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Chronic kidney disease in hypertensive subjects ≥60 years treated in Primary Care.

Thu, 08/17/2017 - 15:47
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Chronic kidney disease in hypertensive subjects ≥60 years treated in Primary Care.

Nefrologia. 2017 Jul - Aug;37(4):406-414

Authors: Salvador-González B, Mestre-Ferrer J, Soler-Vila M, Pascual-Benito L, Alonso-Bes E, Cunillera-Puértolas O, en representación del grupo de investigación del proyecto MARREC-HTA

Abstract
BACKGROUND: Hypertension (HT) is the second leading cause of kidney failure. In hypertensive patients with chronic kidney disease (CKD), blood pressure (BP) control is the most important intervention to minimise progression. For CKD diagnosis, standardised creatinine and estimated glomerular filtration rate (eGFR) testing by CKD-EPI is recommended.
OBJECTIVES: To describe the prevalence and factors associated with a moderate decrease in eGFR (by CKD-EPI) and BP control in subjects with HT.
METHODS: Cross-sectional descriptive study in subjects ≥ 60 years included in the SIDIAP plus database with hypertension and standardised serum creatinine and BP tests in the last 2years.
EXCLUSION CRITERIA: eGFR<30, dialysis or kidney transplantation, prior cardiovascular disease, home care. Primary endpoint: eGFR by CKD-EPI formula. Covariates: demographic data, examination, cardiovascular risk factors, heart failure and auricular fibrillation diagnosis, and drugs (antihypertensive agents acting on renal function, antiplatelet and lipid lowering agents). BP control criteria: ≤130/80mmHg in individuals with albuminuria, ≤140/90 in all other subjects.
RESULTS: Prevalence of eGFR <60=18.8%. Associated factors: age, gender, heart failure, albumin/creatinine ratio, auricular fibrillation, smoking, dyslipidaemia, diabetes and obesity. BP control: 66.14 and 63.24% in eGFR≥60 and eGFR <60, respectively (P<.05). Exposure to drugs was higher in eGFR<60.
CONCLUSION: One in 5hypertensive patients without cardiovascular disease ≥60 years in primary care presented with a moderate decrease in eGFR. In addition to age and sex, albuminuria and heart failure were the main associated factors. Despite the increased exposure to drugs, BP control was lower in CKD.

PMID: 28750875 [PubMed]

Diffuse Extent of Peritubular Capillaritis in Late Antibody-Mediated Rejection: Associations With Levels of Donor-Specific Antibodies and Chronic Allograft Injury.

Thu, 08/17/2017 - 15:47
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Diffuse Extent of Peritubular Capillaritis in Late Antibody-Mediated Rejection: Associations With Levels of Donor-Specific Antibodies and Chronic Allograft Injury.

Transplantation. 2017 May;101(5):e178-e187

Authors: Kozakowski N, Eskandary F, Herkner H, Bond G, Oberbauer R, Regele H, Böhmig GA, Kikić Ž

Abstract
BACKGROUND: Recently, diffuse peritubular capillaritis (ptc) has been suggested to independently predict chronic transplant injury and loss, and although the ptc score is a diagnostic criterion for antibody-mediated rejection, the utility of diffuse ptc is under debate.
METHODS: We evaluated the diagnostic value of ptc characteristics in this cross-sectional study including 85 biopsies of patients with donor-specific antibodies (DSA). Biopsies were reevaluated for the extent (diffuse vs focal), score and leukocytic composition in relation to DSA binding strength (mean fluorescence intensity [MFI]_max). Chronic allograft injury (transplant chronic glomerulopathy [cg] or chronic lesion score CLS]) were associated with ptc features.
RESULTS: Peritubular capillaritis was detected in 50% (76% mononuclear ptc). Peritubular capillaritis scores 1, 2, and 3 were present in 36%, 55%, and 9%, and focal or diffuse ptc in 36% or 64%. Diffuse ptc was associated with DSA MFI_max (median: 4407 vs 2419 [focal ptc; P = 0.04] or 1946 [no ptc; P = 0.004]), cg (58% vs no ptc 24% [P = 0.02]), and higher CLS (mean: 6.81 vs 4.67 [focal ptc, P = 0.01] or 5.18 [no ptc, P = 0.001]), respectively. The association of ptc score of 2 or greater with cg was slightly better than with diffuse ptc. Diffuse ptc and ptc score of 2 or greater remained independently related to cg after adjusting for DSA_MFI_max, C4d, or previous rejection episodes, however lost their independent relation after adjusting for total microcirculation scores. Diffuse ptc was the only ptc characteristic independently related to CLS.
CONCLUSIONS: Our results emphasize the clinical relevance of reporting diffuse ptc, which may relate to DSA binding strength and potentially to chronic graft injury.

PMID: 28252564 [PubMed - indexed for MEDLINE]

HCV Antiviral Therapy in Liver Transplant Candidates and Recipients With Renal Insufficiency.

Thu, 08/17/2017 - 15:47
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HCV Antiviral Therapy in Liver Transplant Candidates and Recipients With Renal Insufficiency.

Transplantation. 2017 May;101(5):924-932

Authors: Verna EC, Brown RS

Abstract
Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective direct-acting antiviral therapy, such that most patients can be cured in the pretransplant or posttransplant setting. In addition, there are now direct-acting antiviral regimens specifically approved for use in patients with severe renal insufficiency. However, patients with pre or posttransplant severe renal insufficiency remain more difficult to treat, due to mechanisms of drug metabolism in hepatic and renal failure, as well as posttransplant drug-drug interactions. Treatment options are even more restricted in non-1 HCV genotypes. Because renal insufficiency is common among patients with HCV, with decompensated cirrhosis, and in the posttransplant setting, this difficult scenario is relatively common. However, ongoing development of pangenotypic regimens with improved safety profiles, as well as additional data on dosing and safety among patients with severe renal insufficiency, will continue to expand options for cure even in these most difficult to treat patients.

PMID: 28212220 [PubMed - indexed for MEDLINE]

Effects of Aspirin Therapy on Ultrasound-Guided Renal Allograft Biopsy Bleeding Complications.

Thu, 08/17/2017 - 15:47
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Effects of Aspirin Therapy on Ultrasound-Guided Renal Allograft Biopsy Bleeding Complications.

J Vasc Interv Radiol. 2017 Feb;28(2):188-194

Authors: Baffour FI, Hickson LJ, Stegall MD, Dean PG, Gunderson TM, Atwell TD, Kurup AN, Schmitz JJ, Park WD, Schmit GD

Abstract
PURPOSE: To determine if patient aspirin exposure and timing affect bleeding risk after renal allograft biopsy.
MATERIALS AND METHODS: Review of 6,700 renal allograft biopsies (in 2,362 unique patients) was performed. Median patient age was 53.0 years [interquartile range 43.0, 62.0]; 56.2% of patients were male. Of biopsies, 4,706 (70.2%) were performed in patients with no aspirin exposure within 10 days of biopsy; 664 (9.9%), were performed within 8-10 days of aspirin exposure; 855 (12.8%), within 4-7 days; and 475 (7.1%), within 0-3 days. Follow-up to 3 months after the procedure was completed in all patients. Biopsies were categorized as protocol or indication; 19.7% were indication biopsies. Bleeding complications were graded based on SIR criteria. Logistic regression models examined the association between aspirin use and bleeding events.
RESULTS: Rate [95% confidence interval] of major bleeding complications was 0.24% [0.14, 0.39], and rate of any bleeding complication was 0.66% [0.46, 0.90]. Bleeding events were significantly associated with patients undergoing indication biopsies compared with protocol biopsies (odds ratio [OR] 2.27, P = .012). Patient factors associated with major bleeding complications in multivariate models included estimated glomerular filtration rate (OR 0.61, P = .016) and platelet count (OR 0.64, P = .033). Aspirin use was not significantly associated with increased risk of bleeding complication except for use of 325 mg of aspirin within 3 days of biopsy (any complication OR 3.87 [1.12, 13.4], P = .032; major complication OR 6.30 [1.27, 31.3], P = .024).
CONCLUSIONS: Renal allograft biopsy bleeding complications are very rare, particularly for protocol biopsies. Use of 325 mg of aspirin within 3 days of renal allograft biopsy was associated with increased bleeding complications.

PMID: 27993506 [PubMed - indexed for MEDLINE]

Glomerular filtration rate affects interpretation of pulmonary function test in a Korean general population: results from the Korea National Health and Nutrition Examination Survey 2010 to 2012.

Thu, 08/17/2017 - 15:47
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Glomerular filtration rate affects interpretation of pulmonary function test in a Korean general population: results from the Korea National Health and Nutrition Examination Survey 2010 to 2012.

Korean J Intern Med. 2016 Nov;31(6):1101-1109

Authors: Kim YS, Kim HY, Ahn HS, Sohn TS, Song JY, Lee YB, Lee DH, Lee JI, Lee TK, Jeong SC, Hong M, Chae HS, Han K, Yeo CD

Abstract
BACKGROUND/AIMS: The pulmonary abnormalities (principally restrictive abnormalities) are characteristic of renal transplant recipients or those with end-stage renal disease. Our aim was to explore whether the prevalence of spirometric abnormalities was influenced by the estimated glomerular filtration rates (GFRs) in a Korean general population.
METHODS: We used data obtained during the 2010 to 2012 Korean National Health and Nutrition Examination Survey, a national cross-sectional survey. We analyzed data from subjects for whom spirometric assays and estimated GFRs were of acceptable quality.
RESULTS: A total of 8,809 subjects (3,868 male and 4,941 female) was included. In both males and females with GFR values < 60 mL/min/1.73 m(2), the linear trends toward the presence of obstructive and restrictive patterns were significant. However, the percent predicted forced vital capacity (FVC) decreased with a decline in the estimated GFR, but only in males (p for trend < 0.0031). Multivariate linear regression analysis showed a decline in the estimated GFR was independently associated with falls in the percent predicted FVC and the forced expiratory volume in 1 second/FVC ratio in both males and females. However, the percent predicted FVC was independently predictive only in males (p = 0.002).
CONCLUSIONS: Impaired pulmonary function was associated with a decline in the estimated GFR. The percent predicted FVC decrease paralleled the decline in estimated GFR in male only. Careful interpretation of pulmonary function test data is required in patients with decreased GFRs or impaired renal function, especially males.

PMID: 26996347 [PubMed - indexed for MEDLINE]

Con: The use of calcineurin inhibitors in the treatment of lupus nephritis.

Thu, 08/17/2017 - 15:47
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Con: The use of calcineurin inhibitors in the treatment of lupus nephritis.

Nephrol Dial Transplant. 2016 Oct;31(10):1567-71

Authors: Fernandez Nieto M, Jayne DR

Abstract
Lupus nephritis (LN) therapy has limited efficacy due to its toxicity, and LN patients suffer high risks of renal and cardiovascular morbidity and mortality. Calcineurin inhibitors (CNIs) have been used for over >30 years in LN treatment and are an established alternative therapy for Class V nephritis, but uncertainty remains about their role in proliferative disease or in the maintenance of remission. More recently, the combination of CNIs with mycophenolate mofetil (MMF) and glucocorticoid combination therapy, 'multitarget' therapy and the use of tacrolimus as opposed to ciclosporin has received attention. Is the evidence now sufficient to support the routine use of regimens including CNIs in LN? Although CNIs appear to have similar efficacy to MMF-based regimens as induction therapy, and are comparable with azathioprine as maintenance treatment, CNI toxicities, such as new-onset hypertension, hyperglycaemia and nephrotoxicity, have been problematic. Multitarget therapy improves the rate of complete remission in short-term studies, but whether this benefit is maintained over the longer term is uncertain. However, patient tolerability is lower and the frequency of serious events is higher in multitarget versus cyclophosphamide-based regimens, and there is a paucity of evidence from non-Asian ethnic groups. CNI-based therapy is also complicated by the absence of standardized dosing and the need for drug level monitoring, as well as by pharmacogenetic differences. Also, multitarget therapy increases the complexity and the cost of treatment. There is insufficient evidence to support the routine use of CNI-based or multitarget therapy for proliferative LN. Further data on long-term renal and cardiovascular outcomes and strategies to improve tolerability and safety are required.

PMID: 27591328 [PubMed - indexed for MEDLINE]

Pro: The use of calcineurin inhibitors in the treatment of lupus nephritis.

Thu, 08/17/2017 - 15:47
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Pro: The use of calcineurin inhibitors in the treatment of lupus nephritis.

Nephrol Dial Transplant. 2016 Oct;31(10):1561-6

Authors: Mok CC

Abstract
Renal disease in systemic lupus erythematosus (SLE) carries significant morbidity and mortality. Cyclophosphamide (CYC)- and mycophenolate mofetil (MMF)-based induction regimens are not ideal in terms of efficacy and toxicity. The adverse effects of CYC, such as infection risk, infertility, urotoxicity and oncogenicity, limit its use in lupus nephritis. Although MMF is non-inferior to CYC as induction therapy and has reduced gonadal toxicity and oncogenic potential, meta-analyses of clinical trials do not show a lower rate of infective and gastrointestinal complications. Tacrolimus (TAC) has recently been shown to have equal efficacy to either MMF or CYC for inducing remission of lupus nephritis. A low-dose combination of MMF and TAC appears to be more effective than intravenous CYC pulses in Chinese patients, and has potential to replace the more toxic CYC regimens in high-risk subgroups. TAC may be considered as another non-CYC alternative for induction therapy of lupus nephritis and in those with refractory disease or intolerance to CYC or MMF. TAC has no negative effect on fertility in younger women, and unlike MMF and CYC, it is safe in pregnancy. However, TAC has a narrow therapeutic window and drug level monitoring is required to ensure drug exposure and minimize acute toxicities. Current evidence for the efficacy of TAC in lupus nephritis is limited to 6 months and the incidence of renal flare after discontinuation of therapy or switching to azathioprine appears to be higher than other induction agents. Long-term data and the incidence of chronic nephrotoxicity of TAC as maintenance therapy in lupus nephritis are currently lacking and further prospective trials are needed to address these issues.

PMID: 27591327 [PubMed - indexed for MEDLINE]

Successful Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Ledipasvir in Renal Transplant Recipients.

Thu, 08/17/2017 - 15:47
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Successful Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Ledipasvir in Renal Transplant Recipients.

Transplantation. 2017 May;101(5):980-986

Authors: Eisenberger U, Guberina H, Willuweit K, Bienholz A, Kribben A, Gerken G, Witzke O, Herzer K

Abstract
BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection after renal allograft transplantation has been an obstacle because of contraindications associated with IFN-based therapies. Direct-acting antiviral agents are highly efficient treatment options that do not require IFN and may not require ribavirin. Therefore, we assessed the efficacy and safety of sofosbuvir and ledipasvir in renal transplant patients with chronic HCV infection.
METHODS: Fifteen renal allograft recipients with therapy-naive HCV genotype (GT) 1a, 1b, or 4 were treated with the combination of sofosbuvir and ledipasvir without ribavirin for 8 or 12 weeks. Clinical data were retrospectively analyzed for viral kinetics and for renal and liver function parameters. Patients were closely monitored for trough levels of immunosuppressive agents, laboratory values, and potential adverse effects.
RESULTS: Ten patients (66%) exhibited a rapid virologic response within 4 weeks (HCV GT1a, n = 4; HCV GT1b, n = 6). The other 5 patients exhibited a virologic response within 8 (HCV GT 1b, n = 4) or 12 weeks (HCV GT4, n = 1). One hundred percent of patients exhibited sustained virologic response at week 12 after the end of treatment. Clinical measures of liver function improved substantially for all patients. Adverse events were scarce; renal transplant function and proteinuria remained stable. Importantly, dose adjustments for tacrolimus were necessary for maintaining sufficient trough levels.
CONCLUSIONS: The described regimen appears to be safe and effective for patients after renal transplant and is a promising treatment regimen for eradicating HCV in this patient population.

PMID: 27495770 [PubMed - indexed for MEDLINE]

Acetazolamide enhances the release of urinary exosomal aquaporin-1.

Thu, 08/17/2017 - 15:47
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Acetazolamide enhances the release of urinary exosomal aquaporin-1.

Nephrol Dial Transplant. 2016 Oct;31(10):1623-32

Authors: Abdeen A, Sonoda H, Oshikawa S, Hoshino Y, Kondo H, Ikeda M

Abstract
BACKGROUND: Renal aquaporin-1 (AQP1), a water channel protein, is known to be secreted into urine, conveyed by nano-sized extracellular vesicles called exosomes. A previous study has demonstrated that acetazolamide (AZ), a diuretic that inhibits carbonic anhydrases, alters the expression level of AQP1 in cultured cells. Here we investigated whether AZ alters the release of urinary exosomal AQP1 in vivo.
METHODS: The effect of AZ on urinary exosomal AQP1 secretion was examined in rats and compared with furosemide (another diuretic), NaHCO3 (an alkalizing agent) and NH4Cl (an acidifying agent). Urine, blood and kidney samples were obtained 2 h after each treatment. Urinary exosomes were isolated by a differential centrifugation technique and urinary exosomal proteins were analyzed by immunoblotting.
RESULTS: The release of exosomal AQP1 into urine was markedly increased after treatment with AZ, accompanied by alkaluria and metabolic acidosis. Immunohistochemistry clearly demonstrated that AZ increased the apical membrane expression of AQP1 in the proximal tubules. AZ did not affect the release of exosomal marker proteins (tumor susceptibility gene 101 protein and apoptosis-linked gene 2 interacting protein X). Treatment with furosemide did not change, whereas NaHCO3 and NH4Cl decreased the exosomal release of AQP1.
CONCLUSION: The present findings indicate that AZ increases the release of exosomal AQP1 into urine in association with enhanced apical membrane expression of AQP1.

PMID: 27190370 [PubMed - indexed for MEDLINE]

Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.

Thu, 08/17/2017 - 15:47
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Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.

Nephrol Dial Transplant. 2016 Oct;31(10):1615-23

Authors: Muta K, Obata Y, Oka S, Abe S, Minami K, Kitamura M, Endo D, Koji T, Nishino T

Abstract
BACKGROUND: Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear.
METHODS: Dahl salt-sensitive rats were used as a model of nephrosclerosis in this study. The rats were divided into three groups: (i) normal-salt diet group, (ii) high-salt diet group (HS), and (iii) HS administered daily with curcumin, a histone acetyltransferase inhibitor (HS+C). At 6 weeks after the treatment, the kidneys were dissected. Morphologic changes were assessed by Masson's trichrome staining. The number of macrophages, fibroblasts and the cells expressing acetylated histone H3 at Lys 9 (H3K9) were assessed by immunohistochemistry.
RESULTS: Although both HS and HS+C rats revealed a marked increase in systolic blood pressure, serum creatinine was increased only in HS rats at 6 weeks. In the HS rats, nephrosclerosis was induced, accompanying a significant accumulation of macrophages and fibroblasts. The inflammation and fibrosis was markedly suppressed in the HS+C group. The level of histone acetylation at Lys 9 was enhanced in the HS rats, whereas curcumin administration suppressed the histone acetylation. Moreover, in the HS rats, interleukin-6 gene expression was associated with acetylated H3K9, as revealed by chromatin immunoprecipitation assay.
CONCLUSIONS: Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension.

PMID: 27190365 [PubMed - indexed for MEDLINE]

Vascularized composite allotransplantation: a closer look at the banff working classification.

Thu, 08/17/2017 - 15:47
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Vascularized composite allotransplantation: a closer look at the banff working classification.

Transpl Int. 2016 Jun;29(6):663-71

Authors: Schneider M, Cardones AR, Selim MA, Cendales LC

Abstract
The first Banff vascularized composite allotransplantation meeting was held in 2007 to standardize criteria for the characterization and reporting of severity and types of rejection. As a result, the 2007 Banff VCA working classification for skin allograft pathology was formalized and now serves as the standard for diagnosis of VCA rejection. Similar to other working classification systems, strengths and limitations have been identified including the adequacy of the specimen, the definition of severity between grades, the reproducibility, the adequacy of the specimens, the types of rejection, and the integration of newer technologies such as molecular and genomic approaches. Although a relatively few number of cases have been performed and followed up to date, additional phenotypes such as antibody-mediated rejection, fibrosis, atrophy, and vascular changes are being reported and characterized based on accumulated experience in the field of VCA and parallels with other solid organs. This study aims to consider strengths and limitations of the Banff VCA working system and highlights ongoing challenges and opportunities available related to histopathology in this emerging field of transplantation.

PMID: 26841362 [PubMed - indexed for MEDLINE]

[Multiple Myeloma - Current Status in Diagnostic Testing and Therapy].

Tue, 08/15/2017 - 12:45

[Multiple Myeloma - Current Status in Diagnostic Testing and Therapy].

Z Orthop Unfall. 2017 Aug 14;:

Authors: Kehrer M, Koob S, Strauss A, Wirtz DC, Schmolders J

Abstract
Background Multiple myeloma is a haematological blood cancer of the bone marrow and is classified by the World Health Organisation (WHO) as a plasma cell neoplasm. In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein. This ultimately causes multiple myeloma symptoms such as bone damage or kidney problems. The annual worldwide incidence of multiple myeloma is estimated to be 6 - 7/100,000 and accounts for 1% of all cancer. In Germany, there are about 6,000 cases of newly diagnosed multiple myeloma per annum. In the current era of new agents, such as immunomodulatory drugs and proteasome inhibitors and antibodies, enormous progress has been achieved in the therapy of multiple myeloma. In orthopaedics, it is essential to be able to recognise the of alarming symptoms of multiple myeloma in clinical routine and to be aware of basic diagnostic features to confirm this disease. Surgical treatment of myeloma-related bone lesions - such as stabilisation of pathological fractures - is an important domain of tumour orthopaedic surgery. Methods A comprehensive literature search was performed in PubMed using the keywords "multiple myeloma" and "diagnostic" or "therapy". This served to evaluate the available primary and secondary literature on the current status of the diagnostic testing and therapy of multiple myeloma. Systematic reviews, meta-analyses and clinical studies as well as international recommendations in therapy were included until the spring of 2016. Results There are now very sensitive screening methods for the diagnosis of multiple myeloma. Accurate diagnosis is generally based on several factors, including physical evaluation, patient history, symptoms, and diagnostic testing results. The standards for initial diagnostic tests are determined by blood and urine tests as well as a bone marrow biopsy and skeletal imaging, such as X-rays, CT scans and MRI scans. Major and minor criteria are required to confirm the diagnosis of multiple myeloma and help to determine the classification and staging of multiple myeloma, and whether it is smoldering myeloma (asymptomatic), symptomatic myeloma, or a monoclonal gammopathy of undetermined significance (MGUS). Multiple myeloma treatment options have increased significantly over the last 10 years. Standard of basic myeloma treatment consists of high dose chemotherapy in combination with autologous stem cell transplantation. Several factors may determine multiple myeloma treatment, such as age and general health, results of laboratory and cytogenetic (genomic) tests as well as symptoms and disease complications. After evaluation of these factors, an individual and often multimodal treatment plan is created and implemented in interdisciplinary cooperation. Conventional treatment options have to be evaluated for older patients (> 70 - 75 years), who are not eligible for high dose chemotherapy and autologous stem cell transplantation due to their age and/or severe comorbidities. It is essential to include supportive therapy in the integral treatment concept, in order to control pain or retain function or mobility. Supportive drugs such as bisphosphonates but also radiation therapy and orthopaedic surgery may be required in order to manage complications of the disease as well as side effects of treatment. Conclusion Current studies show promising results in the treatment of multiple myeloma, due to new agents such as immunomodulatory drugs, proteasome inhibitors and antibodies, which may improve prognosis and survival rate among myeloma patients in the future. However treatment algorithms have become more complex and expensive.

PMID: 28806822 [PubMed - as supplied by publisher]

Absence of JC polyomavirus (JCPyV) in early post-transplant JCPyV nephropathy: A case report.

Tue, 08/15/2017 - 12:45

Absence of JC polyomavirus (JCPyV) in early post-transplant JCPyV nephropathy: A case report.

Transpl Infect Dis. 2017 Aug 14;:

Authors: Janphram C, Worawichawong S, Disthabanchong S, Sumethkul V, Rotjanapan P

Abstract
JC polyomavirus (JCPyV)-associated nephropathy (JCPyVAN) occurs in < 3% of PVAN cases after renal transplantation. We report the first confirmed case to our knowledge of JCPyVAN diagnosed by kidney biopsy in the early 6 months post transplant in Thailand. In this case report, recovery of renal allograft function was not observed after reduction of immunosuppressive agents and administration of intravenous immunoglobulin and cidofovir. Despite persistent JCPyV viruria, no significant further decline in allograft function was documented at 15 months post transplant. This article is protected by copyright. All rights reserved.

PMID: 28805990 [PubMed - as supplied by publisher]

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

Tue, 08/15/2017 - 12:45

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

Nat Genet. 2017 Aug 14;:

Authors: Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, Tan W, Gribouval O, Boyer O, Revy P, Jobst-Schwan T, Schmidt JM, Lawson JA, Schanze D, Ashraf S, Ullmann JFP, Hoogstraten CA, Boddaert N, Collinet B, Martin G, Liger D, Lovric S, Furlano M, Guerrera IC, Sanchez-Ferras O, Hu JF, Boschat AC, Sanquer S, Menten B, Vergult S, De Rocker N, Airik M, Hermle T, Shril S, Widmeier E, Gee HY, Choi WI, Sadowski CE, Pabst WL, Warejko JK, Daga A, Basta T, Matejas V, Scharmann K, Kienast SD, Behnam B, Beeson B, Begtrup A, Bruce M, Ch'ng GS, Lin SP, Chang JH, Chen CH, Cho MT, Gaffney PM, Gipson PE, Hsu CH, Kari JA, Ke YY, Kiraly-Borri C, Lai WM, Lemyre E, Littlejohn RO, Masri A, Moghtaderi M, Nakamura K, Ozaltin F, Praet M, Prasad C, Prytula A, Roeder ER, Rump P, Schnur RE, Shiihara T, Sinha MD, Soliman NA, Soulami K, Sweetser DA, Tsai WH, Tsai JD, Topaloglu R, Vester U, Viskochil DH, Vatanavicharn N, Waxler JL, Wierenga KJ, Wolf MTF, Wong SN, Leidel SA, Truglio G, Dedon PC, Poduri A, Mane S, Lifton RP, Bouchard M, Kannu P, Chitayat D, Magen D, Callewaert B, van Tilbeurgh H, Zenker M, Antignac C, Hildebrandt F

Abstract
Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

PMID: 28805828 [PubMed - as supplied by publisher]

Nonmotor Manifestations of Wilson's Disease.

Tue, 08/15/2017 - 12:45

Nonmotor Manifestations of Wilson's Disease.

Int Rev Neurobiol. 2017;134:1443-1459

Authors: Biswas S, Paul N, Das SK

Abstract
Wilson disease (WD) is an autosomal genetic disorder characterized by excessive copper deposition initially in liver (hepatic variant) followed by brain (neuropsychiatric variant) and other organs such as cornea and kidney due to defect in biliary copper excretion. Predominant presentations of neuropsychiatric variant are extrapyramidal motor dysfunctions such as dystonias, Parkinsonism, choreoathetosis, tremor, and ataxias. Nonmotor symptoms (NMS) can appear before clinical disease expression and during ongoing disease process. NMS may cause confusion and delay in clinical diagnosis. In the early stage, presence of asymptomatic or symptomatic evidence of acute or chronic liver disease with or without KF ring in young subjects against the background of family history of liver disease may be indicative of underlying WD. In WD, common NMS are personality disorders, mood changes, psychosis, cognitive abnormalities, sleep disorders, and autonomic disturbances besides few systemic dysfunctions. Cognitive changes can be diagnosed by neuropsychological assessment, MRI, and SPECT study of brain. Nonmotor manifestations can be managed by metal chelator, antipsychotic agents, mood stabilizers, rarely electroconvulsive therapy, and occasional hepatic transplantation.

PMID: 28805579 [PubMed - in process]

KCNJ11 and KCNQ1 Gene Polymorphisms Are Not Associated with Post-Transplant Diabetes Mellitus in Kidney Allograft Recipients Treated with Tacrolimus.

Tue, 08/15/2017 - 12:45

KCNJ11 and KCNQ1 Gene Polymorphisms Are Not Associated with Post-Transplant Diabetes Mellitus in Kidney Allograft Recipients Treated with Tacrolimus.

Folia Biol (Praha). 2017;63(3):115-119

Authors: Dabrowska-Zamojcin E, Tarnowski M, Szydlowski M, Romanowski M, Dziedziejko V, Safranow K, Domanski L, Pawlik A

Abstract
Post-transplant diabetes mellitus (PTDM) is a metabolic disorder occurring after solid organ transplantation during the therapy with calcineurin inhibitors. ATP-sensitive potassium channels KCNJ11 and KCNQ1 play an important role in the regulation of insulin secretion by β cells and development of diabetes mellitus. Numerous studies have confirmed the association between KCNJ11 and KCNQ1 gene polymorphisms and type 2 diabetes. The aim of this study was to examine the association between KCNJ11 and KCNQ1 gene polymorphisms and posttransplant diabetes mellitus in kidney allograft recipients treated with tacrolimus. The study included 201 patients who received kidney transplants. The patients were subdivided into two subgroups: patients with PTDM (N = 35) and patients without PTDM (N = 166). The association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes was studied in three models of univariate Cox regression analysis, i.e., additive, dominant and recessive. In these three models there were no statistically significant associations between KCNJ11 and KCNQ1 gene polymorphisms and PTDM. The results of this study suggest lack of association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes mellitus in kidney allograft recipients treated with tacrolimus in the Polish population.

PMID: 28805561 [PubMed - in process]

Laparoscopic Sleeve Gastrectomy Improves Renal Transplant Candidacy and Post-Transplant Outcomes in Morbidly Obese Patients.

Tue, 08/15/2017 - 12:45

Laparoscopic Sleeve Gastrectomy Improves Renal Transplant Candidacy and Post-Transplant Outcomes in Morbidly Obese Patients.

Am J Transplant. 2017 Aug 14;:

Authors: Kim Y, Jung AD, Dhar VK, Tadros JS, Schauer DP, Smith EP, Hanseman DJ, Cuffy MC, Alloway RR, Shields AR, Shah SA, Woodle ES, Diwan TS

Abstract
Morbid obesity is a barrier to KT due to inferior outcomes, including higher rates of new-onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. LSG increases transplant eligibility by reducing body mass index (BMI) in KT candidates, but the effect of surgical weight loss on post-transplant outcomes is unknown. Reviewing single-center medical records, we identified all patients who underwent LSG prior to KT from 2011-2016 (n=20). Post-LSG kidney recipients were compared with similar-BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed-rank test were used to compare groups. Among post-LSG patients, mean BMI was 41.5±4.4 kg/m(2) at initial encounter, which decreased to 32.3±2.9 kg/m(2) prior to KT (p<0.01). No complications, readmissions, or mortality occurred following LSG. After KT, one patient (5%) experienced DGF, and no patients experienced NODAT. Allograft and patient survival at one year was 100%. Compared with non-LSG patients, post-LSG recipients had lower rates of DGF (5% vs 20%) and renal dysfunction-related readmissions (10% vs 27.5%) (p<0.05 each). Perioperative complications, allograft survival, and patient survival were similar between groups. These data suggest morbidly obese ESRD patients who undergo LSG to improve transplant candidacy, achieve excellent post-transplant outcomes. This article is protected by copyright. All rights reserved.

PMID: 28805345 [PubMed - as supplied by publisher]

Early Graft Loss in Two Recipients of Mate Kidneys From the Same Donor With Diabetic Nephropathy.

Tue, 08/15/2017 - 12:45

Early Graft Loss in Two Recipients of Mate Kidneys From the Same Donor With Diabetic Nephropathy.

Ther Apher Dial. 2017 Aug 14;:

Authors: Okada D, Okumi M, Tanabe K

PMID: 28805307 [PubMed - as supplied by publisher]

The Kidney Allocation System Does Not Appropriately Stratify Risk of Pediatric Donor Kidneys: Implications for Pediatric Recipients.

Tue, 08/15/2017 - 12:45

The Kidney Allocation System Does Not Appropriately Stratify Risk of Pediatric Donor Kidneys: Implications for Pediatric Recipients.

Am J Transplant. 2017 Aug 14;:

Authors: Nazarian SM, Peng AW, Duggirala B, Gupta M, Bittermann T, Amaral S, Levine MH

Abstract
Kidney Allocation System (KAS) was enacted in 2014 to improve graft utility, while facilitating transplantation of highly-sensitized patients and preserving pediatric access to high-quality kidneys. Central to this system is the Kidney Donor Profile Index (KDPI), a metric intended to predict transplant outcomes based on donor characteristics but derived using only adult donors. We posited that KAS had inadvertently altered the profile and quantity of kidneys made available to pediatric recipients. This question arose from our observation that most pediatric donors carry a KDPI over 35 and have therefore been rendered relatively inaccessible to pediatric recipients under KAS. Here we explore early trends in pediatric transplantation following KAS, including 1) use of pediatric donors, 2) use of Public Health System (PHS) high infectious risk donors, 3) wait time, and 4) living donor transplantation. We note some concerning preliminary changes following KAS implementation, including the allocation of fewer deceased donor pediatric kidneys to children and stagnation in pediatric wait times. Moreover, the poor predictive power of the KDPI for adult donors appears to be even worse when applied to pediatric donors. These early trends warrant further observation and consideration of changes in pediatric kidney allocation if they persist. This article is protected by copyright. All rights reserved.

PMID: 28805300 [PubMed - as supplied by publisher]

Utility of Protocol Kidney Biopsies for De Novo Donor Specific Antibodies.

Tue, 08/15/2017 - 12:45

Utility of Protocol Kidney Biopsies for De Novo Donor Specific Antibodies.

Am J Transplant. 2017 Aug 14;:

Authors: Parajuli S, Reville PK, Ellis TM, Djamali A, Mandelbrot DA

Abstract
There is limited information about the role of protocol kidney biopsies for de novo donor specific antibodies (dnDSA) in kidney transplant recipients, especially in those with stable graft function. We initiated a routine post-transplant DSA monitoring and surveillance biopsy program for dnDSA since 2014. We identified 45 kidney transplant recipients with dnDSA detected between January 2014 and February 2017 that underwent kidney biopsy within 60 days of detection of dnDSA. 29 (64%) had stable graft function and 16 (36%) had impaired graft function at the time of dnDSA detection. Even in the group with stable graft function, we found a high rate of rejection (53%), on biopsy. 88% of patients with impaired graft function had rejection. Those patients with impaired graft function had significantly lower eGFR at 12 months post biopsy and at last follow up. Those with impaired graft function had more graft failures; however, this result was not statistically significant. The high rate of asymptomatic rejection, and the fact that outcomes in asymptomatic patients are poor, is in support of the utility of surveillance biopsies in patients with dnDSA. This article is protected by copyright. All rights reserved.

PMID: 28805293 [PubMed - as supplied by publisher]

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