bluuebunny/crossref_metadata_2025 huggingface dataset:
#4879 PREDICTORS OF KIDNEY DISEASE PROGRESSION IN MALES WITH X-LINKED ALPORT SYNDROME
Authors: Aksenova Marina , Zaikova Natalia , Piruzeeva Oxana , Lepaeva Tatjana , Obuhova Varvara , Nikishina Tatjana , Konkova Natalia
Published: June 2023

Background and Aims

Alport's syndrome is the second most common monogenic cause of end-stage renal disease (ESRD). Males with X-linked Alport's syndrome (XLAS) have a high risk of early ESRD development. The aim of study was to determine the predictors of unfavorable renal prognosis in boys with XLAS.

Method

The children with genetically confirmed XLAS (n = 84, age 8.7±4.3 yrs, eGFR 102±16.2 ml/min/1.73 m2, 59 pts with missense COL4A5 mutations) were included in observation single center study (FU 6.9±2.4 yrs). Seventy three pts (q = 0.87) were treated with ACEi (age of start 7.6±3.3 yrs, dose for Ramipril 2.7±0.8 mg/m2/day). Arterial blood pressure (BP), proteinuria (Pr, mg/m2/day), eGFR (Schwartz equation, ml/min/1,73m2), gene mutation type and ACEi-treatment data (age of pts and disease stage at the therapy start, ACEi dosage, dynamics of Pr and eGFR) were obtained and updated for each patients. BP >90 perc for gender, age and height was defined as uncontrolled (uBP); Pr was categorised according to its level as a low (100-<250 mg/m2/day), moderate (≥250-500 mg/m2/day), high (≥500-1000 mg/m2/day) and nephrotic (≥1000 mg/m2/day). Gene mutations were divided into severe (nonsense, deletion, splicing) and less severe (missense) mutations. The eGFR<60 ml/min/1,73m2 was defined as primary outcome.

Results

Twenty pts (q = 0.24, age 13.5±2.96 yrs) reached the end point during observation period. Non-missense COL4A5 mutations (HR = 4.28, 95% CI 1.47-12.4, p = 0.007), uBP (HR = 20, 95% CI 4.68-29.6, p<0.001), persistent Pr >250 mg/m2/day (HR = 20, 95% CI 3.36-21, p<0.001), absence of ACEi treatment (HR = 10.7, 95% CI 2.45-14.7, p = 0.02) or start therapy at proteinuric stage of disease (HR = 20, 95% CI 2.2-13.8, p<0.001) were the risk factors of disease progression. Multiple regression analysis adjusted for age, initial eGFR revealed that late start of ACEi treatment (β = 0.23, p = 0.036), persistence of uBP (β = 0.26, p = 0.008) and Pr >250 mg/m2/day (β = 0.17, p = 0.04) had independent significance and predict unfavorable renal prognosis (R = 0.76, R2 = 0.57, p<0.000).

Conclusion

Persistent proteinuria and uncontrolled blood pressure, initiation of ACEi treatment at the proteinuric stage of glomerulopathy are the factors of unfavorable prognosis in male with XLAS.
#4881 NEPHROPROTECTION IN BOYS WITH X-LINKED ALPORT SYNDROME: THE SOONER THE BETTER
Authors: Aksenova Marina , Piruzeeva Oxana , Zaikova Natalia , Lepaeva Tatjana , Nikishina Tatjana , Obuhova Varvara , Konkova Natalia
Published: June 2023

Background and Aims

Proteinuria (Pr) is a marker of glomerular diseases progression. The aim of study was to define the efficiency of angiotensin-converting enzyme inhibitors (ACEi) treatment in prevention of Pr development in boys with X-linked Alport's syndrome (XLAS).

Method

Single center observation study included boys with confirmed XLAS (n = 87). Twenty nine pts (1gr) started ACEi (enalapril 4.2±1.4 mg/m2/day) in non-proteinuric stage of disease (Pr≤100 mg/m2/day); mean age 6.2±3.9 yrs, eGFR Schwartz 118±15.2 ml/min/1.73 m2, Pr 67±23 mg/m2/day. Fifty eight pts (2gr) without preemptive ACEi treatment were observed from mean age 6.8±4.9 yrs, eGFR 119±17.3 ml/min/1.73 m2, Pr 87±43 mg/m2/day. Follow up was 6.2±3.9 yrs, mean age at the last observation was 11.7±3.9 yrs vs 14.2±4.6 yrs (p = 0.67) in 1gr and 2gr, respectively. The occurrence of Pr (Pr>100 mg/m2/day) was defined as primary end point of the study.

Results

The pts of 1gr had lower rate (0.48 vs 0.94, p<0.001) and higher age (10.2±3.9 vs 4.9±3.4 yrs, p = 0.3) of Pr occurrence than in 2gr. ACEi treatment reduced risk of Pr onset (OR = 0.05(95%CI 0.013-0.2)) with absolute risk reduction of Pr by 47% (RD = 0.47) and number of treated pts to prevent Pr development (NNT) 2.14. No difference was revealed between 1gr pts with and without Pr development in age of therapy start (7.1±3.3 vs 6.3±2.8 yrs), ACEi dose (2.3±0.8 vs 2.1±0.6 mg/m2/day) and COL4A5 gene mutation type (missense variants 0.72 vs 0.86). Arterial hypertension was a risk factor of Pr occurrence in 1gr (χ2 = 4,42, p = 0.04); children with Pr development was older at the last observation: 13.5±3.2 vs 9.9±3.8 yrs, p = 0.47. No side effects of treatment were observed.

Conclusion

The early ACEi therapy halves the risk of Pr development in boys with XLAS and may prevent the disease progression in these patients.
#4905 PERITONEAL CLEARANCE OF TRACE ELEMENTS IN PERITONEAL DIALYSIS PATIENTS
Authors: Koz Suleyman , Oguz Esin , Sayın Cagla
Published: June 2023

Background and Aims

Both accumulations and deficiencies of trace elements (TE) could be seen in peritoneal dialysis (PD) patients. Peritoneal clearance remains major route of elimination for many solutes including TE, in PD patients. Imbalances of TE may have deleterious effects on the patients. Data on TE balances in PD patients are inadequate. Here, we present some data from a larger study. We aimed to analyze peritoneal clearance of Boron (B), Cupper (Cu), Zinc (Zn), Selenium (Se), Strontium (Sr) and Molybdenum (Mo) in a cohort of PD patients.

Method

This cross-sectional study included three female and five male PD patients giving consent for the study. Mean age was 43,6±5,6 and patients were on continuous ambulatory PD for at least three months. Patients with recent peritonitis were excluded. Peritoneal solutions were individualized, so had different osmolarities. A sample of plasma and 24-hour spent dialysate was analyzed by inductively coupled plasma mass spectrometry (ICP-MS) (Thermo Scientific™ iCAP Q ICP-MS, USA). Sensitivity was on the order of ppb (μg/L). A control group (CG) with glomerular filtration rate ≥ 90 ml/min were used for comparison of plasma levels of TE. Peritoneal clearances were calculated by the following formula:

${{24 \!-\! hour \, spent\, dialysate\, volume \!\times\! \displaystyle\frac{{dialysate\ concentration\ of\ the\ trace\ element}}{{plasma\ concentration\ of\ the\ trace\ element}}}}$

Results

Data on plasma levels, clearances and daily loss of TE are shown in the Table 1. The clearances were ordered from smallest to largest as follows: Zn, Cu, Se, Sr, Mo, Ni, B. On the other hand, spent dialysate daily element losses were ordered from smallest to highest as follows: Cr, Ni, Se, Mo, Cu, Sr, Zn, B

Conclusion

Our study provides data on elimination of some trace elements, which may help to better understand the TE balance in PD patients. Data suggest that B has the highest and Zn the lowest peritoneal clearance values.
#4942 GENOTYPE-PHENOTYPE ANALYSIS IN FAMILIAL RENAL GLUCOSURIA PATIENTS: THE CRUCIAL ROLE OF CONSERVED RESIDUES
Authors: Xu Lubin , Zhao Ruohuan , Zhao Yumo , Tang Xueqing , Si Nuo , Guo Xiuzhi , Nie Min , Chen Limeng
Published: June 2023

Background and Aims

Familial renal glucosuria (FRG) is a hereditary disorder caused by mutations in SLC5A2, the gene encoding sodium-glucose cotransporter 2 (SGLT2) in proximal tubule cells. In this study, we aimed to characterize the genotype-phenotype relationship in FRG patients using data from our cohort and literature review.

Method

We sequenced SLC5A2 in a cohort of 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients using urinary glucose excretion in a 4-hour oral glucose tolerance test (OGTT). We built an open-source online calculator to facilitate the calculation of RTG. Besides, we reviewed published literature and obtained information on SLC5A2 variants and 24-hour urinary glucose (24hUG) in FRG patients.

Results

We identified 27 rare SLC5A2 variants, including 13 novel variants (G484D, R564W, A212S, c.574+1G>C, W649*, S592Cfs*6, Q579*, A89T, Y339*, V39F, G491E, A464E, and G360D), in our cohort and yielded 107 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2mmol/L. Patients carrying two SLC5A2 variants had lower RTG (3.9 vs. 6.2 mmol/L, p = 0.057) and larger amounts of 24-hour urinary glucose excretion (24hUG) (52.39 vs. 7.20 g/1.73m2, p = 2.7*10−8) than those carrying a single variant. Patients with homozygous missense or in-frame indels had mean 24hUG of 82.30g/1.73m2, comparable to those with homozygous truncating variants (81.66g/1.73m2) and significantly more than those with homozygous splicing variants (35.38g/1.73m2, p = 0.026). Patients with homozygous missense variants involving conservative residues had more 24hUG (104.76g/1.73m2) than those with variants at non-conservative residues (46.37g/1.73m2, p = 0.0031).

Conclusion

We built a comprehensive map showing the impact of SLC5A2 variant type, variant location, and zygosity on glucosuria severity. Our results highlighted that conserved residues play an essential role in maintaining the transport function of SGLT2.
#4948 ROLE OF REGENERATING PROTEIN 1A IN THE PROGRESSION OF CHRONIC KIDNEY DISEASE
Authors: Huang Nan , Zhu Xiangyun , Chen Sheng , Wu Xiaodong , Wang Bin , Li Ling
Published: June 2023

Background and Aims

Regenerating protein 1a (Reg 1a) is a secretory protein mostly produced by the pancreas. Serum levels of Reg 1a has been found increased in patients with diabetic nephropathy, which may be a potential indicator of renal dysfunction. Here, we investigated whether Reg 1a was associated with renal function in chronic kidney disease (CKD) and further to evaluate its predictive value of progress in renal dysfunction.

Method

Serum Reg 1a levels were measured by a double antibody sandwich ELISA enzyme-linked immunosorbent assay. Demographics information and clinical biochemical parameters such as blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA) and urinary albumin-to-creatinine ratio (UACR) were collected. Correlations between serum Reg 1a and other factors were presented by Spearman's correlation coefficient and partial correlation analysis. Multivariate logistic regression analysis was utilized to identify the independent risk factors for chronic renal dysfunction and the progress in CKD. Draw the receiver operating characteristic curve (ROC curve) and calculate the area under the curve (AUC) to analyze the effectiveness of the individual serum Reg 1a. Statistical analyses were conducted using SPSS 20.0 software, Med-Calc statistical software.

Results

A total of 640 participants were enrolled in this study including non-CKD subjects (n = 240) and patients with CKD (n = 400). Compared with non-CKD group, participants in CKD group had higher level of serum reg 1a (188.2 [66.7∼387.6] ng/ml vs 23.8 [14.7∼35.1] ng/ml, P<0.001). Serum reg 1a level elevated with increasing grades of CKD. Serum reg 1a was negatively correlated with eGFR and positively associated with age, hypertension, Scr, BUN, UA and UACR (P<0.001). In multiple logistic regression analysis, serum reg 1a was one of independent risk factors to predict renal dysfunction (OR = 1.010 [1.003, 1.018], P = 0.008). The AUC for serum reg 1a to predict CKD was 0.889 [0.862, 0.913], and the AUC for serum reg 1a to screen the eGFR lower than 30 ml/min/1.73 m2 in CKD groups was 0.919 [0.888, 0.944]. Subgroup analysis showed that serum reg 1a is an independent risk factor to predict early progress of UACR (OR = 1.012 [1.002, 1.022], P = 0.016) in CKD patients.

Conclusion

The study provides clinical evidence that serum reg 1a may a meaningful biomarker of early kidney impairment and a useful supplementary factor in the progression of CKD.
#4967 GASDERMIN D IS REQUIRED FOR CONTROL OF NECROPTOTIC CELL DEATH IN AKI
Authors: Tonnus Wulf , Brucker Anne , Linkermann Andreas
Published: June 2023

Background and Aims

Contradicting previous reasoning, it is now established that necrotic rather than apoptotic cell death pathophysiologically drives acute tubular necrosis during AKI. Whereas involvement of necroptosis and ferroptosis has been demonstrated by various groups, the role of pyroptosis, a highly immunogenic form of cell death requiring proteolytic activation of gasdermin protein family members, remains uncertain upon AKI. Thus, we aimed to investigate the role of pyroptosis and its mechanism of action in AKI.

Method

We set to detect gasdermin D (GSDMD) expression in murine renal samples after ischemia/reperfusion injury (AKI) by immunohistochemistry. Furthermore, we investigated GSDMD-deficient mice in IRI and cisplatin-induced AKI. To conclude on mechanisms, we isolated fresh murine renal tubules and measured LDH release over time. We generated MLKL/GSDMDdko mice to investigate the interplay of these caspase-dependent forms of regulated necrosis in AKI.

Results

After IRI, we detected a specific GSDMD signal in areas surrounding necrotic tubules, whereas no such signal could be detected within necrotic areas. Whereas interference with other forms of regulated necrosis leads to reduced injury, GSDMD-deficient mice demonstrated higher levels of serum creatinine and urea as well as more severe tubular injury compared to wildtypes. In line with the findings of immunohistochemistry, we only found GSDMD protein expression in whole kidney lysates but not isolated renal tubules; and no difference in spontaneous cell death propagation was detectable. Co-deletion of MLKL (effector protein of necroptosis) reversed the sensitization to AKI by GSDMD-deficiency. These results could be reproduced in cisplatin-induced AKI.

Conclusion

Here, we found an unexpected protective role for GSDMD, the effector protein of pyroptosis, in two different models of AKI. Mechanistically, our studies indicate the effect of GSDMD to function outside the tubular compartment, specifically surrounding areas of tubular necrosis. These infiltrating innate immune cells appear to interfere with tubular necroptosis in a non-cell autonomous manner. Alongside with these mechanistic insights, our data urge caution when inhibition of pyroptosis is therapeutically considered.
#4977 ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH COVID-19 DURING ANTIOXIDANT THERAPY
Authors: Egamberdieva Dano , Ruzmetova Iroda , Raimkulova Narine
Published: June 2023

Background and Aims

In connection with the coronavirus pandemic of 2020, there have been recent discussions about the role of endothelial function in the course and prognosis of the disease. Purpose of the study. study of endothelial function in patients who have had a coronavirus infection.

Methods

Under observation were 60 patients who underwent COVID-19 of moderate severity on the 14th day of therapy at the age of 57 to 67 years. Patients of the 1st group (30 patients), against the background of standard basic therapy, were prescribed L-carnitine at a dose of 5 g/day for 5 days, followed by a maintenance dose of 1 g/day for 5 days. Group II consisted of 30 patients who met the inclusion criteria for the study, were treated for COVID-19 and did not receive metabolic agents. The state of endothelial function was assessed according to Doppler sonography of the brachial artery using the D.S. Celemajer (1992) using a reactive flush test. Changes in the diameter of the right brachial artery were assessed using a 7.5-12 MHz linear transducer with a phase grating ultrasound system En Visor C Philips. The results of the study were processed statistically using Student's t test for paired and unpaired variables. Differences were considered significant at p<0.05.

Results

After analyzing the data of samples with RG in combination with blood flow velocity indicators, we noted that in response to an increase in blood flow velocity in the control group, the diameter of the brachial artery increased by almost 12%, in patients with COVID-19, the blood flow velocity increased significantly, and the diameter of the artery practically did not change. Thus, with an increase in the mechanical stimulus, i.e. blood flow velocity in patients with COVID-19 did not occur a commensurate increase in the diameter of the vessel. The results obtained indicate a pronounced dysfunction of the endothelium in patients with COVID-19, in particular, EDVD, the indicators of which were two times lower than the control values.

Conclusions

The inclusion of L-carnitine in the regimen of standard therapy for patients with COVID-19 significantly improves the values of EVR compared to the standard basic therapy.
#4983 THE UNEXPECTABLE BALANCE OF PROINFLAMMATORY CELLS IN PERITONEAL DIALYSIS PATIENTS
Authors: Grilo João , Santos Catarina , Monteiro Andreia , Chorão Raquel , Coutinho Joana , Ribeiro Lígia , Filipe Rui , Rocha Ernesto
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is a complex and heterogeneous disease and is increasingly becoming a global public health concern. It is is characterized by a persistent inflammation state which appear to be caused by cytokines, grown factors and hormones. Peritoneal dialysis (PD) accounts for 9% of all kidney replacement therapy (KRT) and over time, some changes are expected to occur in the peritoneal membrane mainly due to exposure to PD solutions, infectious processes and non-infectious complications. This inflammatory process is poorly understood and needs further clarification, but Th17 cells and Th1 cells seem to be involved. Therefore, we aimed to quantify the frequency of peripheral immune cells and the concentration of IL-17A in peripheral blood (PB) and peritoneal effluent (PE) and compare to a healthy control group.

Method

In a cross-sectional study of 26 PD patients and 10 healthy, age and sex-matched controls we evaluated PB and PE frequencies of T lymphocytes, T CD4, T CD8 and Th1 cells by flow cytometry as well as IL-17 concentrations using enzyme-linked immunosorbent assay. Comparisons were performed between PD patients and controls and between the different groups of PD patients according to PD modality, number of exchanges, dialysate tonicity, extraneal use, infusion and daily total volumes, type of peritoneal transport and volume indexes. Statistical analyses were performed using the SPSS statistics version 26.

Results

Table 1 summarizes the main characteristics of PD patients and controls. Overall, in comparison with the control group, the frequency of Th1 cells in PB of PD patients was significantly lower (P = 0.001). On the other hand, frequency of Th1 cells substantially expanded in the PE, as compared to the PB (P = 0.001). PD patients also presented lower Th17 cells frequencies (P = 0.061) and those prescribed Extraneal had the lowest frequencies of Th17 (P = 0.030). IL-17A concentration was significantly higher in PE vs PB of PD patients (P = 0.012). Finally, the frequency of total lymphocytes in high PD transporters was significantly higher in comparison with high-average transporters (P = 0.021).

Conclusion

In our cohort, PE presented high concentrations of proinflammatory cells and cytokines. Th1 cells rather than Th17 cells were increased, pointing to a predominant cytolytic activity but IL-17 was also increased. Treatment with Extraneal associated with a lower frequency of these cells, somehow counterbalancing the inflammatory millieu associated with high glucose concentrations.
#4990 OMEGA-3 FATTY ACID ACTIVATES MITOCHONDRIAL BIOGENESIS AND PINK1 DEPENDENT MITOPHAGY IN KIDNEY AND HEART OF ADENINE INDUCED UREMIC RATS
Authors: Yang Dong Eun , Lee Su MI , Kim Jun Chul , An Won Suk
Published: June 2023

Background and Aims

Mitochondrial homeostasis is controlled by biogenesis, dynamics, and mitophagy. Mitochondrial dysfunction plays a central role in cardiovascular and renal disease and omega-3 fatty acids (FA) are beneficial for cardiovascular disease. We aimed to investigate whether omega-3 FA regulates the expression of mediators of mitochondrial biogenesis, dynamics, and mitophagy in kidney and heart of adenine-induced uremic rats.

Method

Sprague-Dawley rats were divided into three groups: normal control, adenine control, and omega-3 FA. Uremia was induced by feeding diets containing 0.75% adenine and 2.5% protein for the first 3 weeks. During next 4 weeks, they were received 2.5% protein with or without omega-3 FA (300 mg/kg/day). The renal and cardiac expression of PGC-1α, SIRT1/3, Nrf2, DRP-1, OPA1, Mfn1/2, PINK1, BNIP3 and NIX were examined by western blot analysis. The qPCR was used to determine mitochondrial DNA (mtDNA).

Results

Compared to normal, serum creatinine and heart weight/body weight in adenine control was increased and improved in omega-3 FA group. Compared with normal, PGC-1α, SIRT1/3 and Nrf2 were down-regulated in kidney and heart of adenine control. PGC-1α expression of kidney and heart was recovered in omega-3 FA group. DRP-1 of kidney was up-regulated but DRP-1 of heart was down-regulated in adenine control. DRP-1 of heart was recovered in omega-3 FA group. PINK1, BNIP3 and NIX were down-regulated in heart of adenine control and recovered in omega-3 FA group. PINK1 was down-regulated but BNIP3 and NIX were up-regulated in kidney of adenine control and those were mitigated in omega-3 FA group. MtDNA was decreased in kidney and heart of adenine control group but mtDNA of heart was recovered in omega-3 FA group.

Conclusion

DRP-1 related with mitochondrial fission may oppositely work in uremic kidney and heart. Omega-3 FA is beneficial for mitochondrial homeostasis by activating mitochondrial biogenesis and PINK1 dependent mitophagy in kidney and heart of uremic rats.
#4991 IMMUNE MODULATING DRUGS AND ORAL ANTICOAGULATION IN KIDNEY TRANSPLANT: COMPARISON OF DIRECT ORAL ANTICOAGULANTS VERSUS ANTAGONIST OF VITAMIN-K
Authors: Casanova Annalisa , Santoro Francesco , Simone Simona , Alfieri Carlo Maria , Fancone Adele , Strologo Andrea Dello , Grandaliano Giuseppe , Busutti Marco , Comai Giorgia , Grandinetti Valeria , Gesualdo Loreto , Pesce Francesco
Published: June 2023

Background and Aims

Direct oral anticoagulants (DOACs) are a well-known alternative to conventional antagonist of vitamin-K (avK) and have emerged as the preferred choice due to their safety and efficacy profile. However, immune modulating drugs as cyclosporine and tacrolimus, commonly used for transplant recipients, may interfere with DOACs pharmacokinetic. Our study evaluates safety and efficacy profile of direct oral anticoagulants (DOACs) compared to avK in kidney transplant recipients (KTRs) treated with immune modulating agents.

Methods

A multi-center retrospective observational study from 4 Italian hospitals enrolling KTRs on DOACs or avK was carried out. Sixty-six patients on DOACs were compared with fifty patients on avK with similar clinical features. Serial evaluation of renal function and serum levels of immune modulating drugs during 24 months follow-up (FU) was performed.

Results

Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73 m2. Immune-modulating therapy included tacrolimus (n = 47, 71%), cyclosporin (n = 13, 20%), everolimus (n = 10, 7%) and sirolimus (n = 4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p = 0.80) and cyclosporine (+0.12±0.25 p = 0.94) not statistically significant. Only a patient treated with dabigatran 150 mg required a dose adjustment. Levels of tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or avK and no differences in term of mayor bleeding (5.8% vs 4% p = 0.99), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs or avK therapy (-3.9±1 vs −3.8±2 p = 0.82).

Conclusion

DOACs are a potential therapeutic option among kidney transplant recipients treated with immune modulating drugs. Careful evaluation of immunomodulating agent levels during the first two week of therapy should be recommended. No difference in term of bleeding, thromboembolic events and renal function decline was found when comparing with avK therapy.
#5012 THE EFFECT OF GLOMERULAR C3 DEPOSITION ON RENAL OUTCOME IN PATIENTS WITH MEMBRANOUS NEPHROPATHY: DATA OF THE TSN-GOLD STUDY
Authors: Gursu Meltem , Cebeci Egemen , Turkmen Aydin , Dervisoglu Erkan , Sezen Mehmet , Turgutalp Kenan , Sahin Gulizar Manga , Trablus Sinan , Kutlay Sim , Uzun Sami , Üstündağ Sedat , Dursun Belda , Ayli Deniz , Tatar Erhan , Oztop Kenan Evren , Basturk Taner , Cevher Simal Koksal , Yilmaz Zulfikar , Tunca Onur , Sevinç Mustafa , Yadigar Serap , Duranay Murat , Arikan Izzet Hakki , Elcioglu Omer Celal , Karakan Şebnem , Turkmen Kultigin , Torun Dilek , Gungor Ozkan , Artan Ayse Serra , Ozturk Savas , Unsal Abdülkadir , Seyahi Nurhan
Published: June 2023

Background and Aims

We aimed to evaluate the effect of glomerular C3 deposits on clinical and laboratory findings and outcome in patients with idiopathic membranous nephropathy (MN) included in the Primary Glomerular Diseases Study of Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD).

Method

The data of 1595 patients with MN in the database has been evaluated. 114 patients were excluded due to lack of data about C3 staining, 54 patients due to secondary MN and 523 due to lack of data about the follow-up. Patients with glomerular C3 deposits were compared with those with no C3 staining.

Results

Glomerular C3 deposits were detected in kidney biopsy specimens of 601 patients of the 888 patients analysed. The demographic data, clinical and laboratory findings at the time of diagnosis of C3 (+) and C3 (-) groups are presented in Table 1. They were similar except serum albumin level that was lower in C3 (+) group. Subepithelial deposits and interstitial fibrosis was more prominent, IgG, Kappa and Lambda staining more intense, positivity for C1q and IgA was more frequent in C3 (+) group (Table 2).

The study groups were similar regarding remission rates after the first imuunosuppressive treatment (p = 0.582). 155 patients (25.8%) had partial, 152 (25.3%) had complete remission while no remission was detected in 92 patients (15.3%) in C3 (+) group. 69 patients (24.0%) had partial and 81 patients (28.2%) had complete remission; 40 patients (13.9%) had no remission in C3 (-) group. The relapse rates were 17.6% and 19.9% in C3 (+) and C3 (-) groups (p = 0.360). The percentage of patients who died or needed renal replacement therapy (RRT) were higher C3 (+) group (p = 0.013) (Figure 1).

Conclusion

Need for RRT and mortality is higher in patients with C3 deposition showing the importance of C3 deposition in the prognosis of MN. More prominent interstitial fibrosis may be related with the worse outcome.
#5019 MORTALITY FOR COVID-19 IN UNDERGOING MAINTENANCE DIALYSIS PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Wu Chen , Xie Guoqiang , Chen Junzhe , Liu Qin , Wang Honglei , Tang Ying
Published: June 2023

Background and Aims

Since December 2019, patients undergoing maintenance dialysis have been significantly affected by COVID-19, facing higher risk of death than general population. However, current evidences assess the mortality of patients with COVID-19 remains incomplete. We performed meta-analyses of overall mortality in dialysis patients after SARS-CoV-2 infection. In addition, this study investigated the differences among different races,viral variants, hemodialysis and peritoneal dialysis with COVID-19. At the same time, the mortality rate of dialysis patients with the COVID-19 after vaccination was also observed.

Method

We performed a meta-analysis with literature searching in PubMed, EMBASE, Web of Science and Cochrane databases, published between December 1, 2019 and January 10,2023. Two authors separately screened the titles and abstracts of the documents and ruled out irrelevant articles. Fixed effects model and random effects model were used for calculating heterogeneity.

Results

A total of 83 studies included 7278 died from confirmed COVID-19 cases in a pool of 42925 dialysis patients. Overall mortality of COVID-19 in dialysis patients was 22% (95%Confidence Interval [CI]:19%-25%, p<0.01; I2 = 96.74%) from 2020 to 2022. In subgroup analysis, compared with ancestral COVID-19 (23%,95%CI:20%-25%,p<0.01; I2 = 93.01%) and alpha variant (30%, 95% CI:21%-54%,p<0.01;I2 = 95.35%),omicron variant (4%,95%CI:0-14%,p = 0.09; I2 = 0) had a lower morality significantly (Figure 1). The mortality for Asian and non-Asian were 20% (95% CI:16%-25%,p<0.01;I2 = 96.6%) and 24% (95%CI:20%-27%,p<0.01; I2 = 96.32%) respectively. The odds of death for maintenance hemodialysis and peritoneal dialysis were similar (odd ratio [OR] 1.30,95%CI:0.88-1.93,p = 0.191,I2 = 0). Furthermore, we also compared vaccination with unvaccination, and found out that vaccination was associated with lower mortality (OR = 0.18, 95%CI:0.11-0.28,p<0.01;I2 = 71.4%) (Figure 2).

Conclusion

Patients undergoing maintenance dialysis with COVID-19 have a higher morality. These findings suggest that the mortality of omicron variant may be lower than other variants. In our study, there's no significant difference in mortality between hemodialysis and peritoneal dialysis patients with COVID-19. Moreover, vaccines have a good protective effect on dialysis patients.
#5036 THE OUTCOME OF LUMASIRAN TREATMENT IN 10 PAEDIATRIC PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1
Authors: Saffe Sina , Büscher Anja , Doerry Katja , Habbig Sandra , Hansen Matthias , John-Kroegel Ulrike , Kanzelmeyer Nele , Latta Kay , Oh Jun , Kemper Markus
Published: June 2023

Background and Aims

In primary hyperoxaluria type 1 (PH 1) a rare enzymatic defect in the liver leads to a hepatic overproduction of oxalate. The resulting hyperoxaluria can cause nephrocalcinosis, urolithiasis and renal failure. Conservative treatment options such as hyperhydration, citrate and pyridoxine aim to slow the progression of the disease with a liver transplant currently being the only curative treatment. Since November 2020 Lumasiran is approved for use in patients with PH 1. Lumasiran reduces the hepatic oxalate production by RNA interference and may hence reduce hyperoxaluria. To date there is limited real world data available on the effectiveness of the treatment with Lumasiran.

Method

This observational study looked at the outcome of Lumasiran treatment in 10 patients under the age of 18 years with genetically confirmed PH 1. The primary end point was percentage reduction in plasma oxalate in the two patients on haemodialysis and percentage reduction of urinary oxalate excretion in the patients with preserved renal function. Secondary end points were change in nephrocalcinosis, urolithiasis and renal function. The follow up time was 6 months in one patient and 12 months in the other nine patients.

Results

Four of the patients were girls and the median age at the start of treatment was 5.25 years (range 0.3-17.9 years). One of the two patients on haemodialysis showed a decrease in plasma oxalate which allowed for a reduction of dialysis frequency from 5x/week to 3x/week whilst the other patient's dialysis had to be intensified due to worsening systemic oxalosis. In the patients with preserved renal function the median reduction of urinary oxalate was 71% (range 10–91%) after 6 months and 78% (range 61–86%) after 12 months. Two patients reached values in the age specific normal range (Matos et al.). Lumasiran was discontinued after 4 months in one patient and after 8 months in another one due to treatment failure. An improvement in nephrocalcinosis was seen in three patients and two patients showed a subjective reduction in urolithiasis. Renal function improved slightly in one patient and remained stable in the others. Injection site reactions were the only observed side effects.

Conclusion

Our data highlights the heterogeneity of the disease and treatment response to Lumasiran. Despite promising data regarding the benefits of Lumasiran 2 of 10 patients did not benefit from Lumasiran injections. Hence, it is imperative to regularly re-evaluate hyperoxaluria during treatment with Lumasiran. Ideally the data should be entered into a registry for PH 1 patients to monitor the effectiveness and side effects of this novel drug not only in the short- but also the long term.
#5044 FLUID BALANCE AND GLOMERULAR FILTRATION RATE AS PREDICTORS OF OUTCOME AMONG COVID-19 PATIENTS IN THE ICU
Authors: Jogunčić Anes , Djuric Petar , Gradaščević Anisa , Torka Christina , Rosenberg Mark , Gajic Ognjen , Büttner Stefan
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is associated with an increased risk of progression to a severe form in every disease and, moreover, is associated with an increased mortality, and so it is also with coronavirus disease 2019 (COVID-19). AKI is a frequent complication in COVID-19 patients admitted to ICU for severe respiratory failure. ICU treatment itself indirectly could cause or exacerbate renal damage, through suboptimal fluid management, drug toxicity, or low human resources. The aims of this study were to assess AKI prevalence, fluid balance and glomerular filtration rate as a predictor of outcome in COVID-19 patients treated in the intensive care unit.

Method

We retrospectively analysed all adult patients admitted to the ICU at a regional hospital in northern Bavaria, from 1st March to 31st December 2020. Clinical data and laboratory results were retrospectively retrieved from the hospital information system and electronic case files. According to the severity of AKI based on the KDIGO criteria, and laboratory values were followed on the first 7 days on the ICU. In total 320 patients patients were included in the study. Level of significance was set to p<0.05.

Results

The mean age was 65 ± 19 years, 135 (42%) patients were females, 185 (58%) were males. Median length of ICU stay was 7 (2-13 days) in females, and 8 days (4- to 21 days) in males. At the ICU, 177 patients needed some form of ventilation, from which 109 (needed Invasive mechanical ventilation). During ICU stay, 81 patients have died, with fatality rate of 25%. Patients with AKI (n=48, 15%) at the admission to the ICU, had 2.1 times higher risk of death at the ICU than patients without AKI. There was a statistically significant difference in ICU survival based on a glomerular filtration rate, fluid balance, CRP and leukocyte values, F=1.957, p=0.026; Wilk's Λ=0.724, partial η2 = 0.276

Conclusion

Acute kidney injury is common in coronavirus disease 2019, and it is associated with poor clinical outcomes. Even first couple of days at the ICU could point to the outcome, with markers of inflammation, glomerular filtration rate, and fluid balance being most valuable variables.
#5093 DIALYSIS PATIENTS AND BNT162B2MRNA VACCINE TYPE ARE RISK FACTORS FOR IMMUNITY FADING 9 MONTHS AFTER SARS-COV-2MRNA VACCINATION (DIA-VACC STUDY)
Authors: Stumpf Julian , Anders Leona , Siepmann Torsten , Schwöbel Jörg , Karger Claudia , Lindner Tom H , Faulhaber-Walter Robert , Pietzonka Annegret , Langer Torsten , Escher Katja , Anding-Rost Kirsten , Seidel Harald , Hüther Jan , Pistrosch Frank , Martin Heike , Schewe Jens , Stehr Thomas , Meistring Frank , Paliege Alexander , Schneider Daniel , Bast Ingolf , Steglich Anne , Gembardt Florian , Kessel Friederike , Kröger Hannah , Arndt Patrick , Sradnick Jan , Frank Kerstin , Skrzypczyk Sarah , Anft Moritz , Klimova Anna , Mauer René , Röder Ingo , Tonn Torsten , Babel Nina , Hugo Christian
Published: June 2023

Background and Aims

SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis (DP) and kidney transplant patients (KTR). Recently, we demonstrated that established vaccination related immunity (via positive seroconversion) fades faster in DP and at a lesser extent in KTR compared to medical personnel (MP).[1] We hypothesized that a longer follow up period might be able to profoundly show immunity fading differences specific to different patient groups and identify strong fading risk factors that are relevant for patient management especially in vulnerable groups.

Method

We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy MP (125), DP (595), KTR (111), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks.

Results

Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time (see Fig. 1 and Table 1). By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent.

Conclusion

While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population.
#5094 PREGNANCY OUTCOME AFTER KIDNEY TRANSPLANTATION AND IMPACT ON GRAFT FUNCTION
Authors: Alkot Ahmed , Sally Samir , Sakr Mohamed , Zahran Mahmoud , Wasif Salwa El
Published: June 2023

Background and Aims

Within 2 to 3 weeks of a successful renal transplantation, the fertility of women in childbearing age improves; however, pregnancy after kidney transplantation is challenging and may be associated with serious maternal and fetal complications. To study the prevalence of pregnancy and pregnancy related complication after kidney transplantation.

Method

Retrospective cohort study conducted on 236 patients out of 3000 kidney transplant recipient who underwent renal transplantation (RT) at Mansoura Urology and Nephrology Centre between March 1976 and December 2019, divided into two groups, group I; 118 kidney transplant recipient who experienced pregnancy at any time after kidney transplantation and Group II; 118 kidney transplant recipients who didn`t experience pregnancy after renal transplantation, they were matched according to age, duration of renal transplantation and they are comparable in primary immunosuppressant drugs. All kidney recipients were reviewed for preoperative, operative, and post-operative details also we record maternal and fetal complication.

Results

Prevalence of pregnancy in our centre is 191 pregnancies in 118 women who had underwent kidney transplantation between 1976 and 2019. We have found that the mean age of pregnancy between (26.27±4.37 - 29.89±4.6), the mean gestational age between (33.69±6.4 - 33±7.5) weeks, the live birth rate is 126 (66%). Preterm delivery rate in our study is 85 (44.5%), neonatal death 8 (4.1%), miscarriage 59 (30.9%), intrauterine foetal death 6 (3.1%) and birth defect 4 (2%). The prevalence rates of gestational hypertension is 87 (45.5%), preeclampsia 48 (25.1%), gestational diabetes 19 (9.9%), urinary tract infection 36 (18.8%), and graft rejection 8 (4.1%) during pregnancy. caesarean section is the most common method of delivery in our study 133 (69.6%).

Conclusion

The risk of maternal and fetal complications is still high in RT patients and requires multidisciplinary care. All should be considered in patient counselling and clinical decision making. So we recommend educating the transplanted patients to allow for outcome optimization and minimization of complications.
#5120 CARBON FOOTPRINT OF IN-CENTER HEMODIALYSIS: RESULTS OF A FRENCH PILOT STUDY
Authors: Hachad Hafsah , Rey Jocelyne , Dupré Dylan , Marrauld Maurie , Mariat Christophe , Legallais Cecile , Hourmant Maryvonne , Jullien Perrine
Published: June 2023

Background and Aims

Since the beginning of the industrial era, human activities have led to a significant increase in the concentration of greenhouse gases (GHGs) in the atmosphere and are the cause of climate change, the negative effects of which on human health are already visible (1). Paradoxically, the health sector also exerts a major pressure on the environment through carbon-based care activities that emit GHGs (2). In this context, a few studies have highlighted the significant carbon footprint associated with hemodialysis (3). However, to date, no similar study has been conducted in France.

Method

The objective of this work was to evaluate the carbon footprint of a hemodialysis unit in France using the Bilan Carbone ® approach developed by The French Agency for Ecological Transition and the Bilan Carbone Association. Activity data associated with hemodialysis provision at the Charles De Gaulle facility in 2021 was collected and converted to a common measurement unit of tonnes of CO2 equivalents (t CO2-eq) via established emissions factors. This facility, that belongs to the ARTIC 42 association, is located in the town of Saint-Priest en Jarez and provides hemodialysis through a total of 56 hemodialysis generators.

Results

Over the year 2021, the Charles de Gaulle facility provided a total of 25270 hemodialysis treatments ensuring the care of approximately 162 patients (at a rate of 3 sessions per week). The associated annual carbon footprint for the facility was 1436 t CO2-eq. Annual carbon footprint amounted to 8.9 t CO2-eq/patient/year corresponding to 57 kg CO2-eq /treatment. Emissions were essentially indirect, with more than 90% coming from scope 3. The main sources of emissions were: products and services purchase (30% of total emissions, that is 437 t CO2-eq), patients and staff travels (25% of total emissions, that is 361 t CO2-eq), and fixed assets (21% of total emissions, that is 299 t CO2-eq). Energy consumption (particularly electricity) and waste treatment accounted for a small proportion of GHG emissions (respectively 8% et 6%).

Conclusion

Our results confirm the high carbon footprint associated with in-center hemodialysis, showing that it is mainly attributable to indirect emissions. These empirical data will serve as a basis for reflection in the development of a strategy to reduce GHG emissions associated with hemodialysis. This work will hopefully be paving the way for the necessary ecological transition of medical practices, focused on the patient and the ecosystems on which he/she depends.
#5123 EFFICACY AND SAFETY OF PATIROMER IN THE TREATMENT OF CHRONIC HYPERKALEMIA IN ASTURIAS: THE K-ASTUR STUDY
Authors: Sanchez-Alvarez Jose Emilio , Bueno María del Carmen Merino , Pérez Anna Gallardo , Sango Cristina , Zorrilla Carlos Ruiz , Ulloa Catalina
Published: June 2023

Background and Aims

Hyperkalemia is a frequent problem in patients with chronic kidney disease (CKD), especially in those on hemodialysis (HD) and confers increased morbidity and mortality. It is common to carry out urgent HD sessions or increase the number of weekly sessions due to toxic hyperkalemia. Hyperkalemia also prevents the administration or adequate titration of drugs such as renin-angiotensin-aldosterone system (RAAS) inhibitors despite the evidence of their cardiovascular benefits and on the progression of CKD. New drugs have recently entered the market that can help treat chronic hyperkalemia. The aim of the present study was to analyse the efficacy and safety of Patiromer in patients with CKD

Method

Multicenter, prospective, clinical practice study in patients with CKD stages 3-5. Patiromer was administered with the indication of chronic hyperkalemia. Epidemiological and clinical data were analyzed; the evolution of serum potassium and elements involved in bone and mineral metabolism were taken into account.

Results

Finally, 52 patients (71±12 years old, 75% male, 63% diabetic, 54% with heart failure, and 42% receiving RAAS inhibitors) were included in the study. Regarding CKD, 17% were in stage 3b, 31% in stage 4, 38% in stage 5 (not on dialysis) and 13% were on HD. Of the 52 patients included, 46 reached 6 months of follow-up, 2 died, 2 underwent a kidney transplant and 2 were transferred to another center. The initial dose of Patiromer was in all cases 8.4 g administered orally in a single dose. Only one patient required doubling the dose because the therapeutic objectives were not achieved. Taking Patiromer was associated with a decrease in the levels of serum potassium of 27% (5.9 vs 4.6 mEq/L; P<0.001), a decrease that was more pronounced in the first month of treatment. There were no changes in the concentration of serum calcium and magnesium. We did find a decrease of 18% in serum phosphorus (5.1 vs 4.2 mg/dl; P 0.022), with no changes in dieto r phosphate binders. Patiromer was well tolerated and only 2 patients reported mild constipation; none discontinued the medication due to adverse effects.

Conclusion

Patiromer is effective and safe in reducing serum potassium concentrations. Due to its calcium content, it is possible that it favors the reduction in phosphoremia due to a decrease in the intestinal absorption of phosphorus. The use of this drug can help us control potassium levels in patients with CKD, properly titrate the use of ISRAAs, and even reduce the number of HD sessions or dialysis emergencies in some patients.
#5128 PREDICTIVE FACTORS OF RENAL RECOVERY AND END-STAGE KIDNEY DISEASE IN PATIENTS WITH SEVERE ANCA-ASSOCIATED VASCULITIS WITH GLOMERULONEPHRITIS
Authors: Moura Marta Casal , Zubidat Dalia , Patricio Marc , Romeo Maria José Soler , Santos Fernanda Dos , Nardelli Luca , Román Juan León , Sousa Círia , Zand Ladan , Warrington Kenneth , Sethi Sanjeev , Specks Ulrich , Fervenza Fernando Custodio
Published: June 2023

Background and Aims

A significant number of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) still progress to end-stage kidney disease (ESKD, eGFR<15mL/min/1.73m2) despite advances in remission-induction treatment.

Method

A retrospective cohort study on MPO- or PR3-ANCA positive patients with AAV (MPA or GPA) and ESKD at presentation. Renal recovery, dialysis discontinuation and maintenance in ESKD after standard remission-induction, with or without the use of PLEX were compared.

Results

We analyzed 166 patients with biopsy proven active kidney involvement and eGFR <15mL/min/1.73m2 at the time of AAV-GN diagnosis. Patients received glucocorticoids with CYC (n = 84) or with RTX (n = 72) for remission-induction, and 49 also received PLEX. The predictors for renal recovery were erythrocyte sedimentation rate, SCr at diagnosis and minimal or mild chronicity changes. We analyzed 71 patients who started dialysis with or without PLEX within 4 weeks from AAV-GN diagnosis. The predictors for dialysis discontinuation were minimal chronicity changes in kidney biopsy at the time of diagnosis (OR 6.138, [95%CI 1.389-27.118],p = 0.017) and focal glomerular involvement (OR 5.017,[95%CI 1.287-19.567],p = 0.020). Predictors for maintenance in ESKD at 12 months included higher serum creatinine (SCr) at the time of diagnosis (IRR 1.086, [95%CI 1.005-1.173],p = 0.037), moderate (IRR 3.797,[95%CI 1.090-13.225],p = 0.036), or severe chronicity changes in kidney biopsy (IRR 5.883,[95%CI 1.542–22.439],p = 0.009).

Conclusion

In our cohort, kidney recovery, dialysis discontinuation, and maintenance of ESKD in patients with AAV-GN and eGFR<15mL/min/1.73m2 depended on SCr and histologic findings on kidney biopsies at the time of diagnosis and was not affected by the addition of PLEX.