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The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion.

Wed, 10/11/2017 - 15:45

The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion.

Nephrol Dial Transplant. 2017 Jul 08;:

Authors: Aoki S, Saito-Hakoda A, Yoshikawa T, Shimizu K, Kisu K, Suzuki S, Takagi K, Mizumoto S, Yamada S, van Kuppevelt TH, Yokoyama A, Matsusaka T, Sato H, Ito S, Sugawara A

Abstract
Background: Heparan sulphate proteoglycan (HSPG) is present in the glomerular basement membrane (GBM) and is thought to play a major role in the glomerular charge barrier. Reductions and structural alterations of HSPG are observed in different types of kidney diseases accompanied by proteinuria. However, their causal relations remain unknown.
Methods: We generated podocyte-specific exostosin-like 3 gene ( Extl3 ) knockout mice ( Extl3KO ) using a Cre-loxP recombination approach. A reduction of HSPG was expected in the GBM of these mice, because EXTL3 is involved in its synthesis. Mice were separated into three groups, according to the loads on the glomeruli: a high-protein diet group, a high-protein and high-sodium diet group and a hyperglycaemic group induced by streptozotocin treatment in addition to maintenance on a high-protein and high-sodium diet. The urinary albumin:creatinine ratio was measured at 7, 11, 15 and 19 weeks of age. Renal histology was also investigated.
Results: Podocyte-specific expression of Cre recombinase was detected by immunohistochemistry. Moreover, immunofluorescent staining demonstrated a significant reduction of HSPG in the GBM. Electron microscopy showed irregularities in the GBM and effacement of the foot processes in Extl3KO . The values of the urinary albumin:creatinine ratio were within the range of microalbuminuria in all groups and did not significantly differ between the control mice and Extl3KO .
Conclusions: The reduction of HSPG in the GBM did not augment urinary albumin excretion. HSPG's anionic charge appears to contribute little to the glomerular charge barrier.

PMID: 28992095 [PubMed - as supplied by publisher]

p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance.

Wed, 10/11/2017 - 15:45

p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance.

Nephrol Dial Transplant. 2017 Aug 03;:

Authors: Koppe L, Alix PM, Croze ML, Chambert S, Vanholder R, Glorieux G, Fouque D, Soulage CO

Abstract
Background: The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism.
Methods: p-CS and p-CG were measured by high performance liquid chromatography-fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p-cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot.
Results: In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and <6% for p-CG). p-CG exhibited no effect on insulin sensitivity in vivo or in vitro and no synergistic inhibiting effect in combination with p-CS.
Conclusions: The relative proportion of the two p-cresol conjugates, i.e. p-CS and p-CG, is similar in mouse, in contrast to humans, pinpointing major inter-species differences in endogenous metabolism. Biologically, the sulpho- (i.e. p-CS) but not the glucuro- (i.e. p-CG) conjugate promotes insulin resistance in CKD.

PMID: 28992089 [PubMed - as supplied by publisher]

Does Kidney Donor Risk Index implementation lead to the transplantation of more and higher-quality donor kidneys?

Wed, 10/11/2017 - 15:45

Does Kidney Donor Risk Index implementation lead to the transplantation of more and higher-quality donor kidneys?

Nephrol Dial Transplant. 2017 Aug 21;:

Authors: Philipse E, Lee APK, Bracke B, Hartman V, Chapelle T, Roeyen G, de Greef K, Ysebaert DK, van Beeumen G, Couttenye MM, Van Craenenbroeck AH, Hellemans R, Bosmans JL, Abramowicz D

Abstract
Background: The Kidney Donor Risk Index (KDRI) is a quantitative evaluation of the quality of donor organs and is implemented in the US allocation system. This single-centre study investigates whether the implementation of the KDRI in our decision-making process to accept or decline an offered deceased donor kidney, increases our acceptance rate.
Methods: From April 2015 until December 2016, we prospectively calculated the KDRI for all deceased donor kidney offers allocated by Eurotransplant to our centre. The number of the transplanted versus declined kidney offers during the study period were compared to a historical set of donor kidney offers.
Results: After implementation of the KDRI, 26.1% (75/288) of all offered donor kidneys were transplanted, compared with 20.7% (136/657) in the previous period (P < 0.001). The median KDRI of all transplanted donor kidneys during the second period was 0.97 [Kidney Donor Profile Index (KDPI) 47%], a value significantly higher than the median KDRI of 0.85 (KDPI 34%) during the first period (P = 0.047). A total of 68% of patients for whom a first-offered donor kidney was declined during this period were transplanted after a median waiting time of 386 days, mostly with a lower KDRI donor kidney.
Conclusions: Implementing the KDRI in our decision-making process increased the transplantation rate by 26%. The KDRI can be a supportive tool when considering whether to accept or decline a deceased donor kidney offer. More data are needed to validate this score in other European centres.

PMID: 28992075 [PubMed - as supplied by publisher]

Urinary peptide biomarker panel associated with an improvement in estimated glomerular filtration rate in chronic kidney disease patients.

Wed, 10/11/2017 - 15:45

Urinary peptide biomarker panel associated with an improvement in estimated glomerular filtration rate in chronic kidney disease patients.

Nephrol Dial Transplant. 2017 Sep 01;:

Authors: Markoska K, Pejchinovski M, Pontillo C, Zürbig P, Jacobs L, Smith A, Masin-Spasovska J, Stojceva-Taneva O, Polenakovic M, Magni F, Mischak H, Spasovski G

Abstract
Background: An improvement in the glomerular filtration rate (GFR) of chronic kidney disease patients has been an underestimated clinical outcome. Although this may be considered as an unexpected disease course, it may provide some insights into possible mechanisms underlying disease remission and/or regression. Therefore, our aim was to identify urinary peptide biomarkers associated with an improvement in estimated GFR (eGFR) over time and to improve patient stratification.
Methods: Capillary electrophoresis coupled with mass spectrometry (CE-MS) was employed to evaluate the urine peptidome of patients with different types of renal diseases. In total, 376 patients with a slope/year between -1.5% and +1.5% were designated as non-progressors or stable, while 177 patients with a > 5% slope/year were designated as patients with an improved eGFR for state-of-art biomarker discovery and validation.
Results: We detected 384 significant peptide fragments by comparing the CE-MS data of the stable patients and those with improved renal function in our development cohort. Of these 384, a set of 141 peptides with available amino acid sequence information were used to generate a support vector machine-based classification panel. The biomarker panel was applied to our validation cohort, achieving a moderate area under the curve (AUC) value of 0.85 (81% sensitivity and 81% specificity). The majority of the peptides (78%) from the diagnostic panel arose from different types of collagen.
Conclusions: We have developed a panel of urinary peptide markers able to discriminate those patients predisposed to improve their kidney function over time and possibly be treated with more specific or less aggressive therapy.

PMID: 28992073 [PubMed - as supplied by publisher]

Local delivery of liposomal prednisolone leads to an anti-inflammatory profile in renal ischaemia-reperfusion injury in the rat.

Wed, 10/11/2017 - 15:45

Local delivery of liposomal prednisolone leads to an anti-inflammatory profile in renal ischaemia-reperfusion injury in the rat.

Nephrol Dial Transplant. 2017 Jul 08;:

Authors: van Alem CMA, Boonstra M, Prins J, Bezhaeva T, van Essen MF, Ruben JM, Vahrmeijer AL, van der Veer EP, de Fijter JW, Reinders ME, Meijer O, Metselaar JM, van Kooten C, Rotmans JI

Abstract
Background: Treatment of inflammatory kidney diseases with systemic high-dose glucocorticoids (GCs) has severe side effects. Liposomal encapsulation could facilitate local delivery of GCs to the inflamed kidney, as liposomes encapsulate their payload until extravasation at sites of inflammation, potentially resulting in local bioactivity. Our aim was to evaluate the ability of liposomes to accumulate locally after renal ischaemia-reperfusion injury in the rat and to study its effect on macrophages.
Methods: In vitro , human macrophages were incubated with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was studied microscopically and treatment effect was assessed by interkeukin 6 (IL-6) enzyme-linked immunosorbent assay. The mechanism of action was evaluated by analysing GC receptor activation by microscopy and quantitative polymerase chain reaction (qPCR). In vivo , rats were subjected to ischaemia-reperfusion injury and were injected intravenously with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was measured by the FLARE camera and the treatment effect by immunohistochemistry for myeloid cells and qPCR for inflammatory markers.
Results: In vitro , macrophages internalized liposomes after 8 hours. Prednisolone or liposomal prednisolone treatment reduced IL-6 production and both compounds induced translocation of the GC receptor to the nucleus and upregulation of PER1 messenger RNA (mRNA), indicating a similar mechanism of action. In vivo , fluorescent liposomes accumulated in the inflamed kidney. Liposomal prednisolone treatment increased the presence of ED2-positive anti-inflammatory macrophages and both prednisolone and liposomal prednisolone reduced monocyte chemoattractant protein-1 (MCP-1) mRNA production, indicating a reduced pro-inflammatory profile in the kidney.
Conclusions: Liposomal encapsulation is a promising strategy for local delivery of glucocorticoids to the inflamed kidney.

PMID: 28992069 [PubMed - as supplied by publisher]

The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease.

Wed, 10/11/2017 - 15:45

The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease.

Nephrol Dial Transplant. 2017 Aug 23;:

Authors: Hamano H, Ikeda Y, Watanabe H, Horinouchi Y, Izawa-Ishizawa Y, Imanishi M, Zamami Y, Takechi K, Miyamoto L, Ishizawa K, Tsuchiya K, Tamaki T

Abstract
Background: Hepcidin secreted by hepatocytes is a key regulator of iron metabolism throughout the body. Hepcidin concentrations are increased in chronic kidney disease (CKD), contributing to abnormalities in iron metabolism. Levels of indoxyl sulfate (IS), a uremic toxin, are also elevated in CKD. However, the effect of IS accumulation on iron metabolism remains unclear.
Methods: We used HepG2 cells to determine the mechanism by which IS regulates hepcidin concentrations. We also used a mouse model of adenine-induced CKD. The CKD mice were divided into two groups: one was treated using AST-120 and the other received no treatment. We examined control mice, CKD mice, CKD mice treated using AST-120 and mice treated with IS via drinking water.
Results: In the in vitro experiments using HepG2 cells, IS increased hepcidin expression in a dose-dependent manner. Silencing of the aryl hydrocarbon receptor (AhR) inhibited IS-induced hepcidin expression. Furthermore, IS induced oxidative stress and antioxidant drugs diminished IS-induced hepcidin expression. Adenine-induced CKD mice demonstrated an increase in hepcidin concentrations; this increase was reduced by AST-120, an oral adsorbent of the uremic toxin. CKD mice showed renal anemia, decreased plasma iron concentration, increased plasma ferritin and increased iron content in the spleen. Ferroportin was decreased in the duodenum and increased in the spleen. These changes were ameliorated by AST-120 treatment. Mice treated by direct IS administration showed hepatic hepcidin upregulation.
Conclusions: IS affects iron metabolism in CKD by participating in hepcidin regulation via pathways that depend on AhR and oxidative stress.

PMID: 28992067 [PubMed - as supplied by publisher]

Heterozygosity of mitogen-activated protein kinase organizer 1 ameliorates diabetic nephropathy and suppresses epithelial-to-mesenchymal transition-like changes in db/db mice.

Wed, 10/11/2017 - 15:45

Heterozygosity of mitogen-activated protein kinase organizer 1 ameliorates diabetic nephropathy and suppresses epithelial-to-mesenchymal transition-like changes in db/db mice.

Nephrol Dial Transplant. 2017 Jul 12;:

Authors: Loeffler I, Liebisch M, Daniel C, Amann K, Wolf G

Abstract
Background: Progressive diabetic nephropathy (DN) is characterized by tubulointerstitial fibrosis that is caused by accumulation of extracellular matrix. Induced by several factors, matrix-producing myofibroblasts may to some extent originate from tubular cells by epithelial-to-mesenchymal transition (EMT). Although previous data document that activation of hypoxia-inducible factor (HIF) signalling can be renoprotective in acute kidney disease, this issue remains controversial in chronic kidney injury. Here, we studied whether DN and EMT-like changes are ameliorated in a mouse model of type 2 diabetes mellitus with increased stability and activity of the HIF.
Methods: We used db/db mice that were crossed with transgenic mice expressing reduced levels of mitogen-activated protein kinase organizer 1 (MORG1), a scaffold protein interacting with prolyl hydroxylase domain 3 (PHD3), because of deletion of one MORG1 allele.
Results: We found significantly reduced nephropathy in diabetic MORG1 +/- heterozygous mice compared with the diabetic wild-types ( db/db XMORG1 +/+ ). Furthermore, we demonstrated that EMT-like changes in the tubulointerstitium of diabetic wild-type MORG1 +/+ mice are present, whereas diabetic mice with reduced expression of MORG1 showed significantly fewer EMT-like changes.
Conclusions: These findings reveal that a deletion of one MORG1 allele inhibits the development of DN in db/db mice. The data suggest that the diminished interstitial fibrosis in these mice is a likely consequence of suppressed EMT-like changes.

PMID: 28992060 [PubMed - as supplied by publisher]

Tsunamasa Inou: A Pioneer in Artificial Organs and Transplantation in Japan.

Wed, 10/11/2017 - 15:45

Tsunamasa Inou: A Pioneer in Artificial Organs and Transplantation in Japan.

Artif Organs. 2017 Oct;41(10):881-884

Authors: Otsubo O, Yamada Y, Kuzuhara K, Sugimoto H, Kusaba R, Takahashi I, Muto M, Dohi T, Horiuchi T, Watanabe T, Yanagisawa T, Nozaki S, Uchima T, Seo S, Awata R, Nakamoto S

PMID: 28990711 [PubMed - in process]

Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials.

Wed, 10/11/2017 - 15:45

Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials.

Curr Transplant Rep. 2017 Jun;4(2):101-109

Authors: Yamada K, Shah JA, Tanabe T, Lanaspa MA, Johnson RJ

Abstract
PURPOSE: Inter-species transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors.
RECENT FINDINGS: Advances in gene editing technology have allowed for the efficient production of multi-transgenic porcine donors leading improved xenograft survival in baboons, up to 2-years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6 months survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above.
SUMMARY: Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.

PMID: 28989853 [PubMed]

Prevention of chronic renal allograft rejection by AS2553627, a novel JAK inhibitor, in a rat transplantation model.

Wed, 10/11/2017 - 15:45

Prevention of chronic renal allograft rejection by AS2553627, a novel JAK inhibitor, in a rat transplantation model.

Transpl Immunol. 2017 Oct 05;:

Authors: Nakamura K, Kawato Y, Kaneko Y, Hanaoka K, Kubo K, Nakanishi T, Maeda M, Fukahori H, Ito M, Noto T, Inami M, Hirose J, Morokata T

Abstract
BACKGROUND: Janus kinase (JAK) inhibitors are thought to be promising candidates to aid renal transplantation. However, the effectiveness of JAK inhibitors against features of chronic rejection, including interstitial fibrosis/tubular atrophy (IF/TA) and glomerulosclerosis, has not been elucidated. Here, we investigated the effect of AS2553627, a novel JAK inhibitor, on the development of chronic rejection in rat renal transplantation.
METHODS: Lewis (LEW) to Brown Norway (BN) rat renal transplantation was performed. Tacrolimus (TAC) at 0.1mg/kg was administered intramuscularly once a day for 10 consecutive days starting on the day of transplantation (days 0 to 9) to prevent initial acute rejection. After discontinuation of TAC treatment from days 10 to 28, AS2553627 (1 and 10mg/kg) was orally administered with TAC. At 13weeks after renal transplantation, grafts were harvested for histopathological and mRNA analysis. Creatinine and donor-specific antibodies were measured from plasma samples. Urinary protein and kidney injury markers were also evaluated.
RESULTS: AS2553627 in combination with TAC exhibited low plasma creatinine and a marked decrease in urinary protein and kidney injury markers, such as tissue inhibitor of metalloproteinase-1 and kidney injury molecule-1. At 13weeks, histopathological analysis revealed that AS2553627 treatment inhibited glomerulosclerosis and IF/TA. In addition, upregulation of cell surface markers, fibrosis/epithelial-mesenchymal transition and inflammation-related genes were reduced by the combination of AS2553672 and TAC, particularly CD8 and IL-6 mRNAs, indicating that AS2553627 prevented cell infiltration and inflammation in renal allografts.
CONCLUSIONS: These results indicate the therapeutic potential of JAK inhibitors in chronic rejection progression, and suggest that AS2553627 is a promising agent to improve long-term graft survival after renal transplantation.

PMID: 28988984 [PubMed - as supplied by publisher]

Intellectual performance of kidney transplant recipients' offspring: a cross-sectional, multicenter study.

Wed, 10/11/2017 - 15:45

Intellectual performance of kidney transplant recipients' offspring: a cross-sectional, multicenter study.

J Matern Fetal Neonatal Med. 2017 Oct 08;:1-8

Authors: Morales-Buenrostro LE, Alberu J, Mancilla-Urrea E, Vélez-García A, Espinoza-Pérez R, Cruz-Santiago J, Parra-Michel R, Parra-Avila I, Flores-Nava G, Caballero-Andrade G, Niebla-Cardenas A, Pérez-Avendaño R, Angulo-Dominguez A, Lascarez S, Sánchez-Román S

Abstract
OBJECTIVE: The number of successful pregnancies in kidney transplant (KT) recipients has increased in recent years. Little evidence is available about the risk of in utero immunosuppressive exposure for long-term cognitive consequences. The aim of this study was to evaluate the impact of immunosuppression during pregnancy on intellectual performance of children born to KT recipients.
METHODS: Using a cross-sectional design, women who had undergone KT and their children (aged 4+ years) were recruited at the outpatient follow-up in five transplant centers. Women who did not receive immunosuppression during pregnancy with similar distributions of socioeconomic status and length of gestation and their children were also recruited. Children were assessed with Wechsler Intelligence Scales.
RESULTS: The study sample included 50 exposed and 50 unexposed children. No differences between groups in all the proposed confounding factors were found. Full-scale IQ did not differ significantly between both groups. Also, significant differences in any index or subscale score were not observed, with the exception of time required to complete the Wechsler preschool and primary scale of intelligence (WPPSI) Zoo locations subtest, which was done quicker in the unexposed group (p = .007). Exposure to immunosuppression during pregnancy was not a significant predictor of low IQ in logistic regression after adjustment for other factors.
CONCLUSIONS: Immunosuppression therapy during pregnancy of KT women did not affect global intellectual performance of their offspring, except maybe for visuospatial working memory in preschool children.

PMID: 28988522 [PubMed - as supplied by publisher]

Effect of unilateral nephrectomy on urinary angiotensinogen levels in living kidney donors: 1 year follow-up study.

Wed, 10/11/2017 - 15:45

Effect of unilateral nephrectomy on urinary angiotensinogen levels in living kidney donors: 1 year follow-up study.

J Renin Angiotensin Aldosterone Syst. 2017 Oct-Dec;18(4):1470320317734082

Authors: Kendi Celebi Z, Peker A, Kutlay S, Kocak S, Tuzuner A, Erturk S, Keven K, Sengul S

Abstract
BACKGROUND: Urinary angiotensinogen (uAGT) has recently been proposed as a marker of kidney injury and activated intrarenal renin-angiotensin system. We investigated the effects of living donor nephrectomy on uAGT levels, blood pressure, estimated glomerular filtration rate, proteinuria and compensatory hypertrophy in the remaining kidney of living kidney donors.
METHODS: Twenty living kidney donors were included in the study and followed for 1 year. uAGT levels were measured with enzyme-linked immunosorbent assay preoperatively and postoperatively at the 15th day, 1, 6 and 12 months.
RESULTS: Four donors were excluded from the study due to lack of data. The mean baseline estimated glomerular filtration rate was 98 ± 15 ml/min/1.73 m². Serum creatinine, uAGT/creatinine, uAGT/protein levels were higher and estimated glomerular filtration rate was lower than baseline values at all time periods. Urinary protein/creatinine levels increased after donor nephrectomy, but after 6 months they returned to baseline values. Renal volume increased after nephrectomy, but these changes did not show any correlation with uAGT/creatinine, uAGT/protein, estimated glomerular filtration rate or systolic/diastolic blood pressures. uAGT/creatinine at 6 months and urinary protein/creatinine ratio at 12 months showed a positive correlation ( P=0.008, r=0.639).
CONCLUSION: After donor nephrectomy, increasing uAGT levels can be the result of activation of the intrarenal renin-angiotensin system affecting the compensatory changes in the remaining kidney. The long-term effects of increased uAGT levels on the remaining kidney should be examined more closely in future studies.

PMID: 28988519 [PubMed - in process]

Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients.

Wed, 10/11/2017 - 15:45

Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients.

J Natl Med Assoc. 2017 Autumn;109(3):182-191

Authors: Balsam L, Saad C, Arsene C, Fogel J

Abstract
BACKGROUND: Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients.
METHODS: We studied 192 MM patients that underwent ASCT. We compared BP readings and glomerular filtration rate (GFR) at 4 weeks before ASCT, on day of ASCT and post-ASCT at 30, 100 and 180 days.
RESULTS: Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on day of ASCT and at both 30 and 100 days post-ASCT was significantly lower as compared to pre-ASCT SBP and DBP. There was a significantly higher mean GFR at day of ASCT and 30 days post-ASCT and significantly lower mean GFR at 180 days post-ASCT as compared to pre-ASCT. White patients had similar patterns to the total group for SBP, DBP, and GFR except for SBP which was still significantly lower and GFR which was not significantly different at 180 days. African-American patients showed no significant reductions in the mean values of SBP and DBP and no significant increases for GFR in follow-up after day of ASCT. Furthermore, the mean value of GFR was significantly lower at 180 days post-ASCT.
CONCLUSIONS: ASCT in MM patients had a positive impact on SBP and DBP and GFR but the impact was minimal for African-American patients. We recommend that clinicians consider closer follow-up of BP and kidney function and more intense therapy in African-Americans with MM.

PMID: 28987247 [PubMed - in process]

Cytomegalovirus viraemia and mortality in renal transplant recipients in the era of antiviral prophylaxis. Lessons from the western Australian experience.

Wed, 10/11/2017 - 15:45
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Cytomegalovirus viraemia and mortality in renal transplant recipients in the era of antiviral prophylaxis. Lessons from the western Australian experience.

BMC Infect Dis. 2017 Jul 17;17(1):501

Authors: Selvey LA, Lim WH, Boan P, Swaminathan R, Slimings C, Harrison AE, Chakera A

Abstract
BACKGROUND: Cytomegalovirus (CMV) establishes a lifelong infection that is efficiently controlled by the immune system; this infection can be reactivated in case of immunosuppression such as following solid organ transplantation. CMV viraemia has been associated with CMV disease, as well as increased mortality and allograft failure. Prophylactic antiviral medication is routinely given to renal transplant recipients, but reactivation during and following cessation of antiviral prophylaxis is known to occur. The aims of this study were to assess the incidence, timing and impact of CMV viraemia in renal transplant recipients and to determine the level of viraemia associated with adverse clinical outcomes.
METHODS: Data from all adult (18 years and over) Western Australian renal transplant recipients transplanted between 1 January 2007 and 31 December 2012 were obtained from the Australia and New Zealand Dialysis and Transplant registry and were supplemented with data obtained from clinical records. Potential risk factors for detectable CMV viraemia (≥600 copies/ml) and all-cause mortality were assessed using univariable analysis and Cox Proportional Hazards Regression.
RESULTS: There were 438 transplants performed on 435 recipients. The following factors increased the risk of CMV viraemia with viral loads ≥600 copies/ml: Donor positive/Recipient negative status; receiving a graft from a deceased donor; and receiving a graft from a donor aged 60 years and over. CMV viraemia with viral loads ≥656 copies/ml was a risk factor for death following renal transplantation, as was being aged 65 years and above at transplant, being Aboriginal and having vascular disease. Importantly 37% of the episodes of CMV viraemia with viral loads ≥656 copies/ml occurred while the patients were expected to be on CMV prophylaxis.
CONCLUSIONS: CMV viraemia (≥656 copies/ml) was associated with all-cause mortality in multivariable analysis, and CMV viraemia at ≥656 copies/ml commonly occurred during the period when renal transplant recipients were expected to be on antiviral prophylaxis. A greater vigilance in monitoring CMV levels if antiviral prophylaxis is stopped prematurely or poor patient compliance is suspected could protect some renal transplant recipients from adverse outcomes such as premature mortality.

PMID: 28716027 [PubMed - indexed for MEDLINE]

Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

Wed, 10/11/2017 - 15:45
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Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

BMC Infect Dis. 2017 Apr 24;17(1):305

Authors: Vieira AP, Trindade MAB, de Paula FJ, Sakai-Valente NY, Duarte AJDS, Lemos FBC, Benard G

Abstract
BACKGROUND: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient.
CASE PRESENTATION: A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression.
CONCLUSIONS: Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.

PMID: 28438129 [PubMed - indexed for MEDLINE]

Transplant Renal Vein Thrombosis.

Wed, 10/11/2017 - 15:45
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Transplant Renal Vein Thrombosis.

Exp Clin Transplant. 2017 Apr;15(2):123-129

Authors: El Zorkany K, Bridson JM, Sharma A, Halawa A

Abstract
Transplant renal vein thrombosis usually occurs early after surgery with a reported prevalence of 0.1% to 4.2%. It is a devastating event that ultimately leads to graft loss in almost all cases. There are many predisposing factors related to donor, recipient, surgery, and immunosuppression, with mechanical factors being considered the most common causes of transplant renal vein thrombosis. The clinical manifestations of acute renal vein thrombosis are nonspecific and are not dissimilar to the features of urine leak, urinary obstruction, or severe acute rejection. The diagnosis of transplant renal vein thrombosis depends on a high index of clinical suspicion and duplex ultrasonographic scans. Although venography remains the criterion standard, this procedure is invasive and nephrotoxic, due to use of ionizing contrast agents and also due to exposure to ionizing radiation. There are 2 therapies that have been described in the literature for salvaging a renal allograft with transplant renal vein thrombosis: thrombolytic therapy and surgical thrombectomy. The usual end result is renal allograft.

PMID: 28338457 [PubMed - indexed for MEDLINE]

Peripheral Muscle Strength Indicates Respiratory Function Testing in Renal Recipients.

Wed, 10/11/2017 - 15:45
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Peripheral Muscle Strength Indicates Respiratory Function Testing in Renal Recipients.

Exp Clin Transplant. 2017 Feb;15(Suppl 1):249-253

Authors: Ulubay G, Uyanik S, Er Dedekarginoglu B, Serifoglu I, Kupeli E, Savas Bozbas S, Sezer S, Haberal M

Abstract
OBJECTIVES: Muscle wasting occurs in renal recipients due to decreased physical performance, and decreased respiratory muscle strength may occur due to changes in structure and function. Data are scarce regarding the roles of sarcopenia and nutritional status on respiratory muscle function in these patients. Here, we evaluated interactions among peripheral muscle strength, sarcopenia, nutritional parameters, and respiratory muscle function in renal transplant recipients.
MATERIALS AND METHODS: Ninety-nine patients were prospectively enrolled between September and April 2016 at Baskent University. Forced vital capacity values (via pulmonary function tests), respiratory muscle strength (via maximal static inspiratory and expiratory pressures), and peripheral muscle strength (via hand grip strength test) were recorded. Nutritional parameters, fat weight, arm circumference, waist circumference, and C-reactive protein levels were also recorded.
RESULTS: Of 99 patients, 68 were renal transplant recipients (43 men, mean age: 39.09 ± 10.70 y) and 31 were healthy participants (14 men, mean age: 34.94 ± 10.95 y). Forced vital capacity (P < .001, r = 0.65), maximal inspiratory (P = .002, r = 0.39) and expiratory (P < .001, r = 0.4) pressure, and hand grip strength showed significant relations in transplant recipients. Positive correlations were found between serum albumin levels and both hand grip strength (P = .16, r = 0.347) and forced vital capacity (P = .03, r = 0.436). Forced vital capacity was statistically different between renal recipients and healthy participants (P = .013), whereas maximal inspiratory and expiratory pressures were not (P > .05). No statistically significant relation was observed between biochemical parameters and maximal inspiratory and expiratory pressures (P ? .05).
CONCLUSIONS: Respiratory function and peripheral muscle strength were significantly related in renal transplant recipients, with significantly lower peripheral muscle strength suggesting the presence of inadequate respiratory function. Peripheral and respiratory muscle training and nutritional replacement strategies could help to improve postoperative respiratory function.

PMID: 28260479 [PubMed - indexed for MEDLINE]

American Society of Anesthesiologists Classification Versus ARISCAT Risk Index: Predicting Pulmonary Complications Following Renal Transplant.

Wed, 10/11/2017 - 15:45
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American Society of Anesthesiologists Classification Versus ARISCAT Risk Index: Predicting Pulmonary Complications Following Renal Transplant.

Exp Clin Transplant. 2017 Feb;15(Suppl 1):208-213

Authors: Kupeli E, Er Dedekarginoglu B, Ulubay G, Oner Eyuboglu F, Haberal M

Abstract
OBJECTIVES: Patients with chronic renal failure are prone to pulmonary complications. Renal transplant recipients should undergo complete preoperative evaluation to determine risk of postoperative pulmonary complications. The American Society of Anesthesiologists classification and the Assess Respiratory Risk in Surgical Patients in Catalonia risk index correlate well with incidence of postoperative pulmonary complications. Here, we compared their accuracy in predicting pulmonary complications following renal transplant.
MATERIALS AND METHODS: We retrospectively reviewed medical records of renal transplant recipients between years 2004 and 2015. We collected patient data on Assess Respiratory Risk in Surgical Patients in Catalonia risk index, including demographics, smoking history, comorbidities, preoperative pulmonary risk score, laboratory results, surgery information, history of lower respiratory tract infection 1 month pretransplant, urgency of surgery, American Society of Anesthesiologists classification, and pulmonary complications within 1 month posttransplant.
RESULTS: Of 172 patients (123 males; mean age 38.82 y), 22 (12.8%) developed pulmonary complication during the first month posttransplant, including effusion (9 patients), pneumonia (10 patients), respiratory inefficiency (2 patients), and pulmonary embolism (1 patient). Atelectasis was observed in 95.4% of patients with complications. A positive correlation was observed between age and development of complications (r = 0.171; P = .025). Regarding risk score, 75% of patients at high risk and 19.5% at intermediate risk developed pulmonary complications. Patients with low-risk scores had significantly lower complications than intermediate- and high-risk groups (P < .001). A positive correlation was observed between preoperative risk score and complications (r = 0.34; P < .001). There was no association between the American Society of Anesthesiologists scores and postoperative complications (P = .7).
CONCLUSIONS: The American Society of Anesthesiologists classification was found to be a weaker modality to predict pulmonary complications after renal transplant; as it relates to the general health status, than the Assess Respiratory Risk in Surgical Patients in Catalonia risk index.

PMID: 28260470 [PubMed - indexed for MEDLINE]

Sirolimus-Induced Combined Posterior Reversible Encephalopathy Syndrome and Lymphocytic Pneumonitis in a Renal Transplant Recipient: Case Report and Review of the Literature.

Wed, 10/11/2017 - 15:45
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Sirolimus-Induced Combined Posterior Reversible Encephalopathy Syndrome and Lymphocytic Pneumonitis in a Renal Transplant Recipient: Case Report and Review of the Literature.

Exp Clin Transplant. 2017 Feb;15(Suppl 1):170-174

Authors: Gheith O, Cerna M, Halim MA, Nampoory N, Al-Otaibi T, Nair P, Said T, Atteya HA, Katchy K

Abstract
The mammalian target of rapamycin inhibitor sirolimus was introduced into clinical transplant practice in 1999. Dose-related myelosuppression and hyper lipidemia are the most common adverse effects. Pulmonary toxicity has been reported since 2004 and can cause interstitial pneumonitis, organizing pneumonia, and alveolar hemorrhage. Moreover, it can occasionally induce posterior reversible encephalopathy syndrome, as documented in scarce reports. To our knowledge; this is the 1st report of combined posterior reversible encephalopathy syndrome and lymphocytic pneumonitis to be induced by sirolimus. Here, we present a renal transplant recipient with reversible sirolimus-induced brain lesions who was diagnosed after exclusion of infections (viral, bacterial, and fungal), tumors, sarcoidosis, and autoimmune disorders. Both brain lesions and pneumonitis resolved completely after sirolimus discontinuation with excellent patient and graft outcome. Early and gradual sirolimus withdrawal can reverse posterior reversible encephalopathy syndrome and lymphocytic pneumonitis with preservation of stable graft function.

PMID: 28260460 [PubMed - indexed for MEDLINE]

Bariatric Surgery in Renal Transplant Patients.

Wed, 10/11/2017 - 15:45
Related Articles

Bariatric Surgery in Renal Transplant Patients.

Exp Clin Transplant. 2017 Feb;15(Suppl 1):164-169

Authors: Gheith O, Al-Otaibi T, Halim MA, Mahmoud T, Mosaad A, Yagan J, Zakaria Z, Rida S, Nair P, Hassan R

Abstract
OBJECTIVES: The idea of transplanting organs is not new, nor is the disease of obesity. Obese transplant recipients have greater risk of early death than their cohorts, which is not due to increased rejection but due to obesity-related complications, including arterial hypertension, diabetes, and delayed graft function. Here, our aim was to evaluate the effects of bariatric surgery versus lifestyle changes on outcomes of moderate to severely obese renal transplant recipients.
MATERIALS AND METHODS: Twenty-two morbidly obese patients with stable graft function who underwent bariatric surgery were compared with 44 obese patients on lifestyle management (control group). Both groups were evaluated regarding graft and patient outcomes.
RESULTS: The studied groups were comparable demographically. In the bariatric study group versus control group, we observed that the mean body mass index was 38.49 ± 9.1 versus 44.24 ± 6 (P = .024) at transplant and 34.34 ± 7.6 versus 44.38 ± 6.7 (P = .002) at 6 months of bariatric surgery. Both groups received a more potent induction immunosuppression, but this was significantly higher in the obese nonbariatric control group (P < .05). There were more patients with slow and delayed graft functions in the same nonbariatric group. The 2 groups were comparable regarding new-onset diabetes after transplant, total patients with diabetes, and graft outcomes (P > .05).
CONCLUSIONS: Bariatric surgeries are feasible, safe pro cedures for selected obese renal transplant recipients.

PMID: 28260459 [PubMed - indexed for MEDLINE]

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