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Background: The glomerular filtration rate (GFR) is estimated by the serum or plasma concentration of creatinine and/or cystatin C using equations that include demographic data. The equations worldwide most widely used are those of the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) consortium and updated in 2021 to remove the Afro‐American racial correction factor. In 2021 and then in 2023, the European Kidney Function Consortium also developed equations based on creatinine and cystatin C, usable across the full age spectrum, and constructed by including the Q value (i.e. the median creatinine or cystatin C in healthy men and women, which is customizable for specific populations). Methods: The aim of this narrative review is to examine the strengths and weaknesses of each biomarker. Results: Both biomarkers have non‐GFR determinants, namely muscle mass, protein intake and tubular secretion for creatinine; dysthyroidism and systemic corticosteroids for cystatin C, as well as other more debated determinants (diabetes, obesity, proteinuria, inflammatory syndrome). These non‐GFR determinants are the reason why no equation based on a single endogenous biomarker has an accuracy within 30% greater than 90% over the entire age spectrum (in at least one patient in 10, estimated GFR is at least 30% higher or at least 30% lower than the measured GFR). Conclusion: Equations combining the two biomarkers provide a better estimate of GFR, particularly in the subgroup of patients whose estimates based on each of the biomarkers are highly discordant. These patients must also be identified as being at increased risk of morbidity, particularly cardiovascular, and mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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). Results 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%). Conclusions 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. [ABSTRACT FROM AUTHOR]

Of the glomerulonephritis associated with sarcoidosis, membranous nephropathy (MN) is the most prevalent. Coincidence or a causal relationship between these two diseases is unclear. Here, we present for the first time a high prevalence of PLA2R-related MN among patients with MN associated with active sarcoidosis. Our results suggest some causal link between sarcoidosis and PLA2R-related MN. Detection of anti-PLA2R antibodies in serum or PLA2R antigen in biopsy should not be taken as evidence against a secondary cause, particularly sarcoidosis. This important observation can affect treatment decision in these patients. [ABSTRACT FROM AUTHOR]

Background: The association between sarcoidosis and glomerular diseases has not been extensively investigated in a large series and the potential features of this uncommon association remain to be determined. Methods: We retrospectively identified 26 patients with biopsy-proven glomerular lesions that occurred in a sarcoidosis context. Potential remission of glomerular disease and sarcoidosis under specific treatment (steroid and/or immunosuppressive agents) was recorded for all patients. Demographic, clinical and biological characteristics were assessed at the time of kidney biopsy for each patient. Therapeutic data were analyzed for all patients. Results: Glomerular disease occurred after the diagnosis of sarcoidosis in 11 of 26 cases (42%) (mean delay of 9.7 years). In six patients (23%), the glomerulopathy preceded the sarcoidosis diagnosis (mean delay 8 years). In the last nine patients (35%), both conditions occurred simultaneously. The most frequent glomerular disease occurring in sarcoidosis patients was membranous nephropathy in eleven cases. Other glomerular lesions included IgA nephropathy in six cases, focal segmental glomerulosclerosis in four patients, minimal change nephrotic syndrome for three patients and proliferative lupus nephritis in two patients. Granulomatous interstitial nephritis was associated with glomerular disease in six patients and was exclusively found in patients in whom the both disease occurred simultaneously. In nine patients with simultaneous glomerular and sarcoidosis diseases, we observed a strong dissociation between glomerular disease and sarcoidosis in terms of steroid responsiveness. At the end of the follow-up (mean of 8.4 years), six patients had reached end-stage renal disease and three patients had died. Conclusions: A wide spectrum of glomerular lesions is associated with sarcoidosis. The close temporal relationship observed in some patients suggests common causative molecular mechanisms of glomerular injury but complete remission of both diseases in response to exclusive steroid therapy is infrequent [ABSTRACT FROM AUTHOR]

Creatinine-based estimated glomerular filtration rate (eGFR) is imprecise at individual level, due to non-GFR-related serum creatinine determinants, including atypical muscle mass. Cystatin C has the advantage of being independent of muscle mass, a feature that led to the development of race- and sex-free equations. Yet, cystatin C–based equations do not perform better than creatinine-based equations for estimating GFR unless both variables are included together. The new race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation had slight opposite biases between Black and non-Black subjects in the USA, but has poorer performance than that the previous version in European populations. The European Kidney Function Consortium (EKFC) equation developed in 2021 can be used in both children and adults, is more accurate in young and old adults, and is applicable to non-white European populations, by rescaling the Q factor, i.e. population median creatinine, in a potentially universal way. A sex- and race-free cystatin C–based EKFC, with the same mathematical design, has also be defined. New developments in the field of GFR estimation would be standardization of cystatin C assays, development of creatinine-based eGFR equations that incorporate muscle mass data, implementation of new endogenous biomarkers and the use of artificial intelligence. Standardization of different GFR measurement methods would also be a future challenge, as well as new technologies for measuring GFR. Future research is also needed into discrepancies between cystatin C and creatinine, which is associated with high risk of adverse events: we need to standardize the definition of discrepancy and understand its determinants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The association between sarcoidosis and glomerular diseases has not been extensively investigated in a large series and the potential features of this uncommon association remain to be determined.Methods: We retrospectively identified 26 patients with biopsy-proven glomerular lesions that occurred in a sarcoidosis context. Potential remission of glomerular disease and sarcoidosis under specific treatment (steroid and/or immunosuppressive agents) was recorded for all patients. Demographic, clinical and biological characteristics were assessed at the time of kidney biopsy for each patient. Therapeutic data were analyzed for all patients.Results: Glomerular disease occurred after the diagnosis of sarcoidosis in 11 of 26 cases (42%) (mean delay of 9.7 years). In six patients (23%), the glomerulopathy preceded the sarcoidosis diagnosis (mean delay 8 years). In the last nine patients (35%), both conditions occurred simultaneously. The most frequent glomerular disease occurring in sarcoidosis patients was membranous nephropathy in eleven cases. Other glomerular lesions included IgA nephropathy in six cases, focal segmental glomerulosclerosis in four patients, minimal change nephrotic syndrome for three patients and proliferative lupus nephritis in two patients. Granulomatous interstitial nephritis was associated with glomerular disease in six patients and was exclusively found in patients in whom the both disease occurred simultaneously. In nine patients with simultaneous glomerular and sarcoidosis diseases, we observed a strong dissociation between glomerular disease and sarcoidosis in terms of steroid responsiveness. At the end of the follow-up (mean of 8.4 years), six patients had reached end-stage renal disease and three patients had died.Conclusions: A wide spectrum of glomerular lesions is associated with sarcoidosis. The close temporal relationship observed in some patients suggests common causative molecular mechanisms of glomerular injury but complete remission of both diseases in response to exclusive steroid therapy is infrequent. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their TTR variants: ATTRV122I (37%), ATTRV30M (29%), and other variants (34%). Median baseline eGFR was 78 ml/min/1.73 m2. Seventy-two patients (31%) had an eGFR below 60 ml/min/1.73m2 and 27/137 patients (20%) had significant proteinuria (urine protein/creatinine ratio ≥30 mg/mmol). Renal biopsy, performed in four cases, found typical Congo red-positive and TTR-labelled amyloid deposits in all cases. Older age (OR 1.07, p <.001) and a prior history of hypertension (OR 2.09, p =.04) were associated with a higher prevalence of CKD at baseline, whereas higher left ventricular global longitudinal strain (LVGLS) (OR 0.83, p <.001) was associated with a lower prevalence. The estimated change in eGFR was −7.12 [−9.61, −4.63] and −8.21 [−10.81, −5.60] ml/min/1.73 m2 after 12 and 24 months of follow-up, respectively. eGFR decline was independently associated with older age ((67–74], coefficient= −14.35 mL/min/1.73 m2, p <.01, >74, coefficient = −22.93 mL/min/1.73 m2, p <.001, versus <56), ATTRV122I (coefficient = −17.17 mL/min/1.73m2, p <.01, versus ATTRV30M) and LVGLS (coefficient = 1.22, p <.01). These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function. [ABSTRACT FROM AUTHOR]

Context: Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective: We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Summary: The long‐term consequences of pre‐eclampsia (PrE) for renal function have never been determined in patients with sickle cell disease (SCD). Between 2008 and 2015, we screened 306 pregnancies in women with SCD and identified 40 with PrE (13%). The control group consisted of 65 pregnant SCD patients without PrE. In multivariable analysis, PrE events were associated with an increase of 1 log of lactate dehydrogenase level (adjusted odds ratio, aOR = 3·83, P = 0·05), a decrease of 10 g/l of haemoglobin levels (aOR = 2·48, P = 0·006) and one or more vaso‐occlusive crisis during pregnancy (aOR = 16·68, P = 0·002). Estimated glomerular filtration rate (eGFR) was similar in the two groups at steady state but was significantly lower in the PrE group after one year of follow‐up and at last follow‐up (130 vs 148 ml/min/1·73 m2, P < 0·001 and 120 vs 130 ml/min/1·73 m2, P < 0·001, respectively). In multivariable analysis, eGFR had returned to steady‐state levels one year after pregnancy in patients without PrE but continued to decrease in patients with PrE (β = −18·15 ml/min/1·73 m2, P < 0·001). This decline was more marked at the end of follow‐up (β = −31·15 ml/min, P < 0·001). In conclusion, PrE episodes are associated with a significant risk of subsequent renal function decline in SCD patients. [ABSTRACT FROM AUTHOR]

Aims: This prospective study aimed to develop a population pharmacokinetics (PK) model of hydroxyurea (HU) in patients with sickle cell disease. This model can be used to determine the impact of glomerular filtration rate (GFR) on HU kinetics. Methods: We included 30 patients. They underwent HU pharmacokinetics analyses of plasma and urine. Six underwent PK analyses in 2 periods with and without angiotensin‐converting enzyme inhibitor. HU was assayed with a validated high‐performance liquid chromatography‐UV method. Noncompartmental PK analysis was conducted and a population PK model built with Monolix. This model was validated externally on another 56 patients. HU PK was simulated as a function of GFR. Results: The HU PK model was constructed as a 2‐compartment model with first‐order absorption and elimination. The quality criteria were good, including for external validation. We found that estimated GFR (eGFR) and body weight affected HU PK, with lower eGFR or body weight associated with a higher HU area under the curve. We recommend the monitoring of HU through eGFR and body weight, which together account for 47% of its variability. Urinary HU fractions and renal clearance were higher in the glomerular hyperfiltration group and lower in the moderate chronic kidney disease group, respectively. No differences in nonrenal HU clearance were observed. Conclusion: Estimated GFR has an impact on the kinetics of hydroxyurea, and HU dose should be adapted accordingly. Angiotensin‐converting enzyme inhibitor seems to have minor effect on HU PK in adults with sickle cell disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]