bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4085 POLY(ADP-RIBOSE) POLYMERASE 1 AFFECTS THE VASOPRESSIN-MEDIATED AQP2 EXPRESSION VIA AN INTERACTION WITH BETA-CATENIN
Authors: Jang Hyo-Ju , Park Eui-Jung , Jung Hyun Jun , Kwon Tae-Hwan 
Published: June 2023

Abstract

Background and Aims
Poly(ADP-ribosy)lation (PARylation), which is mediated by poly(ADP-ribose) polymerases (PARPs), catalyzes the transfer of ADP-ribose from NAD+ molecules to acceptor proteins, regulates diverse cellular processes. Since PARP1 gene-deficient mice revealed an increase in urine volume, we aimed to examine the role of PARP1, the most abundant type of protein in the PARPs family, in the vasopressin-mediated AQP2 regulation.

Method
1) Immunoblotting for PARP1 in mpkCCDc14 cells; 2) Pulldown assay of biotin-conjugated NAD+ and immunoprecipitation (IP) assay using poly(ADP-ribose) (PAR) antibody; 3) qRT-PCR and immunoblotting for AQP2; and 4) Bioinformatics for elucidating PARP1-interacting proteins in kidney collecting duct (CD) cells.

Results
Immunoblots showed that dDAVP treatment (10−9 M, 2 h, 6 h, 24 h, and 48 h) induced the cleavage of PARP1 (both 89 kDa and 25 kDa) in mpkCCDc14 cells. dDAVP treatment (10−9 M, 24 h) also increased the abundance of total PARylated proteins in biotin-NAD+ pulldown and IP assay of PAR in mpkCCDc14 cells. On the other hand, siRNA-mediated PARP1 knockdown significantly attenuated the dDAVP-induced mRNA and protein abundance, suggesting a role of PARP1 in AQP2 regulation. PARP1 cleavage induced by dDAVP was not changed under PARP1 knockdown, indicating that PARP1 cleavage is unlikely to be involved in AQP2 regulation. In contrast to PARP1 knockdown, PARP1 inhibitor (PJ34) did not reduce the dDAVP-induced AQP2 abundance, despite the significant decrease in the PARylation. The results suggest that dDAVP-regulated AQP2 expression is associated with PARP1 protein per se, but not with PARP1-mediated PARylation. Bioinformatics study revealed that 408 proteins interact with PARP1 in the kidney CD cells. Among them, 49 proteins were mapped on the vasopressin V2 receptor (V2R) signaling pathway. In particular, β-catenin, which is phosphorylated (S552) by dDAVP, was identified as the PARP1-interacting protein mapped on the V2R signaling. Immunoblotting demonstrated that siRNA-mediated knockdown of PARP1 was associated with decreased dDAVP-induced phosphorylation of β-catenin at S552 in mpkCCDc14 cells.

Conclusion
PARP1 is likely to play a role in vasopressin-mediated AQP2 regulation via the protein interaction with β-catenin rather than PARylation of proteins and/or PARP1 cleavage in the kidney CD cells.
#4097 BASELINE CHARACTERISTICS OF THE KOREAN GENETIC COHORT OF INHERITED CYSTIC KIDNEY DISEASE
Authors: Cho Jeong Min , Park Hayne Cho , Lee Jin Woo , Ryu Hyunjin , Kim Yong Chul , Ahn Curie , Lee Kyu-Beck , Kim Yeong Hoon , Han Seungyeup , Kim Yaerim , Bae Eun Hui , Oh Kook-Hwan , Oh Yun Kyu 
Published: June 2023

Abstract

Background and Aims
We report the baseline and genetic characteristics of the nationwide genetic cohort for Korean hereditary cystic kidney disease prior to detailed molecular analysis.

Method
We performed a 3-year prospective, multicenter cohort study at 9 hospitals from May 2019 to May 2022. Patients with more than 3 renal cysts were enrolled and classified into 3 categories: typical and atypical autosomal dominant polycystic kidney disease (ADPKD), and pediatric PKD. Clinical and genetic characteristics were compared among categories. Genetic analysis was performed by using gene panel comprised of 89 ciliopathy-related genes.

Results
A total of 798 patients were enrolled. Mean age was 42.7 ± 17.3 years, and 47.8% were male. Patients were categorized into typical ADPKD (560, 70.2%), atypical ADPKD (165, 20.7%), and pediatric PKD (73, 9.1%). Typical ADPKD by Mayo imaging classification (MIC) I was as follows: 1A 55 (9.9%), 1B 149 (26.9%), 1C 198 (35.8%), 1D 90 (16.3%), and 1E 61 (11.0%) (n = 553). Atypical ADPKD by MIC II included bilateral cystic with bilateral atrophic (31, 37.3%), lopsided (27, 32.5%), unilateral (9, 10.8%), segmental (8, 9.6%), bilateral cystic with unilateral atrophic (7, 8.4%), and asymmetric (1, 1.2%). The mean age was lower in the typical ADPKD group compared to atypical group (45.3 ± 13.3 vs. 48.9 ± 15.8, p = 0.003). Height-adjusted total kidney volume was greater in the typical group than atypical group (947.4 ± 762.5 mL/m vs. 528.2 ± 587.6 mL/m, p&lt;0.001). Pathogenic variants were found in 57.3% of the patients by ciliopathy-related gene panel. Typical ADPKD group demonstrated higher discovery rate (62.3%) compared to atypical ADPKD group (41.8%) or pediatric PKD group (53.4%).

Conclusion
This is the first nationwide cohort for genetic characterization of Korean hereditary cystic kidney disease patients. We report the baseline characteristics and genetic findings of the cohort prior to detailed molecular analysis.
#4098 PATIENT ACUITY AND CARDIOVASCULAR OUTCOME IN HEMODIALYSIS PATIENTS: A KOREAN NATIONWIDE COHORT STUDY
Authors: Kim Hyo Jeong , Park Jung Tak , Heo Ga Young , Kim Kyung Won , Kwon Youg Uk , Kim Soo Hyun , Kim Gui Ok , Kim Hyung Woo 
Published: June 2023

Abstract

Background and Aims
Patients acuity has been reported to be associated with poor outcome in hospitals. However, the effect of the patient acuity of hemodialysis center on the prognosis of individual patients is not well known. In this study, the association between the severity of illness in hemodialysis facility and major adverse cardiac and cerebrovascular event (MACCE) in patients undergoing hemodialysis was investigated.

Method
15,633 participants receiving hemodialysis in the primary health care center who participated in the Periodic Hemodialysis Quality Assessment by Health Insurance Review & Assessment Service (HIRA) were examined. The main predictor was severity-to-nurse ratio, defined as a sum of Charlson comorbidity index of all patients divided by the number of nurses in each hemodialysis facility. The primary and secondary outcome were MACCE, and all-cause mortality, respectively.

Results
During a median follow-up of 5.5 years, MACCE and all-cause mortality occurred in 7,966 (51.0%) and 6,536 (41.8%) participants. Participants with higher severity-to-nurse ratio tended to have higher incidence rate of MACCE. The hazard ratios (HRs) of MACCE for the second, third, and highest quartiles compared with the lowest quartile of severity-to-nurse ratio were 1.05 (95% confidence intervals [CI], 0.98-1.11; P = 0.151), 1.07 (95% CI, 1.00-1.14; P = 0.053), and 1.08 (95% CI, 1.00-1.16; P = 0.040). When treating severity-to-nurse ratio as a continuous variable, MACCE risk increased by 1% per 1 increase in severity-to-nurse ratio (HR, 1.01; 95% CI, 1.00 - 1.02; P = 0.003). Compared to the lowest quartile group, the HRs of all-cause mortality for second, third and fourth quartile were 1.12 (95% CI, 1.04-1.19; P = 0.002), 1.11 (95% CI, 1.03-1.19; P = 0.005), and 1.16 (95% CI, 1.07-1.25; P&lt;0.001), respectively.

Conclusion
As the part of the Joint Project on Quality Assessment Research by HIRA, the present study showed that the patient acuity was strongly associated with an increased risk of poor outcomes in hemodialysis patients.
#4175 PERFORMANCES OF THE 5-YEAR KIDNEY FAILURE RISK EQUATION IN A TERTIARY SINGLE CENTER CHRONIC KIDNEY DISEASE COHORT (CKD CAREMEAU)
Authors: Prouvot Julien , Gerbal Marion , Ahmadpoor Pedram , Garo Florian , Cariou Sylvain , Renaud Sophie , Pambrun Emilie , Reboul Pascal , Moranne Olivier 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is a common disease with a heterogeneous course. The Kidney Failure Risk Equation (KFRE) is designed to predict 5-year End stage renal disease (ESRD). This score has shown poor performance in predicting 5-years ESRD in elderly patients, probably because of a competitive risk with death. Indeed, patients with type 2 diabetes are numerous and older than non-diabetic patients, with higher risks of death, and thus à higher competitive risk. In this context, we aimed to evaluate the performance of the KFRE score at 5 years, in a cohort from a tertiary center, according to diabetic status.

Method
The CKD Caremeau (CKDC) cohort is a single-center tertiary cohort of adults seen by a nephrologist for CKD. We studied CKDC patients included between January 2008 and December 2017 and followed them. We excluded patients younger than 45 years. KFRE score covariates were collected at the first visit, and Renal replacement therapy (RRT) (dialysis or kidney transplantation) and death before ESRD were collected during follow-up through December 2022. Multiple imputation (Monte Carlo) was used for missing albuminuria. Score performance was calculated with discrimination (area under curve (AUC)) and calibration (observed versus predicted risks), according to diabetic status, at 5 years.

Results
Of the 3046 patients included, 1288 (42%) had diabetes. 558 (18%) albuminuria were missing and imputed. For diabetic patients, median follow-up time was 5.3 [3.0–7.6] years, median age was 73 [66–80] years, 843 (65%) patients were males, median eGFR was 38 [27–50], median albuminuria was 204 [57–671] mg/g, 177 (14%) developed ESRD, and 398 (30%) died, with a median 5-years KFRE score of 4 [0.65–17.6] %. For non-diabetic patients, median time of follow-up was 5.5 [3.3–8.2] years, median age was 72 [63–81] years old, 1027 (58%) were males, median eGFR was 40 [27–53], median albuminuria was 113 [38–399] mg/g, 205 (12%) experimented ESRD, and 501 (29%) died, with a median 5-year KFRE score of 2 [0.18–14] %. Discrimination was not modified by diabetic status at 5 years (p = 0.67). Calibration was also unaffected by diabetic status, with an overall overestimation at 5 years.

Conclusion
The performance of the KFRE score was not modified by diabetic status, meaning that age is probably more important than diabetic status for the competitive risk of death in CKD patients.
#4183 A PHENOTYPIC DRIVEN RITUXIMAB MAINTENANCE APPROACH IS EFFECTIVE AND SAFE IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS
Authors: Tonoli Mattia , Affatato Stefania , Guerini Alice , Salviani Chiara , Delbarba Elisa , Gregorini Alessandra Gina , Scolari Francesco , Mescia Federica , Alberici Federico 
Published: June 2023

Abstract

Background and Aims
Rituximab (RTX) has emerged as the first-line treatment to maintain remission in ANCA-Associated Vasculitis (AAV). However, the ideal strategy to RTX re-dosing is still unclear [1].

Method
In this monocentric and retrospective study we evaluated the efficacy and safety of two RTX-based maintenance regimens in patients with AAV. Fixed-dose (FD) RTX dosing, consisting of at least 3 pre-emptive RTX administrations every 6 months, was preferred in patients judged to be at high relapse risk. Instead, a biomarker-guided on-demand (OD) RTX dosing strategy was preferred for patients deemed at lower risk of relapse; this consisted in RTX re-treatment only in case of B-cell repopulation or rise in ANCA titer. The single patient relapse risk was assessed according to the disease phenotype (granulomatous vs vasculitic), the ANCA specificity and the disease status (onset vs relapse). Relapses were defined as increase of disease activity requiring escalation of immunosuppression; major relapses were defined in case of life/organ-threatening manifestations.

Results
The study included 100 patients followed for a median of 24 months (IQR 20-30), 51% treated with an OD and 49% with a FD strategy. The main baseline characteristics of our cohort are shown in the Table; patients treated with a FD strategy were more often GPA, PR3-ANCA positive, with relapsing disease and ENT involvement and less frequent renal involvement. The FD group received a median of 4 (IQR 4-4) administrations of RTX for a median cumulative dose of 2 g (IQR 2-2). Only 6 (11.8%) patients in the OD group received RTX as maintenance therapy with a median of 1 (IQR 1-3) administration of RTX for a median cumulative dose of 0.75 g (IQR 0.5-1.75). Thirteen relapses occurred, 6 in the FD group and 7 in the OD one. Remission rates were comparable in the two cohorts, with respectively 87.6% and 85.9% of the patients in remission at 24 months (Figure 1 - panel A). No significant differences in remission rates across the 2 groups were observed after considering only major flares or after stratification according to clinical diagnosis (MPA/GPA) and ANCA specificity (Figure 1 - panel B to F). Ten and 20 severe infections (p = 0.383) and 3 and 1 cancer (p = 0.581) occurred respectively in the FD and OD group.

Conclusion
In our case series, a phenotypic-driven approach to RTX maintenance showed comparable efficacy and safety between fixed and on-demand dosing, despite different baseline characteristics between the two groups. These results suggest that personalizing RTX maintenance may be a feasible and safe strategy.
#4184 MALE CHRONIC KIDNEY DISEASE IS A STATE OF PREMATURE TESTICULAR AGING
Authors: David Karel , Narinx Nick , De Loor Jetty , Antonio Leen , Vanderschueren Dirk , Claessens Frank , Decallonne Brigitte , Evenepoel Pieter 
Published: June 2023

Abstract

Background and Aims
Sex steroid levels have been reported to be decreased in male patients with chronic kidney disease (CKD), parallel to the severity of the kidney dysfunction. These studies, at large, used immuno-assays, a method that is inferior to gold standard chromatography measurements and, in addition, failed to give insights into the underlying pathophysiology as they lacked data on gonadotropin levels. The aim of this study was to comprehensively map the gonadal status in male CKD patients not yet on dialysis and age- and BMI-matched controls, using gold standard techniques.

Method
We performed a case-control study in 120 male CKD patients (age 65.0 y, BMI 26.8 kg/m2), matched (1:1) with non-CKD controls for age and BMI. We divided CKD patients into 3 categories based on KDIGO classification: CKD 1–2 (n = 24), CKD 3 (n = 42) and CKD 4–5 (n = 54). We measured total testosterone (T) and estradiol (E2) using liquid chromatography tandem mass-spectrometry. Sex hormone binding globulin (SHBG), prolactin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured on the Roche Cobas 8000 platform. Free T levels were calculated via Vermeulen formula. Inhibin B (a readout for testicular Sertoli cell function) was measured by ELISA.

Results
CKD patients showed lower total T (426.0 ng/dL [297.5-516.5] vs. 541.0 ng/dL [452.0-647.8]; p&lt;0.0001) and free T levels (7.4 ng/dL ±3.2 vs. 9.4 ng/dL +/-2.2; p&lt;0.0001) as compared to non-CKD counterparts. SHBG and E2 levels, conversely, were comparable in cases and controls. Inhibin B levels were lower in CKD patients as well (112.7 pg/mL [38.1-189.0] vs. 181.1 [122.2-236.4]; p&lt;0.0001). LH and FSH levels were higher in CKD patients (9.1 IU/L [5.4-16.2] vs. 5.4 IU/L [3.6-8.1]; p&lt;0.0001 and 7.8 IU/L [5.0-20.2] vs. 5.6 IU/L [4.0-9.7]; p&lt;0.0001 respectively). Consequently, the T/LH ratio and inhibin B/FSH ratio, respectively reflecting Leydig and Sertoli cell function, were markedly depressed in CKD (1.8 nmol/IU [0.7-3.0] vs. 4.0 nmol/IU [2.4-5.2]; p&lt;0.0001 and 14.4 ng/IU [1.2-33.6] vs. 32.2 ng/IU [32.2 [16.3-56.7]; p&lt;0.0001). In the CKD cohort, regression analysis identified eGFR and age as independent determinants of T/LH ratio (R2 0.29). According to the T/LH ratio a male CKD patient of 45y old has a testicular age of an 81y old control.

Conclusion
Male patients with CKD not yet on dialysis show low total and free T levels, confirming CKD as a risk factor for male hypogonadism. The low T/LH and inhibin B/FSH ratio point to testicular failure as the underlying pathophysiological mechanism.
#4201 DYNAMICS OF INFLAMMATION EARLY AND LATE AFTER RENAL TRANSPLANTATION: CHARACTERIZATION OF THE IMMUNOLOGICAL PROCESSES IN A RAT RENAL TRANSPLANT MODEL
Authors: Stolz Gudrun , Langer Robert , Zeng Xiaokui , Yang Dai , Hinkeldein Tanja , Dolff Sebastian , Witzke Oliver , Kribben Andreas , Wilde Benjamin 
Published: June 2023

Abstract

Background and Aims
The pathophysiology of rejection after renal transplantation (RTx) has not been unraveled completely. In previous studies, Th17 cells were shown to be involved in several autoimmune diseases affecting the kidney, e.g. lupus nephritis, glomerulonephritis and ANCA vasculitis. The aim of this study was to decipher the dynamics of rejection after RTx with focus on the Th17 cells and IL17 cytokine family.

Method
For this purpose, the established Fischer to Lewis rat RTx model was used. In this model, renal rejection is elicited and develops over time. The donor renal grafts were harvested from Fischer rats and exposed to static cold storage using HTK or UW buffer. The Lewis recipients were treated for 10 days post-transplant with ciclosporin A and then immunosuppressive therapy stopped. Recipients were harvested early (2 hours, 30 days) and late after RTx (12 weeks, 28 weeks). To analyze the dynamics of inflammation, kidney sections were stained for CD3+ (T-cells) and MPO (neutrophils). RT-PCR was used to detect cytokine gene expression of several target genes within the renal grafts. IL17A Elispot was established to analyse circulating Th17 cells in the recipients.

Results
Generally, the cold ischemia time of the renal allograft was associated with the lifetime of the recipients. Furthermore, with increasing cold ischemia time of the graft, intra-renal CD3+ T-cell infiltration was enhanced. An increased CD3+ and a diminished number of MPO+ neutrophils were detected in the renal grafts late after RTx compared to early timepoints. Moreover, the intra-graft IL17C gene expression was enhanced late after renal transplantation while CXCL1 and CXCL2 were upregulated early after renal transplantation. IL17A gene expression reached higher levels than IFNg in later timepoints e.g. 30 days, while in early stages IL17A was below IFNg. The impact of cold storage buffer on the immunogenicity of the renal transplant was investigated, too. The use of UW led to a higher intra-renal CD3+ T-cell infiltration at later timepoints compared with HTK. In early stages after transplantation, higher levels of intra-renal MPO+ neutrophils were found upon cold storage using UW compared to cold storage using HTK.

Conclusion
The inflammatory process during chronic kidney rejection is T-cell driven and may involve the IL17C cascade. The early phase is dominated by neutrophils with enhanced intra-renal expression of CXCL1 and CXCL2. Furthermore, the polarization of the T-cell driven immune response may change depending on the time point after transplantation.
#4202 FLUID OVERLOAD AT THE BEGINNING OF PERITONEAL DIALYSIS: A CROSS-SECTIONAL STUDY TO DETERMINE ITS ASSOCIATION WITH SERUM BIOMARKERS
Authors: Afonso Rita , Pimenta Gonçalo , Matias Patrícia , Vida Ana Carlota , Lobo Sara , Santos Elisabete , Branco Patricia , Calça Rita 
Published: June 2023

Abstract

Background and Aims
Volume management in peritoneal dialysis (PD) patients is of major importance as fluid overload has been associated with cardiovascular and non-cardiovascular morbidity and mortality. Clinical examination itself has a poor diagnostic accuracy for minor deviations from normohydration, highlighting the need of additional tools. The aim of this study was to evaluate the association between serum biomarkers (CA-125 and NT-proBNP) and volume status, evaluated by clinical and bioimpedance analysis, at the initiation of PD technique.

Method
Single-center cross-sectional study including PD patients that started technique between 2017 and 2022. Demographic and clinical data were collected from the electronic records. Parameters evaluated were clinical examination, serum biomarkers, bioimpedance and dialysis adequacy.

Results
A total of 79 patients (51 male) were included with a mean age of 57±15 years. All of them started with CAPD and 52% were under icodextrin. Hypertension, cardiovascular disease and diabetes were present in 94%, 51% and 34%, respectively. The great majority were under renin-angiotensin-aldosterone system inhibitors (91%), beta-blockers (48%) and diuretic therapy (94%). Baseline PET showed that 77% were high or high-average transporters. Mean weekly Kt/V was 2.4±15. The mean residual renal function (RRF) and residual diuresis were 6.7±15 mL/min/1.73 m2 and 1.6±0.8 L (4% anuric), respectively, and 11% had ultrafiltration failure. Median nPCR was 0.9 g/Kg/day (IQR 0.3). Median NT-proBNP and CA-125 were 1337 pg/mL (IQR 3401) and 14.6 U/mL (IQR 17.6), respectively. NT-proBNP was positively associated with overhydration (OH &gt;2 L) (r = 0.31; p = 0.009), CA-125 (r = 0.28; p = 0.01) and icodextrin use (p = 0.002). It was negatively associated with weekly Kt/V (r = -0.35; p = 0.003), RRF (r = -0.36; p = 0.002), ultrafiltration test (UFT) (r = -0.35; p = 0.003) and nPCR (r = -0.28; p = 0.001). CA-125 was positively associated with higher overhydration (OH &gt; 3.6 L), D/P creatinine (r = 0.3; p = 0.004) and icodextrin use (p = 0.001). It was negatively associated with weekly Kt/V (r = -0.3; p = 0.01), UFT (r = -0.25; p = 0.03) and nPCR (r = -0.23; p = 0.04). NT-proBNP was still associated with overhydration in a multivariable analysis, adjusted to diabetes, icodextrin use, RRF and CA-125 (p = 0.024).

Conclusion
Serum NT-proBNP and CA-125 seem to be good markers of overhydration at PD baseline. They were also associated with worse dialytic efficacy and ultrafiltration, lower residual renal function and an early need of icodextrin use. Malnourished patients were associated with higher NT-proBNP and CA-125. Early and effective management of hydration may improve clinical outcomes, allowing personalized dialysis prescription and nutritional support.
#4205 ESTIMATED PROXIMAL TUBULE FLUID PHOSPHATE (EPTFP) CONCENTRATION: AN EARLY MARKER OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD)?
Authors: Rotondi Silverio , Tartaglione Lida , Pasquali Marzia , Perrotta Adolfo , Romano Chiara , Tinti Francesca , Mazzaferro Sandro 
Published: June 2023

Abstract

Background and Aims
MBD develops early in CKD and is associated with kidney damage progression, but CKD-MBD markers, of initial CKD-MBD like FGF23 and α-Klotho are not available in clinical practice. Recently ePTFp has been proposed as a new early marker of MBD. In fact, the progressive reduction of nephron number, with the proportional FGF23 increments, reduce renal tubular phosphate reabsorption to maintain phosphate balance. As a consequence, PTFp concentration per single nephron progressively increases, leading to progression of kidney tubular damage. For this reason, PTFp could represent an innovative early marker of CKD-MBD. We evaluated the relationship of ePTFp with FGF23, α-Klotho and kidney damage progression.

Method
In CKD stage G2-4, we assayed serum FGF23, α-Klotho and ePTFp [ePTFp = (Phosphaturia / creati-ninuria) x creatininemia x 3,33]. The progression of CKD was evaluated during 5 years and the patients were splitted in two groups according to the basal ePTFp median value. 30 healthy subject pro-vided the normal value of ePTFp.

Results
In 68 CKD patients (age 58,9 ± 15.6 y.o. eGFR 45 ± 21 mL/min), ePTFp averaged 2.4±1.3 mg/mg which was higher than the control group (ePTFp = 1.2±0.5; p&lt;.01). ePTFp increased progressively along with the increasing CKD stages with values higher than the control group since stage 2 (Table 1). ePTFp showed a positive correlation with FGF23 (r: 0.69; p&lt;.001) and a negative correlation with α-Klotho (r:-237; p&lt;.05) and eGFR (r:-647; p&lt;.001). Follow-up was available in 30 patients (Table 2) and showed a greater reduction of eGFR in the 15 patient with higher ePTFp (threshold 2 mg/dl) (Fig. 1).

Conclusion
Our data show early and progressive increments of ePTFp in CKD along with increments of FGF23 and PTH and reduction of α-Klotho, as per reciprocal pathophysiologic dependence. ePTFp values &gt; than 2 mg/dl identified patients at highest risk of CKD progression. Accordingly, ePTFp, a surrogate of renal tubular cells phosphate overload, could represent a novel marker of CKD-MBD development and of increased risk of kidney damage potentially helpful to make therapeutic choice.