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1.
Nutrients ; 13(7)2021 Jul 10.
Article in English | MEDLINE | ID: mdl-34371870

ABSTRACT

Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student's t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (-0.020 ± 0.08 vs. -0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. -0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.


Subject(s)
Bone Density/drug effects , Dietary Supplements , Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Kidney Transplantation , Osteoporosis/prevention & control , Osteoporotic Fractures/prevention & control , Absorptiometry, Photon , Adult , Aged , Biomarkers/blood , Calcium/blood , Denmark , Dietary Supplements/adverse effects , Docosahexaenoic Acids/adverse effects , Double-Blind Method , Drug Combinations , Eicosapentaenoic Acid/adverse effects , Female , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Osteoporosis/etiology , Osteoporosis/physiopathology , Osteoporotic Fractures/etiology , Osteoporotic Fractures/physiopathology , Time Factors , Treatment Outcome
3.
PLoS One ; 15(12): e0243759, 2020.
Article in English | MEDLINE | ID: mdl-33326471

ABSTRACT

Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].


Subject(s)
Ergocalciferols/pharmacology , Kidney Transplantation/adverse effects , Biomarkers/blood , Female , Gene Expression Regulation/drug effects , Humans , Inflammation/blood , Inflammation/etiology , Inflammation/immunology , Leukocytes/cytology , Leukocytes/drug effects , Male , Middle Aged
4.
Nutrients ; 12(5)2020 May 14.
Article in English | MEDLINE | ID: mdl-32423040

ABSTRACT

Intake of industrially produced trans fatty acids (iTFAs) has previously been associated with dyslipidemia, insulin resistance, hypertension and inflammation, as well as increased cardiovascular (CV) morbidity and mortality. iTFA intake declined in Norway after the introduction of legislative bans against iTFA consumption. However, the relationship between the current iTFA intake and CV health is unclear. The aim of the present study was to investigate the association between current iTFA intake, reflected by plasma iTFA levels, and established CV risk factors. We also examined the associations between plasma ruminant TFA levels and CV risk factors. In this cross-sectional study, we included 3706 participants from a Norwegian general population, born in 1950 and residing in Akershus County, Norway. The statistical method was multivariable linear regression. Plasma iTFA levels were inversely associated with serum triglycerides (p < 0.001), fasting plasma glucose (p < 0.001), body mass index (p < 0.001), systolic and diastolic blood pressure (p = 0.001 and p = 0.03) and C-reactive protein (p = 0.001). Furthermore, high plasma iTFA levels were associated with higher education and less smoking and alcohol consumption. We found that plasma ruminant trans fatty acids (rTFA) levels were favorably associated with CV risk factors. Furthermore, plasma iTFA levels were inversely associated with CV risk factors. However, our results might have been driven by lifestyle factors. Overall, our findings suggest that the current low intake of iTFAs in Norway does not constitute a threat to CV health.


Subject(s)
Diet/adverse effects , Dietary Fats/blood , Eating/physiology , Life Style , Trans Fatty Acids/blood , Aged , Blood Glucose/analysis , Blood Pressure , Body Mass Index , C-Reactive Protein/analysis , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Diet/standards , Diet Surveys , Fasting/blood , Feeding Behavior/physiology , Female , Heart Disease Risk Factors , Humans , Linear Models , Male , Norway , Nutrition Policy , Triglycerides/blood
5.
Eur J Clin Nutr ; 74(12): 1707-1717, 2020 12.
Article in English | MEDLINE | ID: mdl-32341488

ABSTRACT

BACKGROUND: A high intake of linoleic acid (LA), the major dietary polyunsaturated fatty acid (PUFA), has previously been associated with reduced cardiovascular (CV) morbidity and mortality in observational studies. However, recent secondary analyses from clinical trials of LA-rich diet suggest harmful effects of LA on CV health. METHODS: A total of 3706 participants, all born in 1950, were included in this cross-sectional study. We investigated associations between plasma phospholipid levels of LA and CV risk factors in a Norwegian general population, characterized by a relative low LA and high marine n-3 PUFA intake. The main statistical approach was multivariable linear regression. RESULTS: Plasma phospholipid LA levels ranged from 11.4 to 32.0 wt%, with a median level of 20.8 wt% (interquartile range 16.8-24.8 wt%). High plasma LA levels were associated with lower serum low-density lipoprotein cholesterol levels (standardized regression coefficient [Std. ß-coeff.] -0.04, p = 0.02), serum triglycerides (Std. ß-coeff. -0.10, p < 0.001), fasting plasma glucose (Std. ß-coeff. -0.10, p < 0.001), body mass index (Std. ß-coeff. -0.13, p < 0.001), systolic and diastolic blood pressure (Std. ß-coeff. -0.04, p = 0.03 and Std. ß-coeff. -0.02, p = 0.02, respectively) and estimated glomerular filtration rate (Std. ß-coeff. -0.09, p < 0.001). We found no association between plasma LA levels and high-density lipoprotein cholesterol levels, glycated hemoglobin, carotid intima-media thickness, or C-reactive protein. CONCLUSION: High plasma LA levels were favorably associated with several CV risk factors in this study of a Norwegian general population.


Subject(s)
Carotid Intima-Media Thickness , Linoleic Acid , Aged , Cross-Sectional Studies , Diet , Humans , Norway/epidemiology , Risk Factors
6.
Eur J Nutr ; 59(4): 1505-1515, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31123865

ABSTRACT

PURPOSE: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) might improve cardiovascular (CV) health. We conducted a cross-sectional study to investigate associations between plasma phospholipid levels of marine n-3 PUFAs and CV risk factors, educational level, physical activity and smoking habits. METHODS: A total of 3706 individuals from a general population, all born in 1950 and residing in Akershus County, Norway, were included in this study. The main statistical approach was multivariable adjusted linear regression. RESULTS: Plasma marine n-3 PUFA levels ranged from 2.7 to 20.3 wt%, with a median level of 7.7 wt% (interquartile range 4.3-11.1 wt%). High levels of plasma marine n-3 PUFAs were associated with lower serum triglycerides [Standardized regression coefficient (Std.ß-coeff.) - 0.14, p < 0.001], body mass index (Std. ß-coeff. -0.08, p < 0.001), serum creatinine (Std. ß-coeff. -0.03, p = 0.05), C-reactive protein levels (Std. ß-coeff. - 0.03, p = 0.04), higher levels of serum high-density lipoprotein cholesterol (Std. ß-coeff. 0.08, p < 0.001) and low-density lipoprotein cholesterol (Std. ß-coeff. 0.04, p = 0.003). High levels of plasma marine n-3 PUFAs were also associated with lower glycated hemoglobin (Std. ß-coeff. - 0.04, p = 0.01), however, only in individuals without diabetes. We found no associations between plasma marine n-3 PUFA levels and fasting plasma glucose or carotid intima-media thickness. High levels of plasma marine n-3 PUFAs were associated with higher educational level, more physical activity and lower prevalence of smoking. CONCLUSION: In this cross-sectional study of Norwegian individuals born in 1950, high levels of plasma marine n-3 PUFAs were favourably associated with several CV risk factors, suggesting that fish consumption might improve CV health.


Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Diet/methods , Fatty Acids, Omega-3/blood , Health Surveys/methods , Seafood , Cross-Sectional Studies , Fatty Acids, Unsaturated , Female , Humans , Male , Middle Aged , Norway/epidemiology , Risk Assessment
7.
Transplantation ; 103(11): e325-e333, 2019 11.
Article in English | MEDLINE | ID: mdl-31397802

ABSTRACT

Following successful kidney transplantation, recipients usually regain fertility. Post-engraftment pregnancies should be planned and the teratogenic mycophenolic acid should be replaced with azathioprine before conception. To avoid unintentional pregnancies, pre-conception counseling is mandatory in women of reproductive age who are scheduled for a kidney transplant. Counseling should be repeated after transplantation. Female recipients should receive advice to use long-acting reversible contraception and avoid pregnancy for a minimum of 1 year following transplantation. Conception should be deferred even longer in female recipients with moderate to severe proteinuria, uncontrolled hypertension or reduced graft function and be very carefully discussed in highly HLA-sensitized patients. The recipient wishes, values and acceptance of pregnancy-related risk should receive attention. Assisted fertilization increases the risk of pre-eclampsia, but still result in live births. Pregnancy management in kidney transplant recipients should be provided by a multidisciplinary team consisting of a nephrologist, a midwife and an obstetrician with expertise in high-risk pregnancies. Until measurement of unbound fraction of calcineurin inhibitors becomes clinically available, we recommend to adjust calcineurin inhibitor dose according to whole blood trough level, even though it overestimates the effective drug concentration during pregnancy. If nephrotoxicity is suspected, the calcineurin inhibitor dose should be reduced. Breastfeeding should be accepted after kidney transplantation since infant immunosuppressive drug exposure via breastmilk is extremely low. The prevalence of congenital malformations in children fathered by male recipients, including patients on mycophenolic acid therapy at the time of conception, is at level with the general population.


Subject(s)
Azathioprine/therapeutic use , Immunosuppression Therapy/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/adverse effects , Reproductive Health , Abatacept/therapeutic use , Basiliximab/therapeutic use , Breast Feeding , Calcineurin Inhibitors/administration & dosage , Contraceptive Agents , Counseling , Decision Making , Female , Graft Rejection , HLA Antigens , Humans , Immunosuppressive Agents/therapeutic use , Infant, Newborn , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Lactation , Male , Patient Care Team , Pregnancy , Pregnancy Complications/prevention & control , Pregnancy Complications/therapy , Pregnancy Outcome
8.
J Ren Nutr ; 29(3): 169-180, 2019 05.
Article in English | MEDLINE | ID: mdl-30309780

ABSTRACT

OBJECTIVE: High consumption of trans-fatty acids (TFAs) is associated with increased mortality. DESIGN AND METHODS: Observational cohort study of 1.988 Norwegian renal transplant recipients with a median follow-up time of 9.6 years. We assessed multivariable adjusted associations between plasma levels of industrial and ruminant TFAs with patient and graft survival. Plasma phospholipid fatty acid levels were determined by gas chromatography at 10 weeks after transplantation. RESULTS: During follow-up, there were 595 deaths, and 805 grafts were lost. Plasma industrial TFA levels dropped from 0.3 wt% in years 1999-2004 to reach a plateau of 0.2 wt% from year 2005 and beyond, whereas plasma levels of ruminant TFAs remained stable throughout the study period. In the former era (years 1999 to 2004, n = 902), we found multivariable adjusted associations between plasma industrial TFA levels and mortality (hazard ratio 4.44, P = .02) and graft loss (hazard ratio 4.22, P = .01). In the latter era (years 2005 to 2011, n = 1,086), there were no associations between plasma industrial TFA levels and patient or graft survival. Plasma ruminant TFAs were not associated with mortality or graft loss in either eras. CONCLUSION: In this Norwegian transplant cohort, plasma industrial TFA levels dropped from around 0.3 wt% in the former era to 0.2 wt% in the latter era. While plasma industrial TFA was significantly associated with survival in the former era, no associations were found with survival in the latter era. This finding suggests that lowering industrial TFA consumption from modest to low levels could possibly influence health beneficially after renal transplantation.


Subject(s)
Kidney Transplantation/mortality , Trans Fatty Acids/adverse effects , Adult , Aged , Animals , Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Cohort Studies , Dairy Products , Female , Graft Survival/physiology , Humans , Inflammation/blood , Kidney Failure, Chronic/surgery , Male , Middle Aged , Norway , Phospholipids/blood , Proportional Hazards Models , Risk Factors , Trans Fatty Acids/administration & dosage , Trans Fatty Acids/blood
9.
Tidsskr Nor Laegeforen ; 138(17)2018 10 30.
Article in Norwegian | MEDLINE | ID: mdl-30378400

ABSTRACT

Background: Para- and post-infectious glomerulonephritis may be caused by various microbiological agents. We present a case of parvovirus B19 infection causing a post-infectious glomerulonephritis. Case presentation: A 30-year-old woman was admitted to hospital after four weeks of fever, flank pain and general oedema. Laboratory measurements showed elevated creatinine and alanine aminotransferase, whereas haemoglobin, albumin and thrombocyte levels were low. The urine analyses were positive for both haematuria and proteinuria. Ultrasound and CT scan of the thorax and abdomen showed multiple increased lymphoid nodes, bilateral pleural effusion, periportal oedema and ascites. C3 was low, and C4 normal. Additional immunological laboratory tests were negative. Viral serology was positive for parvovirus B19 immunoglobulin M and immunoglobulin G, confirming glomerulonephritis triggered by infection. The patient's symptoms resolved without any specific treatment, and a few months later creatinine had normalised. Interpretation: This case report illustrates the importance of microbiological laboratory work-up to further investigate acute kidney failure of unknown cause.


Subject(s)
Glomerulonephritis , Parvoviridae Infections/complications , Parvovirus B19, Human/isolation & purification , Acute Disease , Adult , Female , Glomerulonephritis/diagnosis , Glomerulonephritis/virology , Humans
10.
J Ren Nutr ; 28(5): 333-339, 2018 09.
Article in English | MEDLINE | ID: mdl-29703632

ABSTRACT

OBJECTIVE: The major n-6 polyunsaturated fatty acids linoleic acid (LA) and arachidonic acid (AA) play a role in inflammation and glucose metabolism, which could affect patient and renal transplant survival. DESIGN AND METHODS: In this single center cohort study of 1988 Norwegian renal transplant recipients, we assessed associations between plasma levels of LA and AA at baseline, measured by gas chromatography, and patient and graft survival, as well as inflammation and cardiovascular risk markers. RESULTS: During follow-up (median of 9.6 years), 595 patients died and 805 renal transplants were lost, either due to recipient death or graft failure. In multivariable survival analysis, we found no associations with mortality for plasma levels of LA (hazard ratios: 0.99, 95% confidence intervals: 0.96-1.01) or AA (hazard ratios: 1.01, 95% confidence intervals: 0.96-1.06). No associations were found for cardiovascular mortality, overall graft loss, or death-censored graft loss. Plasma glucose, proglycemic marker chemerin, and proinflammatory marker growth differentiation factor 15 were inversely associated with plasma LA and positively associated with plasma AA levels in multivariable analysis. CONCLUSIONS: We found no associations between plasma levels of LA or AA and patient or graft survival. Plasma levels of LA and proglycemic indices were inversely associated, signaling a possible beneficial effect of LA consumption for prevention of posttransplantation diabetes mellitus.


Subject(s)
Fatty Acids, Unsaturated/blood , Graft Survival , Kidney Transplantation , Transplant Recipients/statistics & numerical data , Biomarkers/blood , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Norway , Risk Factors , Survival Analysis
11.
Prog Transplant ; 27(4): 386-391, 2017 12.
Article in English | MEDLINE | ID: mdl-29187131

ABSTRACT

BACKGROUND: Cardiovascular disease is the leading cause of death in renal transplant recipients. An association between haptoglobin genotype 2-2 and cardiovascular disease has been found in patients with diabetes mellitus and liver transplant recipients. To date, the role of haptoglobin genotype after renal transplantation has not been studied. METHODS: In this single-center retrospective cohort study of 1975 adult Norwegian transplant recipients, who underwent transplantation between 1999 and 2011, we estimated the risk of all-cause and cardiovascular mortality and overall and death-censored graft loss for patients with haptoglobin genotype 2-2 compared to genotype 2-1 or 1-1, after adjustment for confounders and competing risks. RESULTS: We found no associations between haptoglobin genotype 2-2 and cardiovascular mortality (subdistributional hazard ratio 1.08, 95% confidence interval 0.78-1.49; P = .63). We also failed to detect any association between haptoglobin 2-2 genotype and all-cause mortality, overall graft loss, and death-censored graft loss. Similar results were found in the subpopulation of transplant recipients with diabetes. CONCLUSION: In this large cohort of kidney transplant recipients, we could not demonstrate any association between haptoglobin 2-2 genotype and patient or graft survival after renal transplantation.


Subject(s)
Cardiovascular Diseases/genetics , Graft Survival , Haptoglobins/genetics , Kidney Transplantation , Adolescent , Adult , Aged , Aged, 80 and over , Female , Genotype , Humans , Male , Middle Aged , Norway , Retrospective Studies
12.
Transpl Int ; 30(8): 827-840, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28436117

ABSTRACT

In stable renal transplant recipients with hyperparathyroidism, previous studies have indicated that vitamin D agonist treatment might have anti-proteinuric effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory effects. Early introduction of paricalcitol in de novo renal transplant recipients might reduce proteinuria and prevent progressive allograft fibrosis. We performed a single-center, prospective, randomized, open-label trial investigating effects of paricalcitol 2 µg/day added to standard care. Participants were included 8 weeks after engraftment and followed for 44 weeks. Primary end point was change in spot urine albumin/creatinine ratio. Exploratory microarray analyses of kidney biopsies at study end investigated potential effects on gene expression. Secondary end points included change in glomerular filtration rate (GFR), pulse wave velocity (PWV), and endothelial function measured by peripheral arterial tonometry as reactive hyperemia index (RHI). Seventy-seven de novo transplanted kidney allograft recipients were included, 37 receiving paricalcitol. Paricalcitol treatment lowered PTH levels (P = 0.01) but did not significantly reduce albuminuria (P = 0.76), change vascular parameters (PWV; P = 0.98, RHI; P = 0.33), or influence GFR (P = 0.57). Allograft gene expression was not influenced. To summarize, in newly transplanted renal allograft recipients, paricalcitol reduced PTH and was well tolerated without negatively affecting kidney function. Paricalcitol did not significantly reduce/prevent albuminuria, improve parameters of vascular health, or influence allograft gene expression.


Subject(s)
Ergocalciferols/administration & dosage , Kidney Transplantation/methods , Administration, Oral , Animals , Ergocalciferols/adverse effects , Gene Expression/drug effects , Glomerular Filtration Rate/drug effects , Humans , Hyperemia/physiopathology , Hyperparathyroidism/drug therapy , Hyperparathyroidism/prevention & control , Kidney/drug effects , Kidney/pathology , Kidney/physiopathology , Parathyroid Hormone/blood , Prospective Studies , Proteinuria/prevention & control , Pulse Wave Analysis , Receptors, Calcitriol/agonists
13.
Transplantation ; 101(6): 1282-1289, 2017 06.
Article in English | MEDLINE | ID: mdl-27362306

ABSTRACT

BACKGROUND: Previous reports indicate that posttransplantation diabetes mellitus (PTDM) is associated with overall renal graft loss, but not death-censored graft loss. METHODS: In this single-center retrospective cohort study of 2749 adult Norwegian renal transplant recipients, transplanted between 1999 and 2011, we estimated overall and death-censored renal graft loss hazard ratios in patients diagnosed with PTDM, impaired glucose tolerance and diabetes before transplantation, using multivariable Cox proportional hazard regression analysis. RESULTS: A total of 893 renal grafts were lost during the study period, either due to recipient death (n = 540) or death-censored graft loss (n = 353).When the observational time started at time of transplantation, diabetes before transplantation was associated with both overall and death-censored graft loss. Pretransplantation diabetes was also associated with a steeper decline in renal graft function, a higher risk of acute rejections and more renal grafts lost due to acute rejection.In patients with a functional renal graft 1 year after transplantation, PTDM was associated with overall graft loss (hazard ratio, 1.46; 95% confidence interval, 1.13-1.88; P < 0.001), but not death-censored graft loss (hazard ratio, 1.25; 95% confidence interval, 0.80-1.96; P = 0.33). We found no significant associations between PTDM and change in renal function during the first 5 years or acute rejection risk during the first year after renal transplantation.Impaired glucose tolerance was not associated with either overall or death-censored graft loss. CONCLUSIONS: The present study confirms previous findings of an increased risk of overall but not death-censored renal graft loss in renal transplant recipients with PTDM. Longstanding diabetes might increase the risk of acute rejections.


Subject(s)
Diabetes Mellitus/etiology , Graft Rejection/etiology , Graft Survival , Kidney Transplantation/adverse effects , Acute Disease , Adult , Aged , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Female , Graft Rejection/diagnosis , Graft Rejection/mortality , Humans , Kaplan-Meier Estimate , Kidney Transplantation/mortality , Male , Middle Aged , Norway , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
14.
Tidsskr Nor Laegeforen ; 136(18): 1572, 2016 Oct.
Article in Norwegian | MEDLINE | ID: mdl-27731609
15.
Transpl Int ; 29(5): 568-78, 2016 May.
Article in English | MEDLINE | ID: mdl-26875590

ABSTRACT

Current diagnostic criteria for post-transplantation diabetes mellitus (PTDM) are either fasting plasma glucose ≥7.0 mmol/l (≥126 mg/dl) or postchallenge plasma glucose ≥11.1 mmol/l (≥200 mg/dl) 2 h after glucose administration [oral glucose tolerance test (OGTT) criterion]. In this retrospective cohort study of 1632 renal transplant recipients (RTRs) without known diabetes mellitus at the time of transplantation, we estimated mortality hazard ratios for patients diagnosed with PTDM by either conventional glucose criteria or the proposed glycated haemoglobin (HbA1c) criterion [HbA1c ≥6.5% (≥48 mmol/mol)]. During a median follow-up of 7.0 years, 311 patients died. Compared with nondiabetic patients and after adjustment for confounders, patients diagnosed with PTDM based on chronic hyperglycaemia early after transplantation (manifest PTDM) or by the OGTT criterion at 10 weeks post-transplant suffered a higher mortality risk (HR 1.59, 95% CI 1.06-2.38, P = 0.02 and HR 1.56, 95% CI 1.04-2.38, P = 0.03, respectively). In contrast, patients diagnosed with PTDM by the HbA1c criterion at 10 weeks or between 10 weeks and 1 year post-transplant were not associated with mortality (HR 0.96, 95% CI 0.61-1.51, P = 0.86 and 1.58, 95% CI 0.74-3.36, P = 0.24 respectively). After adjustment for confounders and competing risks, only patients with manifest PTDM had a significantly higher cardiovascular mortality risk (subdistributional HR 2.31, 95% CI 1.19-4.47, P < 0.001). Since many cases with PTDM were only identified by the OGTT, we recommend monitoring fasting plasma glucose early after renal transplantation followed by an OGTT at 2-3 months post-transplant in patients without overt diabetes mellitus.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Glycated Hemoglobin/analysis , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Aged , Diabetes Complications/therapy , Diabetes Mellitus/therapy , Female , Glucose Tolerance Test , Humans , Hyperglycemia/diagnosis , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/complications , Male , Middle Aged , Norway , Registries , Retrospective Studies , Risk Factors , Steroids/therapeutic use , Time Factors , Treatment Outcome
16.
J Ren Nutr ; 26(3): 196-203, 2016 05.
Article in English | MEDLINE | ID: mdl-26776249

ABSTRACT

OBJECTIVE: Renal transplant recipients (RTR) suffer high rates of bone loss and increased risk of fracture. Marine n-3 polyunsaturated fatty acids (n-3 PUFA), found mainly in fish and seafood, may have beneficial effects on bone and are positively associated with bone mineral density (BMD) in healthy elderly. The aim of this study was to investigate if this association prevails despite the more complex causes of bone loss in RTR. DESIGN, SUBJECTS, AND METHODS: A total of 701 RTR were included in a cross-sectional analysis. BMD of lumbar spine, proximal femur, and distal forearm were measured by dual energy x-ray absorptiometry scan, and blood samples were drawn in the fasting state for measurement of plasma fatty acid composition 10 weeks posttransplant. Multiple linear regression analysis was used to assess the association between plasma marine n-3 PUFA levels and BMD. RESULTS: Mean age was 52.2 years, and two-thirds were men. Based on femoral neck T-scores, 26% of patients were osteoporotic and 52% osteopenic. Z-scores increased significantly across quartiles of marine n-3 PUFA levels, and marine n-3 PUFA was a positive predictor of BMD at total hip and lumbar spine after multivariate adjustment. No association was found between n-6 PUFA content and BMD. CONCLUSIONS: Plasma marine n-3 PUFA levels were positively associated with BMD at the hip and lumbar spine 10 weeks posttransplant.


Subject(s)
Bone Density/physiology , Fatty Acids, Omega-3/blood , Kidney Transplantation , Bone Diseases, Metabolic/epidemiology , Cross-Sectional Studies , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Female , Femur Neck , Humans , Kidney Transplantation/adverse effects , Lumbar Vertebrae , Male , Middle Aged , Osteoporosis/epidemiology
18.
Transpl Int ; 28(10): 1162-71, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25970153

ABSTRACT

The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We evaluated 167 patients without diabetes 8-10 weeks after kidney transplantation, performing oral glucose tolerance tests and measuring VAT content from dual-energy X-ray absorptiometry scans. Median VAT weight in normal glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg, impaired glucose tolerance patients 1.3 kg and patients with post-transplant diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups). Percentage VAT of total body fat was associated with fasting (R(2) = 0.094, P < 0.001) and 2-h glucose concentration (R(2) = 0.062, P = 0.001), while BMI was only associated with 2-h glucose concentration (R(2) = 0.029, P = 0.028). An association between BMI and 2-h glucose concentration was lost in adjusted models, as opposed to the associations between VAT as percentage of total body fat and glucose concentrations (R(2) = 0.132, P < 0.001 and R(2) = 0.097, P = 0.001, respectively for fasting and 2-h glucose concentration). In conclusion, VAT is more closely related to impaired glucose metabolism than BMI after kidney transplantation. The association with central obesity should encourage additional studies on lifestyle interventions to prevent PTDM.


Subject(s)
Diabetes Mellitus/etiology , Glucose/metabolism , Insulin Resistance , Intra-Abdominal Fat/metabolism , Kidney Transplantation , Postoperative Complications/etiology , Absorptiometry, Photon , Adult , Aged , Blood Glucose/analysis , Body Composition , Body Mass Index , Cross-Sectional Studies , Diabetes Mellitus/chemically induced , Diabetes Mellitus/metabolism , Glucose Tolerance Test , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Immunoglobulins, Intravenous , Immunosuppressive Agents/adverse effects , Insulin/blood , Intra-Abdominal Fat/diagnostic imaging , Lipids/blood , Methylprednisolone/adverse effects , Middle Aged , Postoperative Complications/metabolism , Prednisolone/adverse effects , Rituximab/therapeutic use , Tissue Donors
19.
Transplantation ; 99(8): 1730-7, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25757216

ABSTRACT

BACKGROUND: The association between aortic stiffness and all-cause mortality in kidney transplant recipients (KTRs) is uncertain, and aortic stiffness has not yet been incorporated into risk prediction tools. METHODS: During 2007 to 2012, we measured carotid-femoral pulse wave velocity (PWV; SphygmoCor apparatus) 8 weeks after transplantation. The association between PWV and mortality was assessed in a Cox regression analysis adjusting for seven risk factors from a previously validated model. Internal validation was performed by bootstrap resampling, and discrimination and overfitting evaluated by Harrell's C and the calibration slope. RESULTS: Of 1497 KTRs, 1040 (69%) had a valid PWV measurement. During a median follow-up of 4.2 years, 82 patients died. The association between PWV and mortality showed a ceiling effect, and PWV was truncated at 12 m/sec. Each 1 m/sec increase in PWV, up to 12 m/sec, was associated with mortality, hazard ratio (HR) 1.36 (95% CI, 1.14-1.62; P = 0.001). An interquartile range increase (3.8 m/sec) tripled the hazard of mortality, HR, 3.21 (95% CI, 1.63-6.31), similar to the effect of being approximately 20 years older (interquartile range increase (21.6 years); HR, 3.06 [95% CI, 1.87-5.29]). The PWV improved model discrimination with an increase in Harrell's C from 0.76 to 0.78; C difference, 0.024 (95% CI, 0.005-0.043; P = 0.01). Overfitting was moderate with a calibration slope of 0.89, and the final model was adjusted accordingly. A spreadsheet version is presented to estimate expected 5-year survival. CONCLUSIONS: The PWV is a strong risk factor for mortality in KTRs.


Subject(s)
Kidney Transplantation/mortality , Transplant Recipients , Vascular Stiffness , Adult , Aged , Female , Humans , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Linear Models , Male , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Pulse Wave Analysis , Reproducibility of Results , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
20.
Transplantation ; 99(3): 629-35, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25162478

ABSTRACT

BACKGROUND: Posttransplant diabetes mellitus (PTDM) is usually detected 2 to 3 months after transplantation by fasting plasma glucose (fPG) ≥ 7.0 mmol/L (≥ 126 mg/dL) and/or 2 hr post-challenge plasma glucose ≥ 11.1 mmol/L (≥ 200 mg/dL) during an oral glucose tolerance test (OGTT). Recently, glycosylated hemoglobin (HbA1c) of 6.5% or higher (≥ 47.5 mmol/mol) has been proposed as an alternative diagnostic criterion (the HbA1c criterion). We aimed to assess the sensitivity of applying the HbA1c criterion alone or in combination with a single measurement of fPG of 7.0 mmol/L or higher (≥ 126 mg/dL) at 10 weeks after transplantation as screening tests for the diagnosis of PTDM. METHODS: From 1999 to 2011, measurements of fPG, HbA1c, and OGTT were performed in 1,619 nondiabetic renal transplant recipients. RESULTS: The HbA1c criterion detected 38.0% of patients with PTDM diagnosed with the standard diagnostic criteria. The specificity was 86.3%. When the HbA1c threshold value was lowered to 6.2% (44.3 mmol/mol), sensitivity increased to 57.8% with a corresponding reduced specificity of 80.4%. A combination of the HbA1c criterion and fPG of 7.0 mmol/L or higher (126 mg/dL) at 10 weeks after transplantation improved diagnostic precision with a sensitivity of 77.7% and a specificity of 96.1%. CONCLUSION: The proposed diagnostic HbA1c criterion failed to detect most cases of PTDM, and one of four cases of PTDM was detected by OGTT alone. This indicates that the HbA1c threshold value likely needs to be lowered for renal transplant recipients and supports continued use of OGTT as a diagnostic tool for detection of PTDM.


Subject(s)
Diabetes Mellitus/diagnosis , Glycated Hemoglobin/analysis , Adult , Blood Glucose/chemistry , Diabetes Complications/blood , Diabetes Mellitus/blood , Female , Glucose Tolerance Test , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Male , Middle Aged , Postoperative Complications , Reproducibility of Results , Sensitivity and Specificity
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