Vitamin C deficiency after kidney transplantation: a cohort and cross-sectional study of the TransplantLines biobank.

PURPOSE: Vitamin C deficiency is associated with excess mortality in kidney transplant recipients (KTR). We aim to evaluate plasma vitamin C status at different post-transplantation moments and assess the main characteristics associated with vitamin C deficiency in KTR. METHODS: Plasma vitamin C was assessed in 598 KTR at 3-, 6-, 12-, 24-, and 60-months post-transplantation, 374 late KTR with a functioning graft ≥ 1 year, and 395 potential donors. Vitamin C deficiency was defined as plasma vitamin C ≤ 28 µmol/L. Diet was assessed by a 177-item food frequency questionnaire. Data on vitamin C-containing supplements use were extracted from patient records and verified with the patients. RESULTS: Vitamin C deficiency ranged from 46% (6-months post-transplantation) to 30% (≥ 1 year post-transplantation). At all time points, KTR had lower plasma vitamin C than potential donors (30-41 µmol/L vs 58 µmol/L). In cross-sectional analyses of the 953 KTR at their first visit ≥ 12 months after transplantation (55 ± 14 years, 62% male, eGFR 55 ± 19 mL/min/1.73 m2), the characteristics with the strongest association with vitamin C deficiency were diabetes and smoking (OR 2.67 [95% CI 1.84-3.87] and OR 1.84 [95% CI 1.16-2.91], respectively). Dietary vitamin C intake and vitamin C supplementation were associated with lower odds (OR per 100 mg/day 0.38, 95% CI 0.24-0.61 and OR 0.21, 95% CI 0.09-0.44, respectively). CONCLUSION: Vitamin C deficiency is frequent among KTR regardless of the time after transplantation, especially among those with diabetes and active smokers. The prevalence of vitamin C deficiency was lower among KTR with higher vitamin C intake, both dietary and supplemented. Further research is warranted to assess whether correcting this modifiable risk factor could improve survival in KTR.

Phase angle and donor type are determinants of coronary artery calcification in stable kidney transplant recipients at twelve months after transplantation.

BACKGROUND AND AIM: Coronary artery calcification (CAC) partially explains the excess cardiovascular morbidity and mortality after kidney transplantation. This study aimed to investigate determinants of CAC in stable kidney transplant recipients at 12 months post-transplantation. METHODS AND RESULTS: CAC-score was quantified by the Agatston method using non-contrast enhanced computed tomography, and age- and sex-standardized CAC-percentiles were calculated. Univariable and multivariable multinomial logistic regression was performed to study potential determinants of CAC. The independent determinants were included in multivariable multinomial logistic regression adjusting for potential confounders. 203 KTRs (age 54.0 ± 14.7 years, 61.1% male) were included. Participants were categorized into four groups according to CAC percentiles (p = 0 [CAC-score = 0], n = 68; p ≥ 1%-p ≤ 50% [CAC score = 29.0 (4.0-166.0)], n = 31; p > 50 ≤ 75% [CAC score = 101.0 (23.8-348.3)], n = 26; and p>75% [CAC score = 581.0 (148.0-1652)], n = 83). Upon multivariable multinomial logistic regression, patients with a narrower phase angle and patients who had received a graft from a deceased donor had a higher risk of being in the >75th CAC-percentile. CONCLUSIONS: This study identifies not only metabolic and transplant-related factors, but also phase angle, a composite marker of cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. This study offers new perspectives for future research into the value of bioelectrical impedance analysis in relation to vascular calcification in kidney transplant recipients.

Hyaline and Cystic Degeneration of Uterine Leiomyomas: CT and MR Imaging with Histopathological Sample Analyses.

Leiomyomas are the most common solid benign uterine neoplasms; they are usually asymptomatic and are identified incidentally. Yet, responsive to stimulation by estrogens, leiomyomas may expand, potentially outgrowing their blood supply to undergo hemorrhage, fibrosis, calcification, and atrophy. These pathologic mechanisms commonly lead to leiomyomas degeneration, i.e., red, hyaline, cystic, or myxoid. Magnetic resonance (MR) imaging is the most accurate imaging technique for the characterization of leiomyomas. In cases of degeneration, variable features on T2-weighted and contrast-enhanced images can be found. With no recent radiologic pathologic correlation literature available on this matter, herewith, we provide computed tomography (CT)/MR imaging along with histopathological specimens of two young women who were diagnosed with hyaline or hyaline and cyst degeneration of uterine leiomyomas at our university hospital. We report on the imaging features of uterine leiomyomas using CT and MR imaging and discuss the available literature on imaging signs that may be suggestive of hyaline or cyst degeneration using either of the imaging examination methods.

Urinary Copper Excretion Is Associated with Long-Term Graft Failure in Kidney Transplant Recipients.

INTRODUCTION: In chronic kidney disease, proteinuria increases urinary copper excretion, inducing oxidative tubular damage and worsening kidney function. We investigated whether this phenomenon occurred in kidney transplant recipients (KTRs). In addition, we studied the associations of urinary copper excretion with the biomarker of oxidative tubular damage urinary liver-type fatty-acid binding protein (u-LFABP) and death-censored graft failure. METHODS: This prospective cohort study was performed in the Netherlands between 2008 and 2017, including outpatient KTR with a functioning graft for longer than 1 year, who were extensively phenotyped at baseline. Twenty-four-hour urinary copper excretion was measured by inductively coupled plasma mass spectrometry. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (57% men, 53 ± 13 years, estimated glomerular filtration rate [eGFR] 52 ± 20 mL/min/1.73 m2), baseline median urinary copper excretion was 23.6 (interquartile range 11.3-15.9) µg/24 h. Urinary protein excretion was positively associated with urinary copper excretion (standardized ß = 0.39, p < 0.001), and urinary copper excretion was positively associated with u-LFABP (standardized ß = 0.29, p < 0.001). During a median follow-up of 8 years, 109 (16%) KTR developed graft failure. KTR with relatively high copper excretion were at higher risk of long-term graft failure (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.32-1.86 per log2, p < 0.001), independent of multiple potential confounders like eGFR, urinary protein excretion, and time after transplantation. A dose-response relationship was observed over increasing tertiles of copper excretion (HR: 5.03, 95% CI: 2.75-9.19, tertile 3 vs. 1, p < 0.001). u-LFABP was a significant mediator of this association (74% of indirect effect, p < 0.001). CONCLUSION: In KTR, urinary protein excretion is positively correlated with urinary copper excretion. In turn, higher urinary copper excretion is associated with an independent increased risk of kidney graft failure, with a substantial mediating effect through oxidative tubular damage. Further studies are warranted to investigate whether copper excretion-targeted interventions could improve kidney graft survival.

Low selenium intake is associated with risk of all-cause mortality in kidney transplant recipients.

BACKGROUND: Deficiency of the essential trace element selenium is common in kidney transplant recipients (KTR), potentially hampering antioxidant and anti-inflammatory defence. Whether this impacts the long-term outcomes of KTR remains unknown. We investigated the association of urinary selenium excretion, a biomarker of selenium intake, with all-cause mortality; and its dietary determinants. METHODS: In this cohort study, outpatient KTR with a functioning graft for longer than 1 year were recruited (2008-11). Baseline 24-h urinary selenium excretion was measured by mass spectrometry. Diet was assessed by a 177-item food frequency questionnaire, and protein intake was calculated by the Maroni equation. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (43% men, 52 ± 12 years), baseline urinary selenium excretion was 18.8 (interquartile range 15.1-23.4) µg/24-h. During a median follow-up of 8 years, 229 (33%) KTR died. KTR in the first tertile of urinary selenium excretion, compared with those in the third, had over a 2-fold risk of all-cause mortality [hazard ratio 2.36 (95% confidence interval 1.70-3.28); P < .001], independent of multiple potential confounders including time since transplantation and plasma albumin concentration. The most important dietary determinant of urinary selenium excretion was protein intake (Standardized ß 0.49, P < .001). CONCLUSIONS: Relatively low selenium intake is associated with a higher risk of all-cause mortality in KTR. Dietary protein intake is its most important determinant. Further research is required to evaluate the potential benefit of accounting for selenium intake in the care of KTR, particularly among those with low protein intake.

Plasma Copper Concentration Is Associated with Cardiovascular Mortality in Male Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of cardiovascular mortality. We investigated whether, in KTR, post-transplantation copper status is associated with the risk of cardiovascular mortality and potential effect modification by sex. In this cohort study, plasma copper was measured using mass spectrometry in extensively-phenotyped KTR with a functioning allograft >1-year. Cox regression analyses with the inclusion of multiplicative interaction terms were performed. In 660 KTR (53 ± 13 years old, 56% male), the median baseline plasma copper was 15.42 (IQR 13.53-17.63) µmol/L. During a median follow-up of 5 years, 141 KTR died, 53 (38%) due to cardiovascular causes. Higher plasma copper was associated with an increased risk of cardiovascular mortality in the overall KTR population (HR 1.37; 95% CI, 1.07-1.77 per 1-SD, p = 0.01). Sex was a significant effect modifier of this association (Pinteraction = 0.01). Among male KTR, higher plasma copper concentration was independently associated with a two-fold higher risk of cardiovascular mortality (HR 2.09; 95% CI, 1.42-3.07 per 1-SD, p < 0.001). Among female KTR, this association was absent. This evidence offers a rationale for considering a sex-specific assessment of copper's role in cardiovascular risk evaluation. Further studies are warranted to elucidate whether copper-targeted interventions may decrease cardiovascular mortality in male KTR.

Plasma Thallium Concentration, Kidney Function, Nephrotoxicity and Graft Failure in Kidney Transplant Recipients.

The nephrotoxic effects of heavy metals have gained increasing scientific attention in the past years. Recent studies suggest that heavy metals, including cadmium, lead, and arsenic, are detrimental to kidney transplant recipients (KTR) even at circulating concentrations within the normal range, posing an increased risk for graft failure. Thallium is another highly toxic heavy metal, yet the potential consequences of the circulating thallium concentrations in KTR are unclear. We measured plasma thallium concentrations in 672 stable KTR enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study using inductively coupled plasma mass spectrometry. In cross-sectional analyses, plasma thallium concentrations were positively associated with kidney function measures and hemoglobin. We observed no associations of thallium concentration with proteinuria or markers of tubular damage. In prospective analyses, we observed no association of plasma thallium with graft failure and mortality during a median follow-up of 5.4 [interquartile range: 4.8 to 6.1] years. In conclusion, in contrast with other heavy metals such as lead, cadmium, and arsenic, there is no evidence of tubular damage or thallium nephrotoxicity for the range of circulating thallium concentrations observed in this study. This is further evidenced by the absence of associations of plasma thallium with graft failure and mortality in KTR.

Plasma Lead Concentration and Risk of Late Kidney Allograft Failure: Findings From the TransplantLines Biobank and Cohort Studies.

RATIONALE & OBJECTIVE: Heavy metals are known to induce kidney damage, and recent studies have linked minor exposures to cadmium and arsenic with increased risk of kidney allograft failure, yet the potential association of lead with late graft failure in kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Prospective cohort study in The Netherlands. SETTING & PARTICIPANTS: We studied outpatient KTRs (n = 670) with a functioning graft for ≥1 year recruited at a university setting (2008-2011) and followed for a median of 4.9 (interquartile range, 3.4-5.5) years. Additionally, patients with chronic kidney disease (n = 46) enrolled in the ongoing TransplantLines Cohort and Biobank Study (2016-2017, ClinicalTrials.gov identifier NCT03272841) were studied at admission for transplant and at 3, 6, 12, and 24 months after transplant. EXPOSURE: Plasma lead concentration was log2-transformed to estimate the association with outcomes per doubling of plasma lead concentration and also considered categorically as tertiles of lead distribution. OUTCOME: Kidney graft failure (restart of dialysis or repeat transplant) with the competing event of death with a functioning graft. ANALYTICAL APPROACH: Multivariable-adjusted cause-specific hazards models in which follow-up of KTRs who died with a functioning graft was censored. RESULTS: Median baseline plasma lead concentration was 0.31 (interquartile range, 0.22-0.45) µg/L among all KTRs. During follow-up, 78 (12%) KTRs experienced graft failure. Higher plasma lead concentration was associated with increased risk of graft failure (hazard ratio, 1.59 [95% CI, 1.14-2.21] per doubling; P = 0.006) independent of age, sex, transplant characteristics, estimated glomerular filtration rate, proteinuria, smoking status, alcohol intake, and plasma concentrations of cadmium and arsenic. These findings remained materially unchanged after additional adjustment for dietary intake and were consistent with those of analyses examining lead categorically. In serial measurements, plasma lead concentration was significantly higher at admission for transplant than at 3 months after transplant (P = 0.001), after which it remained stable over 2 years of follow-up (P = 0.2). LIMITATIONS: Observational study design. CONCLUSIONS: Pretransplant plasma lead concentrations, which decrease after transplant, are associated with increased risk of late kidney allograft failure. These findings warrant further studies to evaluate whether preventive or therapeutic interventions to decrease plasma lead concentration may represent novel risk-management strategies to decrease the rate of kidney allograft failure.

Polyphenols and Novel Insights Into Post-kidney Transplant Complications and Cardiovascular Disease: A Narrative Review.

Kidney transplantation is the preferred treatment for end-stage kidney disease. It is, however, not devoid of complications. Delayed graft function related to ischemia-reperfusion injury (IRI), calcineurin inhibitor (CNI) nephrotoxicity, diabetes, and a particularly high-rate cardiovascular disease (CVD) risk, represent important complications following kidney transplantation. Oxidative stress and chronic low-grade inflammation are mechanisms of disease incompletely abrogated in stable kidney transplant recipient (KTR), contributing to the occurrence of these complications. Polyphenols, bioactive compounds with recognized antioxidant and anti-inflammatory properties have been strongly associated with prevention of CVD in the general population and have been shown to decrease IRI and antagonize CNI nephrotoxicity in animal experimental models, therefore they may have a role in prevention of complications in KTR. This narrative review aims to summarize and discuss current evidence on different polyphenols for prevention of complications, particularly prevention of CVD in KTR, pointing toward the need of further studies with potential clinical impact.

Low Circulating Concentrations of Very Long Chain Saturated Fatty Acids Are Associated with High Risk of Mortality in Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2-6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64-0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35-0.82), 0.48 (0.30-0.75), and 0.51 (0.33-0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups.

Content-Based Medical Image Retrieval and Intelligent Interactive Visual Browser for Medical Education, Research and Care.

Medical imaging is essential nowadays throughout medical education, research, and care. Accordingly, international efforts have been made to set large-scale image repositories for these purposes. Yet, to date, browsing of large-scale medical image repositories has been troublesome, time-consuming, and generally limited by text search engines. A paradigm shift, by means of a query-by-example search engine, would alleviate these constraints and beneficially impact several practical demands throughout the medical field. The current project aims to address this gap in medical imaging consumption by developing a content-based image retrieval (CBIR) system, which combines two image processing architectures based on deep learning. Furthermore, a first-of-its-kind intelligent visual browser was designed that interactively displays a set of imaging examinations with similar visual content on a similarity map, making it possible to search for and efficiently navigate through a large-scale medical imaging repository, even if it has been set with incomplete and curated metadata. Users may, likewise, provide text keywords, in which case the system performs a content- and metadata-based search. The system was fashioned with an anonymizer service and designed to be fully interoperable according to international standards, to stimulate its integration within electronic healthcare systems and its adoption for medical education, research and care. Professionals of the healthcare sector, by means of a self-administered questionnaire, underscored that this CBIR system and intelligent interactive visual browser would be highly useful for these purposes. Further studies are warranted to complete a comprehensive assessment of the performance of the system through case description and protocolized evaluations by medical imaging specialists.

Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients.

BACKGROUND: Diarrhea is common among kidney transplant recipients (KTR). Exhaled hydrogen (H2) is a surrogate marker of small bowel dysbiosis, which may drive diarrhea. We studied the relationship between exhaled H2 and diarrhea in KTR, and explored potential clinical and dietary determinants. METHODS: Clinical, laboratory, and dietary data were analyzed from 424 KTR participating in the TransplantLines Biobank and Cohort Study (NCT03272841). Fasting exhaled H2 concentration was measured using a model DP Quintron Gas Chromatograph. Diarrhea was defined as fast transit time (types 6 and 7 according to the Bristol Stool Form Scale, BSFS) of 3 or more episodes per day. We studied the association between exhaled H2 and diarrhea with multivariable logistic regression analysis, and explored potential determinants using linear regression. RESULTS: KTR (55.4 ± 13.2 years, 60.8% male, mean eGFR 49.8 ± 19.1 mL/min/1.73 m2) had a median exhaled H2 of 11 (5.0-25.0) ppm. Signs of small intestinal bacterial overgrowth (exhaled H2 ≥ 20 ppm) were present in 31.6% of the KTR, and 33.0% had diarrhea. Exhaled H2 was associated with an increased risk of diarrhea (odds ratio 1.51, 95% confidence interval 1.07-2.14 per log2 ppm, p = 0.02). Polysaccharide intake was independently associated with higher H2 (std. ß 0.24, p = 0.01), and a trend for an association with proton-pump inhibitor use was observed (std. ß 0.16 p = 0.05). CONCLUSION: Higher exhaled H2 is associated with an increased risk of diarrhea in KTR. Our findings set the stage for further studies investigating the relationship between dietary factors, small bowel dysbiosis, and diarrhea after kidney transplantation.

Novel Combined Antioxidant Strategy against Hypertension, Acute Myocardial Infarction and Postoperative Atrial Fibrillation.

Reactive oxygen species (ROS) play a physiological role in the modulation of several functions of the vascular wall; however, increased ROS have detrimental effects. Hence, oxidative stress has pathophysiological impacts on the control of the vascular tone and cardiac functions. Recent experimental studies reported the involvement of increased ROS in the mechanism of hypertension, as this disorder associates with increased production of pro-oxidants and decreased bioavailability of antioxidants. In addition, increased ROS exposure is found in ischemia-reperfusion, occurring in acute myocardial infarction and cardiac surgery with extracorporeal circulation, among other settings. Although these effects cause major heart damage, at present, there is no available treatment. Therefore, it should be expected that antioxidants counteract the oxidative processes, thereby being suitable against cardiovascular disease. Nevertheless, although numerous experimental studies agree with this notion, interventional trials have provided mixed results. A better knowledge of ROS modulation and their specific interaction with the molecular targets should contribute to the development of novel multitarget antioxidant effective therapeutic strategies. The complex multifactorial nature of hypertension, acute myocardial infarction, and postoperative atrial fibrillation needs a multitarget antioxidant strategy, which may give rise to additive or synergic protective effects to achieve optimal cardioprotection.

Plasma Vitamin C and Risk of Late Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Biobank and Cohort Study.

Recent studies have shown that depletion of vitamin C is frequent in outpatient kidney transplant recipients (KTR) and that vitamin C is inversely associated with risk of death. Whether plasma vitamin C is associated with death-censored kidney graft failure remains unknown. We investigated KTR who participated in the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study. The primary outcome was graft failure (restart of dialysis or re-transplantation). Overall and stratified (pinteraction < 0.1) multivariable-adjusted Cox regression analyses are presented here. Among 598 KTR (age 51 ± 12 years-old; 55% males), baseline median (IQR) plasma vitamin C was 44.0 (31.0-55.3) µmol/L. Through a median follow-up of 9.5 (IQR, 6.3‒10.2) years, 75 KTR developed graft failure (34, 26, and 15 events over increasing tertiles of vitamin C, log-rank p < 0.001). Plasma vitamin C was inversely associated with risk of graft failure (HR per 1-SD increment, 0.69; 95% CI 0.54-0.89; p = 0.004), particularly among KTR with triglycerides ≥1.9 mmol/L (HR 0.46; 95% CI 0.30-0.70; p < 0.001; pinteraction = 0.01) and among KTR with HDL cholesterol ≥0.91 mmol/L (HR 0.56; 95% CI 0.38-0.84; p = 0.01; pinteraction = 0.04). These findings remained materially unchanged in multivariable-adjusted analyses (donor, recipient, and transplant characteristics, including estimated glomerular filtration rate and proteinuria), were consistent in categorical analyses according to tertiles of plasma vitamin C, and robust after exclusion of outliers. Plasma vitamin C in outpatient KTR is inversely associated with risk of late graft failure. Whether plasma vitamin C‒targeted therapeutic strategies represent novel opportunities to ease important burden of graft failure necessitates further studies.

Introduction of the Grayscale Median for Ultrasound Tissue Characterization of the Transplanted Kidney.

Ultrasound examination is advised for early post-kidney transplant assessment. Grayscale median (GSM) quantification is novel in the kidney transplant field, with no systematic assessment previously reported. In this prospective cohort study, we measured the post-operative GSM in a large cohort of adult kidney transplant recipients (KTR) who consecutively underwent Doppler ultrasound directly after transplantation (within 24 h), compared it with GSM in nontransplanted patients, and investigated its association with baseline and follow-up characteristics. B-mode images were used to calculate the GSM in KTR and compared with GSM data in nontransplanted patients, as simulated from summary statistics of the literature using a Mersenne twister algorithm. The association of GSM with baseline and 1-year follow-up characteristics were studied by means of linear regression analyses. In 282 KTR (54 ± 15 years old, 60% male), the median (IQR) GSM was 55 (45-69), ranging from 22 to 124 (coefficient of variation = 7.4%), without differences by type of donation (p = 0.28). GSM in KTR was significantly higher than in nontransplanted patients (p < 0.001), and associated with systolic blood pressure, history of cardiovascular disease, and donor age (std. ß = 0.12, -0.20, and 0.13, respectively; p < 0.05 for all). Higher early post-kidney transplant GSM was not associated with 1-year post-kidney transplant function parameters (e.g., measured and estimated glomerular filtration rate). The data provided in this study could be used as first step for further research on the application of early postoperative ultrasound in KTR.

Creatine homeostasis and protein energy wasting in hemodialysis patients.

Muscle wasting, low protein intake, hypoalbuminemia, low body mass, and chronic fatigue are prevalent in hemodialysis patients. Impaired creatine status may be an often overlooked, potential contributor to these symptoms. However, little is known about creatine homeostasis in hemodialysis patients. We aimed to elucidate creatine homeostasis in hemodialysis patients by assessing intradialytic plasma changes as well as intra- and interdialytic losses of arginine, guanidinoacetate, creatine and creatinine. Additionally, we investigated associations of plasma creatine concentrations with low muscle mass, low protein intake, hypoalbuminemia, low body mass index, and chronic fatigue. Arginine, guanidinoacetate, creatine and creatinine were measured in plasma, dialysate, and urinary samples of 59 hemodialysis patients. Mean age was 65 ± 15 years and 63% were male. During hemodialysis, plasma concentrations of arginine (77 ± 22 to 60 ± 19 µmol/L), guanidinoacetate (1.8 ± 0.6 to 1.0 ± 0.3 µmol/L), creatine (26 [16-41] to 21 [15-30] µmol/L) and creatinine (689 ± 207 to 257 ± 92 µmol/L) decreased (all P < 0.001). During a hemodialysis session, patients lost 1939 ± 871 µmol arginine, 37 ± 20 µmol guanidinoacetate, 719 [399-1070] µmol creatine and 15.5 ± 8.4 mmol creatinine. In sex-adjusted models, lower plasma creatine was associated with a higher odds of low muscle mass (OR per halving: 2.00 [1.05-4.14]; P = 0.04), low protein intake (OR: 2.13 [1.17-4.27]; P = 0.02), hypoalbuminemia (OR: 3.13 [1.46-8.02]; P = 0.008) and severe fatigue (OR: 3.20 [1.52-8.05]; P = 0.006). After adjustment for potential confounders, these associations remained materially unchanged. Creatine is iatrogenically removed during hemodialysis and lower plasma creatine concentrations were associated with higher odds of low muscle mass, low protein intake, hypoalbuminemia, and severe fatigue, indicating a potential role for creatine supplementation.

The Association between Body Composition Measurements and Surgical Complications after Living Kidney Donation.

Obesity is considered a risk factor for peri- and postoperative complications. Little is known about this risk in overweight living kidney donors. The aim of this study was to assess if anthropometric body measures and/or surgical determinants are associated with an increased incidence of peri- and postoperative complications after nephrectomy. We included 776 living kidney donors who donated between 2008 and 2018 at the University Medical Center Groningen. Prenephrectomy measures of body composition were body mass index (BMI), body surface area (BSA), waist circumference, weight, and waist-hip ratio. Incidence and severity of peri- and postoperative complications were assessed using the Comprehensive Complication Index. Mean donor age was 53 ± 11 years; 382 (49%) were male, and mean BMI at donor screening was 26.2 ± 3.41 kg/m2. In total, 77 donors (10%) experienced peri- and postoperative complications following donor nephrectomy. Male sex was significantly associated with fewer surgical complications (OR 0.59, 0.37-0.96 95%CI, p = 0.03) in binomial logistic regression analyses. Older age (OR: 1.03, 1.01-1.05 95%CI, p = 0.02) and a longer duration of surgery (OR: 1.01, 1.00-1.01 95%CI, p = 0.02) were significantly associated with more surgical complications in binomial logistic regression analyses. Multinomial logistic regression analyses did not identify any prenephrectomy measure of body composition associated with a higher risk of surgical complications. This study shows that higher prenephrectomy BMI and other anthropometric measures of body composition are not significantly associated with peri- and postoperative complications following living donor nephrectomy.

Functional vitamin K status and risk of incident chronic kidney disease and microalbuminuria: a prospective general population-based cohort study.

BACKGROUND: Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate (Gla) protein (dp-ucMGP), a marker of vitamin K status, is associated with renal function and may serve as a potentially modifiable risk factor for incident chronic kidney disease (CKD). We aimed to assess the association between circulating dp-ucMGP and incident CKD. METHODS: We included 3969 participants with a mean age of 52.3 ± 11.6 years, of whom 48.0% were male, enrolled in the general population-based Prevention of REnal and Vascular ENd-stage Disease study. Study outcomes were incident CKD, defined as either development of an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or microalbuminuria. Associations of dp-ucMGP with these outcomes were quantified using Cox proportional hazards models and were adjusted for potential confounders. RESULTS: Median plasma dp-ucMGP was 363 [interquartile range (IQR) 219-532] pmol/L and mean serum creatinine- and serum cystatin C-based eGFR (eGFRSCr-SCys) was 95.4 ± 21.8 mL/min/1.73 m2. During 7.1 years of follow-up, 205 (5.4%) participants developed incident CKD and 303 (8.4%) developed microalbuminuria. For every doubling of plasma dp-ucMGP, hazard ratios for the development of incident CKD and microalbuminuria were 1.85 [95% confidence interval (CI) 1.59-2.16; P < 0.001] and 1.19 (95% CI 1.07-1.32; P = 0.001), respectively. These associations lost significance after adjustment for baseline eGFRSCr-SCys [0.99 (95% CI 0.88-1.12; P = 0.86)] and baseline age [1.03 (95% CI 0.94-1.14; P = 0.50)], respectively. CONCLUSIONS: The associations of plasma dp-ucMGP with incident CKD and microalbuminuria were driven by the respective baseline effects of renal function and age.

Serum uric acid is associated with increased risk of posttransplantation diabetes in kidney transplant recipients: a prospective cohort study.

BACKGROUND: Serum uric acid (SUA) is associated with fasting glucose in healthy subjects, and prospective epidemological studies have shown that elevated SUA is associated with increased risk of type 2 diabetes. Whether SUA is independently associated with higher risk of posttransplantation diabetes mellitus (PTDM) in kidney transplant recipients (KTR) remains unknown. METHODS: We performed a longitudinal cohort study of 524 adult KTR with a functioning graft ≥1-year, recruited at a university setting (2008-2011). Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the association between time-updated SUA and risk of PTDM (defined according the American Diabetes Association's diagnostic criteria). RESULTS: Mean (SD) SUA was 0.43 (0.11) mmol/L at baseline. During 5.3 (IQR, 4.1-6.0) years of follow-up, 52 (10%) KTR developed PTDM. In univariate prospective analyses, SUA was associated with increased risk of PTDM (HR 1.75, 95% CI 1.36-2.26 per 1-SD increment; P < 0.001). This finding remained materially unchanged after adjustment for components of the metabolic syndrome, lifestyle, estimated glomerular filtration rate, immunosuppressive therapy, cytomegalovirus and hepatitis C virus infection (HR 1.89, 95% CI 1.32-2.70; P = 0.001). These findings were consistent in categorical analyses, and robust in sensitivity analyses without outliers. CONCLUSIONS: In KTR, higher SUA levels are strongly and independently associated with increased risk of PTDM. Our findings are in agreement with accumulating evidence supporting SUA as novel independent risk marker for type 2 diabetes, and extend the evidence, for the first time, to the clinical setting of outpatient KTR.