bluuebunny/crossref_metadata_2025 huggingface dataset:
#5511 EXPLORING THE IMPACT OF POTENTIAL UREMIC TOXINS IN CHRONIC KIDNEY DISEASE BY PROTEOMICS: POTENTIAL BENEFITS OR ADVERSE EFFECTS?
Authors: Grgurevic Lovorka , Vojtušek Ivana , Novak Rudjer , Salai Grgur , Hrkac Stela , Brinar Ivana Vukovic
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is a progressive disorder characterized by a gradual reduction in kidney function. Proteomics, a large-scale analysis of protein modifications, has been used to study CKD and identify potential therapeutic targets. Studies have found that CKD is associated with changes in the expression of numerous proteins, including those involved in inflammation, cell adhesion, and metabolism. Additionally, proteomic studies have been used to identify potentially novel uremic toxins, which are compounds that accumulate in the body due to impaired kidney function.

Method

We performed a cross-sectional shotgun-proteomic study of pooled plasma across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants’ plasma by liquid-chromatography/mass-spectrometry.

Results

Our results of proteomic profiling of the plasma of the patients with CKD1-5, including those after kidney transplantation, unequivocally showed that the key processing of the disease, regardless of the type and function of the observed protein groups, occurs in stage 2 of CKD, which we could call the stage - a tipping point. Through the analysis of 453 proteins, 7 established uremic toxins of "middle molecular mass" were identified. Further analysis was conducted to identify potential candidates for new uremic toxins, resulting in the identification of 15 novel proteins that may have a systemic inflammatory effect, atherogenic potential, or increase the risk of cardiovascular diseases.

Conclusion

These findings suggest that proteomics can be used to identify novel uremic toxins and provide new insights into the pathophysiology of CKD and selected toxins arrange by toxic, beneficial effect or both. Further research is needed to validate these findings and explore the potential therapeutic implications of targeting these uremic toxins.
#5613 ASSESSMENT OF THE PROGRESSION OF CKD TAKING INTO ACCOUNT METABOLIC CHANGES
Authors: Karimdjanova Guzal , Egamberdieva Dano , Ruzmetova Iroda
Published: June 2023

Background and Aims

To study was to study the relationship between the metabolic syndrome and the risk of CKD progression in a representative sample of patients who were hospitalized at the Department of Cardiology and Interventional Cardiology of the Republican Specialized Scientific and Practical Medical Center for Therapy and Medical Rehabilitation.

Method

In the prospective part of the study, information on demographic characteristics, including age, gender, education, and occupation, was collected from doctor's visits using a standard questionnaire. Metabolic syndrome was defined according to international guidelines in the presence of three or more of the following risk factors: waist circumference >102 cm in men or >88 cm in women; serum triglyceride level ≥1.70 mmol/l; HDL cholesterol level <1.04 mmol/l in men or <1.30 mmol/l in women; BP ≥ 130/85 mm Hg, including achieved; serum glucose level ≥6.11 mmol/l. The criteria for determining the metabolic syndrome were used.

Results

Demographic characteristics of patients are presented in the table. Mean serum creatinine was similar, but GFR was estimated to be lower among those with metabolic syndrome compared to those without. The percentage of individuals with CKD and elevated serum creatinine was statistically significantly higher among those with metabolic syndrome. It turned out that low HDL cholesterol, elevated plasma glucose and abdominal obesity were statistically significantly associated with the risk of developing C5 CKD and elevated serum creatinine. In addition, there was a significant relationship between the number of metabolic syndrome components and the percentage of C5 CKD or elevated serum creatinine (P<0.015 and P=0.02, respectively). In the multivariate model, patients with 1, 2, 3, and 4 or 5 components of the metabolic syndrome had 1.51; 1.50; 2.13 and 2.72 times higher chances of CKD C5 CKD, respectively, compared to individuals without metabolic syndrome components. Overall, patients with metabolic syndrome had a 64% increase in the odds of CKD compared to the comparison group without metabolic syndrome.

Conclusion

In the present study, a positive and significant relationship was found between the metabolic syndrome and the risk of C5 CKD in the examined patients. The risk of CKD increased progressively with an increase in the number of components of the metabolic syndrome.
#5677 UPAR ACTIVATION BY UPARANT INDUCED FUNCTIONAL AND STRUCTURAL RECOVERY OF PODOCYTES AFTER FSGS-SERUM DAMAGE
Authors: Deborah Mattinzoli , Silvia Armelloni , Min LI , Daniele Dalonzo , Maria Defenza , Masami Ikehata , Carlo Maria Alfieri , Vincenzo Pavone , Giuseppe Castellano
Published: June 2023

Background and Aims

Idiopathic focal segmental glomerular sclerosis (FSGS) is characterized by progressive damage to the renal parenchyma leading to end-stage renal disease, frequent recurrence after kidney transplantation and no specific therapeutic intervention. Since the podocytes (PODO) are the principal target of FSGS injury, their protection could be an efficient, targeted therapy. In this context, we investigated a potential therapeutic approach based on a new peptide, UPARANT, capable of modulating the Urokinase-type plasminogen activator receptor (uPAR) on PODO.

Method

PODO were activated with 4% sera of 5 patients with recurrent FSGS for 48 h and then treated with 100 nM of UPARANT for 48 h. Proteins were then extracted for TMT proteomics. The Gene Ontology system database, valid for large-scale analysis, was used to identify the significantly enriched biological pathways and molecular functions. An in vitro model of a glomerular filtration barrier composed of PODO-endothelial co-culture was used to assess the change in filtration capacity by albumin (BSA) permeability test. The difference from baseline BSA percentage was measured after damage induced with sera from three FSGS patients and after 48 h of treatment with UPARANT.

Results

First, we found that UPARANT could counteract the BSA permeability induced by FSGS sera in the PODO-endothelial co-culture (P = .04, P = .03, and P = .02, respectively). The proteomic analysis of PODO indicated that UPARANT induced the positive regulation of plasma membrane repair mechanisms (Annexin 2 P = .007 and AHNAK P = .03); this process was strongly linked to the activation of molecular functions related to both S100 and calcium-dependent proteins. Moreover, UPARANT induced the overexpression of Endophilin-B1 (P = .02) and Vimentin (P = .02), both involved in the assembly and organization of the actin filament.

Conclusion

We demonstrated that UPARANT efficiently counteracts in vitro the effects of FSGS sera on PODO, leading to the recovery of the spatial organization of PODO, acting on the structural integrity of the plasma membrane and restoring cytoskeletal plasticity and dynamism. This might result in vivo in the protection of the integrity of the filtration barrier.
#5686 CANCER STATUS AND MORTALITY IN ELDERLY INCIDENT HEMODIALYSIS PATIENTS
Authors: Cho Hyunjeong , Park Miran , Sun In O , Park Woo Yeong , Cho Jang-Hee , Kwon Soon Hyo , Hwang Won Min , Hong Yu Ah , Shin Sung Joon , Chung Sungjin , Yoo Kyung Don
Published: June 2023

Background and Aims

Chronic kidney disease and elderly people are associated with an increased risk of malignancy. But it remains unclear whether older patients with active cancer or a history of previous cancer and those without a cancer history carry the same mortality risk after initiation of hemodialysis (HD). Hence, we investigated the prognosis according to cancer status in elderly patients who started HD.

Method

Using a retrospective cohort of the Korean Society of Geriatric Nephrology, in this analysis, we included 2,085 patients older than 70 years who initiated hemodialysis between 2010 and 2017. Primary outcome of all-cause mortality was assessed using the Kaplan-Meier survival estimator and Cox proportional hazards regression analysis.

Results

At recruitment, 262 (12.6%) had a history of previous cancer and 55 (2.6%) had active cancer. During a median follow-up of 3.2 years, 1357 (65.1%) died. All-cause mortality was significantly higher in the active cancer group than in the previous cancer group and the no cancer group (85.5% vs 68.3% vs 64.0%, p < 0.002). Kaplan-Meier analysis revealed that all-cause mortality was significantly different among the 3 groups (p < 0.001, by log-rank test). After adjustment for various clinical factors, multivariate Cox regression analysis showed a strong association of active cancer with all-cause mortality (HR:1.89; 95%CI: 1.36–2.64; p < 0.001). However, previous cancer was not related to an increased risk of overall mortality (HR:1.07; 95%CI: 0.90–1.28; p = 0.448)

Conclusion

Active cancer was associated with high mortality in incident older hemodialysis patients. But patients with a history of previous cancer had a similar mortality risk compared to patients without a cancer history. Therefore, our study suggests that older cancer survivors may be able to maintain dialysis successfully.
#5759 ASSOCIATION BETWEEN PHYSICAL ACTIVITY LEVEL QUESTIONNAIRES AND DAILY STEP COUNTS IN PATIENTS ON HEMODIALYSIS
Authors: Reboredo Maycon Moura , Alvarenga Bárbara , de Jesus Luciana , Paticcié Gabriela , Da Silva Carlos Miguel , Amorim Amanda , de Souza Camila , Segura-Ortí Eva , Pinheiro Bruno , Lucinda Leda
Published: June 2023

Background and Aims

In patients on hemodialysis, sedentary lifestyle is highly prevalent and associated with elevated mortality. The sedentary lifestyle of these patients can be confirmed by assessing the physical activity level (PAL) evaluated by accelerometers and questionnaires. Considering that the PAL questionnaires are quick to perform and inexpensive, the aim of this study was to evaluate the association of three PAL questionnaires with daily step counts measured by an accelerometer in patients on hemodialysis.

Method

A cross-sectional study was conducted with patients aged ≥18 years who were undergoing hemodialysis treatment for at least three months. Patients were excluded if presented severe and unstable comorbidities, psychiatric or cognitive disorders, and hospitalization in the past three months. The daily step counts were recorded in the ActiGraph accelerometer (wGT3X-BT) during seven days, and analyzed by excluding the first and last day of recording and calculating the mean among the valid days (≥ 8 hours of wear time). Subsequently, the Human Activity Profile (HAP) questionnaire, the International Physical Activity Questionnaire (IPAQ) and the physical functioning domain of the 36-Item Short Form Survey (PF SF-36) were applied. The normality of the data was analyzed using the Shapiro‒Wilk test. The associations between each PAL questionnaire score and daily step counts were tested using Spearman´s correlation coefficients. Then, three multiple linear regression models were constructed with daily step counts as the dependent variable and PAL questionnaire score and potential confounders (age, gender, educational level, time on dialysis, hemoglobin, and body mass index) as independent variables. A p value <0.05 was considered as statistically significant.

Results

This study included 105 patients (59.2 ± 12.5 years, 60.0% male). Daily step counts correlated significantly with the questionnaires scores (HAP, ρ = 0.552, p < 0.001; IPAQ, ρ = 0.386, p < 0.001; PF SF-36, ρ = 0.337, p < 0.001). After adjusting for potential confounders, the multiple linear regression models showed an association between daily step counts with the HAP questionnaire score (R2 = 0.31; adjusted R2 = 0.26; p < 0.001) and PF SF-36 score (R2 = 0.23; adjusted R2 = 0.18; p = 0.001).

Conclusion

The PAL questionnaires were associated with daily step counts measured by an accelerometer in patients on hemodialysis. However, our results suggest that the HAP was the best questionnaire to evaluate PAL in these patients.
#5799 COMPENSATORY HYPERTROPHY OF THE KIDNEY CONTRIBUTES TO LOSS OF KLOTHO KIDNEY THROUGH PAKT SIGNALING
Authors: Pérez-Gomez Aurora , Diaz-Tocados Juan Miguel , Coral Juan Diego Dominguez , Enriquez Maite Caus , García-Carrasco Alicia , Bardaji Ana Martinez , Revilla José Manuel Valdivielso
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) represents a significant public health burden worldwide, mainly driven by the increase of the incidence of associated risk factors like diabetes. Decreased renal Klotho expression is an early feature of CKD, driving an increase on circulating FGF23 and phosphate. These alterations in mineral metabolism have a direct negative impact on the progression of renal dysfunction and can cause bone alterations, vascular calcification and heart failure. In parallel, during the early stages of CKD, kidneys activate molecular mechanisms of hypertrophy in an attempt to counteract the loss of renal function. The PI3K/Akt/mTOR pathway, activated by growing factors like insulin-like growing factor-1 (IGF-1) participates in compensatory renal growth. The aim of the present study is to investigate the possible role of PI3K/Akt activation on renal Klotho levels during renal compensatory hypertrophy.

Method

We generated a mice model of kidney compensatory hypertrophy (UNX mice) in which kidney klotho levels and circulating mineral metabolism parameters were analyzed. Furthermore, some of the mice were treated with inhibitors of the PI3K/Akt/mTOR pathway. In vitro, proximal tubular epithelial human cells (PTEC) were stimulated with IGF-1 in order to activate the PI3K/Akt pathway, and the effects on Klotho expression were determined.

Results

UNX mice present with an activation of the PI3K/Akt/mTOR pathway in kidney, which correlates with the loss on renal Klotho expression. Moreover, UNX mice showed an increase on both, plasma phosphate and FGF23, and a decrease in the fractional excretion of phosphate (% FEPi). Renal function, estimated by BUN plasma levels, was unaltered. Pharmacological inhibition of the pathway restored Klotho and decreased FGF23 levels, normalizing renal phosphate excretion and blood levels. In vitro, IGF-1 stimulated PI3K/Akt activation in PTEC and induced a decline on Klotho expression, which was restored with PI3K/AKT inhibitors.

Conclusion

The overactivation of PI3K/Akt/mTOR pathway in renal hypertrophy modulates Klotho expression and has direct effects on FGF23 and phosphate. Our findings constitute an important breakthrough in the research of new therapeutic targets in order to maintain renal Klotho levels, and it may be useful in the treatment of kidney disease patients.
#5887 RESULTS OF KIDNEY TRANSPLANTATION IN VERY-HIGHLY SENSITIZED PATIENTS INCLUDED IN AN EXCHANGE PROGRAM BASED ON VIRTUAL CROSSMATCH
Authors: Fernández Florentino Villanego , Mazuecos Auxiliadora , Lopez Veronica , Guindo María del Carmen de Gracia , Alonso Marta , Nuez Pablo Castro de la , Blanco Gabriel Bernal , Rodríguez-Benot Alberto , Marquez Antonia Alvarez
Published: June 2023

Background and Aims

In 2012, a kidney transplant (KT) exchange program for very-highly sensitized patients (panel reactive antibody [PRA] ≥95%) began in Andalusia between the 5 KT centers based on virtual crossmatch.

Method

Retrospective cohort study of KT recipients within the Andalusian very-highly sensitized patients’ program from 2012 to December 2021. Survival was analyzed using Kaplan-Meier. We performed a multivariable analysis using Cox regression for pre-KT risk factors for graft survival.

Results

During the study period, 213 KT were performed. The median PRA was 98%. of them, 18.7% were KT from type-III non-heart-beating donors and 69.5% were retransplanted patients. The median time on renal replacement therapy until KT was 1509 days and, from their inclusion in the very-highly sensitized patients’ program, 334 days. The median post-KT follow-up time was 1103 days. Patient/graft survival was 97.5%/91.7% and 82%/76.5% at one year and 5 years, respectively. Graft survival was lower in patients who had received more than one KT (P = .029). However, we found no differences when comparing PRA (< or ≥98%) or type of donor. In the multivariable analysis, the number of previous KT was a predictor of graft loss. We had more detailed information on renal function and post-KT complications in patients from 3 centers (n=104). Six patients (5.7%) developed donor-specific antibodies (DSA) (1 class I, 3 class II, 2 class I and II) after a median of 267.5 days post-KT. Ten patients (9.3%) presented acute rejection (AR) diagnosed by biopsy: 4 T-cell-mediated rejection (3.7%) and 6 antibody-mediated rejection (5.6%). Active antibody-mediated chronic rejection (CR) was diagnosed in 5 patients and BK nephropathy in 2. Three graft losses were due to immunological causes (1 RA, 2 RC). Median renal function at one year was: Crp 1.3 mg/dl and glomerular filtration rate 55.1 ml/min.

Conclusion

Despite being a high-risk group, the survival results have been very satisfactory. The number of previous KT is a risk factor for graft survival.
#6178 ANCA-ASSOCIATED VASCULITIS FOLLOWING PFIZER-BIONTECH COVID-19 VACCINE: TRUE ASSOCIATION OR CIRCUMSTANTIAL?
Authors: Marouço Catarina , Pereira Tiago Assis , Fonseca Nuno Moreira , Menezes Maria Do Mar , Carvalho Dulce , Magriço Rita , Nolasco Fernando
Published: June 2023

Background and Aims

Antineutrophil cytoplasmatic antibody (ANCA)- associated vasculitis (AAV) is a small vessel vasculitis hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. Vaccines per se stimulate the immune system, including the innate and the adaptive immune response. Therefore, it is possible that an excess of autoimmunity is observed after vaccine administration. Vaccination (notably influenza) is a recognized trigger for the relapse of ANCA-associated vasculitis. ANCA associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination.

Results

We report the case of a Caucasian, 62 year-old-man, with a previous history of type 2 diabetes mellitus, hypertension and atrial fibrillation. Blood analysis one year before presentation showed preserved renal function and normal urinalysis. He received the first dose of Pfizer-BioNTech COVID-19 vaccine and two weeks later routine blood analysis showed acute kidney injury with serum Creatinine 1.75 mg/dL with de novo hematuria, a protein to creatinine ratio (RPC) 1.1 mg/g and candersartan (4 mg twice daily) was started. The patient received the second dose of COVID-19 vaccine 21 days after the first injection. Two weeks later he developed anorexia, nausea and de novo hematuria. He was admitted at the emergency department with deteriorating renal function with a sCr of 5.5 mg/dL, worsening hematuria with dysmorphic red blood cells and proteinuria (RPC 2.9 mg/g). Renal ultrasound was normal. Immunological studies revealed an elevated ANCA-MPO titer of 561. A kidney biopsy was performed and showed a crescentic necrotizing glomerulonephritis. Immunofluorescence confirmed pauciimmune glomerulonephritis. He was diagnosed with renal limited myeloperoxidase (MPO) ANCA AAV. He started 3 pulses of 500mg I.V methylprednisolone followed by prednisolone 1 mg/kg/day after that. He also started rituximab (4 doses of 500mg I.V once week apart). Despite the immunosuppression, the patient never recovered renal function and remained dialysis dependent.

Conclusion

Whether autoimmune diseases can be triggered after vaccination remains a matter of discussion among experts. ANCA associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination, which prompts the question whether this response could be a direct reaction to the RNA present in the vaccine. While an association with de novo ANCA vasculitis and COVID-19 vaccine may be possible, further investigation is necessary.
#6192 COGNITIVE DYSFUNTION AND ASSOCIATED RISK FACTORS IN PERITONEAL PATIENTS
Authors: Knezevic Violeta , Azasevac Tijana , Celic Dejan , Bozic Dusan , Veselinov Vladimir , Petrovic Lada
Published: June 2023

Background and Aims

Patients with cognitive dysfunction (CD)are at greater risk of having a poor quality of life, hospitalization and mortality. Although CD in chronic kidney disease is current, most of the studies performed are cross-sectional. The aim of this cross-sectional study was to determine the presence of CD in the patients on peritoneal dialysis (PD)and to identify possible risk factors associated with CD.

Method

We performed a study to evaluate the CD of 30 PD patients in our institution using the mini-mental state (MMSE), and a score of <25 was considered to indicate cognitive dysfunction. Demographic, clinical and laboratory parameters, adequacy of dialysis and drugs were analyzed. The statistical analysis included the chi-square test, t-test of independent samples, Mann-Whitney, and correlation.

Results

We evaluated 30 patients mean age of 57.27 years (SD±12.086); 56.7% were male. About 66.7% of our patients were in marriage, 73.3% were not actively working, 13.3 had a lower level of education, and 56.7% lived in a city. The most prevalent comorbidities were glomerulonephritris and hypertension, both with 30.0%. 19 (57.6%) patients had average fast membrane characteristics. 15 of them (50%) had a daily dose of calcium phosphate binder >2g.MMSE test with a score lower than 25 was present in 36,7% of patients (IQR=4). Statistical analysis revealed a positive correlation between MMSE and weekly total Kt/V urea index (WTKt/V), and the t-test of independent samples showed that patients with better MMSE score values have significantly higher average WTKt/V values (t=-3.062, p<0.011).

Conclusion

MMSE test with a score less than 25 was present in 36.7% of patients and patients with better MMSE scores have significantly higher average WTKt/V values.
#6375 HYPOPROTEIC DIET SUPPLEMENTED WITH KETOANALOGUES VERSUS CONVENTIONAL DIET IN PATIENTS WITH ADVANCED DIABETIC KIDNEY DISEASE AND SEVERE PROTEINURIA
Authors: Mocanu Carmen-Antonia , Mircescu Gabriel , Ismail Gener , Garneata Liliana
Published: June 2023

Background and Aims

Low-protein diets seem to have an important role in the management of advanced chronic kidney disease (CKD). In addition, this type of nutritional regimen may defer kidney replacement therapy by improving metabolic abnormalities. However, low-protein diets (LPDs) may be more difficult to integrate in patients with diabetic kidney disease (DKD), because of the already complex dietary intervention in these patients. This is a comparative study that aimed to assess the effects of a ketoanalogue-supplemented low-protein diet (sLPD) versus a conventional diet on the progression of CKD and proteinuria in patients with advanced DKD.

Method

Ninety-seven adult patients with DKD and heavy proteinuria (>3g/g creatininuria) who proved to be compliant to protein restriction in a 3-month run-in phase were enrolled to receive a LPD (0.6g mixed protein/kg-day) supplemented with ketoanalogues of essential amino acids (Ketosteril®, Bad Homburg, Germany, 1 tb/10 kg dry ideal body weight per day) for 12 months. Ninety-two patients completed the study (5 patients received preemptive kidney transplant). The control group was made up of seventy-four adult patients with DKD and heavy proteinuria who received a conventional diet for 12 months. Efficacy outcomes were variation of the estimated glomerular filtration (eGF) and variation of proteinuria.

Results

At baseline, patients from the sLPD group had a median age of 61 years (95% CI 58 to 67), were mostly male (66%) and predominantly on insulin (68%). Patients in the control group had a median age of 60 years (95% CI 56 to 61), 62% were male and, similarly, the majority were on insulin (62%). All patients had poorly controlled diabetes, with a glycated hemoglobin of 8.1% (95% CI 8.0 to 8.3) in the sLPD group and 8.2% (95% CI 7.9 to 8.6) in the conventional-diet group respectively (P = .84). Although the median eGF was different between groups: 24.78 mL/min (95% CI 20.00 to 30.00) in sLPD patients versus 12.61 mL/min (95% CI 11.70 to 13.11) in conventional diet patients (p<0.0001), proteinuria was similar at baseline: 5.26 g/g creatininuria (95% CI 4.98 to 5.22) in sLPD patients and 4.05 g/g creatininuria (95% CI 3.70 to 5.80) in control group patients (P = .44). After 12 months, the decline of eFG (mL/min/month) was four-times slower in the sLPD group versus the control group [0.11 (95% CI 0.1 to 0.14) versus 0.43 (95% CI 0.30 to 0.57), p<0.0001]. A twofold reduction in proteinuria (g/month) was observed in sLPD patients compared to conventional diet patients [0.29 (95% CI 0.28 to 0.32) versus 0.12 (95% CI 0.09 to 0.15), p<0.0001].

Conclusion

Low-protein diets supplemented with ketoanalogues of essential amino acids seem to be more efficient in reducing kidney function decline and proteinuria than conventional diets.
#6376 TREATMENT OF DABIGATRAN INTOXICATION IN CRITICALLY ILL PATIENTS WITH ACUTE KIDNEY INJURY: THE ROLE OF SUSTAINED LOW-EFFICIENCY DIALYSIS
Authors: Pacchiarini Maria Chiara , Regolisti Giuseppe , Greco Paolo , Motta Tommaso Di , Benigno Giuseppe Daniele , Delsante Marco , Fiaccadori Enrico , Mario Francesca Di
Published: June 2023

Background and Aims

Dabigatran, a direct thrombin inhibitor, is a commonly used direct oral anticoagulant (DOAC) prescribed for non-valvular atrial fibrillation. Despite its benefits in term of safety/effectiveness along with the possibility to treat patients who were ineligible for vitamin K inhibitors (VKAs), a great degree of attention is required in elderly patients with multiple comorbidities. Notably, dabigatran mainly undergoes renal elimination, and dose adjustment is recommended in patients with Chronic Kidney Disease (CKD). In this regard, the onset of an abrupt decrease of kidney function may further affect dabigatran pharmacokinetic profile, increasing the risk of acute intoxication. Idarucizumab is the approved antagonist in the case of dabigatran-associated major bleeding or concomitant need of urgent surgery, but its clinical use is limited by the lack of data in patients with Acute Kidney Injury (AKI). Given the dabigatran PK parameters (low MW, low Vd, negligible protein binding), the early start of Extracorporeal Kidney Replacement Therapy (EKRT) may represent the optimal reversal strategy. We present a case series of three critically ill patients with AKI and dabigatran overdose treated with Sustained Low-Efficiency Dialysis (SLED).

Methods

Three critically ill patients (Table 1) were admitted to the Renal Intensive Care Unit (ICU) for stage 3 AKI and intercurrent dabigatran intoxication. SLED sessions with Regional Citrate Anticoagulation (RCA) were prescribed with SURDIAL X machine, ELISIO-21M filter (Nipro Co., Osaka, Japan) [blood flow rate 200 mL/min, dialysis fluid rate 300 mL/min; citrate flow rate 350 mL/h (ACD Fresenius Kabi, Italia)]. Dabigatran plasma levels (dilute thrombin time, dTT) along with coagulation parameters were monitored before, during and after SLED session.

Results

A rapid and sustained decreased of plasma dabigatran level was observed in each patient in course of SLED sessions. No clinically relevant post-treatment rebound was reported (Figure 1).

Conclusions

SLED meets the requirements to be a viable reversal anticoagulation option in the context of dabigatran overdose. Indeed, it efficiently provides dabigatran removal, by reaching a safe plasma concentration within the first hours and avoiding significant rebound effect.
#6475 AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE WITH COMPLETE SITUS INVERSUS: A CASE REPORT
Authors: Mrabet Sanda , Rihem Dahmane , Emah Sidina , Boukadida Raja , Azzabi Awatef , Guedri Yosra , Wissal Sahtout , Zellama Dorsaf
Published: June 2023

Background and Aims

Association between complete Situs inversus and autosomal polycystic kidney disease is rare. The Medline search revealed only three such cases. We report the fourth one. Recent studies have revealed ciliary dysfunction as a cause of both conditions.

Method

we report a case of association of familial hereditary polycystic kidney disease with a situs inversus.

Results

A 32-year-old patient with a familial history of polycystic kidney disease and stroke was admitted to Nephrology for severe renal failure with hypertension. On examination, the patient had a blood pressure of 160/100mmHg. The abdomen was soft, with bilateral palpable renal masses with irregular surfaces. Neurological examination was without abnormalities. The blood test showed creatinemia at 829µmol/L, urea at 44mmol/L, correct ionogram, CO2 at 19 mmol/L, calcemia at 1.98mmol/L and uric acid at 860 µmol/L. The 24-hour proteinuria was 1.5g. The cytobacteriological examination of the urine was negative. The chest X-ray showed a situs inversus of the heart. On abdominal ultrasound, the kidneys were polycystic, the liver was seen on left and the spleen on the right. The patient was put on antihypertensive treatment with a calcium channel blocker and Purinol. Given the clinical and biological improvement, the patient was discharged with close monitoring at the outpatient clinic with possible preparation for hemodialysis. In addition, a cerebral MRI angiography was requested to detect cerebral damage because of the family history of stroke.

Conclusion

Polycystic kidney disease is caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene. Several proteins that are encoded by genes associated with polycystic kidney disease have been identified in primary cilia in renal tubular epithelia. These findings have suggested that abnormalities in cilia formation and function may play a role in the pathogenesis of PKD. Treatment options for PKD are still being explored but further research can develop solutions to increase the life expectancy of patients diagnosed with PKD. Cases like this are rare but could provide more information on the causes of PKD and Situs Inversus leading to these new solutions.
#6559 THE ROLE OF MEDIUM-CHAIN FATTY ACIDS IN RENAL METABOLISM AND DISEASES
Authors: Yiting Wu
Published: June 2023

Background and Aims

Through metabolomics research, it was found that in mice with chronic kidney disease, the distribution of lipids in the kidneys was different from that of healthy individuals, and medium-chain fatty acids were reduced. In order to explore the role of medium-chain fatty acids in kidney metabolism and disease, we conducted this systematic review.

Method

Systematic review. The pubmed database was used to search for keywords such as medium chain fat acids, medium chain triglyceride, MCFA, MCT, chronic kidney disease, CKD, and renal fibrosis.

Results

In chronic kidney disease, long-chain fatty acids decrease and medium-chain fatty acids increase. The increase of medium-chain fatty acids may be a compensatory mechanism. Compared with long-chain fatty acids, medium-chain fatty acids are more easily metabolized through the tricarboxylic acid cycle, thus providing more energy. MCFAs are readily oxidized by cells,including cardiomyocytes, and provide a very efficient. source of energy production. MCFAs display metabolic,biological and physical properties that are distinct fromLCFAs, which may contribute to their reported benefits on the kidney's energy status and function. Only few deleterious effects have been reported with the use of MCFAs, many of which have been reported mainly when MCTs were administered as the main dietary energy source representing >50% of the total energy intake. These include decreased absorption of LCTs, which may result in deficiency in essential polyunsaturated LCFA, steatorrhea, gastrointestinal discomfort, increased risk of ketogenesis and acidosis, and in some studies, though not all, changes in blood lipid profile such as a raise in triglycerides or nonhigh-density lipoprotein cholesterol

Conclusion

Studies in animal models indicate that MCFAs may favourably modulate kidney disease progression. Medium-chain fatty acids have protective effects on the kidney and provide new ideas for the relief and treatment of chronic kidney disease.
#6666 RISK FACTORS FOR CHRONIC KIDNEY DISEASE AFTER ACUTE KIDNEY INJURY IN ELDERLY SUBJECTS
Authors: Mahmoud Nouha Ben , Ghabi Faten , Hammouda Mouna , Salem Meriem Ben , Salah Manel Ben , Letaief Ahmed , Sabra Aloui , Skhiri Habib
Published: June 2023

Background and Aims

Acute kidney injury (AKI) in the elderly is a fairly frequent phenomenon that is favored by functional changes in the kidney and the impact of many chronic diseases whose incidence increases with age. This exposes this particular population to a higher risk of developing chronic kidney disease (CKD). The risk of developing a new CKD in elderly subjects has been estimated to be 4 times that of the population without an episode of AKI in several studies. Our objective was to identify risk factors in this population

Method

This is a retrospective descriptive study that included patients over 65 years of age for AKI with recovery of normal renal function between January 2002 and December 2015 and who were followed up to one year after discharge. In order to achieve our objective, we collected data related to the patients' age, history, multitargeted or not, mechanism of AKI, KDIGO stage, glomerular filtration rate (GFR) at hospital discharge, using a pre-designed form.

Results

Among 93 patients who were followed up 18 had developed CKD with a median delay of 6.5±0.4 months. The sex ratio was 0.93 (M/F). In our population 37% were diabetics; 52 of them were multitargeted and 62 had a GFR < 60 ml/min at discharge. 11 patients had required extra renal purification. The most important mechanism of ARF was pre renal (59.1%). Among the risk factors studied (diabetes, hypertension, use of ESRD, anemia, mechanism of AKI) in our population, only hypertension was statistically significant for the development of AKI. Ten patients among 93 were hypertensive.

Conclusion

Our results suggest that the development of CKD occurred most often in the first year following an episode of AKI, hence the need for close follow-up at one year in this high-risk population
#6715 COGNITIVE IMPAIRMENT IS ASSOCIATED WITH INCREASED MORTALITY IN HEMODIALYSIS PATIENTS
Authors: Shсherbakov Evgeniy , Pyatchenkov Mikhail
Published: June 2023

Background and Aims

Patients on dialysis are at substantially higher risk for developing cognitive impairment compared with the general population. At the same time cognitive impairment is a strong and independent risk factor for all-cause mortality. Given that the approaches used to access the prevalence of cognitive disfunction widely vary in different patient populations, their true burden in hemodialysis patients remains poorly understood. The aim of our study was to determine the association between cognitive impairment and overall survival and mortality in patients undergoing hemodialysis treatment.

Method

A total of 69 chronic hemodialysis patients (47 men and 22 women) were included. The median age of patients was 61 [47-69] years. The median duration of hemodialysis treatment was 32 [21-72] months. The study of cognitive status was conducted using the Montreal Cognitive Assessment (MoCA) questionnaire. The test results are between 0 and 30 points. A score of 26 points or more is considered the norm, less than 26 indicates the presence of cognitive impairment. The end point was a fatal outcome from acute pathology or progression of a chronic disease. The analysis of survival and mortality was evaluated using survival tables, the construction of Kaplan-Mayer curves with the Mantel-Cox log–rank criterion. The risks of the influence of cognitive impairment on mortality were assessed using Cox regression.

Results

During the 24-month follow-up period, 23 patients died. Structure of mortality over the observation period: acute coronary syndrome – 6 (26 %), COVID-19 – 6 (26 %), acute cerebrovascular accident – 2 (9%), thromboembolic complications – 3 (13%), another causes – 6 (26 %). In patients with cognitive impairment on hemodialysis, the average survival value was 16.33 months ± 1.70 months [CI 95% 12.99-19.66] and 20.48 months±1.32 months [CI 95% 17.88-23.07] in patients without cognitive impairment. According to the Mantel-Cox log-rank criterion, there was a statistically significant decrease in overall survival in patients with cognitive impairment, P = .02. The mortality rate of dialysis patients with cognitive impairment was 51%, without cognitive impairment – 19%. Relative risk of death in the group of patients with cognitive impairment using Cox regression: Hazard ratio (HR) :2.90 [95% CI 1.11-7.37, P = .03].

Conclusion

Our results support the notion that cognitive impairment may be an independent predictor of all-cause mortality in hemodialysis patients. There are limitations on the sample size of patients in our study. Further larger-scale observations a large cohort of patients are required.
#6755 NOVEL ASPECT OF NATURAL FLAVONOL FISETIN VIA INHIBITING ACSL4-MEDIATED TUBULAR FERROPTOSIS AGAINST FIBROTIC KIDNEY DISEASE
Authors: Wang Bo , Yang Letian , MA Liang , Fu Ping
Published: June 2023

Background and Aims

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) progression, whereas no effective anti-fibrotic therapies exist. We previously reported that natural flavonol fisetin alleviated septic acute kidney injury and protected against hyperuricemic nephropathy in mice. However, the versatile role and potential mechanism of fisetin against fibrotic kidney disease have not been well characterized. Recently, tubular ferroptosis contributes to the pathogenesis of CKD with a persistent inflammatory and profibrotic response.

Method

Here, we found that fisetin significantly improved tubular injury, inflammation, and tubulointerstitial fibrosis in adenine diet- and unilateral ureteral obstruction (UUO)-induced CKD mice. The renoprotective effects of fisetin were also confirmed to suppress inflammatory response and fibrogenesis in adenine- or TGF-β1-stimulated tubular epithelial cells.

Results

Mechanistically, fisetin inhibited ferroptosis in the kidneys of CKD mice as well as in injured tubular epithelial cells, as evidenced by a decrease of ACSL4, COX2, HMGB1, and an increase of GPX4. Meanwhile, fisetin effectively restored ultrastructural abnormalities of mitochondrial morphology and relieved the elevated iron, the downregulated GSH and GSH/GSSG, as well as the upregulated lipid peroxide MDA in the kidneys of CKD mice. Notably, abnormal expression of ferroptosis key marker ACSL4 was verified in renal tubules of CKD patients (IgAN, MN, FSGS, LN, and DN) and mice (adenine and UUO), which was also observed in injured tubular cells. Furthermore, ACSL4 knockdown inhibited tubular ferroptosis, while ACSL4 overexpression blocked anti-ferroptotic effect of fisetin and reversed the cytoprotective, anti-inflammation, and anti-fibrosis of fisetin in injured tubular cells.

Conclusion

In summary, we for the first time explored a novel aspect of fisetin via inhibiting ACSL4-mediated tubular ferroptosis against fibrotic kidney diseases.
#6895 ANCA AND IGA NEPHROPATHY: ASSOCIATION OR PROGNOSTIC FACTOR
Authors: Mahmoud Nouha Ben , Salem Meriem Ben , Salah Manel Ben , Letaief Ahmed , Hammouda Mouna , Sabra Aloui , Skhiri Habib
Published: June 2023

Background and Aims

ImmunoglobulinA(IgA) nephropathy (IgAN), the most prevalent form of primary glomerulonephritis worldwide, is characterized by mesangial cell proliferation, matrix expansion, and mainly mesangial IgA deposition, often in conjunction with C3 and IgG and/or IgM. Its pathogenisis is enigmatic, It is reported that approximately 35-42% of IgAN patients have a history of macrohematuria before kidney biopsy. Its a benign pathology which somtimes could be associated with cresentic proliferation and more rarely by the presence of ANCA antibodies.

Method

We retrospectively analyzed the epidemiologic, clinical and histological data of 27 patients with Ig A nephropathy proven by biopsy and we compared 2 groups ANCA positive and ANCA negative patients.

Results

The present study involved 27 patients, 18 men and 9 women, the average age was 27.9 years 3 patients were ANCA positive compared to 24 ANCA negative ; (2 were MPO-ANCA and 1 PR3-ANCA). ANCA positive patients were older, with more severe initial renal function, lower hemoglobin, and a higher percentage of general symptoms than the ANCA negative ones Histologically, therewas a significantly higher percentage of fibrinoid necrosis in glomeruli in ANCA-positive IgAN patients ANCA-positive patients with IgA nephropathy had a higher percentage of crescentic glomeruli (54.5%) compared with ANCA-negative patients with crescentic IgA nephropathy (26%). The ANCA positive patients was all treated by solumedrol boli and oral corticotherapy and showed more severe prognosis, the 3 patients progressed to ESKD. 4 ANCA-negative patients were treated with oral corticotherapy, some from the other 20 patients have been put on renin angiotensin system bloquers treatment and thy shoxed a better renal prognosis.

Conclusion

IgAN patients with ANCA positivity showed more severe clinical and histological features when compared with ANCA-negative IgAN patients and lower renal prognosis. The ANCA antibodies should be screened in patients with severe forms of IgAN.
Activity of Tivozanib in Non-clear Cell Renal Cell Carcinoma: Subgroup Analysis From a Phase II Randomized Discontinuation Trial
Authors: Barata Pedro C , Chehrazi-Raffle Alexander , Allman Kimberly D , Asnis-Alibozek Aviva , Kasturi Vijay , Pal Sumanta K
Published: June 2023

Background

Non-clear cell renal cell carcinoma (nccRCC) is a blanket term for a collection of heterogeneous and biologically diverse RCC histologies, including but not limited to papillary, chromophobe, and unclassified subtypes. Tivozanib is a selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) that demonstrated activity in RCC with clear cell component. The objective of this analysis was to determine the efficacy of tivozanib in histologically unclassified/mixed RCC.

Methods

We identified patients with nccRCC enrolled in Study 201 (NCT00502307) between October 2007 and July 2008. This was a phase II randomized discontinuation trial of tivozanib in patients with RCC who had no prior VEGFR-targeted treatment. Clinical outcomes including investigator-assessed objective response rate (ORR), disease control rate (DCR, defined by complete response + partial response + stable disease), and progression-free survival (PFS) were examined.

Results

Of the 272 patients enrolled, 46 (16.9%) patients had nccRCC: 11 (4%) papillary, 2 (0.7%) chromophobe, 2 (0.7%) collecting duct, and 31 (11.4%) mixed/unclassified. Of the 46 patients with nccRCC, 38 were continuously treated with tivozanib and the best ORR was 21.1% (confirmed) and 31.6% (confirmed and unconfirmed). The DCR was 73.7% and median PFS was 6.7 months (95% confidence interval, 125-366 days). There were no new safety signals compared to the ITT population. Limitations include the small number of individual nccRCC subtypes and the randomized discontinuation design.

Conclusion

Tivozanib demonstrated activity and a favorable safety profile in patients with nccRCC. These data add to the body of evidence supporting the use of VEGFR-TKI in advanced nccRCC.
(Z)-3-Hexenol integrates drought and cold stress signaling by activating abscisic acid glucosylation in tea plants
Authors: Jin Jieyang , Zhao Mingyue , Jing Tingting , Wang Jingming , Lu Mengqian , Pan Yuting , Du Wenkai , Zhao Chenjie , Bao Zhijie , Zhao Wei , Tang Xiaoyan , Schwab Wilfried , Song Chuankui
Published: June 2023

Cold and drought stresses severely limit crop production and can occur simultaneously. Although some transcription factors and hormones have been characterized in plants subjected each stress, the role of metabolites, especially volatiles, in response to cold and drought stress exposure is rarely studied due to lack of suitable models. Here, we established a model for studying the role of volatiles in tea (Camellia sinensis) plants experiencing cold and drought stresses simultaneously. Using this model, we showed that volatiles induced by cold stress promote drought tolerance in tea plants by mediating reactive oxygen species and stomatal conductance. Needle trap microextraction combined with GC-MS identified the volatiles involved in the crosstalk and showed that cold-induced (Z)-3-hexenol improved the drought tolerance of tea plants. In addition, silencing C. sinensis alcohol dehydrogenase 2 (CsADH2) led to reduced (Z)-3-hexenol production and significantly reduced drought tolerance in response to simultaneous cold and drought stress. Transcriptome and metabolite analyses, together with plant hormone comparison and abscisic acid (ABA) biosynthesis pathway inhibition experiments, further confirmed the roles of ABA in (Z)-3-hexenol–induced drought tolerance of tea plants. (Z)-3-Hexenol application and gene silencing results supported the hypothesis that (Z)-3-hexenol plays a role in the integration of cold and drought tolerance by stimulating the dual-function glucosyltransferase UGT85A53, thereby altering ABA homeostasis in tea plants. Overall, we present a model for studying the roles of metabolites in plants under multiple stresses and reveal the roles of volatiles in integrating cold and drought stresses in plants.
Genome- and transcriptome-wide off-target analyses of a high-efficiency adenine base editor in tomato
Authors: Sretenovic Simon , Green Yumi , Wu Yuechao , Cheng Yanhao , Zhang Tao , Van Eck Joyce , Qi Yiping
Published: June 2023

Adenine base editors (ABEs) are valuable, precise genome editing tools in plants. In recent years, the highly promising ADENINE BASE EDITOR8e (ABE8e) was reported for efficient A-to-G editing. However, compared to monocots, comprehensive off-target analyses for ABE8e are lacking in dicots. To determine the occurrence of off-target effects in tomato (Solanum lycopersicum), we assessed ABE8e and a high-fidelity version, ABE8e-HF, at 2 independent target sites in protoplasts, as well as stable T0 lines. Since ABE8e demonstrated higher on-target efficiency than ABE8e-HF in tomato protoplasts, we focused on ABE8e for off-target analyses in T0 lines. We conducted whole-genome sequencing (WGS) of wild-type (WT) tomato plants, green fluorescent protein (GFP)–expressing T0 lines, ABE8e-no-gRNA control T0 lines, and edited T0 lines. No guide RNA (gRNA)–dependent off-target edits were detected. Our data showed an average of approximately 1,200 to 1,500 single-nucleotide variations (SNVs) in either GFP control plants or base-edited plants. Also, no specific enrichment of A-to-G mutations were found in base-edited plants. We also conducted RNA sequencing (RNA-seq) of the same 6 base-edited and 3 GFP control T0 plants. On average, approximately 150 RNA–level SNVs were discovered per plant for either base-edited or GFP controls. Furthermore, we did not find enrichment of a TA motif on mutated adenine in the genomes and transcriptomes in base-edited tomato plants, as opposed to the recent discovery in rice (Oryza sativa). Hence, we could not find evidence for genome- and transcriptome-wide off-target effects by ABE8e in tomato.