibrosis, mean (SD) age 11 (3.4) years (range 5.6-19.3), with pulmonary pseudomonas exacerbations were randomly assigned to receive a 14 day course of tobramycin (15 mg/kg/day) either in three infusions (group A) (n = 10) or a single daily infusion (group B) (n = 12), combined with ceftazidime (200 mg/kg/day as three intravenous injections). Efficacy was assessed by comparison of pulmonary, nutritional, and inflammatory indices on days 1 and 14. Cochlear and renal tolerance were assessed on days 1 and 14. Tobramycin concentration was measured in serum and sputum 1, 2, 3, 4, 8, and 24 hours after the start of the infusion. Analysis was by non-parametric Wilcoxon test. Variables improving (p < 0.05) in both groups A and B were, respectively: weight/height (+4% and +3.1%), plasma prealbumin (+66 and +63 mg/l), forced vital capacity (FVC) (+14% and +11%), forced expiratory volume in one second (+15% and +14%), and forced expiratory flow between 25% and 75% of FVC (+13% and +21%). Improvement was not significantly different between groups. Renal and cochlear indices remained within the normal range. Serum peak concentration of tobramycin on day 1 was 13.2 (7.1) mg/l in group A and 42.5 (11.2) mg/l in group B (p < 0.001); serum trough was 1.1 (0.8) mg/l in group A and 0.3 (0.2) mg/l in group B (p < 0.01). Tobramycin concentrations in sputum were two to three times higher in group B than group A. Once daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in cystic fibrosis patients.

  7. Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases.

    PubMed

    Han, Eugene; Lee, Yong Ho

    2017-12-01

    As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.

  8. [MALIGNANT TUMORS IN OVARIAN MATURE CYSTIC TERATOMAS INTRAOPERATIVE DIAGNOSTIC BASIS].

    PubMed

    Khachatryan, A

    2016-11-01

    Extremely rare ovarian primary tumors formed in a mature cystic teratomaare described in the literature. This research work studies the frequency of malignant mature cystic teratoma, as well as their clinical and morphological features and necessity of intraoperative histological examination of all teratomas. Cases histories of 56 patients, suffering from ovarian mature cystic teratomahave been studied in MC Shengavit in the period of 2003 - 2015. Among them 4 patients with the somatic malignancies were identified. Morphological methods, which are considered to be "gold standard" of tumor investigation, were used in staining the slides with hematoxylin - eosin. According to the literature the secondary malignant transformation rarely occurs and is typical in postmenopausal women, with a frequency of 0.17-3%. According to the results of our study, malignant tumors in mature cystic teratomas were observed in 4 (7,14%) from the total number of mature cystic teratomas (n=56). There was not revealed a correlation between the duration of the complaints, age of the patients, sizes of ovarian mature teratoma and malignization degree. Thus, the greatest difficulties of clinical diagnosis of malignant tumors in the ovarian mature cystic teratomas were in the early stage of the disease, because of a variety of clinical manifestations, not pathognomonic for malignization. All mentioned symptoms may be observed in the patients with usual mature cystic teratomas. Тhis cases confirm the necessity to take tissue samples from the other ovary for intraoperative histopathological evaluation in each case of mature cystic teratomas. It is necessary to examine a large number of tumor sites, to prevent errors in the assessment of the maturity degree of teratoma.

  9. CFTR Modulators for the Treatment of Cystic Fibrosis.

    PubMed

    Pettit, Rebecca S; Fellner, Chris

    2014-07-01

    Defects in a single gene lead to the defective proteins that cause cystic fibrosis, making the disease an ideal candidate for mutation-targeted therapy. Although ivacaftor is currently the only FDA-approved CFTR modifier, others are in development.

  10. Comparative biology of cystic fibrosis animal models.

    PubMed

    Fisher, John T; Zhang, Yulong; Engelhardt, John F

    2011-01-01

    Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

  11. A systematic review of clinical value of three-dimensional printing in renal disease.

    PubMed

    Sun, Zhonghua; Liu, Dongting

    2018-04-01

    The aim of this systematic review is to analyse current literature related to the clinical value of three-dimensional (3D) printed models in renal disease. A literature search of PubMed and Scopus databases was performed to identify studies reporting the clinical application and usefulness of 3D printed models in renal disease. Fifteen studies were found to meet the selection criteria and were included in the analysis. Eight of them provided quantitative assessments with five studies focusing on dimensional accuracy of 3D printed models in replicating renal anatomy and tumour, and on measuring tumour volume between 3D printed models and original source images and surgical specimens, with mean difference less than 10%. The other three studies reported that the use of 3D printed models significantly enhanced medical students and specialists' ability to identify anatomical structures when compared to two-dimensional (2D) images alone; and significantly shortened intraoperative ultrasound duration compared to without use of 3D printed models. Seven studies provided qualitative assessments of the usefulness of 3D printed kidney models with findings showing that 3D printed models improved patient's understanding of renal anatomy and pathology; improved medical trainees' understanding of renal malignant tumours when compared to viewing medical images alone; and assisted surgical planning and simulation of renal surgical procedures with significant reductions of intraoperative complications. The cost and time associated with 3D printed kidney model production was reported in 10 studies, with costs ranging from USD$100 to USD$1,000, and duration of 3D printing production up to 31 h. The entire process of 3D printing could take up to a few days. This review shows that 3D printed kidney models are accurate in delineating renal anatomical structures and renal tumours with high accuracy. Patient-specific 3D printed models serve as a useful tool in preoperative planning and

  12. A systematic review of clinical value of three-dimensional printing in renal disease

    PubMed Central

    2018-01-01

    The aim of this systematic review is to analyse current literature related to the clinical value of three-dimensional (3D) printed models in renal disease. A literature search of PubMed and Scopus databases was performed to identify studies reporting the clinical application and usefulness of 3D printed models in renal disease. Fifteen studies were found to meet the selection criteria and were included in the analysis. Eight of them provided quantitative assessments with five studies focusing on dimensional accuracy of 3D printed models in replicating renal anatomy and tumour, and on measuring tumour volume between 3D printed models and original source images and surgical specimens, with mean difference less than 10%. The other three studies reported that the use of 3D printed models significantly enhanced medical students and specialists’ ability to identify anatomical structures when compared to two-dimensional (2D) images alone; and significantly shortened intraoperative ultrasound duration compared to without use of 3D printed models. Seven studies provided qualitative assessments of the usefulness of 3D printed kidney models with findings showing that 3D printed models improved patient’s understanding of renal anatomy and pathology; improved medical trainees’ understanding of renal malignant tumours when compared to viewing medical images alone; and assisted surgical planning and simulation of renal surgical procedures with significant reductions of intraoperative complications. The cost and time associated with 3D printed kidney model production was reported in 10 studies, with costs ranging from USD$100 to USD$1,000, and duration of 3D printing production up to 31 h. The entire process of 3D printing could take up to a few days. This review shows that 3D printed kidney models are accurate in delineating renal anatomical structures and renal tumours with high accuracy. Patient-specific 3D printed models serve as a useful tool in preoperative planning

  13. Multi-institutional analysis of CT and MRI reports evaluating indeterminate renal masses: comparison to a national survey investigating desired report elements.

    PubMed

    Hu, Eric M; Zhang, Andrew; Silverman, Stuart G; Pedrosa, Ivan; Wang, Zhen J; Smith, Andrew D; Chandarana, Hersh; Doshi, Ankur; Shinagare, Atul B; Remer, Erick M; Kaffenberger, Samuel D; Miller, David C; Davenport, Matthew S

    2018-04-17

    To determine the need for a standardized renal mass reporting template by analyzing reports of indeterminate renal masses and comparing their contents to stated preferences of radiologists and urologists. The host IRB waived regulatory oversight for this multi-institutional HIPAA-compliant quality improvement effort. CT and MRI reports created to characterize an indeterminate renal mass were analyzed from 6 community (median: 17 reports/site) and 6 academic (median: 23 reports/site) United States practices. Report contents were compared to a published national survey of stated preferences by academic radiologists and urologists from 9 institutions. Descriptive statistics and Chi-square tests were calculated. Of 319 reports, 85% (271; 192 CT, 79 MRI) reported a possibly malignant mass (236 solid, 35 cystic). Some essential elements were commonly described: size (99% [269/271]), mass type (solid vs. cystic; 99% [268/271]), enhancement (presence vs. absence; 92% [248/271]). Other essential elements had incomplete penetrance: the presence or absence of fat in solid masses (14% [34/236]), size comparisons when available (79% [111/140]), Bosniak classification for cystic masses (54% [19/35]). Preferred but non-essential elements generally were described in less than half of reports. Nephrometry scores usually were not included for local therapy candidates (12% [30/257]). Academic practices were significantly more likely than community practices to include mass characterization details, probability of malignancy, and staging. Community practices were significantly more likely to include management recommendations. Renal mass reporting elements considered essential or preferred often are omitted in radiology reports. Variation exists across radiologists and practice settings. A standardized template may mitigate these inconsistencies.

  14. Supporting cystic fibrosis disease management during adolescence: the role of family and friends.

    PubMed

    Barker, D H; Driscoll, K A; Modi, A C; Light, M J; Quittner, A L

    2012-07-01

    Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours' supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. The provision of support appears to be distinct from adolescent's perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes. © 2011 Blackwell Publishing Ltd.

  15. Supporting cystic fibrosis disease management during adolescence: the role of family and friends

    PubMed Central

    Barker, D. H.; Driscoll, K. A.; Modi, A. C.; Light, M. J.; Quittner, A. L.

    2012-01-01

    Background Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. Methods Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. Results Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours’ supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. Conclusions The provision of support appears to be distinct from adolescent’s perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes. PMID:21771002

  16. Highlights from the 2017 North American Cystic Fibrosis Conference.

    PubMed

    Martiniano, Stacey L; Toprak, Demet; Ong, Thida; Zemanick, Edith T; Daines, Cori L; Muhlebach, Marianne S; Esther, Charles R; Dellon, Elisabeth P

    2018-04-16

    The 31st annual North American Cystic Fibrosis Conference (NACFC) was held in Indianapolis, IN on November 2-4, 2017. Abstracts of presentations from the conference were published in a supplement to Pediatric Pulmonology [2017; Pediatr Pulmonol Suppl. 52: S1-S776]. The current review summarizes several major topic areas addressed at the conference: the pathophysiology and basic science of cystic fibrosis (CF) lung disease, clinical trials, clinical management issues, and quality improvement (QI). In this review, we describe emerging concepts in several areas of CF research and care. © 2018 Wiley Periodicals, Inc.

  17. The influence of renal manifestations to the progression of autosomal dominant polycystic kidney disease

    PubMed Central

    Idrizi, A; Barbullushi, M; Petrela, E; Kodra, S; Koroshi, A; Thereska, N

    2009-01-01

    Background: Renal stones, urinary tract infections (UTI) and gross hematuria (GH) are the most important renal manifestations of autosomal dominant polycystic kidney disease (ADPKD). They are not only common, but are also frequent cause of morbidity, influencing renal dysfunction. The aim of this study was to evaluate the frequency of these manifestations in our patients with ADPKD and their impact on renal function. Methods: One hundred eighty ADPKD patients were included in the study. Subjects were studied for the presence of UTI, gross hematuria frequency and responsible factors of nephrolithiasis. Survival times were calculated as the time to renal replacement therapy or time of serum creatinine value up to 10 mg/dl. Kaplan-Meier product-limit survival curves were constructed, and log rank test was used to compare the survival curves. Results: Kidney stones were present in 76/180 (42% of pts). The stones were composed of urate (47%) calcium oxalate (39%), and other compounds 14%. UTI was observed in 60% (108 patients). Patients treated with urinary disinfectants had a significant lower frequency of urinary infection (p<0.001) and hematuria (p<0.001) after one year than untreated patients. Gross hematuria was present in 113 patients (63%). In 43 patients hematuria was diagnosed before age 30 (38%), while in 70 patients it was diagnosed after age 30 (62%). Conclusions: UTI is frequent in our ADPKD patients. The correct treatment of UTI decreases its frequency and has beneficial role in the rate of progression to renal failure in ADPKD patients. Patients with recurrent episodes of gross hematuria may be at risk for more severe renal disease. PMID:19918304

  18. Microbiology of airway disease in a cohort of patients with Cystic Fibrosis

    PubMed Central

    Lambiase, Antonietta; Raia, Valeria; Pezzo, Mariassunta Del; Sepe, Angela; Carnovale, Vincenzo; Rossano, Fabio

    2006-01-01

    Background Recent reports document an increasing incidence of new Gram-negative pathogens such as Stenotrophomonas maltophilia and Alcaligenes xylosoxidans isolated from patients with Cystic Fibrosis, along with an increase in common Gram-negative pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex. Furthermore, the increase in multidrug-resistance of such organisms makes the therapeutic management of these patients more problematic. Therefore, careful isolation and identification, and accurate studies of susceptibility to antibiotics are critical for predicting the spread of strains, improving therapeutic measures and facilitating our understanding of the epidemiology of emerging pathogens. The first aim of this study was to determine the incidence and the prevalence of colonization by Gram-negative organisms isolated from respiratory samples of Cystic Fibrosis patients in the Regional Referral Cystic Fibrosis Centre of Naples; the second was to evaluate the spectrum of multidrug-resistance of these organisms. Methods Patients (n = 300) attending the Regional Cystic Fibrosis Unit were enrolled in this study over 3 years. Sputum was processed for microscopic tests and culture. An automated system, Phoenix (Becton Dickinson, Sparks, Maryland, USA), was used for phenotypic identification of all strains; the API 20 NE identification system (bioMérieux, Marcy l'Etoile, France) was used when the identification with the Phoenix system was inaccurate. A PCR-RFLP method was used to characterize the organisms in the Burkholderia cepacia complex. A chemosusceptibility test on microbroth dilutions (Phoenix) was used. Primary outcomes such as FEV1 were correlate with different pathogens. Results During the period of study, 40% of patients was infected by Pseudomonas aeruginosa, 7% by Burkholderia cepacia complex, 11% by Stenotrophomonas maltophilia and 7% by Alcaligenes xylosoxidans. Of the strains isolated, 460 were multidrug-resistant. Multiresistant

  19. 76 FR 40497 - Medicare Program; Changes to the End-Stage Renal Disease Prospective Payment System for CY 2012...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ...] RIN 0938-AQ27 Medicare Program; Changes to the End-Stage Renal Disease Prospective Payment System for... through Federal Digital System (FDsys), a service of the U.S. Government Printing Office. This database... Internet on the CMS Web site. The Addenda to the End-Stage Renal Disease (ESRD) Prospective Payment System...

  20. The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease.

    PubMed

    Adenwalla, Sherna F; Graham-Brown, Matthew P M; Leone, Francesca M T; Burton, James O; McCann, Gerry P

    2017-08-01

    Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work.

  1. The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease

    PubMed Central

    Adenwalla, Sherna F.; Leone, Francesca M.T.; Burton, James O.; McCann, Gerry P.

    2017-01-01

    Abstract Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work. PMID:28852490

  2. Dialysis for end stage renal disease financed through the Brazilian National Health System, 2000 to 2012

    PubMed Central

    2014-01-01

    Background Chronic kidney disease has become a public health problem worldwide. Its terminal stage requires renal replacement therapy – dialysis or transplantation – for the maintenance of life, resulting in high economic and social costs. Though the number of patients with end-stage renal disease treated by dialysis in Brazil is among the highest in the world, current estimates of incidence and prevalence are imprecise. Our aim is to describe incidence and prevalence trends and the epidemiologic profile of end-stage renal disease patients receiving publically-financed dialysis in Brazil between 2000 and 2012. Methods We internally linked records of the High Complexity Procedure Authorization/Renal Replacement Therapy (APAC/TRS) system so as to permit analyses of incidence and prevalence of dialysis over the period 2000-2012. We characterized temporal variations in the incidence and prevalence using Joinpoint regression. Results Over the period, 280,667 patients received publically-financed dialysis, 57.2% of these being male. The underlying disease causes listed were hypertension (20.8%), diabetes (12.0%) and glomerulonephritis (7.7%); for 42.3%, no specific cause was recorded. Hemodialysis was the therapeutic modality in 90.1%. Over this period, prevalence increased 47%, rising 3.6% (95% CI 3.2% - 4.0%)/year. Incidence increased 20%, or 1.8% (1.1% – 2.5%)/year. Incidence increased in both sexes, in all regions of the country and particularly in older age groups. Conclusions Incidence and prevalence of end-stage renal disease receiving publically-financed dialysis treatment has increased notably. The linkage approach developed will permit continuous future monitoring of these indicators. PMID:25008169

  3. Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes

    PubMed Central

    2017-01-01

    Diabetes is a common and important complication of cystic fibrosis, an autosomal recessive genetic disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cystic fibrosis–related diabetes (CFRD) is associated with profound detrimental effects on the disease course and mortality and is expected to increase in prevalence as the survival of patients with cystic fibrosis continues to improve. Despite progress in the functional characterization of CFTR molecular defects, the mechanistic basis of CFRD is not well understood, in part because of the relative inaccessibility of the pancreatic tissue and the limited availability of representative animal models. This review presents a concise overview of the current understanding of CFRD pathogenesis and provides a cutting-edge update on novel findings from human and animal studies. Potential contributions from paracrine mechanisms and β-cell compensatory mechanisms are highlighted, as well as functional β-cell and α-cell defects, incretin defects, exocrine pancreatic insufficiency, and loss of islet cell mass. State-of-the-art and emerging treatment options are explored, including advances in insulin administration, CFTR modulators, cell replacement, gene replacement, and gene editing therapies. PMID:29264462

  4. The role of renal function loss on circadian misalignment of cytokines EPO, IGF-1, IL-6 and TNF-alfa in chronic renal disease.

    PubMed

    van der Putten, Karien; Koch, Birgit; van Someren, Eus; Wielders, Jos; Ter Wee, Piet; Nagtegaal, Elsbeth; Gaillard, Carlo

    2011-01-01

    Chronic inflammation plays a pivotal role in the development of renal disease. Circadian sleep-wake rhythm is disturbed in renal disease. Awareness of other disturbed rhythms, such as inflammation processes, can affect the treatment of patients with renal disease. Knowledge of possibly related circadian misalignment of the cytokines erythropoietin (EPO), Insulin Growth Factor-1 (IGF-1) and interleukins (IL) however is limited. We therefore performed an observational study. The objective of this study was to characterize levels of EPO, IGF-1 and inflammation markers IL-6 and TNF-α, related to renal function. The study population consisted of patients with various degrees of renal function, admitted to our hospital. During 24 hours, blood of 28 subjects with various degrees of renal function was collected every 2 hours. The patients were stable, not acutely ill and they were waiting for a procedure, such as elective surgery. Circadian parameters of EPO, IGF-1, IL-6 and TNF-α were measured in serum and were correlated with glomerular filtration rate (GFR) and Hb, using Pearson correlations. Although diurnal variations in EPO level were found in 15 out of 28 patients, the curves did not show a consistent phase. The presence of an EPO rhythm was not related to GFR. No diurnal rhythm could be detected for IGF-1, IL-6 and TNF-α. Mean levels of IGF-1 were correlated inversely to mean levels of EPO (p=0.03). When divided based on GFR and Hb subjects with GFR 10-30 ml/min and lower Hb had the highest IGF-1 levels (p=0.02). A relationship between Il-6, TNF-α and EPO or GFR was not found. The existence of a circadian (mis)alignment of EPO, IGF-1, IL-6 and TNF-α was not found. The association between high IGF-1 and low Hb suggests that EPO and IGF-1 have an alternating role, dependent on GFR, in stimulating erythropoiesis. These results could have consequences for the treatment of anemia.

  5. Kidney disease in heart failure: the importance of novel biomarkers for type 1 cardio-renal syndrome detection.

    PubMed

    Palazzuoli, Alberto; McCullough, Peter A; Ronco, Claudio; Nuti, Ranuccio

    2015-08-01

    Chronic kidney disease (CKD) in heart failure (HF) has been recognized as an independent risk factor for adverse outcome, although the most important clinical trials tend to exclude patients with moderate and severe renal insufficiency. Despite this common association, the precise pathophysiological connection and liaison between heart and kidney is partially understood. Moreover, is it not enough considering how much cardio-renal syndrome type 1 is attributable to previous CKD, and how much to new-onset acute kidney injury (AKI). Neither development of AKI, its progression and time nor duration is related to an adverse outcome. An AKI definition is not universally recognized, and many confounding terms have been used in literature: "worsening renal function", "renal impairment", "renal dysfunction", etc., are all names that contribute to misunderstanding, and do not facilitate an universal classification. Therefore, AKI development should be the consequence of the basal clinical characteristics of patients, different primitive kidney disease and hemodynamic status. AKI could also be the mirror of several underlying associated diseases poorly controlled. Finally, it is not clear which is the optimal laboratory tool for identifying patients with an increased risk of AKI. In the current report, we review the different kidney diseases' impact in HF, and we analyze the modalities for AKI recognition during HF focusing our attention about some new biomarkers with potential application in the current setting.

  6. Risk of Nodal Metastasis in Major Salivary Gland Adenoid Cystic Carcinoma.

    PubMed

    Megwalu, Uchechukwu C; Sirjani, Davud

    2017-04-01

    Objective To determine the risk of nodal metastasis, examine risk factors for nodal metastasis, and evaluate the impact of nodal metastasis on survival in patients with major salivary gland adenoid cystic carcinoma. Study Design Retrospective cohort study from a large population- based cancer database. Methods Data were extracted from the SEER 18 database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute. The study cohort included 720 patients diagnosed with major salivary gland adenoid cystic carcinoma between 1988 and 2013. Results The overall rate of lymph node metastasis was 17%. T3 disease (odds ratio, 4.74) and T4 disease (odds ratio, 9.24) were associated with increased risk of nodal metastasis. Age, sex, and site were not associated with nodal metastasis. Nodal metastasis was associated with worse overall survival (hazard ratio, 2.56) and disease-specific survival (hazard ratio, 3.27), after adjusting for T stage, presence of distant metastasis, site, surgical resection, radiotherapy, neck dissection, age, sex, race, marital status, and year of diagnosis. Conclusion Major salivary gland adenoid cystic carcinoma carries significant risk of nodal metastasis. Advanced T stage is associated with increased risk of nodal metastasis. Nodal metastasis is associated with worse survival.

  7. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease.

    PubMed

    Germain, Dominique P; Waldek, Stephen; Banikazemi, Maryam; Bushinsky, David A; Charrow, Joel; Desnick, Robert J; Lee, Philip; Loew, Thomas; Vedder, Anouk C; Abichandani, Rekha; Wilcox, William R; Guffon, Nathalie

    2007-05-01

    Fabry disease, an inherited deficiency of the lysosomal enzyme alpha-galactosidase A, causes progressive intralysosomal accumulation of globotriaosylceramide (GL-3) and premature death from renal, cardiac, and cerebrovascular manifestations. To determine the long-term safety and efficacy of recombinant human alpha-galactosidase A, an open-label, phase III extension study was conducted, involving 58 patients who had classic Fabry disease and completed a 20-wk, double-blind, randomized, placebo-controlled, phase III study of agalsidase beta and were transitioned to an extension trial to receive biweekly 1 mg/kg agalsidase beta for up to an additional 54 mo. GL-3 accumulation was evaluated in the capillary endothelia of the skin, kidney, and heart. Renal function was assessed. By month 54, all patients with optional kidney biopsies (n = 8) maintained complete GL-3 clearance in renal capillary endothelial cells and multiple cell types. Continued, complete clearance of skin (31 of 36) and heart (six of eight) capillary endothelium was demonstrated. Mean plasma GL-3 levels remained decreased in the normal range. Median serum creatinine and estimated GFR remained stable (normal) in patients with renal data at month 54 (n = 41). Six patients had renal disease progression; most (four of six) were older than 40 yr and had significant proteinuria at baseline and evidence of sclerotic glomeruli pretreatment. Adverse events were generally mild and unrelated to treatment. The most common treatment-related adverse events were infusion-associated reactions, which decreased over time. Long-term agalsidase beta therapy stabilizes renal function in patients without renal involvement at baseline, maintains reduction of plasma GL-3, and sustains GL-3 clearance in capillary endothelial cells and multiple renal cell types.

  8. Tubular Obstruction Leads to Progressive Proximal Tubular Injury and Atubular Glomeruli in Polycystic Kidney Disease

    PubMed Central

    Galarreta, Carolina I.; Grantham, Jared J.; Forbes, Michael S.; Maser, Robin L.; Wallace, Darren P.; Chevalier, Robert L.

    2015-01-01

    In polycystic kidney disease (PKD), renal parenchyma is destroyed by cysts, hypothesized to obstruct nephrons. A signature of unilateral ureteral obstruction, proximal tubular atrophy leads to formation of atubular glomeruli. To determine whether this process occurs in PKD, kidneys from pcy mice (moderately progressive PKD), kidneys from cpk mice (rapidly progressive PKD), and human autosomal dominant PKD were examined in early and late stages. Integrity of the glomerulotubular junction and proximal tubular mass were determined in sections stained with Lotus tetragonolobus lectin. Development of proximal tubular atrophy and atubular glomeruli was determined in serial sections of individual glomeruli. In pcy mice, most glomerulotubular junctions were normal at 20 weeks, but by 30 weeks, 56% were atrophic and 25% of glomeruli were atubular; glomerulotubular junction integrity decreased with increasing cyst area (r = 0.83, P < 0.05). In cpk mice, all glomerulotubular junctions were normal at 10 days, but by 19 days, 26% had become abnormal. In early-stage autosomal dominant PKD kidneys, 50% of glomeruli were atubular or attached to atrophic tubules; in advanced disease, 100% were abnormal. Thus, proximal tubular injury in cystic kidneys closely parallels that observed with ureteral obstruction. These findings support the hypothesis that, in renal cystic disorders, cyst-dependent obstruction of medullary and cortical tubules initiates a process culminating in widespread destruction of proximal convoluted tubules at the glomerulotubular junction. PMID:24815352

  9. Retreatment of Recurrent Cystic Craniopharyngioma With Chromic Phosphorus P 32

    PubMed Central

    Kumar, P.P.; Good, R.R.; Skultety, F.M.; Jones, E.O.; Chu, W.K.

    1986-01-01

    A cystic craniopharyngioma in a two-year-old boy recurred six months after surgery and postoperative external-beam radiotherapy. Successful retreatment was accomplished with radioisotope injection of 0.5 mCi of chromic phosphorus P 32 into the intracranial cyst, which delivered approximately 300.00 Gy to the cyst wall. The patient's symptoms were relieved, and he is without evidence of disease or cystic fluid accumulation four years after intracavitary 32P irradiation. ImagesFigure 1Figure 2Figure 3 PMID:3735454

  10. Lung Infections Associated with Cystic Fibrosis

    PubMed Central

    Lyczak, Jeffrey B.; Cannon, Carolyn L.; Pier, Gerald B.

    2002-01-01

    While originally characterized as a collection of related syndromes, cystic fibrosis (CF) is now recognized as a single disease whose diverse symptoms stem from the wide tissue distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR). Defective CFTR protein impacts the function of the pancreas and alters the consistency of mucosal secretions. The latter of these effects probably plays an important role in the defective resistance of CF patients to many pathogens. As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases. These factors have led to the successful management of many CF-related infections with the notable exception of chronic lung infection with the gram-negative bacterium Pseudomonas aeruginosa. The virulence of P. aeruginosa stems from multiple bacterial attributes, including antibiotic resistance, the ability to utilize quorum-sensing signals to form biofilms, the destructive potential of a multitude of its microbial toxins, and the ability to acquire a mucoid phenotype, which renders this microbe resistant to both the innate and acquired immunologic defenses of the host. PMID:11932230

  11. [The classics of Italian nephrology: the monograph ''Le nefropatie'' (Renal diseases) 1880-1946].

    PubMed

    Ferrata, Adolfo

    2007-01-01

    This paper, the first of the new feature ''The Classics of Italian Nephrology'', describes the monograph published in 1940 ''Le nefropatie. Manuale per i medici e studenti'' (Renal Diseases. Handbook for Doctors and Students). It was written by Adolfo Ferrata (1880-1946), who is remembered today for his important contributions to the advancement of hematology. The book, which has more than 400 pages and many illustrations, especially of pathologic anatomy, is the product of teamwork involving several pupils and coworkers of Ferrata. It describes all aspects of medical renal diseases known at the time, and from an historical viewpoint represents an interesting testimony of the nephrological practice in Italy in the 1940s.

  12. A classification tree for the prediction of benign versus malignant disease in patients with small renal masses.

    PubMed

    Rendon, Ricardo A; Mason, Ross J; Kirkland, Susan; Lawen, Joseph G; Abdolell, Mohamed

    2014-08-01

    To develop a classification tree for the preoperative prediction of benign versus malignant disease in patients with small renal masses. This is a retrospective study including 395 consecutive patients who underwent surgical treatment for a renal mass < 5 cm in maximum diameter between July 1st 2001 and June 30th 2010. A classification tree to predict the risk of having a benign renal mass preoperatively was developed using recursive partitioning analysis for repeated measures outcomes. Age, sex, volume on preoperative imaging, tumor location (central/peripheral), degree of endophytic component (1%-100%), and tumor axis position were used as potential predictors to develop the model. Forty-five patients (11.4%) were found to have a benign mass postoperatively. A classification tree has been developed which can predict the risk of benign disease with an accuracy of 88.9% (95% CI: 85.3 to 91.8). The significant prognostic factors in the classification tree are tumor volume, degree of endophytic component and symptoms at diagnosis. As an example of its utilization, a renal mass with a volume of < 5.67 cm3 that is < 45% endophytic has a 52.6% chance of having benign pathology. Conversely, a renal mass with a volume ≥ 5.67 cm3 that is ≥ 35% endophytic has only a 5.3% possibility of being benign. A classification tree to predict the risk of benign disease in small renal masses has been developed to aid the clinician when deciding on treatment strategies for small renal masses.

  13. Microbiome in the pathogenesis of cystic fibrosis and lung transplant-related disease.

    PubMed

    Cribbs, Sushma K; Beck, James M

    2017-01-01

    Significant advances in culture-independent methods have expanded our knowledge about the diversity of the lung microbial environment. Complex microorganisms and microbial communities can now be identified in the distal airways in a variety of respiratory diseases, including cystic fibrosis (CF) and the posttransplantation lung. Although there are significant methodologic concerns about sampling the lung microbiome, several studies have now shown that the microbiome of the lower respiratory tract is distinct from the upper airway. CF is a disease characterized by chronic airway infections that lead to significant morbidity and mortality. Traditional culture-dependent methods have identified a select group of pathogens that cause exacerbations in CF, but studies using bacterial 16S rRNA gene-based microarrays have shown that the CF microbiome is an intricate and dynamic bacterial ecosystem, which influences both host immune health and disease pathogenesis. These microbial communities can shift with external influences, including antibiotic exposure. In addition, there have been a number of studies suggesting a link between the gut microbiome and respiratory health in CF. Compared with CF, there is significantly less knowledge about the microbiome of the transplanted lung. Risk factors for bronchiolitis obliterans syndrome, one of the leading causes of death, include microbial infections. Lung transplant patients have a unique lung microbiome that is different than the pretransplanted microbiome and changes with time. Understanding the host-pathogen interactions in these diseases may suggest targeted therapies and improve long-term survival in these patients. Published by Elsevier Inc.

  14. Nutrient Status of Adults with Cystic Fibrosis

    PubMed Central

    GORDON, CATHERINE M.; ANDERSON, ELLEN J.; HERLYN, KAREN; HUBBARD, JANE L.; PIZZO, ANGELA; GELBARD, RONDI; LAPEY, ALLEN; MERKEL, PETER A.

    2011-01-01

    Nutrition is thought to influence disease status in patients with cystic fibrosis (CF). This cross-sectional study sought to evaluate nutrient intake and anthropometric data from 64 adult outpatients with cystic fibrosis. Nutrient intake from food and supplements was compared with the Dietary Reference Intakes for 16 nutrients and outcomes influenced by nutritional status. Attention was given to vitamin D and calcium given potential skeletal implications due to cystic fibrosis. Measurements included weight, height, body composition, pulmonary function, and serum metabolic parameters. Participants were interviewed about dietary intake, supplement use, pulmonary function, sunlight exposure, and pain. The participants’ mean body mass index (±standard deviation) was 21.8±4.9 and pulmonary function tests were normal. Seventy-eight percent used pancreatic enzyme replacement for malabsorption. Vitamin D deficiency [25-hydroxyvitamin D (25OHD)<37.5 nmol/L] was common: 25 (39%) were deficient despite adequate vitamin D intake. Lipid profiles were normal in the majority, even though total and saturated fat consumption represented 33.0% and 16.8% of energy intake, respectively. Reported protein intake represented 16.9% of total energy intake (range 10%–25%). For several nutrients, including vitamin D and calcium, intake from food and supplements in many participants exceeded recommended Tolerable Upper Intake Levels. Among adults with cystic fibrosis, vitamin D deficiency was common despite reported adequate intake, and lipid profiles were normal despite a relatively high fat intake. Mean protein consumption was adequate, but the range of intake was concerning, as both inadequate or excessive intake may have deleterious skeletal effects. These findings call into question the applicability of established nutrient thresholds for patients with cystic fibrosis. PMID:18060897

  15. Gentamicin Nephrotoxicity in Subclinical Renal Disease.

    NASA Astrophysics Data System (ADS)

    Frazier, Donita L.

    The purpose of the present study was to examine the pharmacokinetic disposition of gentamicin and to define the mechanisms which predispose to nephrotoxicity in subclinical renal disease. Subtotally nephrectomized beagle dogs were used as a model for human beings with compromised renal function secondary to a reduced number of functional nephrons. Using ultrastructural morphometry, light microscopy and clinical chemistry data, the model was defined and the nephrotoxic responses of intact dogs administered recommended doses of drug were compared to the response of subtotally nephrectomized dogs administered reduced doses based on each animal's clearance of drug. Lysosomal and mitochondrial morphometric changes suggested mechanisms for increased sensitivity. To determine if increased sensitivity in this model was dependent on altered serum concentrations, variable rate infusions based on individual pharmacokinetic disposition of drug were administered using computer-driven infusion pumps. Identical serum concentration-time profiles were achieved in normal dogs and subtotally nephrectomized dogs, however, toxicity was significantly greater in nephrectomized dogs. The difference in the nephrotoxic response was characterized by administering supratherapeutic doses of drug to dogs. Nephrectomized dogs given a recommended dose of gentamicin became oliguric during the second week of treatment and increasingly uremic after withdrawal of drug. In contrast, intact dogs administered 2 times the recommended dose of gentamicin become only slightly polyuric during week 4 of treatment. The need to individualize dosage regimens based on drug clearance and not serum creatinine nor creatinine clearance alone was substantiated by describing the pharmacokinetic disposition of gentamicin in spontaneously occurring disease states. Four individualized dosage regimens with differing predicted efficacy were then administered to nephrectomized dogs to determine their relative nephrotoxic

  16. Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

    PubMed Central

    Sweeney, William E; Frost, Philip; Avner, Ellis D

    2017-01-01

    AIM To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). METHODS We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation. We administered TSV by oral gavage in the same doses to the orthologous PCK model (from PN30 to PN90) to assess efficacy and toxicity in animals where developmental processes are complete. The following parameters were assessed: Body weight, total kidney weight; kidney weight to body weight ratios; and morphometric determination of a cystic index and a measure of hepatic disease. Renal function was assessed by: Serum BUN; creatinine; and a 12 h urinary concentrating ability. Validation of reported targets including the level of angiogenesis and inhibition of angiogenesis (active VEGFR2/KDR) was assessed by Western analysis. RESULTS This study demonstrates that: (1) in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis: EGFR, ErbB2, c-Src and KDR; and (2) this reduction of kinase activity resulted in significant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. The amelioration of disease by TSV was not associated with any apparent toxicity. CONCLUSION The data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD. PMID:28729967

  17. [Cystic echinococcosis in the Mersin province (119 cases)].

    PubMed

    Aksu, Müzeyyen; Sevimli, Feride Kırcalı; Ibiloğlu, Ibrahim; Arpacı, Rabia Bozdoğan

    2013-01-01

    This study was made to emphasize the importance of cystic echinococcosis in the Mersin province and to contribute to informarion regarding the geographic distribution of infection in Turkey. Seven different pathology laboratory records in the Mersin province between the period 2011-2012 were evaluated according to age, sex and organ involvement. In study period, a total of 119 cases of cystic echinococcosis were determined. Male patients constituted 52.94% of the cases, and female, 47.05%. The age distribution of these cases was between 5 and 76 years. Most of the cases appeared in 41-50 (22.68%) year old patients. The most common localizations for cystic echinococcosis was determined in the liver (n: 53, 44.53%) and lung (n: 39, 32.77%), followed by the kidney (n: 4, 3.36%), spleen (n: 3, 2.52%) and gall bladder (n: 3, 2.52%). In 3 cases (2.52%), multiorgan involvement was seen. Cystic echinococcosis is an important health problem in Turkey. The stray dogs, which play an important role in the contagiousness of the disease, should be kept under control and treated. Also, slaughtering of animals must be preformed under the supervision of veterinary surgeons and destruction of infected organs should be carried out under proper conditions in slaughterhouses.

  18. Preliminary Investigation of Cardiovascular-Renal Disorders in Dogs with Chronic Mitral Valve Disease.

    PubMed

    Martinelli, E; Locatelli, C; Bassis, S; Crosara, S; Paltrinieri, S; Scarpa, P; Spalla, I; Zanaboni, A M; Quintavalla, C; Brambilla, P

    2016-09-01

    Veterinary literature lacks data about cardiovascular-renal disorders (CvRD) and cardiorenal-anemia syndrome (CRAS) in dogs. A direct correlation exists between ACVIM class and IRIS stage; chronic kidney disease (CKD) complicates chronic mitral valve disease (CMVD) more often than does anemia in dogs. One hundred and fifty-eight client-owned dogs with CMVD. Signalment, physical examination findings, electrocardiography, thoracic radiographs, echocardiography, and blood analysis were retrospectively evaluated to assess the prevalence of CKD and anemia in dogs with CMVD and to investigate the relationships among ACVIM class, IRIS stage, and survival. The prevalence of CKD and anemia in dogs with CMVD was significantly higher than in the general population of dogs. Dogs being treated for heart failure had a significantly higher prevalence of CKD than did dogs that had not received treatment. A statistically significant direct correlation was found between ACVIM class and IRIS stage. Severe heart disease, severe renal disease or both, furosemide administration, and advanced age at diagnosis of heart disease were associated with shorter survival time. Survival time of dogs affected by CvRD was statistically shorter than survival time of dogs affected by CMVD alone. Chronic mitral valve disease is associated with increased prevalence of CKD and anemia in dogs. Treatment for medical management of heart failure may play a role in inducing CKD. Class of heart disease and IRIS stage were directly correlated. Cardiovascular-renal disorders decrease survival time compared to the only presence of CMVD alone, whereas anemia does not play a central role in worsening heart function. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  19. Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

    PubMed Central

    Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.; Starzl, T. E.

    1975-01-01

    Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy. Images Fig 1 PMID:1091152

  20. Dual core quantum dots for highly quantitative ratiometric detection of trypsin activity in cystic fibrosis patients

    NASA Astrophysics Data System (ADS)

    Castelló Serrano, Iván; Stoica, Georgiana; Matas Adams, Alba; Palomares, Emilio

    2014-10-01

    We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for recessive genetic diseases like human cystic fibrosis. In a screening program in which the goal is to detect disease and also the carrier status, early diagnosis could be of great help.We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for