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Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. The 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI2009) was recommended worldwide until 2021, when it was recalibrated to remove the African-American race factor. The CKD-EPI2009 and CKD-EPIcr2021 equations overestimate GFR of adults aged 18–30 years, with a strong overestimation in estimated GFR (eGFR) at age 18 years. CKD-EPICr2021 does not perform better than CKD-EPI2009 in US population, overestimating GFR in non-Black subjects, and underestimating it in Black subjects with the same magnitude. CKD-EPICr2021 performed worse than the CKD-EPI2009 in White Europeans, and provides no or limited performance gains in Black European and Black African populations. The European Kidney Function Consortium (EKFC) equation, which incorporates median normal value of serum creatinine in healthy population, overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. The new EKFC equation based on cystatin C (EKFCCC) shares the same mathematical construction, namely, it incorporates the median cystatin C value in the general population, which is independent of sex and ethnicity. EKFCCC is therefore a sex-free and race-free equation, which performs better than the CKD-EPI equation based on cystatin C. Despite advances in the field of GFR estimation, no equation is perfectly accurate, and GFR measurement by exogenous tracer clearance is still required in specific populations and/or specific clinical situations.

Background Patients with end‐stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT). Methods In a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross‐sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross‐sectional area normalized for height2, reported in cm2/m2) and MD (mean attenuation of muscle cross‐sectional area, expressed in Hounsfield units). We determined age‐specific and sex‐specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival. Results Among the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm2/m2 in men and 42.3 ± 7.3 cm2/m2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22–12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30–10.7, P = 0.015), and body mass index > 25 kg/m2 (aOR 2.94, 95% CI: 1.4–6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06–4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02–4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03–1.09, P = 0.0003). Low SMI was not associated with mortality. Conclusions Myosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT.

Background Computed tomography (CT) scan–defined myosteatosis is a common feature in ESKD patients receiving kidney transplantation (KT) and is associated with mortality after KT. We aimed to explore the impact of myosteatosis and other CT scan based morphometric data on the occurrence of early surgical complications after KT. Methods We retrospectively measured on an unenhanced cross‐sectional CT scan taken at the middle of the third lumbar vertebra performed within the previous year or at the time of KT: surface muscle index (total lumbar cross‐sectional muscle area [CSMA] divided by height squared), subcutaneaous adipose tissue index, visceral adipose tissue index and muscle density (MD: mean CT attenuation of CSMA). Vessel to skin distance was the distance between iliac vein and skin. Myosteatosis was defined as MD below age‐ and sex‐specific normal values. Logistic regression models were constructed to identify predictive factor of 90 days postoperative surgical complications with Clavien–Dindo score greater than or equal to 2, CD ≥ 2). Results Among the N = 200 patients, 61.5% were male with a mean age of 54.8 (± 13.8) years and a mean BMI of 25.1 (± 4.4) kg/m2. Sixty patients (30%) developed at least one postoperative complication (CD ≥ 2) in the first 3 months after KT. In two different multivariate analyses, MD (aOR: 0.95 for one Hounsfield unit increase, 95% CI: 0.91–0.99, p = 0.028) and myosteatosis status (aOR: 4.64, 95% CI: 2.18–9.90, p < 0.0001) were the only independent risk factors for postsurgical complication. Conclusions Myosteatosis is independently associated with the occurrence of CD ≥ 2 postoperative complication within 90 days of surgery.

Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective.

Albuminuria is considered to be a relevant biomarker for the detection of early glomerular damage in patients with sickle cell disease (SCD). Improvements in our understanding of the pathophysiological processes and molecular mechanisms underlying albuminuria are required, because increasing numbers of patients with SCD are developing chronic kidney disease. The early recognition of sickle cell nephropathy (SCN) and studies of the natural course of this emerging renal disease are therefore crucial, together with identification of the associated clinical and biological risk factors, to make it possible to initiate kidney-protective therapy at early stages of renal impairment. The pathophysiological process underlying SCN remains hypothetical, but chronic haemolysis-related endothelial dysfunction and the relative renal hypoxia triggered by repeated vaso-occlusive crises have been identified as two potential key factors. The optimal preventive and curative management of albuminuria in the context of SCD is yet to be established, but recent studies have suggested that hydroxyurea therapy, the cornerstone of SCD treatment, could play a key role in reducing albuminuria. The place of conventional kidney-protecting measures, such as renin–angiotensin system inhibitors, in the treatment of SCD patients also remains to be determined.

The induction of specific and sustainable tolerance is a challenging issue in organ transplantation. The discovery of the immunosuppressive properties of apoptotic cells in animal models has paved the way for their use in human transplantation. In this work, we aimed to define a stable, reproducible, and clinically compatible production procedure of human apoptotic cells (Apo-cells). Using a clinically approved extracorporeal photopheresis technique, we have produced and characterized phenotypically and functionally human apoptotic cells. These Apo-cells have immunosuppressive properties proved and in NOD/SCID/γC mice by their capacity to modulate an allogeneic response following both a direct and an indirect antigen presentation. These results brought the rationale for the use of Apo-cells in tolerance induction protocol for organ transplantation.

Background Inter-individual variations of non-glomerular filtration rate (GFR) determinants of serum creatinine, such as muscle mass, account for the imperfect performance of estimated GFR (eGFR) equations. We aimed to develop an equation based on creatinine and total lumbar muscle cross-sectional area measured by unenhanced computed tomography scan at the third lumbar vertebra. Methods The muscle mass–based eGFR (MMB-eGFR) equation was developed in 118 kidney donor candidates (iohexol clearance) using linear regression. Validation cohorts included 114 healthy subjects from another center (51Cr-EDTA clearance, validation population 1), 55 patients with chronic diseases (iohexol, validation population 2), and 60 patients with highly discordant creatinine and cystatin C–based eGFR, thus presumed to have atypical non-GFR determinants of creatinine (51Cr-EDTA, validation population 3). Mean bias was the mean difference between eGFR and measured GFR, precision the standard deviation (SD) of the bias, and accuracy the percentage of eGFR values falling within 20% and 30% of measured GFR. Results In validation population 1, performance of MMB-eGFR was not different from those of CKD-EPICr2009 and CKD-EPICr2021. In validation population 2, MMB-eGFR was unbiased and displayed better precision than CKD-EPICr2009, CKD-EPICr2021 and EKFC (SD of the biases: 13.1 vs 16.5, 16.8 and 15.9 mL/min/1.73 m2). In validation population 3, MMB-eGFR had better precision and accuracy {accuracy within 30%: 75.0% [95% confidence interval (CI) 64.0–86.0] vs 51.5% (95% CI 39.0–64.3) for CKD-EPICr2009, 43.3% (95% CI 31.0–55.9) for CKD-EPICr2021, and 53.3% (95% CI 40.7–66.0) for EKFC}. Difference in bias between Black and white subjects was −2.1 mL/min/1.73 m2 (95% CI −7.2 to 3.0), vs −8.4 mL/min/1.73 m2 (95% CI −13.2 to −3.6) for CKD-EPICr2021. Conclusion MMB-eGFR displayed better performances than equations based on demographics, and could be applied to subjects of various ethnic backgrounds. Lay Summary Performances of creatinine- and demographic-based estimated glomerular filtration rate (eGFR) equations are insufficient in patients for whom non-GFR determinants of serum creatinine level, including low or high muscle masses, are not standard. The total lumbar muscle cross-sectional area (MCSA) taken at the middle of the third lumbar vertebra, and easily measured from unenhanced computed tomography (CT) scan images, is a surrogate marker of total body muscle mass. The muscle mass–based eGFR equation (MMB-eGFR, which included plasma creatinine and MCSA) displayed better performances than conventional creatinine-based eGFR equations in patients with chronic diseases, especially if they had atypical muscle mass. MMB-eGFR performance, including its bias, is only marginally affected by ethnicity. For patients who have CT scans as part of their medical follow-up (especially patients with chronic diseases and thus at risk for sarcopenia), the MMB-eGFR equation might offer the possibility of a more personalized eGFR, without additional cost. Graphical Abstract Graphical Abstract

Creatinine clearance after cimetidine administration (Cim-CreatClr) was once proposed as a method of glomerular filtration rate (GFR) measurement, but has been largely abandoned. We investigated whether a new short procedure for Cim-CreatClr determination could be considered an appropriate method for GFR measurement. A 150-min protocol involving oral cimetidine administration was developed to determine Cim-CreatClr. In total, 168 patients underwent simultaneous assessments of creatinine clearance before and after cimetidine administration [basal creatinine clearance (Basal-CreatClr) and Cim-CreatClr, respectively], renal iohexol clearance and plasma iohexol clearance (R-iohexClr and P-iohexClr, respectively). We compared the agreement between the various methods of GFR measurement, using Bland-Altman plots to determine biases, precisions (standard deviation of the biases) and accuracy (proportions of GFR values falling within 10, 15 and 30% of the mean: P10, P15 and P30, respectively). After cimetidine administration, Basal-CreatClr decreased by 19.8% [95% reference limits of agreement (95% LoA): -2.2 to 41.7%]. The bias between Cim-CreatClr and P-iohexClr was -0.6% (95% LoA -26.8 to 28%); the precision was 14.0%; P10, P15 and P30 were 57.1% [95% confidence interval (95% CI) 49.3 to 64.7%], 73.2% (95% CI 65.8 to 79.7%) and 97.0% (95% CI 93.2 to 99.0%), respectively. Due to the positive bias (16.7%; 95% LoA -3.6 to 36.9%) of Cim-CreatClr relative to R-iohexClr, accuracy of Cim-CreatClr relative to R-iohexClr was poor despite a good precision (10.3%). Our study shows a high level of agreement between Cim-CreatClr and P-iohexClr. These results suggest that this short Cim-CreatClr procedure is a valid method for GFR measurement, which might be useful, in particular, in situations in which P-iohexClr is not suitable or not available.

Epidemiology of opportunistic infections (OI) after kidney allograft transplantation in the modern era of immunosuppression and the use of OI prevention strategies are poorly described. We retrospectively analyzed a single-center cohort on kidney allograft adult recipients transplanted between January 2008 and December 2013. The control group included all kidney recipients transplanted in the same period, but with no OI. We analyzed 538 kidney transplantations (538 patients). The proportion of OI was 15% (80 and 72 patients). OI occurred 12.8 (6.0–31.2) months after transplantation. Viruses were the leading cause (n = 54, (10%)), followed by fungal (n = 15 (3%)), parasitic (n = 6 (1%)), and bacterial (n = 5 (0.9%)) infections. Independent risk factors for OI were extended criteria donor (2.53 (1.48–4.31), p = 0.0007) and BK viremia (6.38 (3.62–11.23), p < 0.0001). High blood lymphocyte count at the time of transplantation was an independent protective factor (0.60 (0.38–0.94), p = 0.026). OI was an independent risk factor for allograft loss (2.53 (1.29–4.95), p = 0.007) but not for patient survival. Post-kidney transplantation OIs were mostly viral and occurred beyond one year after transplantation. Pre-transplantation lymphopenia and extended criteria donor are independent risk factors for OI, unlike induction therapy, hence the need to adjust immunosuppressive regimens to such transplant candidates.