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The evolution of donation after circulatory death donor kidney repair in the United Kingdom.

Thu, 10/19/2017 - 12:45

The evolution of donation after circulatory death donor kidney repair in the United Kingdom.

Curr Opin Organ Transplant. 2017 Oct 17;:

Authors: Hosgood SA, Nicholson ML

Abstract
PURPOSE OF REVIEW: The increasing reliance on marginal donors has driven research to investigate ways to repair and improve the quality of kidneys for transplantation. Normothermic perfusion technologies provide an opportunity for improved preservation, organ assessment and resuscitation/repair of damaged kidneys. This review describes the evolution of normothermic perfusion in kidney transplantation in the United Kingdom.
RECENT FINDINGS: One hour of normothermic perfusion can be used to restore function and improve early graft function of extended criteria donor kidneys. A large multicentre trial is investigating the impact of normothermic perfusion on delayed graft function in a series of donation after circulatory death kidneys. Normothermic perfusion is also a platform for the delivery of therapies to the kidney to upregulate and modulate repair mechanisms or prevent injurious processes, such as activation of caspase-3 with the delivery of caspase-3 targeted small interfering RNAs. Normothermic perfusion can also be used to assess the quality and anatomical structure of a kidney to judge suitability for transplantation.
SUMMARY: Normothermic perfusion technology is a useful adjunct in kidney transplantation. It can improve early graft function by upregulating protective mechanisms. It also has the advantage of providing a functional assessment of the kidney and as a platform for the delivery of therapies or graft manipulation to target ischaemia reperfusion injury or the immune response. This technology can be used to expand the organ donor pool and prevent the unnecessary discard of kidneys.

PMID: 29045248 [PubMed - as supplied by publisher]

Autoantibodies targeting ficolin-2 in systemic lupus erythematosus patients with active nephritis.

Thu, 10/19/2017 - 12:45

Autoantibodies targeting ficolin-2 in systemic lupus erythematosus patients with active nephritis.

Arthritis Care Res (Hoboken). 2017 Oct 17;:

Authors: Colliard S, Jourde-Chiche N, Clavarino G, Sarrot-Reynauld F, Gout E, Deroux A, Fougere M, Bardin N, Bouillet L, Cesbron JY, Thielens NM, Dumestre-Pérard C

Abstract
OBJECTIVE: Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease characterized by production of various autoantibodies. The aim of this study was to investigate the presence of anti-ficolin-2 antibodies in SLE patients and to evaluate the association between the levels of these autoantibodies, clinical manifestations, and disease activity.
METHODS: This is a comparative study using a cohort of 165 SLE patients and 48 healthy subjects. SLE patients were further divided into two groups, with "low disease activity" (SLEDAI score ≤ 4, n = 88) and with "high disease activity" (SLEDAI score > 4, n = 77). Clinical manifestations were defined according to the physician in charge. Active lupus nephritis (LN) was documented by kidney biopsy. Detection of anti-ficolin-2 antibodies was performed by ELISA.
RESULTS: Levels of the anti-ficolin-2 autoantibodies were significantly higher in SLE patients as compared to healthy subjects and associated with the SLEDAI score. They were found positive in 61/165 (37%) SLE patients. Presence of anti-ficolin-2 antibodies was significantly related only to renal involvement, with a very high prevalence (86%) of anti-ficolin-2 antibodies in SLE patients with active LN. Patients with active proliferative LN had significantly more positive anti-ficolin-2 antibodies than those with non-proliferative LN. The combination of anti-ficolin-2, anti-ficolin-3 and anti-C1q demonstrated a very high specificity (98%) for the diagnosis of active LN.
CONCLUSION: Our results support the usefulness of anti-ficolin-2 as a complementary serological biomarker for the diagnosis of active lupus with renal manifestation. This article is protected by copyright. All rights reserved.

PMID: 29045037 [PubMed - as supplied by publisher]

Donor-derived renal mixed fungal infections in cardiac death donor kidney transplant recipients.

Thu, 10/19/2017 - 12:45

Donor-derived renal mixed fungal infections in cardiac death donor kidney transplant recipients.

Nephrology (Carlton). 2017 Nov;22(11):926

Authors: Zhen W, Yeyong Q, Bingyi S, Yu F

PMID: 29044961 [PubMed - in process]

Fresh tissue parathyroid allotransplantation with short-term immunosuppression: 1-year follow-up.

Thu, 10/19/2017 - 12:45

Fresh tissue parathyroid allotransplantation with short-term immunosuppression: 1-year follow-up.

Clin Transplant. 2017 Aug 12;:

Authors: Yucesan E, Goncu B, Basoglu H, Ozten Kandas N, Ersoy YE, Akbas F, Aysan E

Abstract
BACKGROUND: Permanent hypoparathyroidism is a serious problem and requires medications indefinitely. Parathyroid allotransplantation (PA) with short-term immunosuppression is definitive choice but long-term results are not clear.
METHOD: We performed PA from two donors to two recipients. Both recipients were 39-year-old females. Donors were a 32-year-old female and a 36-year-old male, who both have chronic kidney disease. Routine tests, viral markers, and cross-matches were analyzed individually. The parathyroid glands were resected from the living donors, fragmented quickly in the operation room and injected into the left deltoid muscles of the two recipients.
RESULTS: Methylprednisolone was administered on post-PA day one and two. Recipients were discharged from the hospital without complications. Calcium and PTH levels were observed throughout 1 year. We did not observe any complications during the follow-up period. Medications ceased in post-transplantation week 1 for Case 1 and after 1 month for Case 2.
CONCLUSION: Fresh tissue PA with short-term immunosuppression appears to be a promising technique that is easy to perform, is cost-effective, has low risk of side effects and minimal complications with compatibility for HLA conditions. A longer follow-up period and more case studies are needed to determine the risks and benefits of this procedure for future cases.

PMID: 29044732 [PubMed - as supplied by publisher]

The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic Kidney Disease.

Thu, 10/19/2017 - 12:45

The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic Kidney Disease.

J Bone Miner Res. 2017 Oct 17;:

Authors: Yadav AK, Kumar V, Kumar V, Banerjee D, Gupta KL, Jha V

Abstract
Use of active forms of vitamin D is advocated in CKD patients for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤20ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH)2D levels increased in the cholecalciferol group but not in the placebo group [between-group difference in mean change: 23.40 ng/ml; 95% CI: 19.76 to 27.06; p < 0.001 and 14.98 pg/ml ,95% CI: 4.48 to 27.18, p = 0.007, respectively]. Intact parathormone (iPTH) decreased in the cholecalciferol group [between-group difference in mean change -100.73 pg/ml (95% CI: -150.50 to -50.95, p < 0.001). Serum total and bone-specific alkaline phosphatase (SAP, BAP) and serum C-terminal cross-linked collagen type I telopeptides (CTX-1) were significantly reduced in cholecalciferol group (between group difference for change in mean: -20.25 U/L (95% CI: -35.14 to-5.38, p = 0.008 for SAP; -12.54, 95%CI: -22.09 to -2.98, p = 0.013 for BAP and -0.21, 95%CI: -0.38 to -0.05, p = 0.05 for CTX-1). Correlation analysis showed significant correlation of Δ 25(OH)D with Δ iPTH (r = -0.409, p < 0.0001), Δ 1,25(OH)2D (r = 0.305, p = 0.001), Δ SAP (r = -0.301, p = 0.002), ΔBAP (r = -0.264, p = 0.004), and ΔCTX-1 (r = -0.210, p = 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD. This article is protected by copyright. All rights reserved.

PMID: 29044707 [PubMed - as supplied by publisher]

First Report of Granulicatella sp. Endocarditis in a Kidney Transplant Patient.

Thu, 10/19/2017 - 12:45

First Report of Granulicatella sp. Endocarditis in a Kidney Transplant Patient.

J Bras Nefrol. 2017 Jul-Sep;39(3):341-344

Authors: Paula FJ, Neves PDMM, Bridi RA, Song ATW, David-Neto E

Abstract
Granulicatella and Abiotrophia are genera of fastidious Gram-positive cocci commensal of the oral, genitourinary, and intestinal flora. We report the first case of infective endocarditis caused by Granulicatella sp. in a kidney transplant recipient. A 67-year-old male kidney transplant recipient was admitted to the hospital for investigation of fever, abdominal pain, and diarrhea. On physical examination, he was dehydrated. Laboratory tests identified impaired renal function (creatinine level of 15.5 mg/dl; reference, 3.0 mg/dl), metabolic acidosis, and electrolyte disturbances. Cryptosporidium sp. was identified as the cause of the diarrhea, and the infection was treated with nitazoxanide. On admission, cultures of blood, urine, and stool samples were negative. Echocardiography results were normal. Despite the antimicrobial treatment, the fever persisted. A transthoracic echocardiogram revealed infective endocarditis of the mitral valve, and Granulicatella spp. were isolated in blood cultures. Although the patient was treated with penicillin and amikacin, he evolved to septic shock of pulmonary origin and died. Infective endocarditis caused by Granulicatella sp. should be suspected in cases of culture-negative endocarditis.

PMID: 29044345 [PubMed - in process]

Brazilian Chronic Dialysis Survey 2016.

Thu, 10/19/2017 - 12:45

Brazilian Chronic Dialysis Survey 2016.

J Bras Nefrol. 2017 Jul-Sep;39(3):261-266

Authors: Sesso RC, Lopes AA, Thomé FS, Lugon JR, Martins CT

Abstract
INTRODUCTION: National chronic dialysis data are important for the treatment planning.
OBJECTIVE: To report data of the annual survey of the Brazilian Society of Nephrology about chronic kidney disease patients on dialysis in July 2016.
METHODS: A survey based on data of dialysis centers from the whole country. The data collection was performed by using a questionnaire filled out on-line by the dialysis centers.
RESULTS: 309 (41%) of the dialysis units in the country answered the questionnaire. In July 2016, the total estimated number of patients on dialysis was 122,825. The estimated prevalence and incidence rates of chronic maintenance dialysis were 596 (range: 344 in the North region and 700 in the Southeast) and 193 patients per million of population (pmp), respectively. The annual incidence rate of patients with diabetic nephropathy was 79 pmp. The annual gross mortality rate was 18.2%. For prevalent patients, 92% were on hemodialysis and 8% on peritoneal dialysis, and 29,268 (24%) were on a waiting list of renal transplant. A venous catheter was the vascular access for 20.5% of the hemodialysis patients. The prevalence rates of positive serology for hepatitis B and C showed a tendency to reduce from 2013 (1.4% and 4.2%, respectively) to 2016 (0.7% and 3.7%, respectively).
CONCLUSION: The absolute number and the prevalence and incidence rates of patients on dialysis continue to rise steadily; the gross mortality rate remained stable. Regional inequities are evident in these rates.

PMID: 29044335 [PubMed - in process]

Hospital do Rim, São Paulo: A World Leader in Kidney Transplantation.

Thu, 10/19/2017 - 12:45

Hospital do Rim, São Paulo: A World Leader in Kidney Transplantation.

J Bras Nefrol. 2017 Jul-Sep;39(3):234-235

Authors: Jolissaint JS, Tullius SG

PMID: 29044333 [PubMed - in process]

CYP3A genotypes of donors but not those of the patients increase the risk of acute rejection in renal transplant recipients on calcineurin inhibitors: a pilot study.

Thu, 10/19/2017 - 12:45

CYP3A genotypes of donors but not those of the patients increase the risk of acute rejection in renal transplant recipients on calcineurin inhibitors: a pilot study.

Eur J Clin Pharmacol. 2017 Oct 18;:

Authors: Gervasini G, García-Pino G, Vergara E, Mota-Zamorano S, García-Cerrada M, Luna E

Abstract
PURPOSE: We aimed to determine whether polymorphisms in CYP3A genes may affect the risk of acute rejection episodes (ARE) in renal transplant recipients treated with calcineurin inhibitors (CNIs).
METHODS: One hundred and thirty seven patients and their respective donors were screened, by RT-PCR techniques, for three polymorphisms previously related with CNI pharmacokinetics and pharmacodynamics (CYP3A4*1B, CYP3A4*22 and CYP3A5*3). Genotypes of donors and recipients were associated by logistic regression models with ARE risk and exposure to CNIs. Clinical and pharmacokinetic parameters were recorded at four time-points after transplant (1 week and 1, 5 and 12 months).
RESULTS: Nineteen patients (13.86%) experienced ARE. Patients who received a kidney from a donor carrying the CYP3A4*1B or CYP3A5*1 variant experienced ARE more frequently than those whose donor carried wild-type genotypes [OR = 6.29 (1.62-24.39), p = 0.008 and OR = 3.42 (1.06-11.01), p = 0.039, respectively]. The combined analysis of the CYP3A4*1B/3A5*1 alleles also revealed an increased risk in patients whose donors carried both variants [OR = 6.24 (1.60-24.33), p = 0.007]. The CYP3A genotype of the recipient did not affect ARE risk, although it did determine the degree of exposure to CNI throughout the first year after transplant. Patients with one or two variant alleles displayed lower concentration-to-dose ratios (CDRs) than non-carriers, with differences increasing with time after transplant (p values = 0.039, 0.004, 6.0 e-04 and 2.7 e-07 in the four time-points).
CONCLUSIONS: Our preliminary findings suggest that the determination of the CYP3A genotype of the donor, but not that of the recipient, may be useful to predict the incidence of acute rejection in renal transplantation.

PMID: 29043387 [PubMed - as supplied by publisher]

Focal segmental glomerulosclerosis associated with mitochondrial disease.

Thu, 10/19/2017 - 12:45

Focal segmental glomerulosclerosis associated with mitochondrial disease.

Clin Nephrol Case Stud. 2017;5:20-25

Authors: Lim K, Steele D, Fenves A, Thadhani R, Heher E, Karaa A

Abstract
Primary mitochondrial diseases (MD) are complex, heterogeneous inherited diseases caused by mutations in either the mitochondrial or nuclear DNA. Glomerular diseases in MD have been reported with tRNA mutation m.3243A>G causing a syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). We describe here a case of focal segmental glomerulosclerosis (FSGS) associated with a new tRNA mutation site. A 34-year-old man with a history of living related kidney transplantation, diabetes, hearing loss, and developmental delay presented to the outpatient clinic with complaints of new behavioral difficulties, worsening symptoms, and brain involvement on imaging. Physical examination was remarkable for difficulty hearing, a pattern of dysarthric speech, and cerebellar gait. Laboratory investigations including lactate levels were unremarkable. Based on this set of clinical circumstances, concern for an underlying genetic abnormality was raised. Multiple metabolic tests were unremarkable. Whole exome sequencing revealed a mitochondrial MT-TW tRNA change at position m.5538G>A. Genotype-phenotype correlations are consistent with this tRNA mutation as a cause of his symptoms. To the best of our knowledge, this is the first case describing FSGS-associated MD caused by an m.5538 G>A mutation. Consideration of an underlying MD should be made in patients presenting with deafness, neurologic changes, diabetes, and renal failure.

PMID: 29043143 [PubMed]

Costimulation pathway blockade in kidney transplant recipients with de-novo rheumatoid arthritis.

Thu, 10/19/2017 - 12:45

Costimulation pathway blockade in kidney transplant recipients with de-novo rheumatoid arthritis.

Clin Nephrol Case Stud. 2017;5:16-19

Authors: Sheta M, Riad S, Deepak U, Issa N, Birkenbach M, Ibrahim HN, Kukla A

Abstract
The best approach to treatment of de-novo rheumatoid arthritis in solid organ transplant recipients on typical immunosuppression is not well established. The use of biologics targeting specific cell types, cytokines, and immunological pathways has been gaining interest in the treatment of both, auto- and alloimmunity. We present a case of de-novo rheumatoid arthritis in a kidney transplant recipient 10 years post-transplant while receiving cyclosporine, mycophenolate mofetil, and also prednisone. Initial presentation included features of polymyalgia rheumatica and nephrotic range proteinuria. Kidney biopsy showed membranous nephropathy. The patient was initially treated with methotrexate, while mycophenolate mofetil was discontinued. Clinical symptoms improved, but creatinine significantly increased, which led to discontinuation of methotrexate and mycophenolate mofetil was restarted. The kidney function improved, but the patient experienced a flare of rheumatoid arthritis. Costimulatory blocker, abatacept, was initiated and cyclosporine was gradually tapered off. Graft function remained stable for a follow-up period of 7 years. Joint pain, weakness, and stiffness resolved. Follow-up plain film radiographs at 5 years post initial presentation showed no new joint erosions in hands or feet. Costimulatory blockers may broaden the therapeutic choices of transplant recipients with de-novo autoimmune diseases.

PMID: 29043142 [PubMed]

Neutralizing Antibody-Mediated Response and Risk of BK Virus-Associated Nephropathy.

Thu, 10/19/2017 - 12:45

Neutralizing Antibody-Mediated Response and Risk of BK Virus-Associated Nephropathy.

J Am Soc Nephrol. 2017 Oct 17;:

Authors: Solis M, Velay A, Porcher R, Domingo-Calap P, Soulier E, Joly M, Meddeb M, Kack-Kack W, Moulin B, Bahram S, Stoll-Keller F, Barth H, Caillard S, Fafi-Kremer S

Abstract
BK virus-associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype-specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months. After transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed BKVAN. At any time, patients with high NAb titers against the replicating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence interval [95% CI], 0.26 to 0.73; P=0.002). Each log10 increase in NAb titer decreased the risk of developing viremia by 56%. Replicating strains were consistent with donor transmission in 95% of cases of early BKV replication. Genotype mismatch between recipients' neutralization profiles before transplant and their subsequently replicating strain significantly increased the risk of developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; P=0.04). A NAb titer against the donor's strain <4 log10 before transplant significantly associated with BKV replication after transplant (HR, 1.88; 95% CI, 1.06 to 3.45; P=0.03). BKV genotype-specific NAb titers may be a meaningful predictive marker that allows patient stratification by BKV disease risk before and after transplant.

PMID: 29042457 [PubMed - as supplied by publisher]

Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment.

Thu, 10/19/2017 - 12:45

Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment.

J Am Soc Nephrol. 2017 Oct 17;:

Authors: Lefaucheur C, Viglietti D, Hidalgo LG, Ratner LE, Bagnasco SM, Batal I, Aubert O, Orandi BJ, Oppenheimer F, Bestard O, Rigotti P, Reisaeter AV, Kamar N, Lebranchu Y, Duong Van Huyen JP, Bruneval P, Glotz D, Legendre C, Empana JP, Jouven X, Segev DL, Montgomery RA, Zeevi A, Halloran PF, Loupy A

Abstract
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.

PMID: 29042454 [PubMed - as supplied by publisher]

Peritoneal dialysis is associated with better cognitive function than hemodialysis over a one-year course.

Thu, 10/19/2017 - 12:45

Peritoneal dialysis is associated with better cognitive function than hemodialysis over a one-year course.

Kidney Int. 2017 Oct 14;:

Authors: Neumann D, Mau W, Wienke A, Girndt M

Abstract
Impaired cognitive functioning in patients with end-stage renal disease may reduce their capabilities to adhere to complex medical or dietary regimens and to fully participate in medical decisions. With decreasing renal function, cognitive abilities are likely to decline, with cognitive dysfunction improving after initiation of dialysis and even being generally reversible after successful renal transplantation. However, little is known about cognitive changes particularly regarding different treatment modalities. To gain further insight into this, we focused on a one-year course of cognitive functions, comparing peritoneal to hemodialysis patients. Within the CORETH-project, two validated neurocognitive tests, assessing executive functioning (Trail Making Test-B) and attention (d2-Revision-Test) and the self-reported Kidney Disease Quality of Life Short Form Cognitive Function-subscale, were administered to 271 patients at baseline and after one year. Subsamples were matched by propensity score, adjusting for age, comorbidity, education, and employment status for 96 hemodialysis and 101 peritoneal dialysis patients. The effects of time and treatment modality were investigated, controlling for well-known confounders. Both tests revealed improvement over one year. Peritoneal dialysis was associated with better outcomes than hemodialysis at baseline and follow-up, but comparability between groups may be limited. The opposite pattern applied to self-reporting. Hemodialysis patients had to be excluded from cognitive testing more often than peritoneal dialysis patients. As such, the number of exclusions may have biased the findings, limiting generalizability. Thus, our findings suggest an improvement of cognitive functioning and support previous indications for peritoneal dialysis being associated with better cognitive functions during a one-year course than hemodialysis.

PMID: 29042081 [PubMed - as supplied by publisher]

APOL1 nephropathy risk variants do not associate with subclinical atherosclerosis or left ventricular mass in middle-aged black adults.

Thu, 10/19/2017 - 12:45

APOL1 nephropathy risk variants do not associate with subclinical atherosclerosis or left ventricular mass in middle-aged black adults.

Kidney Int. 2017 Oct 14;:

Authors: Gutiérrez OM, Limou S, Lin F, Peralta CA, Kramer HJ, Carr JJ, Bibbins-Domingo K, Winkler CA, Lewis CE, Kopp JB

Abstract
Prior studies reported associations of APOL1 nephropathy risk variants with subclinical atherosclerosis. However, these findings were limited to older individuals with high comorbidities. To evaluate this in younger individuals, we calculated associations of APOL1 risk variants (high risk [2 risk variants] vs. low risk [0-1 risk variant]) with prevalent, incident, or progressive coronary artery calcification, a carotid intima media thickness over the 90th percentile, and left ventricular hypertrophy in 1315 black participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. The mean age of this cohort was 44.6 years and their mean estimated glomerular filtration rate was 102.5 ml/min/1.73m(2). High-risk participants were found to be younger and have a higher prevalence of albuminuria than low-risk participants. In Poisson regression models adjusted for comorbidities and kidney function, the risk of prevalent coronary artery calcification (relative risk [95% confidence interval] 1.12 [0.72,1.71]), the incident coronary artery calcification (1.50 [0.87,2.59]), and the progression of coronary artery calcification (1.40 [0.88,2.23]) did not significantly differ in high vs. low-risk participants. Furthermore, the risk of carotid intima media thickness over the 90th percentile (1.28 [0.78,2.10]) and left ventricular hypertrophy (1.02[0.73,1.43]) did not significantly differ in high vs. low-risk participants in fully-adjusted models. Thus, APOL1 risk variants did not associate with subclinical markers of atherosclerosis or left ventricular hypertrophy in middle-aged black adults with preserved kidney function.

PMID: 29042080 [PubMed - as supplied by publisher]

Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort.

Thu, 10/19/2017 - 12:45
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Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort.

Nephrol Dial Transplant. 2017 Oct 05;:

Authors: Björk J, Grubb A, Gudnason V, Indridason OS, Levey AS, Palsson R, Nyman U

Abstract
Background: Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund-Malmö creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as well as the Full Age Spectrum creatinine equation (FASCr) and its combination with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys).
Methods: A total of 805 individuals, 74-93 years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)] and the ability to detect mGFR <60 mL/min/1.73 m2.
Results: All equations had a P30 >90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD-EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed similar ability to detect mGFR <60 mL/min/1.73 m2 based on the area under the receiver operating characteristic curves. MEANLMR+CAPA, FASCr+Cys and CKD-EPICr+Cys all exhibited consistent improvements compared with the corresponding creatinine-based equations.
Conclusion: None of the creatinine-based equations was clearly superior overall in this community-dwelling elderly cohort. The addition of cystatin C improved all of the creatinine-based equations.

PMID: 29040701 [PubMed - as supplied by publisher]

Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Thu, 10/19/2017 - 12:45
Related Articles

Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Nephrol Dial Transplant. 2017 Oct 11;:

Authors: Locatelli F, Karaboyas A, Pisoni RL, Robinson BM, Fort J, Vanholder R, Rayner HC, Kleophas W, Jacobson SH, Combe C, Port FK, Tentori F

Abstract
Background: With its convective component, hemodiafiltration (HDF) provides better middle molecule clearance compared with hemodialysis (HD) and is postulated to improve survival. A previous analysis of Dialysis Outcomes and Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for high replacement fluid volume HDF versus HD. Randomized controlled trials have not shown uniform survival advantage for HDF; in secondary (non-randomized) analyses, better outcomes were observed in patients receiving the highest convection volumes.
Methods: In a 'real-world' setting, we analyzed patients on dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009-15). Adjusted Cox regression was used to study HDF (versus HD) and mortality, overall and by replacement fluid volume.
Results: Among 8567 eligible patients, 2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median follow-up was 1.5 years during which 1988 patients died. The adjusted mortality hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD and 1.08 (0.92-1.28) for HDF >20 L replacement fluid volume versus HD. Similar results were found for cardiovascular and infection-related mortality. In an additional analysis aiming to avoid treatment-by-indication bias, we did not observe lower mortality rates in facilities using more HDF (versus HD).
Conclusions: Our results do not support the notion that HDF provides superior patient survival. Further trials designed to test the effect of high-volume HDF (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately inform clinical practices.

PMID: 29040687 [PubMed - as supplied by publisher]

A young blood environment decreases aging of senile mice kidneys.

Thu, 10/19/2017 - 12:45
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A young blood environment decreases aging of senile mice kidneys.

J Gerontol A Biol Sci Med Sci. 2017 Oct 13;:

Authors: Huang Q, Ning Y, Liu D, Zhang Y, Li D, Zhang Y, Yin Z, Fu B, Cai G, Sun X, Chen X

Abstract
Whether changes in internal body environment affect kidney aging remains unclear. Specifically, it is unknown whether transplanted kidneys from older donors recover from tissue damage after placement in younger recipients. In this study, a parabiosis animal model was established to investigate the effects of a young internal body environment on aged kidneys. The animals were divided into six groups: young (Ycon) and old (Ocon) control groups, isochronic youth-youth group (Y-IP), elderly-elderly group (O-IP) and heterochronic youth (Y-HP) elderly (O-HP) group. After parabiosis, tubule and interstitial tissue scores in the O-HP group were significantly lower than in the Ocon and O-IP groups. The expression of aging-related protein p16 and SA-β-gal in the O-HP group was significantly reduced compared with the Ocon and O-IP groups. Autophagy factor Atg5 and LC3BII were significantly upregulated, while the expression of the autophagic degradation marker (P62) was significantly downregulated in the O-HP group compared with the Ocon and O-IP groups. With the same comparison, the positive cells of TUNEL staining and the expression of IL-6 and IL-1β were significantly reduced, while the total/cleaved caspase-3 and total/pNF-κB were significantly increased in the O-HP group. The results demonstrated that a young blood environment significantly reduces kidney aging. These findings provide new evidence supporting an increase in the upper age limit for human kidney transplantation donors.

PMID: 29040401 [PubMed - as supplied by publisher]

Decreased NK cell immunity in kidney transplant recipients late post-transplant and increased NK-cell immunity in patients with recurrent miscarriage.

Thu, 10/19/2017 - 12:45
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Decreased NK cell immunity in kidney transplant recipients late post-transplant and increased NK-cell immunity in patients with recurrent miscarriage.

PLoS One. 2017;12(10):e0186349

Authors: Zhu L, Aly M, Wang H, Karakizlis H, Weimer R, Morath C, Kuon RJ, Toth B, Opelz G, Daniel V

Abstract
BACKGROUND: There is evidence that NK-cell reactivity might affect graft outcome in transplant recipients and pregnancy in women.
METHOD: NK-cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients before and after renal transplantation, patients with recurrent miscarriage (RM) and healthy controls (HC).
RESULTS: Patients late post-transplant (late-Tx) with functioning renal transplants showed abnormally low CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0.021) whereas RM patients exhibited abnormally high numbers of these cells (vs HC p = 0.043). CD56dimCD16+perforin+granzyme+ NK-cell counts were strikingly different between the two patient groups (p<0.001). In addition, recipients late-Tx showed abnormally low CD8+ NK-cells (vs HC p<0.001) in contrast to RM patients who showed an abnormal increase (vs HC p = 0.008). CD8+ NK-cell counts were strongly different between the two patient groups (p<0.001). Higher perforin+granzyme+CD56dimCD16+ and CD8+ NK-cells were associated with impaired graft function (p = 0.044, p = 0.032). After in-vitro stimulation, CD56dimCD16+ and CD56brightCD16dim/- NK-cells showed strong upregulation of CD107a and IFNy, whereas the content of perforin decreased dramatically as a consequence of perforin release. Recipients late post-Tx showed less in-vitro perforin release (= less cytotoxicity) than HC (p = 0.037) and lower perforin release was associated with good graft function (r = 0.738, p = 0.037). Notably, we observed strong in-vitro perforin release in 2 of 6 investigated RM patients. When circulating IL10+CD56bright NK-cells were analyzed, female recipients late post-Tx (n = 9) showed significantly higher relative and absolute cell numbers than RM patients (p = 0.002 and p = 0.018, respectively); and high relative and absolute IL10+CD56bright NK-cell numbers in transplant recipients were associated with low serum creatinine (p = 0.004 and p = 0.012) and high glomerular filtration rate (p = 0.011 and p = 0.002, respectively). Female recipients late post-Tx exhibited similar absolute but higher relative numbers of IL10+IFNy- NK-cells than RM patients (p>0.05 and p = 0.016, respectively).
CONCLUSION: NK-cells with lower cytotoxicity and immunoregulatory function might contribute to good long-term graft outcome, whereas circulating NK-cells with normal or even increased cytotoxicity and less immunoregulatory capacity are observed in patients with RM.

PMID: 29040297 [PubMed - in process]

Kidney Transplantation and the Impact on Health-Related Quality of Life in Frail Patients.

Thu, 10/19/2017 - 12:45
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Kidney Transplantation and the Impact on Health-Related Quality of Life in Frail Patients.

Transplantation. 2017 Oct 17;:

Authors: Hoffman AL, Matemavi P

PMID: 29040170 [PubMed - as supplied by publisher]

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