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Background: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation., Methods: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus., Results: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001)., Conclusions: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection., Clinical Trials Registration: NCT02538172., Competing Interests: Potential conflicts of interest. O. M. reports research grants from Lophius Biosciences (acquired by Mikrogen), the Novartis Foundation, and the Swiss Transplant Cohort Study; participation on a data and safety monitoring board for Syneos and in advisory boards of MSD, Biotest, and Takeda; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, paid to their institution. H. H. H. reports grants from Moderna paid to their institution; consulting fees from AiCuris, Allovir, Moderna, VeraTX, and Roche; and honoraria from VeraTX, Takeda, Biotest, and Gilead. P. J. reports serving as an unpaid member of the steering group of a trial funded by Terumo and research grants to their institution from Appili Therapeutics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The harm caused by the long interdialytic interval in three-times-per-week haemodialysis regimens (3×WHD) may relate to fluid accumulation and associated high ultrafiltration rate (UFR). Four-times-per-week haemodialysis (4×WHD) may offer a solution, but its impact on mortality, hospitalization and vascular access complications is unknown., Methods: From the AROii cohort of incident in-centre haemodialysis patients, 3×WHD patients with a UFR >10 mL/kg/h were identified. The hazard for the outcomes of mortality, hospitalization and vascular access complications in those who switched to 4×WHD compared with staying on 3×WHD was estimated using a marginal structural Cox proportional hazards model. Adjustment included baseline patient and treatment characteristics with inverse probability weighting used to adjust for time-varying UFR and cardiovascular comorbidities., Results: From 10 637 European 3×WHD patients, 3842 (36%) exceeded a UFR >10 mL/kg/h. Of these, 288 (7.5%) started 4×WHD and at baseline were more comorbid. Event rates while receiving 4×WHD compared with 3×WHD were 12.6 compared with 10.8 per 100 patient years for mortality, 0.96 compared with 0.65 per year for hospitalization and 14.7 compared with 8.0 per 100 patient years for vascular access complications. Compared with 3×WHD, the unadjusted hazard ratio (HR) for mortality on 4×WHD was 1.05 [95% confidence interval (CI) 0.78-1.42]. Following adjustment for baseline demographics, time-varying treatment probability and censoring risks, this HR was 0.73 (95% CI 0.50-1.05; P = 0.095). Despite these adjustments on 4×WHD, the HR for hospitalization remained elevated and vascular access complications were similar to 3×WHD., Conclusions: This observational study was not able to demonstrate a mortality benefit in patients switched to 4×WHD. To demonstrate the true benefits of 4×WHD requires a large, well-designed clinical trial. Our data may help in the design of such a study., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Glomerular filtration rate (GFR) is commonly used to monitor chronic kidney disease (CKD) progression, but its validity for evaluating kidney function changes over time has not been comprehensively evaluated. We assessed the performance of creatinine-based equations for estimating GFR slope according to patient characteristics and specific CKD diagnosis., Methods: In the NephroTest cohort study, we measured GFR 5324 times by chromium 51-labeled ethylenediamine tetraacetic acid renal clearance in 1955 adult patients with CKD Stages 1-4 referred to nephrologists (Stages 1-2, 19%) and simultaneously estimated GFR with both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations for isotope dilution mass spectrometry traceable creatinine; absolute and relative GFR slopes were calculated using a linear mixed model., Results: Over a median follow-up of 3.4 [interquartile range (IQR) 2.0-5.6] years, the decline in mean absolute and relative measured GFR (mGFR) and CKD-EPI and MDRD estimated GFR (eGFR) was 1.6 ± 1.2, 1.5 ± 1.4 and 1.3 ± 1.3 mL/min/1.73 m2/year and 5.9 ± 5.3, 5.3 ± 5.3 and 4.8 ± 5.2%/year, respectively; 52% and 55% of the patients had MDRD and CKD-EPI eGFR slopes within 30% of mGFR slopes. Both equations tended to overestimate the GFR slope in the youngest patients and underestimate it in the oldest, thus producing inverse associations between age and mGFR versus eGFR slope. Other patient characteristics and specific CKD diagnoses had little effect on the performance of the equations in estimating associations., Conclusions: This study shows little bias, but poor precision in GFR slope estimation for both MDRD and CKD-EPI equations. Importantly, bias strongly varied with age, possibly due to variations in muscle mass over time, with implications for clinical care and research., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: There is little information in haemodialysis (HD) patients on whether temporal changes in serum calcium, phosphate or intact parathyroid hormone (iPTH) are associated with mortality., Methods: We analysed associations of phosphate, total calcium and iPTH with all-cause and cardiovascular mortality in 8817 incident HD patients from the European second Analyzing Data, Recognizing Excellence and Optimizing Outcomes (AROii) cohort enrolled in 2007-09, which were prospectively followed for a median of 3 years, using time-dependent Cox proportional hazards models. We evaluated changes in risk over time depending on changes in phosphate, calcium or iPTH., Results: The association of phosphate and iPTH with all-cause mortality was U-shaped, with the lowest risk ranges between 1.20 and 1.89 mmol/L for phosphate and between 239 and 710 ng/L for iPTH. For total calcium, the associations were J-shaped, with an increased risk for all-cause mortality at levels >2.36 mmol/L. Lowest risk ranges for cardiovascular mortality did not change markedly for all three parameters. If iPTH was below the lowest risk range at baseline (iPTH <239 ng/L), a subsequent increase in levels was associated with improved survival. For phosphate, an increase or decrease out of the lowest risk range was associated with increased mortality risk. For calcium, this was only the case when the values increased above the lowest risk range., Conclusion: In the AROii cohort, the ranges of bone mineral biomarkers associated with the lowest mortality ranges were largely consistent with the current Kidney Disease: Improving Global Outcomes chronic kidney disease-mineral and bone disorder guideline recommendations. Allowing a suppressed iPTH to increase was associated with a lower mortality, whereas shifts of phosphate or calcium outside the lowest risk range increased mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Muscle wasting predicts mortality in patients with end-stage renal disease (ESRD), but its role in the progression of chronic kidney disease (CKD) is uncertain. We studied CKD outcomes associated with low muscle mass, assessed by urinary creatinine excretion (UCr)., Methods: The NephroTest cohort included 1429 patients with CKD stages 1-4 and both measured glomerular filtration rate (mGFR) (by (51)Cr-EDTA) and estimated glomerular filtration rate (eGFR) (by CKD-Epidemiology Collaboration equation). We used cause-specific Cox models to estimate hazard ratios (HRs) for the competing risks of ESRD and death associated with gender-specific UCr quartiles., Results: UCr was 13.6 ± 3.2 mmol/24 h (0.17 ± 0.05 mmol/kg/24 h) in men and 9.2 ± 2.1 (0.14 ± 0.05) in women. It was positively associated with mGFR, but not with eGFR. Over a median follow-up of 3.6 (2.1-5.8) years, 229 patients developed ESRD and 113 patients died before ESRD. Compared with patients in the highest UCr quartile, those in the lowest quartile had a higher crude HR (95% confidence interval) for pre-ESRD death: 4.3 (2.4-7.7), which was weakened, but remained statistically significant, independent of demographics, mGFR and several other factors: 2.1 (1.04-4.3). Their crude ESRD risk was not higher: HR: 0.95 (0.65-1.4), and even tended to be lower after adjusting for mGFR and log-proteinuria: HR: 0.70 (0.45-1.1). Adjustment for eGFR instead of mGFR reversed this relationship: HR: 1.7 (1.1-2.7)., Conclusions: In early stage CKD, low UCr is associated with higher risk for mortality, but not for ESRD. Using creatinine-based equation to adjust for GFR may bias the relationship of UCr with ESRD risk., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Glomerular filtration rate (GFR) estimating equations using the combination of creatinine and cystatin C (eGFRcr-cys) are more accurate than equations using either alone (eGFRcr or eGFRcys). New guidelines suggest measuring cystatin C as a confirmatory test when eGFRcr may be inaccurate, but do not specify demographic or clinical conditions in which eGFRcys or eGFRcr-cys are more accurate than eGFRcr nor which estimate to use in such circumstances., Methods: We compared the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 1119 subjects in the CKD-EPI cystatin C external validation dataset. Subgroups were defined by eGFRcr, age, sex, diabetes status and body mass index (BMI). The reference test was GFR measured using urinary or plasma clearance of exogenous filtration markers. Cystatin C and creatinine assays were traceable to primary reference materials. Accuracy was defined as the absolute difference in eGFR compared with mGFR., Results: The mean mGFR was 70 ± 41 (SD) mL/min/1.73 m(2). eGFRcys was more accurate than eGFRcr at lower BMI and less accurate at higher BMI, especially at higher levels of eGFRcr. There were small differences in accuracy in people according to the diabetes status. eGFRcr-cys was as accurate or more accurate than eGFRcr or eGFRcys in these and all other subgroups., Conclusions: eGFRcr-cys, but not eGFRcys, is more accurate than eGFRcr in most subgroups we studied, suggesting preferential use of eGFRcr-cys when serum cystatin C is measured as a confirmatory test to obtain more accurate eGFR. Further studies are necessary to evaluate diagnostic strategies for using eGFRcys and eGFRcr-cys., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Context: Vitamin D deficiency is common in patients with chronic kidney disease (CKD). Current guidelines recommend treatment strategies in these patients similar to those for the general population, but the vitamin D nutritional status sufficient to prevent PTH levels from increasing in CKD is unknown. OBJECTIVE, MAIN OUTCOME MEASURE: Our aim was to study the relation between circulating PTH and 25(OH)D levels and to search for a 25(OH)D threshold associated with a significant PTH increase., Design, Setting, and Patients: In the hospital-referred NephroTest cohort study, we measured 25(OH)D, PTH, and glomerular filtration rate (mGFR) by ⁵¹Cr-EDTA renal clearance in 929 adult patients with nondialysis CKD stages 1 to 5 and no vitamin D supplementation. Patients' mean age was 60.1 ± 14.7 years; 71% were men, and 9% were black. Their median mGFR was 37.8 mL/min/1.73 m²., Results: We found a 25(OH)D threshold of 8 ng/mL with an upper limit of 20 ng/mL (95% confidence interval) by linear piecewise regression modeling of log-PTH for 25(OH)D adjusted for mGFR, age, race, and ionized calcium level. The smoothed curve confirmed that PTH concentration rose steeply when circulating 25(OH)D levels fell to less than 20 ng/mL., Conclusions: Spontaneous 25(OH)D levels greater than 20 ng/mL seem sufficient to control serum PTH in CKD patients. This result reinforces guidelines to supplement vitamin D only if less than 30 ng/mL.

Aims: Fabry disease is a lysosomal storage disorder due to deficient alpha-galactosidase A activity, characterised by glycosphingolipids deposition in tissues. Patients have a common arterial involvement and contract progressive renal and cardiac disease. Although short-term effects of enzyme replacement therapy (ERT) on target organs have been established, no data are available on the long-term outcome., Methods and Results: We studied the effects of ERT (agalsidase beta, 1 mg/kg/14 days) on arterial and cardiac structure and function during a longitudinal study beginning in 1999, with 4.5 ± 0.4 years follow-up (four visits) in 30 patients (age: 33 ± 12 years). In addition, we studied 16 untreated Fabry patients during 2.6 ± 1.6 years (two visits). Aortic stiffness was determined by carotid-femoral pulse wave velocity, central pulse pressure by aplanation tonometry, and carotid and radial intima-media thickness and diameter by high definition echotracking device. Left ventricular mass was determined by MRI. A significant decrease in aortic stiffness (-0.56 ± 0.13 m/s/yr, p = 0.0002) was observed after ERT whereas central pulse pressure did not change. Carotid intima-media thickness (IMT) increased (+18 ± 6 µm/yr; p < 0.005) whereas radial IMT remained stable. Radial artery diameter decreased (-50 ± 20 µm/years, p < 0.05) whereas carotid diameter did not change. Carotid circumferential wall stress was reduced (-1.7 ± 0.6 kPa/yrs, p < 0.01). Left ventricular mass index significantly decreased (-7.8 ± 2.3 g/m(2)/yr, p < 0.005)., Conclusion: A sustained reduction in aortic stiffness and left ventricular hypertrophy, and a limited radial artery wall thickening were observed after long-term enzyme replacement therapy. There was no significant benefit of treatment on carotid hypertrophy.

Background: Little is known about normal kidney function level and the prognostic significance of low estimated glomerular filtration rate (eGFR) in the elderly., Methods: We determined age and sex distribution of eGFR with both the Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 8705 community-dwelling elderly aged ≥ 65 years and studied its relation to 6-year mortality. In a subsample of 1298 subjects examined at 4 years, we assessed annual eGFR decline and clinically relevant markers including microalbuminuria (3-30 mg/mmol creatinine) with diabetes, proteinuria ≥ 50 mg/mmol, haemoglobin <11 g/L or resistant hypertension despite three drugs., Results: Median (interquartile range) MDRD eGFR was 78 (68-89) mL/min/1.73 m(2) in men and 74 (65-83) in women; there were 79 (68-87) and 77 (67-85) for CKD-EPI eGFR, respectively. Prevalence of MDRD eGFR <60 mL/min/1.73 m(2) was 13.7% and of CKD-EPI eGFR was 12.9%. After adjustment for several confounders, only those with an eGFR <45 mL/min/1.73 m(2) had significantly higher all-cause and cardiovascular mortality than those with an eGFR of 75-89 mL/min/1.73 m(2) whatever the equation. In the subsample men and women with an MDRD eGFR of 45-59 mL/min/1.73 m(2), 15 and 13% had at least one clinical marker and 15 and 3% had microalbuminuria without diabetes, respectively; these percentages were 41 and 21% and 23 and 10% in men and women with eGFR <45, respectively. Mean MDRD eGFR decline rate was steeper in men than in women, 1.75 versus 1.41 mL/min/1.73 m(2)/year., Conclusions: Moderately decreased eGFR is more often associated with clinical markers in men than in women. In both sexes, eGFR <45 mL/min/1.73 m(2) is related to poor outcomes. The CKD-EPI and the MDRD equations provide very similar prevalence and long-term risk estimates in this elderly population.

Background: Glomerular filtration rate (GFR) decline with age increases the risk of inappropriate dosing of drugs. We investigated the determinants and the mortality associated with the use of drugs that are contraindicated or require dose adjustment according to kidney function among the community-dwelling elderly., Methods: The Three-City population-based study included 8701 participants ≥65 years from 1999 to 2001. Exposure to the risk of inappropriate drug dosage was defined as reported use of either a contraindicated drug or one requiring dose adjustment according to the individual baseline glomerular filtration rate estimated (eGFR) with the Modification of Diet in Renal disease study equation. Six-year mortality was analysed using Cox models adjusted for several sociodemographic, biologic and clinical risk factors., Results: The overall percentage of exposure to the risk of inappropriate drug use was 13.3% (contraindication, 0.8%): it was 52.5% (4.5%) in those with an eGFR of 30-59 and 96% (48%) in those <30 mL/min/1.73 m(2). Antihypertensive agents, fibrates and psycholeptics accounted for most of the drugs with dosing recommendations and antidiabetic agents and antihistamines for those contraindicated. Individuals at risk were more likely to be men, older, and under treatment for hypertension or hypercholesterolemia. Exposure to either risk was independently related to higher all-cause mortality (hazard ratio 1.4, 95% confidence interval 1.0-1.9) in participants with eGFR <60 mL/min/1.73 m(2)., Conclusions: Contraindicated drug prescription was uncommon but >10% of the population took drugs requiring renal dosing adjustments. Regular monitoring of eGFR may prevent excess mortality associated with inappropriate drug prescription in the elderly.

Background: Damages to large arteries are related to bone disease in end-stage renal disease and contribute to cardiovascular mortality. An outward remodeling and stiffening of carotid artery already exist at an earlier stage of chronic kidney disease (CKD). We made the hypothesis that bone disease could be associated with the carotid outward remodeling in parallel with the decline of renal function in this population., Methods: One hundred and seven patients (60.4 +/- 14.6 years) with CKD (mean glomerular filtration rate = 34 +/- 17 mL/min/1.73 m(2)) were included in this cross-sectional study. Common carotid artery diameter, intima-media thickness and carotid stiffness were determined with an echotracking system. Bone evaluation was performed by bone densitometry and the measurement of a bone-remodeling marker, bone-specific alkaline phosphatase (BSALP)., Results: After adjustment for age, sex, mean blood pressure, carotid pulse pressure and glomerular filtration rate, bone mineral densities measured at the radius, hip and lumbar spine were significantly and negatively correlated with carotid internal diameter (P = 0.0001, P = 0.0003, P = 0.01, respectively). This association exists only in patients with glomerular filtration rate < or =38 mL/min/ 1.73 m(2). BSALP was independently and positively correlated with carotid internal diameter and explained 13% of the variance., Conclusions: Bone mineral density and serum marker of bone remodeling are independently correlated with arterial remodeling in CKD patients suggesting a crosstalk between kidney, arterial wall and bone.

Background: The long-term risk of chronic kidney disease (CKD) in lithium (Li)-treated patients has been well established in the recent years., Methods: We have evaluated GFR and serum calcium monitoring in 1179 Li-treated outpatients from an ambulatory laboratory database study. This has been performed in a single private laboratory in Paris from February 1997 to December 2004. Estimated GFR (eGFR) has been calculated using the abbreviated MDRD equation., Results: During an 8-year period, 695 patients (59%) had at least one serum creatinine measurement, whereas 484 had no creatinine measurement. The former group had also more frequent serum Li measurements. Mean serum lithium levels, were similar in both groups, 0.65 mmol/l vs 0.62 mmol/l. The percentage of patients with CKD stage 3 (eGFR 30-59 ml/min/1.73 m(2)) were 36%, 53%, 73% and 77%, and with CKD stage 4, 3%, 5%, 5%, 8% in patients aged 20-39, 40-59, 60-69, and > or = 70 years respectively. There was no significant rise in creatinine measurements (from 35% of the patients with at least one serum creatinine in 2003 to 39% in 2004; P = 0.66) despite intervention to intensify GFR monitoring by physicians. Serum calcium was tested at least once in 212 patients (18%) of whom 15 (7%) were found with hypercalcaemia., Conclusion: A very high percentage of Li-treated outpatients have low eGFR. GFR monitoring is neglected in these patients, the majority of whom are no longer attending specialized clinics. Hypercalcaemia is less common but serum calcium monitoring is even more neglected. Ambulatory laboratory database surveillance provides a powerful means to contribute to CKD screening and monitoring.