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Tuesday, November 22, 2016

Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients

 

by Colin R. Lenihan, Sumi Sukumaran Nair, Chandan Vangala, Venkat Ramanathan, Maria E. Montez-Rath, Wolfgang C. Winkelmayer
Posttransplantation bone disease is a significant problem, with few well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated with hip fracture in the general population and are widely prescribed for kidney transplant recipients.
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Are Octogenarians With End-Stage Renal Disease Candidates for Renal Transplantation?

 

by Lønning, Kjersti; Midtvedt, Karsten; Leivestad, Torbjørn; Reisæter, Anna V.; Line, Pål-Dag; Hartmann, Anders; Heldal, Kristian
imageBackground: Elderly patients are the fastest-growing group in need of renal transplantation. This study puts focus on renal transplant recipients in their 80th year or longer at time of engraftment. Is there evidence to support an absolute upper age limit for renal transplantation? Methods: Recipients in their 80th year or longer, transplanted between 1983 and 2015, were included. Data were retrieved from the Norwegian Renal Registry in the end of October 2015. Graft and patient survivals were compared with recipients aged 70 to 79 years at transplantation. Results: Forty-seven patients older than 79 years were transplanted in the defined period. Median age 80.1 years, 81% were men. Median time on dialysis before transplantation was 18.5 months. All patients received an allograft from a deceased donor (median donor age, 61.8 years). In the death-censored graft survival model, there was no statistical difference between the groups. We found improved patient and graft survivals after introduction of mycophenolate mofetil and induction with basiliximab. Patients transplanted before 2000 had increased risk of death compared with those transplanted after 2000 (hazard ratio, 3.2; 95% confidence interval, 1.2-8.7). Median uncensored graft survival for patients transplanted after the year 2000 was 5.0 year (95% confidence interval, 2.4-7.6). Median patient survival was 5.0 years (3.1-6.9) and 5-year patient survival was 55%. Conclusions: Age by itself should not be an absolute contraindication against renal transplantation. An estimated 5-year survival rate of 55% post-engraftment for an 80-year-old patient is in our opinion more than acceptable.
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Tuesday, November 15, 2016

Renal Tubular Toxicity Associated With Rosuvastatin Therapy

 

by Frank L. Ward, Rohan John, Joanne M. Bargman, Rory F. McQuillan
Preapproval clinical trials examining the safety and efficacy of rosuvastatin demonstrated an increased incidence of proteinuria, hematuria, rhabdomyolysis, and other acute kidney injury of unknown cause at high doses. The latter cases manifested with urine sediment findings and in some cases, renal histology, indicating renal tubular injury in the absence of rhabdomyolysis. Despite these provocative findings, there have been very few reports in the literature regarding non−rhabdomyolysis-mediated acute kidney injury associated with high-dose rosuvastatin since its widespread introduction more than a decade ago, suggesting that it is either a rare entity or systematically underdiagnosed and under-reported.
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Wednesday, November 9, 2016

Reduction of extended-release tacrolimus dose in low immunological risk kidney transplant recipients increases risk of rejection and appearance of DSA - a randomized study

 

by Philippe Gatault, Nassim Kamar, Matthias Büchler, Charlotte Colosio, Dominique Bertrand, Antoine Durrbach, Laeticia Albano, Joseph Rivalan, Yannick Le Meur, Marie Essig, Nicolas Bouvier, Christophe Legendre, Bruno Moulin, Anne-Elisabeth Heng, Pierre-François Weestel, Johnny Sayegh, Bernard Charpentier, Lionel Rostaing, Eric Thervet, Yvon Lebranchu

Abstract

The aim of this study (NCT01744470) was to determine the efficacy and safety of two different doses of extended-release tacrolimus (TacER) in kidney transplant recipients (KTR) between 4 and 12 months post-transplantation. Stable steroid-free KTR were randomized (1:1) after 4 months: Group A 50%-reduction in TacER dose with targeted TacERC0>3μg/L; Group B no change in TacER dose (TacERC0=7-12μg/L). The primary outcome was eGFR at 1 year. Of 300 patients, intent-to-treat analysis included 186 patients (Group A 87, Group B 99). TacERC0 were lower in Group A than in Group B at 6 (4.1±2.7 vs 6.7±3.9μg/L, p<0.0001) and 12 months (5.6±2.0 vs 7.4±2.1μg/L, p<0.0001). eGFR was similar in both groups at 12 months (Group A 56.0±17.5ml/min/1.73m², Group B 56.0±22.1ml/min/1.73m²). More rejection episodes occurred in Group A (Group A 11, Group B 3; p=0.016). At one year, sub-clinical inflammation was more frequent in Group A than in Group B (i>0: 21.4% vs. 8.8%, p=0.047; t>0: 19.6% vs. 8.7%, p=0.076, i+t: 1.14±1.21 vs 0.72±1.01, p=0.038). DSA appeared only in Group A (6 patients vs. 0, p=0.008). TacERC0 should be maintained above 7μg/L during the first year post-transplantation in low immunological risk steroid-free KTR receiving moderate dose of MPA.

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Monday, November 7, 2016

Correlates and Outcomes of Posttransplant Smoking in Solid Organ Transplant Recipients: A Systematic Literature Review and Meta-Analysis

Alberto Carlos Reino Buelvas
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Message: Background: Despite smoking being an absolute or relative contraindication for transplantation, about 11% to 40% of all patients continue or resume smoking posttransplant. This systematic review with meta-analysis investigated the correlates and outcomes associated with smoking after solid organ transplantation. Methods: We searched PubMed, EMBASE, CINAHL, and PsycINFO from inception until January 2016, using state-of-the art methodology. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed for correlates/outcomes investigated 5 times or more. Results: Seventy-three studies (43 in kidney, 17 in heart, 12 in liver, 1 in lung transplantation) investigated 95 correlates and 24 outcomes, of which 6 correlates and 4 outcomes could be included in the meta-analysis. The odds of smoking posttransplant were 1.33 times higher in men (95% CI, 1.12-1.57). Older indiv iduals were significantly less likely to smoke (OR, 0.48; 95% CI, 0.38-0.62), as were patients with a higher body mass index (OR, 0.68; 95% CI, 0.52-0.89). Hypertension (OR, 1.16; 95% CI, 0.77-1.75), diabetes mellitus (OR, 0.52; 95% CI, 0.15-1.78), and having a history of cardiovascular disease (OR, 0.92; 95% CI, 0.77-1.09) were not significant correlates. Posttransplant smokers had higher odds of newly developed posttransplant cardiovascular disease (OR, 1.41; 95% CI, 1.02-1.95), nonskin malignancies (OR, 2.58; 95% CI, 1.26-5.29), a shorter patient survival time (OR, 0.59; 95% CI, 0.44-0.79), and higher odds of mortality (OR, 1.74; 95% CI, 1.21-2.48). Conclusions: Posttransplant smoking is associated with poor outcomes. Our results might help clinicians to understand which patients are more likely to smoke posttransplant, guide interventional approaches, and provide recommendations for future research.
imageBackground: Despite smoking being an absolute or relative contraindication for transplantation, about 11% to 40% of all patients continue or resume smoking posttransplant. This systematic review with meta-analysis investigated the correlates and outcomes associated with smoking after solid organ transplantation. Methods: We searched PubMed, EMBASE, CINAHL, and PsycINFO from inception until January 2016, using state-of-the art methodology. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed for correlates/outcomes investigated 5 times or more. Results: Seventy-three studies (43 in kidney, 17 in heart, 12 in liver, 1 in lung transplantation) investigated 95 correlates and 24 outcomes, of which 6 correlates and 4 outcomes could be included in the meta-analysis. The odds of smoking posttransplant were 1.33 times higher in men (95% CI, 1.12-1.57). Older individuals were significantly less likely to smoke (OR, 0.48; 95% CI, 0.38-0.62), as were patients with a higher body mass index (OR, 0.68; 95% CI, 0.52-0.89). Hypertension (OR, 1.16; 95% CI, 0.77-1.75), diabetes mellitus (OR, 0.52; 95% CI, 0.15-1.78), and having a history of cardiovascular disease (OR, 0.92; 95% CI, 0.77-1.09) were not significant correlates. Posttransplant smokers had higher odds of newly developed posttransplant cardiovascular disease (OR, 1.41; 95% CI, 1.02-1.95), nonskin malignancies (OR, 2.58; 95% CI, 1.26-5.29), a shorter patient survival time (OR, 0.59; 95% CI, 0.44-0.79), and higher odds of mortality (OR, 1.74; 95% CI, 1.21-2.48). Conclusions: Posttransplant smoking is associated with poor outcomes. Our results might help clinicians to understand which patients are more likely to smoke posttransplant, guide interventional approaches, and provide recommendations for future research.
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Thursday, November 3, 2016

Resolution of Calciphylaxis After Urgent Kidney Transplantation in 3 Patients With End-Stage Kidney Failure

 

by Nordheim, Espen; Dahle, Dag Olav; Syse, Ingrid Marie; Åsberg, Anders; Reisæter, Anna V.; Hartmann, Anders
imageBackground: Calcific uremic arteriolopathy (CUA), also referred to as calciphylaxis, is a rare and serious complication of kidney failure with limited treatment options. Kidney transplantation (KTX) restores kidney function and is hence a potential treatment option for CUA. We present 3 patients who had their CUA lesions successfully healed after urgent KTX. Methods: Data were retrospectively retrieved from hospital records at our national transplant center. Results: All 3 patients had previously been kidney transplanted and had experienced graft loss and were in stage 5 kidney failure when CUA developed. One patient was on warfarin treatment for pulmonary embolism. Skin lesions developed in the lower limbs in all 3 patients. Multidisciplinary care including intensified hemodialysis did not induce any clinically relevant improvement of the lesions. The recipients were enlisted on a clinically urgent waitlist for KTX and received a deceased donor kidney after 2 to 4 weeks. All recipients experienced good graft function. The lesions healed completely within 6 weeks in 2 patients. In the third patient, partial healing occurred after 2 months and complete healing was achieved 4 months after transplantation. Conclusions: These cases indicate that urgent KTX may contribute to an efficient treatment for end-stage renal disease patients with CUA.
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Emphysematous Cystitis

 

A 72-year-old woman with poorly controlled hyperlipidemia and diabetes presented to the emergency department with a 5-day history of lower abdominal pain. She also had fever and reported nausea and vomiting. Physical examination revealed lower abdominal tenderness. Blood tests revealed leukocytosis associated with a left shift (neutrophil count of 11,800 per cubic millimeter) and elevation of the levels of C-reactive protein (24.0 mg per deciliter) and glucose (735 mg per deciliter [41 mmol per liter]). A plain radiograph of the kidneys, ureters, and bladder showed air surrounding the bladder (Panel A, arrows). An abdominal computed tomographic scan revealed an area of gas dissecting the bladder wall, bilateral hydronephrosis, and intramural gas with a cobblestone or beaded-necklace appearance (Panel B, arrows), findings consistent with emphysematous cystitis. The patient was treated with broad-spectrum antimicrobial agents and placement of a Foley catheter. Subsequently, a urine culture was positive for Escherichia coli; the patient was treated with antibiotics and recovered uneventfully. Emphysematous cystitis is a urinary tract infection that is associated with gas formation and is commonly caused by E. coli and Klebsiella pneumoniae.

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Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor {kappa}B-induced inflammation

 

by Wu, M., Gu, J., Mei, S., Xu, D., Jing, Y., Yao, Q., Chen, M., Yang, M., Chen, S., Yang, B., Qi, N., Hu, H., Wüthrich, R. P., Mei, C.
Background

Inflammation plays an important role in polycystic kidney disease (PKD). The current study aimed to examine the efficacy of the anti-inflammatory compound resveratrol in PKD and to investigate its underlying mechanism of action.

Methods

Male Han:SPRD (Cy/+) rats with PKD were treated with 200 mg/kg/day resveratrol or vehicle by gavage for 5 weeks. Human autosomal dominant (AD) PKD cells, three-dimensional (3D) Madin-Darby canine kidney cells and zebrafish were treated with various concentrations of resveratrol or the nuclear factor B (NF-B) inhibitor QNZ.

Results

Resveratrol treatment reduced blood urea nitrogen levels and creatinine levels by 20 and 24%, respectively, and decreased two-kidney/total body weight ratio by 15% and cyst volume density by 24% in Cy/+ rats. The proliferation index and the macrophage infiltration index were reduced by 40 and 43%, respectively, in resveratrol-treated cystic kidneys. Resveratrol reduced the levels of the pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and complement factor B (CFB) in Cy/+ rat kidneys in parallel with the decreased activity of NF-B (p50/p65). The activation of NF-B and its correlation with pro-inflammatory factor expression were confirmed in human ADPKD cells and kidney tissues. Resveratrol and QNZ inhibited the expression of MCP-1, TNF-α and CFB and reduced NF-B activity in ADPKD cells. Moreover, NF-B blockage minimized the inhibition of inflammatory factor production by resveratrol treatment. Furthermore, resveratrol or QNZ inhibited cyst formation in the 3D cyst and zebrafish models.

Conclusions

The NF-B signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future.

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