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Living donor age and kidney transplant outcomes: an assessment of risk across the age continuum.

Thu, 02/07/2013 - 12:27

Living donor age and kidney transplant outcomes: an assessment of risk across the age continuum.

Transpl Int. 2013 Feb 6;

Authors: Sapir-Pichhadze R, Young A, Joseph Kim S

Abstract
Detailed data on living donor age, and its interplay with recipient age, in predicting allograft and recipient outcomes are wanting. We used the Scientific Registry of Transplant Recipients (2000-2009, n = 49 589) to assess the effect of living donor age on delayed graft function (DGF), total graft failure, death-censored graft failure, death with graft function, and graft failure with death as a competing risk using logistic and Cox proportional hazards models. Potential nonlinear associations were modeled using fractional polynomial functions. There was a significant 1.87-fold increase in the adjusted odds of DGF in the oldest versus youngest age groups. The 10-year adjusted hazard ratios (HR) for total graft failure, death-censored graft failure, and death with graft function increased in a nonlinear fashion across the range of living donor age studied. Graft failure was most accentuated in the youngest recipient age groups in competing risk models. Adjustment for renal function at 6- and 12-months post-transplant markedly attenuated the association between living donor age and graft/patient outcomes. Our findings confirm the important influence of living donor age on transplant outcomes and provide detailed estimates of risk across the living donor age continuum.

PMID: 23384401 [PubMed - as supplied by publisher]

Native renal function after combined liver-kidney transplant for type 1 hepatorenal syndrome: initial report on the use of postoperative Technetium-99 m-mercaptoacetyltriglycine scans.

Thu, 02/07/2013 - 12:27

Native renal function after combined liver-kidney transplant for type 1 hepatorenal syndrome: initial report on the use of postoperative Technetium-99 m-mercaptoacetyltriglycine scans.

Transpl Int. 2013 Feb 6;

Authors: Vagefi PA, Qian JJ, Carlson DM, Aparici CM, Hirose R, Vincenti F, Wojciechowski D

Abstract
Type 1 hepatorenal syndrome (HRS) is characterized by rapid deterioration of renal function. We sought to assess native kidney function after combined kidney-liver transplant (CLKTx) performed for type 1 HRS. We performed a retrospective, cross-sectional, single-center study. All patients with Type 1 HRS who received a CLKTx at the University of California, San Francisco from 1997 to 2007 were screened for enrollment. Patients with a baseline estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m(2) were eligible. Twenty-three patients were identified and consented to receive a Technetium-99 m-mercaptoacetyltriglycine (MAG3) nuclear scan to measure the native kidney contribution to overall renal function. Only 4 of the 23 subjects (17.4%) demonstrated native renal function that consisted of a contribution ≥50% of total renal function. Several factors and comorbidities such as age, gender, race, duration of HRS, need for and duration of renal replacement therapy, need for pressors, urine sodium, proteinuria, and use of octreotide/midodrine were analyzed and not found to be significant in predicting native renal function. The assessment of post-transplant native renal function following CLKTx may allow for improved accuracy in identifying the patients in need of CLKTx, and thus allow for greater optimization of dual-organ allocation strategies in patients with concomitant liver and renal failure.

PMID: 23384317 [PubMed - as supplied by publisher]

The silence of Good Samaritan kidney donation in Australia: a survey of hospital websites.

Thu, 02/07/2013 - 12:27

The silence of Good Samaritan kidney donation in Australia: a survey of hospital websites.

Clin Transplant. 2013 Feb 5;

Authors: Bramstedt KA, Dave S

Abstract
It is common for living donor candidates to use the Internet as a tool to enhance their decision-making process. Specifically, the websites of transplant hospitals can potentially be a vital source of information for those contemplating living donation. In an effort to explore the low incidence of Good Samaritan kidney donation (donations to strangers) in Australia, two raters conducted a nine-attribute website content analysis for all hospitals which participate in these transplants (n = 15). Overall, the concept of living donation is relatively silent on Australian hospital websites. Only four hospitals mention their living donor program, and only one mentions their Good Samaritan program. No site linked directly to Australia's AKX Paired Kidney Exchange Program - the only program which facilitates pair and chain transplants in Australia. Further, information about deceased donation is nearly absent as well. An individual with the altruistic desire to donate will generally find scant or absent information about donation at the website of their local transplant hospital, although this information could easily be present as an educational tool which supports the consent process. Using a hospital website to educate the public about a clinical service should not be viewed as ethically problematic (solicitation), but rather an ethical essential.

PMID: 23383858 [PubMed - as supplied by publisher]

Pre-existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation.

Thu, 02/07/2013 - 12:27

Pre-existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation.

Clin Transplant. 2013 Feb 6;

Authors: Taber DJ, Meadows HB, Pilch NA, Chavin KD, Baliga PK, Egede LE

Abstract
The aim of this study was to examine the impact of pre-existing diabetes mellitus (DM) on acute rejection, graft loss, and mortality following kidney transplant and whether glycemic control or cardiovascular disease (CVD) risk control with medications influenced outcomes. This was a cohort study of 1002 renal transplants conducted between 2000 and 2008. Patients were included if they received a kidney transplant within the allotted time and were at least 18 yr of age. Cox regression was used to assess acute rejection, graft failure, or death controlling for relevant sociodemographic, clinical, and post-transplant variables. Five-yr patient survival (83% vs. 93%, p < 0.001) and graft survival (74% vs. 79%, p = 0.005) were significantly lower in patients with pre-existing DM. Sequential Cox regression models demonstrated that pre-existing DM was consistently associated with a higher risk of death (HR 2.3-3.0, p < 0.01) and graft failure (HR 1.5-1.8, p < 0.04) in all models except after adjusting for CVD medication use (HR 1.9, p = 0.174 and HR 1.5, p = 0.210, respectively). These data suggest pre-existing DM is a significant risk factor for graft failure and death following renal transplantation and aggressive CVD risk reduction with medications may be an important strategy to reduce mortality and graft failure.

PMID: 23383719 [PubMed - as supplied by publisher]

Combination of pulse methylprednisolone infusions with cyclosporine-based immunosuppression is safe and effective to treat recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation.

Thu, 02/07/2013 - 12:27

Combination of pulse methylprednisolone infusions with cyclosporine-based immunosuppression is safe and effective to treat recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation.

Clin Transplant. 2013 Feb 6;

Authors: Shishido S, Satou H, Muramatsu M, Hamasaki Y, Ishikura K, Hataya H, Honda M, Asanuma H, Aikawa A

Abstract
BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric kidney allografts is associated with poor graft survival. Several therapeutic regimens have been proposed, with conflicting results. METHODS: Ten pediatric patients with recurrent FSGS after kidney transplantation were treated with a protocol of methylprednisolone (MP) infusions in combination with cyclosporine (CsA)-based immunosuppression. The patients received a drug regimen with infusions of 20 mg/kg MP on three consecutive days at week 1, week 3, and week 5, and then monthly until six months after transplantation. If a complete or partial remission (PR) was obtained, MP pulse continued every three months until 24 months after transplantation. The CsA dose was adjusted according to AUC0-4. RESULTS: Seven of 10 patients (70%) achieved complete remission (CR) with stable renal function within 18 months of beginning of treatment. One of two patients with PR entered CR 3.5 yr after transplantation. One patient lost her graft due to recurrence four months after transplantation. After observation for 26-119 months, seven patients maintained remission with normal glomerular filtration rate. Few major side effects were observed in association with the high-dose MP infusion therapy. CONCLUSIONS: MP infusion therapy in combination with CsA-based immunosuppression could be safe and effective in treating recurrent FSGS after kidney transplantation.

PMID: 23383697 [PubMed - as supplied by publisher]

Assessment of renal allograft fibrosis by transient elastography.

Thu, 02/07/2013 - 12:27

Assessment of renal allograft fibrosis by transient elastography.

Transpl Int. 2013 Feb 6;

Authors: Sommerer C, Scharf M, Seitz C, Millonig G, Seitz HK, Zeier M, Mueller S

Abstract
Transient elastography (TE, Fibroscan) has been established as a noninvasive assessment tool of liver fibrosis. We evaluated potentials and limitations of TE for identifying renal allograft fibrosis. The technical possibility of kidney examination by TE was assessed in two 10-week-old German landrace pigs and kidney stiffness (KS) was evaluated in 164 renal transplant patients. KS could be determined in all animals at the pole and pars media (29 ± 10 kPa vs. 31 ± 17 kPa). In human renal allografts KS was successfully performed in 94.5% of the test series with reliable results in 72% of the measurements. Mean KS at the pole or pars media were comparable (35.0 ± 19.9 kPa vs. 33.2 ± 18.6 kPa). Significantly higher KS was detected in renal allografts with histologically confirmed advanced fibrosis. Body-mass-index, skin-allograft distance, and peri or intrarenal fluid accumulation were important confounders of successful KS measurements (BMI: r = -0.31; P < 0.001; distance: r = -0.50; P < 0.001). Notably, KS did not correlate with renal function. TE represents a noninvasive approach in selected transplant recipients to identify allografts with severe fibrosis. The heterogeneous kidney morphology and several other confounding factors negatively affect measurability of KS by TE. Further technical modifications are required to improve applicability of TE for kidney assessment.

PMID: 23383606 [PubMed - as supplied by publisher]

Assessment of arterial stiffness in patients with CKD stage 5 when initiating chronic hemodialysis for vascular access and for preventing cardiovascular events.

Thu, 02/07/2013 - 12:27
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Assessment of arterial stiffness in patients with CKD stage 5 when initiating chronic hemodialysis for vascular access and for preventing cardiovascular events.

Rom J Intern Med. 2012 Jul-Sep;50(3):225-31

Authors: Mateş A, Golea O, Tudoran M, Tudoran C, Pescariu S, Velciov S

Abstract
We consider that re-assessment of the vascular status is necessary, even mandatory, in patients with CKD when initiating dialysis because of two reasons:--assessment of vascular remodelling is important for establishing the artery-venous fistula as it can supply appreciative data on its success and duration;--vascular remodelling plays an important part in cardio-vascular pathology of patients dialysed, with the required consecutive prophylactic measures. In chronic kidney disease, calcium deposits at extra-skeletal level also affect the vessels, determining calcifications of both the vascular intima and media. Atherosclerosis and arteriosclerosis are present in patients with CKD and they contribute to diminishing the elasticity of the artery wall by vascular remodelling. Vascular remodelling determines thickening of the artery wall, respectively of the thickness of the arterial intima-media. Thus, arteries lose their elasticity, and the wall of the arterial tree wall turns stiff. Arterial stiffness is a process that precedes the development-proper of atherosclerosis, determined by cumulative exposure to various risk factors. Atherosclerosis is a focal process, in which indemne areas alternate with areas with atheroma plaques at intima level, and arteriosclerosis is a diffuse process located at the level of the arterial media. Non-invasive assessment of arterial stiffness can be achieved by analyzing pulse wave velocity and the augmentation index. We studied a group of 35 patients with chronic kidney insufficiency, CKD, stage 5, with an average age of 52.03 +/- 17.36 years, of whom 15 (43%) were females and 20 (57%) were males. The investigated parameters presented the following average values: PWV = 16.7 +/- 1.27 m/s; IMT = 1.63 +/- 0.18 mm; Aix = 36.14 +/- 9.98%; AAI = 0.78 +/- 0.2. The assessment of vascular stiffness in chronically dialysed patients offers better appreciation of vascular stiffness. Knowing the amplitude of the vascular remodelling process is of special importance for deciding the place and modality of performing the vascular access with regard to replacing the kidney function and to preventing cardiovascular events in dialysed patients.

PMID: 23330290 [PubMed - indexed for MEDLINE]

Post-transplant Lymphoproliferative Disorder--a case of late-onset T-cell lymphoma after failed renal transplant.

Thu, 02/07/2013 - 12:27
Related Articles

Post-transplant Lymphoproliferative Disorder--a case of late-onset T-cell lymphoma after failed renal transplant.

Adv Perit Dial. 2012;28:94-6

Authors: Dalal P, Bichu P, Dhawan V, Ariyamuthu V, Malhotra K, Misra M, Khanna R

Abstract
Post-transplant lymphoproliferative disease (PTLD) is a rare but life-threatening complication after solid organ transplantation. The risk of PTLD varies with recipient age, serostatus of the donor and the recipient for Epstein-Barr virus, type of organ transplanted, and intensity of immunosuppression. The risk of PTLD is highest in the early post-transplant period, but the cumulative risk increases with time. We report a case of PTLD occurring 17 years after renal transplantation in a 59-year-old woman.

PMID: 23311222 [PubMed - indexed for MEDLINE]

Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis.

Thu, 02/07/2013 - 12:27
Related Articles

Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis.

Int J Hematol. 2012 Sep;96(3):295-300

Authors: Nishiwaki S, Nakayama T, Saito S, Mizuno H, Ozaki T, Takahashi Y, Maruyama S, Nishida T, Murata M, Kojima S, Naoe T

Abstract
We have demonstrated that adipose tissue-derived mesenchymal stem cells (ADSCs) from mice are capable of reconstituting the hematopoietic microenvironment, and facilitate hematopoiesis more effectively than bone marrow-derived mesenchymal stem cells (BMSCs) in mouse. The ready accessibility of fat tissue rich in MSCs and the higher hematopoiesis-supporting capacities of ADSCs suggest that ADSCs might represent a new therapeutic modality for the regeneration of impaired hematopoiesis. As a further step towards their use in clinical practice, we established human BMSCs and ADSCs from healthy volunteers of similar age, and compared their proliferation capacities, hematopoiesis-supporting properties, and safety. In vitro cell proliferation studies revealed that ADSCs have a higher population doubling number than BMSCs. In vitro co-culture assays showed that ADSCs not only support human CD34(+) peripheral blood stem cells (PBSCs), but also yield significantly more non-adherent hematic cells than BMSCs. In vitro progenitor assays revealed that ADSCs promote a higher frequency of early progenitors than do BMSCs. Interestingly, BM cellularity in irradiated mice that had received ADSCs tended to be higher than that of mice treated with BMSCs. When MSCs were injected into the BM cavity of tibiae, we observed no evidence of MSC-induced toxicity either during or after treatment. In addition, no microscopic abnormalities were observed in the bone marrow and major organs.

PMID: 22782260 [PubMed - indexed for MEDLINE]

Cyclosporine a impairs nucleotide binding oligomerization domain (nod1)-mediated innate antibacterial renal defenses in mice and human transplant recipients.

Wed, 02/06/2013 - 12:10

Cyclosporine a impairs nucleotide binding oligomerization domain (nod1)-mediated innate antibacterial renal defenses in mice and human transplant recipients.

PLoS Pathog. 2013 Jan;9(1):e1003152

Authors: Tourneur E, Ben Mkaddem S, Chassin C, Bens M, Goujon JM, Charles N, Pellefigues C, Aloulou M, Hertig A, Monteiro RC, Girardin SE, Philpott DJ, Rondeau E, Elbim C, Werts C, Vandewalle A

Abstract
Acute pyelonephritis (APN), which is mainly caused by uropathogenic Escherichia coli (UPEC), is the most common bacterial complication in renal transplant recipients receiving immunosuppressive treatment. However, it remains unclear how immunosuppressive drugs, such as the calcineurin inhibitor cyclosporine A (CsA), decrease renal resistance to UPEC. Here, we investigated the effects of CsA in host defense against UPEC in an experimental model of APN. We show that CsA-treated mice exhibit impaired production of the chemoattractant chemokines CXCL2 and CXCL1, decreased intrarenal recruitment of neutrophils, and greater susceptibility to UPEC than vehicle-treated mice. Strikingly, renal expression of Toll-like receptor 4 (Tlr4) and nucleotide-binding oligomerization domain 1 (Nod1), neutrophil migration capacity, and phagocytic killing of E. coli were significantly reduced in CsA-treated mice. CsA inhibited lipopolysaccharide (LPS)-induced, Tlr4-mediated production of CXCL2 by epithelial collecting duct cells. In addition, CsA markedly inhibited Nod1 expression in neutrophils, macrophages, and renal dendritic cells. CsA, acting through inhibition of the nuclear factor of activated T-cells (NFATs), also markedly downregulated Nod1 in neutrophils and macrophages. Silencing the NFATc1 isoform mRNA, similar to CsA, downregulated Nod1 expression in macrophages, and administration of the 11R-VIVIT peptide inhibitor of NFATs to mice also reduced neutrophil bacterial phagocytosis and renal resistance to UPEC. Conversely, synthetic Nod1 stimulating agonists given to CsA-treated mice significantly increased renal resistance to UPEC. Renal transplant recipients receiving CsA exhibited similar decrease in NOD1 expression and neutrophil phagocytosis of E. coli. The findings suggest that such mechanism of NFATc1-dependent inhibition of Nod1-mediated innate immune response together with the decrease in Tlr4-mediated production of chemoattractant chemokines caused by CsA may contribute to sensitizing kidney grafts to APN.

PMID: 23382681 [PubMed - in process]

Persistent defective membrane trafficking in epithelial cells of patients with familial hemophagocytic lymphohistiocytosis type 5 due to STXBP2/MUNC18-2 mutations.

Wed, 02/06/2013 - 12:10

Persistent defective membrane trafficking in epithelial cells of patients with familial hemophagocytic lymphohistiocytosis type 5 due to STXBP2/MUNC18-2 mutations.

Pediatr Blood Cancer. 2013 Feb 4;

Authors: Stepensky P, Bartram J, Barth TF, Lehmberg K, Walther P, Amann K, Philips AD, Beringer O, Zur Stadt U, Schulz A, Amrolia P, Weintraub M, Debatin KM, Hoenig M, Posovszky C

Abstract
BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare primary immune disorder defined by mutations in the syntaxin binding protein 2 (STXBP2) alias MUNC18-2. Despite defective immunity and a hyper-inflammatory state, clinical findings such as neurological, gastrointestinal, and bleeding disorders are present in a significant number of patients and suggest an impaired expression and function of STXBP2 in cells other than cytotoxic lymphocytes. PROCEDURE: We investigated four patients with FHL5 suffering from severe enteropathy and one of whom also had renal tubular dysfunction despite successful hematopoietic stem cell transplantation (HSCT). Gastrointestinal and renal biopsy specimens were analyzed by immunohistochemistry and electron microscopy. RESULTS: Histopathology revealed an intracytoplasmatic accumulation of PAS-positive granules and an enlarged intracytoplasmatic CD10-positive band along the apical pole of enterocytes. Electron microscopy revealed short microvilli and granules filled with electro lucent material. In addition, we described mildly dilated renal tubules and electron micrographs displayed a higher number of cytoplasmic inclusions, electrodense lysosomal and electrolucent endosomal vesicles. CONCLUSION: Mutations in STXBP2 do not only affect cytotoxic T lymphocytes but also cause changes in the intestinal and renal epithelium resulting in severe, osmotic diarrhea and renal proximal tubular dysfunction. These defects persist after successful treatment of hemophagocytic lymphohistocytosis by HSCT. Clinical manifestations in FHL5 patients despite successful HSCT may therefore be related to defective membrane trafficking in the gut and kidney. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

PMID: 23382066 [PubMed - as supplied by publisher]

Postoperative cardiac tamponade after kidney transplantation: a possible consequence of alemtuzumab-induced cytokine release syndrome.

Wed, 02/06/2013 - 12:10

Postoperative cardiac tamponade after kidney transplantation: a possible consequence of alemtuzumab-induced cytokine release syndrome.

Transplantation. 2013 Feb 15;95(3):e18-9

Authors: Adams PS, Shapiro R, Hilmi IA

PMID: 23380870 [PubMed - in process]

Vildagliptin and Pioglitazone in Patients With Impaired Glucose Tolerance After Kidney Transplantation: A Randomized, Placebo-Controlled Clinical Trial.

Wed, 02/06/2013 - 12:10

Vildagliptin and Pioglitazone in Patients With Impaired Glucose Tolerance After Kidney Transplantation: A Randomized, Placebo-Controlled Clinical Trial.

Transplantation. 2013 Feb 15;95(3):456-462

Authors: Werzowa J, Hecking M, Haidinger M, Lechner F, Döller D, Pacini G, Stemer G, Pleiner J, Frantal S, Säemann MD

Abstract
BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation affecting graft and patient survival. Currently, no guidelines exist for the management of renal transplant patients with impaired glucose tolerance (IGT), a risk factor for the development of NODAT and an independent predictor of death. METHODS: In a population of 48 stable renal transplant recipients at least 6 months from time of transplantation with newly diagnosed IGT, we tested the dipeptidylpeptidase-4 inhibitor vildagliptin, the thiazolidinedione pioglitazone, or placebo for 3 months in addition to lifestyle counseling. Outcome measures were difference in change in oral glucose tolerance test between the groups and between baseline and end of study as well as change in HbA1c, serum lipids, and renal and hepatic function. RESULTS: In both treatment groups, 2-hr plasma glucose at 3 months was significantly reduced compared with baseline (vildagliptin: -20±24 mg/dL; P=0.002 and pioglitazone: -23±29 mg/dL; P=0.004), and pioglitazone also significantly improved fasting plasma glucose (-11±14 mg/dL; P=0.003), although the primary outcome (difference in change in 2-hr plasma glucose among the three groups) did not reach statistical significance. Furthermore, HbA1c was decreased in both treatment arms (vildagliptin: -0.1%±0.3%; P=0.046 and pioglitazone: -0.2%±0.3%; P=0.029). In the placebo group, no significant changes in these parameters were observed. Only mild adverse events occurred and at a similar rate in all three groups. CONCLUSIONS: These data demonstrate that both vildagliptin and pioglitazone are of potential benefit in patients with IGT after renal transplantation in addition to lifestyle modification.

PMID: 23380864 [PubMed - as supplied by publisher]

Incidence and impact of de novo donor-specific alloantibody in primary renal allografts.

Wed, 02/06/2013 - 12:10

Incidence and impact of de novo donor-specific alloantibody in primary renal allografts.

Transplantation. 2013 Feb 15;95(3):410-7

Authors: Everly MJ, Rebellato LM, Haisch CE, Ozawa M, Parker K, Briley KP, Catrou PG, Bolin P, Kendrick WT, Kendrick SA, Harland RC, Terasaki PI

Abstract
BACKGROUND: To date, limited information is available describing the incidence and impact of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSA) in the primary renal transplant patient. This report details the dnDSA incidence and actual 3-year post-dnDSA graft outcomes.
METHODS: The study includes 189 consecutive nonsensitized, non-HLA-identical patients who received a primary kidney transplant between March 1999 and March 2006. Protocol testing for DSA via LABScreen single antigen beads (One Lambda) was done before transplantation and at 1, 3, 6, 9, and 12 months after transplantation then annually and when clinically indicated.
RESULTS: Of 189 patients, 47 (25%) developed dnDSA within 10 years. The 5-year posttransplantation cumulative incidence was 20%, with the largest proportion of patients developing dnDSA in the first posttransplantation year (11%). Young patients (18-35 years old at transplantation), deceased-donor transplant recipients, pretransplantation HLA (non-DSA)-positive patients, and patients with a DQ mismatch were the most likely to develop dnDSA. From DSA appearance, 9% of patients lost their graft at 1 year. Actual 3-year death-censored post-dnDSA graft loss was 24%.
CONCLUSION: We conclude that 11% of the patients without detectable DSA at transplantation will have detectable DSA at 1 year, and over the next 4 years, the incidence of dnDSA will increase to 20%. After dnDSA development, 24% of the patients will fail within 3 years. Given these findings, future trials are warranted to determine if treatment of dnDSA-positive patients can prevent allograft failure.

PMID: 23380861 [PubMed - in process]

Poor bladder compliance contributes to renal impairment after kidney transplantation?

Wed, 02/06/2013 - 12:10

Poor bladder compliance contributes to renal impairment after kidney transplantation?

J Formos Med Assoc. 2013 Feb;112(2):109

Authors: Chou YH, Lin SL

PMID: 23380614 [PubMed - in process]

Transnational validation of the Australian algorithm for virtual crossmatch allocation in kidney paired donation.

Wed, 02/06/2013 - 12:10

Transnational validation of the Australian algorithm for virtual crossmatch allocation in kidney paired donation.

Hum Immunol. 2013 Feb 1;

Authors: Böhmig GA, Fidler S, Christiansen FT, Fischer G, Ferrari P

Abstract
An independent pool of 16 incompatible live donor-recipient pairs registered at the Vienna transplant unit was applied to test whether virtual crossmatch allocation used in the Australian kidney paired donation (KPD) program reliably predicts negative crossmatches. High resolution HLA data were entered into the computer-matching algorithm and allocation was performed excluding any DSA >2000MFI. CDC and flow crossmatch data of recipients against any of the donors were available for 112 crossmatch combinations. The computer program identified 19 possible pairings in 2-way or 3-way chains in multiple combinations. The top ranked combination included one 3-way and two 2-way ABO-compatible chains. Where crossmatches were available all recipients were CDC crossmatch negative with the computer-matched donor. Excluding allocation of KPD donors in the presence of DSA >2000MFI had a negative predictive of 99.9% for CDC and 96.4% for flow crossmatch. In the 12 pairings with ⩾1 DSA against crossmatched donors there was a negative CDC and flow crossmatch. These results show excellent correlation between matching using virtual crossmatch and actual crossmatch results. Using the 2000MFI cut-off the number of potentially unacceptable CDC and flow crossmatch positive pairings identified by virtual crossmatching is low, but some potential crossmatch negative pairings are missed.

PMID: 23380140 [PubMed - as supplied by publisher]

Survey of the Effects of a Column for Adsorption of β2-Microglobulin in Patients With Dialysis-Related Amyloidosis in Japan.

Wed, 02/06/2013 - 12:10

Survey of the Effects of a Column for Adsorption of β2-Microglobulin in Patients With Dialysis-Related Amyloidosis in Japan.

Ther Apher Dial. 2013 Feb;17(1):40-47

Authors: Gejyo F, Amano I, Ando T, Ishida M, Obayashi S, Ogawa H, Ono T, Kanno Y, Kitaoka T, Kukita K, Kurihara S, Sato M, Shin J, Suzuki M, Takahashi S, Taguma Y, Takemoto Y, Nakazawa R, Nakanishi T, Nakamura H, Hara S, Hiramatsu M, Furuya R, Masakane I, Tsuchida K, Motomiya Y, Morita H, Yamagata K, Yoshiya K, Yamakawa T, The Society of β2-Microglobulin Adsorption Therapy

Abstract
Dialysis-related amyloidosis is a serious complication of long-term hemodialysis. Its pathogenic mechanism involves accumulation of β2-microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2-microglobulin, has been available since 1996 to treat dialysis-related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis-related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self-evaluation by patients, worsening of symptoms was inhibited in 84.9-96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis-related amyloidosis in most patients.

PMID: 23379492 [PubMed - as supplied by publisher]

[The clinical course and treatment of fungal infections in the early period after kidney transplantation].

Wed, 02/06/2013 - 12:10

[The clinical course and treatment of fungal infections in the early period after kidney transplantation].

Urologiia. 2012 Sep-Oct;(6):26-8, 30-2

Authors:

Abstract
The article discusses the critical issues of clinical manifestations and treatment of fungal infections in patients after kidney transplantation. In fungal infection, which is usually detected in the composition of microbial associations, lungs are more often affected. In this case, mortality reaches 60%. Affecting the renal transplant by Candida spp. or Aspergillus spp. can lead to the loss of function of transplanted kidneys. At the current stage, lipid formulations of amphotericin B are drugs of choice for antimycotic therapy in posttransplant period. Nephrotoxic effect of amphotericin B is reversible and does not represent a serious threat to the function of the transplantate. Administration of lipid formulations of amphotericin B is the most justified, since it does not affect the concentration ofimmunosuppressive drugs in the blood serum of patients after transplantation.

PMID: 23379235 [PubMed - in process]

Detrimental effects of prolonged warm renal ischaemia-reperfusion injury are abrogated by supplemental hydrogen sulphide: an analysis using real-time intravital microscopy and polymerase chain reaction.

Wed, 02/06/2013 - 12:10
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Detrimental effects of prolonged warm renal ischaemia-reperfusion injury are abrogated by supplemental hydrogen sulphide: an analysis using real-time intravital microscopy and polymerase chain reaction.

BJU Int. 2012 Dec;110(11 Pt C):E1218-27

Authors: Zhu JX, Kalbfleisch M, Yang YX, Bihari R, Lobb I, Davison M, Mok A, Cepinskas G, Lawendy AR, Sener A

Abstract
UNLABELLED: What's known on the subject? and What does the study add? Hydrogen sulphide (H(2) S) has recently been classified as a member of the gasotransmitter family. Its physiological and pathophysiological effects are rapidly expanding with numerous studies highlighting the protective effects of H(2) S on ischaemia-reperfusion injury (IRI) in various organ systems, e.g. heart, liver, CNS and lungs. The mechanisms behind its protective effects reside in its vasodilatory, anti-inflammatory and anti-oxidant characteristics. These specific mechanistic profiles appear to be different across different tissues and models of IRI. We recently showed that supplementation of preservation solutions with H(2) S during periods of prolonged cold renal storage and subsequent renal transplantation leads to a massive and significant survival, functional and tissue protective advantage compared with storage in standard preservation solution alone. However, there have only been a few studies that have evaluated the effects of H(2) S against warm renal IRI; although these studies have focused primarily upon shorter periods of warm renal pedicle clamping, they have shown a clear survival benefit to H(2) S supplementation. The present study adds to the existing literature by evaluating the effects of H(2) S in a model of warm IRI with clinically relevant, prolonged warm ischaemia-reperfusion times (1 h ischaemia, 2 h reperfusion). We show an unprecedented view into real-time renal and hepatic perfusion with intravital microscopy throughout the reperfusion period. We show, for the first time, that supplemental H(2) S has multiple protective functions against the warm IRI-induced tissue damage, which may be clinically applicable to both donation after cardiac death models of renal transplantation, as well as to uro-oncological practices requiring surgical clamping of the renal pedicle, e.g. during a partial nephrectomy.
OBJECTIVE: • To determine the protective role of supplemental hydrogen sulphide (H(2) S) in prolonged warm renal ischaemia-reperfusion injury (IRI) using real-time intravital microscopy (IVM).
MATERIALS AND METHODS: • Uninephrectomised Lewis rats underwent 1 h of warm ischaemia and 2 h of reperfusion during intraperitoneal treatment with phosphate buffer saline (IRI, n = 10) or 150 µmol/L NaHS (IRI+H(2) S, n = 12) and were compared with sham-operated rats (n = 9). • Blood was collected for measurement of serum creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). • IVM was performed to assess renal and hepatic microcirculation. • Kidneys were sectioned for histology and real-time quantitative polymerase chain reaction for markers of inflammation.
RESULTS: • The mean (sd) Cr concentration raised to 72.8(2.5) µmol/L after IRI from 11.0 (0.7) µmol/L (sham) but was partially inhibited with H(2) S to 62.8 (0.9) µmol/L (P < 0.05). • H(2) S supplementation during IRI increased renal capillary perfusion on IVM, and improved acute tubular necrosis and apoptotic scores on histology (P < 0.05). • Supplemental H(2) S decreased expression of the pro-inflammatory markers toll-like receptor 4, tumour necrosis factor α, interleukin 8, C-C chemokine receptor type 5, interferon γ and interleukin 2 (P < 0.05). • Distant organ (liver) dysfunction after renal IRI was limited with H(2) S supplementation: blunting of the ALT and AST surge, decreased hepatic sinusoidal vasodilation, and decreased leukocyte infiltration in post-sinusoidal venules (P < 0.05). • H(2) S supplementation directly inhibited interleukin 8-induced neutrophil chemotaxis in vitro (P < 0.05).
CONCLUSIONS: • These findings are the first to show the real-time protective role of supplemental H(2) S in prolonged periods of warm renal IRI, perhaps acting by decreasing leukocyte migration and limiting inflammatory responses. • The protective effects of H(2) S suggest potential clinical applications in both donors after cardiac death models of renal transplantation and oncological practices requiring vascular clamping.

PMID: 23046222 [PubMed - indexed for MEDLINE]

The alternative Iranian model of living renal transplantation.

Wed, 02/06/2013 - 12:10
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The alternative Iranian model of living renal transplantation.

Kidney Int. 2012 Sep;82(6):625-6

Authors: Delmonico FL

Abstract
The experience of the Iranian model should be carefully considered by those who suggest a pilot trial of a regulated market in organ sales. Mahdavi-Mazdeh's candid report makes clear that a fixed price as the basis of regulation is not possible. Iran is proceeding with an independent program of deceased organ donation in cities such as Shiraz. Mahdavi-Mazdeh's report is encouraging for the prospect of a revitalized expansion of deceased donation.

PMID: 22935881 [PubMed - indexed for MEDLINE]

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