bluuebunny/crossref_metadata_2025 huggingface dataset:
#5734 RENAL AUTOLOGOUS CELL THERAPY (REACT™) FOR DIABETIC CHRONIC KIDNEY DISEASE: PHASE II TRIAL WITH BILATERAL CORTEX INJECTIONS AND RE-DOSING TRIGGERS
Authors: Stavas Joseph , Silva Arnold , Aqeel Ahmed , Prakash Rachita , Yanover Melissa , Wooldridge Tom , Cooper Kerry
Published: June 2023

Background and Aims

Well-based therapies may repair diseased nephrons and stabilize and enhance kidney function to delay the onset of end-stage kidney disease and improve co-morbidities. REACT™ is a novel product formed of cryopreserved autologous homologous selected renal cells, undergoing phase III clinical trials for diabetic kidney disease (DKD). We describe an open label phase II study to evaluate how patients respond to REACT™ injections in both kidneys and a redosing trigger, as being evaluated in a Phase III blinded data trial (proact 1 & 2 trials).

Method

REGEN 007 is a multi-center Phase II, open label 1:1 randomized controlled trial enrolling up to 50 patients ages 30-80 years with DKD, who have an eGFR of 20 - 50 mL/min/1.73 m2. Each patient undergoes a percutaneous kidney biopsy and ex vivo culture expansion of their selected renal cells. Patients are then randomized to an arm where they receive two REACT™ injections, one in each kidney, three months apart if they meet inclusion criteria, or an arm with an initial single REACT™ dose in one kidney and a 2nd REACT™ dose in the contralateral kidney > 90 days apart, based on a sustained eGFR decline of ≥ 20%, and/or an increase in the urine albumin to creatinine ratio (UACR) from baseline of ≥ 30% and ≥ 30 mg/g. CT-guided bilateral percutaneous renal cortex injections of REACT™ are performed under conscious sedation. Trial design, inclusion and exclusion criteria can be found at the National Clinical Trial Registry (Trial number 05018416).

Results

Thirty-one of the targeted 50 participants have been enrolled with the following characteristics at screening: 64.0% males, 97.0% Non-Hispanic/Latino. Mean age 62.9 years, serum creatinine (sCr) 2.0 mg/dL ±0.50, Cystatin C 2.0 mg/L ±0.40, eGFR (sCr + Cystatin C) 31.2 ml/min/1.72m2 ±7.88, HgbA1C 7.4% ± 1.14, Hgb 12.9 g/dL ± 1.78, K+ 4.6 mEq/L ± 0.44, Bicarbonate 20.3 mEq/L ± 3.0, and a median UACR 662 mg/g [SD 705.8]. Percent baseline medications are: Angiotensin Converting Enzyme inhibitors 25.8, Angiotensin Converting Enzyme receptor Blockers 48.4, beta blockers 64.5, diuretics 64.4, glucose lowering agents 100, Sodium glucose Cotransporter 2 inhibitors 32.3, and platelet inhibitors 67.7. Efficacy endpoint is an eGFR slope improvement from first injection to 18 months after last injection. REACT™ and procedure related serious adverse events are expected to be commensurate with ongoing trials and standard of care

Conclusion

REACT™ cell-based therapy has the potential to effect nephron structure and function by stabilizing or improving DKD progression and its comorbidities. Current phase II and III trials are underway to determine efficacy, safety, renal function-dependent dosing, and time to treatment with bilateral kidney injections of REACT™.
#5737 THE ASSOCIATION OF SERUM IRISIN WITH EARLY PATENCY LOSS OF ARTERIOVENOUS FISTULA
Authors: Li Xiejia , Wu Hong , Li Zheng , Yang Lingzhi , Liu Hong
Published: June 2023

Background and Aims

In patients receiving hemodialysis (HD), arteriovenous fistula (AVF) is the preferred form of vascular access owing to its long-term patency and low risk of infection. Early patency loss of AVF (≤1 year) is associated with higher risk of mortality and morbidity. Irisin is thought to play a protective role in the regulation of endothelial function and vascular calcification. However, the relationship between serum irisin level and early patency loss of AVF is unclear.

Method

In 73 end-stage kidney disease (ESKD) patients, including pre-dialysis patients who receive AVF placement for the first time (n = 10), HD patients with early patency loss of AVF (n = 24), HD patients that lose AVF function more than 1 year (n = 39), fasting (>8 hours) serum irisin levels and other biochemical parameters (hemoglobin, serum albumin, calcium, phosphate, intact parathyroid hormone, triglyceride, total cholesterol, D-Dimer, fibrinogen, FGF23, C-reactive protein) were measured before receiving access placement or after AVF thrombosis. All patients had radial-cephalic fistula.

Results

Among 73 patients (median age 58 years, 60.3% male, 31.5% diabetes mellitus (DM)), patients with early patency loss of AVF had significantly higher serum irisin levels, and lower fibrinogen, compared with other two groups. Other characteristics had no significant difference among these three groups (shown in Table 1).

Conclusion

HD patients with early patency loss of AVF had higher serum irisin levels compared with pre-dialysis patients and HD patients whose AVF patency maintained more than 1 year. The increase of irisin may be related to its putative role in compensatory mechanisms against vascular injury, which is then lost with longer dialysis duration and aggravated vascular damage.
#5764 STUDY OF THE INFLUENCE OF PHYSICAL ACTIVITY ON THE FUNCTION OF EXTERNAL RESPIRATION IN PATIENTS WITH CKD IN THE PROCESS OF REHABILITATION
Authors: Saipova Durdona , Ruzmetova Iroda , Egamberdieva Dano
Published: June 2023

Background and Aims

Chronic kidney disease is a global health problem in which patients performance decreases as renal dysfunction progresses. The aim was to study of the function of external respiration in patients with CKD in the dynamics of a 12-week rehabilitation program.

Method

The study included 130 patients with CKD stages 2-3, aged 45 to 65 years, whose average age was 58.7 ± 0.73 years, and the proportion of women in the sample was 47.7%. All patients were examined of urea, serum creatinine, hemoglobin level. To determine exercise tolerance, a cardiorespiratory exercise test and spirogram were performed. Patients of the main group, depending on the initial CRET parameters, were divided into 2 subgroups: 1 subgroup - 67 patients who performed light intensity exercises; 2 subgroups - 33 patients who performed medium-intensity exercises for 12 weeks 3 times a week. The choice of training intensity was made according to the level of individual or subjective perception of the load and was calculated using the approximate heart rate. The control group consisted of patients with CKD stages 2-3 who did not perform physical training.

Results

An analysis of the spinographic parameters of patients with CKD revealed that the FEV1 and FVC indicators are of great importance in assessing the results of rehabilitation measures. There were positive results of 12 weeks of physical training with a more pronounced increase in FEV1. Patients in the light intensity training group achieved 35-45% of maximum heart rate or 40% of peakO2 consumption, and in the moderate intensity training group, 45-55% of maximum heart rate and 50-60% of peakO2 were achieved. The index (FEV1/FVC, in %) showed significant differences both in the initial indicators and in the dynamics.

Conclusion

In patients with pre-dialysis stages of CKD, a significant effect was revealed with the combined use of standard therapy and physical activity of light and moderate intensity, which ensures the preservation of positive dynamics in terms of the degree of increase in diastolic blood pressure at the time of exercise and respiratory parameters (FEV-1 and FVC, p<0.05).
#5768 ASSOCIATION OF HIGH SERUM PHOSPHORUS WITH INCREASED MORTALITY RISK IN PATIENTS ON PERITONEAL DIALYSIS: RESULTS FROM COLOMBIA
Authors: Gomez Rafael , Qureshi Abdul Rashid Tony , LI Xiejia , Stachowska-Pietka Joanna , Debowska Malgorzata , Waniewski Jacek , Lindholm Bengt
Published: June 2023

Background and Aims

Elevated levels of serum phosphorus (PO4) in patients with kidney failure are associated with complications such as cardiovascular (CV) disease, bone disease and impaired wound healing, and increased mortality in hemodialysis patients. A recent PDOPPS study (Lopes et al NDT 2023) showed that high PO4 is associated with increased mortality also in patients undergoing peritoneal dialysis (PD). We explored PO4 levels in a large cohort of patients undergoing chronic PD in Colombia to determine the association of PO4 levels with mortality.

Method

In an observational study of 8113 prevalent PD patients treated with APD (n = 2692) or CAPD (n = 5421), PO4 levels together with demographic and clinical data, including dialysate to plasma ratio of creatinine at 240 min (D/PCr240min at peritoneal equilibration test) and body mass index (BMI), were recorded. During follow-up for a median of 1.99 years, 3169 patients died, and 988 patients underwent kidney transplantation (KT). We divided patients into 5 groups (P1 to P5) according to their baseline PO4 levels (first available measurement) with the following cut-off values for groups: up to 3.5, 4.5, 5.5, 6.5, and over 6.5 mg/dL, respectively. The association of baseline PO4 levels with all-cause and CV mortality risk was analyzed with a competing-risk regression model and KT as a competing risk.

Results

Characteristics of patients classified into groups P1 (16%), P2 (33%), P3 (27%), P4 (13%), and P5 (9%) are presented in Table. P5-patients were in general younger, more often men, less often diabetic (DM), and had lower hemoglobin (Hb) and serum albumin compared to P1-patients. All-cause mortality risk (after adjusting for age, sex, BMI, albumin, Hb, D/PCr240min, residual renal function, DM, and hypertension) was increased in P4- and P5-patients compared with P2-patients, sub-hazard ratio (sHR) of 1.14 (95% Cl: 1.01-1.27) and sHR of 1.27 (95% Cl: 1.10-1.46), respectively. Higher PO4 levels were not associated with significantly increased CV mortality risk for P4-patients, sHR of 1.10 (95% Cl: 0.93-1.31), or for P5-patients, sHR = 1.14 (95% Cl: 0.93-1.39) compared to P2-patients.

Conclusion

Among 8113 PD patients in Colombia, 49% had baseline PO4 >4.5 mg/dL and 22% PO4 > 5.5 mg/dL. Baseline PO4 levels > 5.5 mg/dL (P4 and P5 groups) were associated with increased all-cause mortality. These results are in agreement with the results of the PDOPPS study and suggest that effective management of hyperphosphatemia is important to improve clinical outcomes in PD patients.
#5782 AN EXCEPTIONAL CASE OF A PATIENT WITH TWO RARE GENETIC VARIANTS OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND ALPORT SYNDROME
Authors: Venda João , Henriques Andreia Dos Santos , Leal Rita , Alves Rui
Published: June 2023

Background

Alport syndrome and autosomal dominant polycystic kidney disease (ADPKD) belong to the most prevalent monogenic causes of chronic kidney disease (CKD) and both progress to end stage renal disease (ESRD). Alport syndrome, is caused by mutations in genes encoding collagen IV protein family. Inheritance might be X-linked, autosomal recessive, autosomal dominant or digenic and several pathogenic variants have been identified. ADPKD is mostly caused by mutations in PKD1and PKD2 genes but recently, the GANAB gene, that encodes the glucosidase IIa subunit, has been identified has a cause of a milder form of ADPKD. We present a case report of a patients with CKD-4, bilateral sensorineural hearing loss and multiple renal cysts where two unrelated and distinct genetic variants of both diseases were concomitantly found.

Case report

A 63-year-old caucasian male with medical history of arterial hypertension, hematuria and bilateral sensorineural hearing loss since his 40 years-old, with cochlear implant surgery 13 years ago was referred to the Nephrology unit due to progressive CKD, currently stage 4. His mother had ESRD of unknown etiology, in peritoneal dialysis since the age of 78 years and he has two healthy sons (aged 16 and 20 years old). Physical examination was irremarkable. Laboratorial workout showed serum creatinine of 2.7 mg/dL, ratio albumin/creatinine of 105mg/g with 11 erythrocytes in urinary sediment. Renal ultrasound showed normal sized kidneys with more than 10 cysts in each kidney, the biggest with 44mm. Genetic testing via next generation sequencing was performed revealing heterozygous mutations in COL4A3 (c.4421T>C p.(Leu1474Pro)), reported in ClinVar, and described in literature as an autosomal dominant variant present in Alport families. A mutation in the GANAB (c.2281A>G p.(Thr761Ala)) gene, classified as variants of unknown significance in was also detected, but this mutations is not reported in gnomAD or ClinVar. The patient was referred for genetic counseling.

Conclusion

We describe a rare case of possible overlap of ADPKD and Alport syndrome. The COL4A3 mutation is described has having a risk ≥ 20% of developing ESRD, but the association of a mild variant of ADPKD might increase exponentially this risk.
#5788 MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: A SINGLE CENTER EXPERIENCE
Authors: A Kishan , Muske Sravani , Harindranath Haritha , Vankalakunti Mahesha , C G Sreedhara
Published: June 2023

Background and Aims

Monoclonal gammopathy of renal significance is an organ-threatening manifestation of paraproteinemia. It can be secondary to the clonal proliferation of either plasma cells or mature B-lymphocytes. The underlying clonal disorder does not meet the current hematologic criteria for immediate myeloma-specific therapy. With the advent of routine use of light chain detection by immunofluroscence technique in tissue biopsy, more cases of monoclonal gammopathy of renal significance are being diagnosed but there remains a therapeutic uncertainty. Data regarding the prognosis and outcomes of the various clinical manifestations of monoclonal gammopathy of renal significance is limited due to its rarity and under diagnosis. MGRS if left untreated can lead to end-stage renal disease and premature death.

Method

This is a retrospective study conducted at the Institute of Nephro-urology, Bangalore by retrieving the data from the digital medical records of our institute. Demographic and clinical details of the patients diagnosed with monoclonal gammopathy of renal significance from 1 st January 2018 to 31 st October 2022 were collected. Myeloma related light chain cast nephropathy was excluded from the study. Follow-up data were collected usingout patient data base, through telephone, and from the records at the cancer institute where the patient was referred post-diagnosis at our institute. The data collected was entered in excel and analyzed using SPSS software version 27.0.

Results

Fifty eight patients (n = 52) were diagnosed with the disease during the study period. MGRS contributed to 1.27% of all the renal biopsies conducted at our institute during the study period. The mean age of the study population was 52.1 with 95% CI [48.5 to 55.6] with a male: female ratio of 1.36:1 and 36.5% (n = 19) ofstudy cohort aged above 60 years. Among clinical presentations CKD (n = 23) was the main clinical presentation followed by AKI, Nephrotic syndrome, Nephritic syndrome and RPGN as the other presentations. Dialysis requirement was noted in 35% at initial presentation. Most common histiopathological presentation was Amyloidosis (n = 15) followed by Light chain deposition disease LCDD (n = 14), monoclonal non-amyloid deposition disease NADD (n = 6), Light chain proximal tubulopathy LCPT (n = 5), Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease PGNMIDD (n = 9) and others (n = 3). The patient survival at the time of analysis was 22.7% and death censored renal survival was 80%.

Conclusion

MGRS contributed to 1.27% of all the renal biopsies conducted at our institute during the study period. Because of its variable clincal presentation,one needs high degree of clinical suspicion for early diagnosis. MGRS unlike MGUS carries significant morbidity and mortality.
#5801 EXTENDED LOW DOSE RITUXIMAB REGIMEN FOR THE TREATMENT OF ADULT PATIENTS WITH STEROID-DEPENDENT AND FREQUENTLY RELAPSING MINIMAL CHANGE DISEASE
Authors: Toral Irene Mínguez , Pérez Javier Villacorta , Vallejo Maria García , Iglesias Jorge Sánchez , Fernández Guillermo , Piris Marcos , Cebrián Fernando Caballero , Casillas Esther , Lopes Vanessa , Lucas Milagros Fernandez
Published: June 2023

Background and Aims

Patients with frequently relapsing and steroid-dependent minimal change disease (MCD) imply a therapeutic challenge for nephrologists. The use of steroid sparing agents such as cyclosporine, rituximab and mycophenolate, allows minimization of steroids exposure among these patients. In children and adults, Rituximab has demonstrated safety and efficacy in some studies although there is no established treatment regimen. This study aims to demonstrate that a low dose extended regimen of rituximab is an effective alternative for preventing relapses among these patients.

Method

This is a single-centre retrospective descriptive study of a case series of adult MCD patients from Ramón y Cajal’ Hospital in Madrid, Spain. Since 2019, patients with steroids-dependent or frequently relapsing MCD were treated with a low dose extended protocol of Rituximab as follows; 500 mg of rituximab once remission is achieved with steroid therapy, and four additional doses at month +6, +18 and +30 during the follow-up. Relapse free survival was analyzed after rituximab therapy.

Results

Eight patients with a median age of 42 years (22–70 years) who received at least one dose of intravenous rituximab were included. Four of the patients (50%) had previously received additional immunosuppressive regimens (including cyclophosphamide, chlorambucil cyclosporine, mycophenolate or ACTH). Two of them (25%) had frequent relapses and the remaining six (75%) had steroid-dependent behaviour. After a median of 2 years (IQR, 1,4-3,3) of follow-up, 6 out of 8 (75%) patients stayed under remission, experiencing the remaining two one relapse at one month and at one year, respectively, after the first rituximab dose. Comparing relapses during the two years-period before and after rituximab use, the median relapse rate per patient dropped from 2.8 (IQR, 2-4) to 0.5 (IQR, 0-1; P = 0.001) (Fig. 1). No patient experienced rituximab related side effects nor infections during the study period.

Conclusion

In MCD patients, the administration of rituximab in an extended low-dose regimen as corticosteroid-sparing therapy appears to be safe and effective in most of the patients for preventing relapses. This regimen allows minimization exposure to rituximab as well as disease remission during a longer period of time.
#5805 ACCURACY OF FIXED 24-H AMBULATORY BLOOD PRESSURE RECORDINGS FOR DIAGNOSING HIGH 48-H AMBULATORY BLOOD PRESSURE IN HEMODIALYSIS PATIENTS
Authors: Theodorakopoulou Marieta , Iatridi Foteini , Pella Eva , Karpetas Antonios , Georgiou Areti , Sampani Erasmia , Karkamani Eleni , Tsitouridis Alexandros , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2023

Background and Aims

Hypertension is highly prevalent in hemodialysis patients. Ambulatory-BP-monitoring (ABPM) during the 44-h interdialytic interval is recommended for hypertension diagnosis and management in these subjects. This study assessed the diagnostic accuracy of fixed 24-h ABPM recordings with 44-h BP in hemodialysis patients.

Method

242 Greek hemodialysis patients that underwent valid 48-h ABPM (Mobil-O-Graph NG device) were included in the analysis. We used 44-h BP used as reference method and tested the accuracy of the following BP metrics: 1st 24-h without HD period (20h-1st), 1st 24-h including HD period (24h-1st) and 2nd 24-h (24h-2nd).

Results

All studied metrics showed strong correlations with 44-h SBP/DBP (20h-1st: r = 0.973/0.978, 24h-1st: r = 0.964/0.972 and 24h-2nd: r = 0.978/0.977, respectively). In Bland-Altman analysis, small between-method differences (−1.70, −1.19 and +1.45 mmHg) with good 95% limits-of-agreement ([−10.83 to 7.43], [−11.12 to 8.74] and [−6.33 to 9.23] mmHg, respectively) for 20h-1st, 24h-1st and 24h-2nd SBP were observed. The sensitivity/specificity and κ-statistic for diagnosing 44-h SBP≥130 mmHg were high for 20h-1st SBP (87.2%/96.0%, κ-statistic = 0.817), 24h-1st SBP (88.7%/96.0%, κ-statistic = 0.833) and 24h-2nd SBP (95.0%/88.1%, κ-statistic = 0.837). Similar observations were made for DBP. In ROC-analyses, all studied BP metrics showed excellent performance with high Area-Under-the-Curve values (20h-1st: 0.983/0.992; 24h-1st: 0.984/0.987 and 24h-2nd: 0.982/0.989 for SBP/DBP respectively).

Conclusion

Fixed 24-h ABPM recordings during either the first or the second day of interdialytic interval have high accuracy and strong agreement with 44-h BP in hemodialysis patients. Thus, ABPM recordings of either the first or the second interdialytic day could be used for hypertension diagnosis and management in these subjects.
#5807 FACTORS ASSOCIATED WITH KALEMIA IN RENAL DISEASE
Authors: Maelys Granal , Fouque Denis , Michel Ducher , Fauvel Jean Pierre
Published: June 2023

Background and Aims

International recommendations promote a strict potassium diet in order to avoid hyperkalemia in chronic kidney disease patients. However, efficiency of such a dietary counseling has never been demonstrated. The objectives of this study were to define the relationship between kalemia, dietary potassium intake estimated by kaliuresis and renal function and to define the factors associated with kalemia in patients using artificial intelligence.

Method

To this extent, data from patients followed in a nephrology unit, included in the UniverSel study and whose kalemia (measured on the day of urine collection; n = 367) were analyzed. The association between kalemia and thirty-four variables concerning the patients' characteristics, their biological work-up, their medications and their answers to the UniverSel dietary self-questionnaire on kalemia were assessed using a Bayesian network.

Results

The patients included had a wide range of estimated glomerular filtration rate, but few had stage 5 chronic kidney disease (CKD). Kalemia was negatively and linearly correlated to estimated glomerular filtration rate (p<0.001) but was not correlated to kaliuresis (p = 0.55). Kaliuresis was not correlated to estimated glomerular filtration rate (p = 0.08). Factors associated with kalemia were analyzed using a Bayesian network. The 5 variables most associated with kalemia were, in descending order, estimated glomerular filtration rate, original nephropathy, age, diabetes, and plasma bicarbonate level. RAS-blockers prescription was also associated to kalemia. Consumption of potassium rich food were poorly associated to kalemia.

Conclusion

Our results do not support a strict control of potassium intake in stage 1 to 4 CKD patients. Our results reinforce the interest of a multidimensional management including personalized therapy and strict correction of metabolic acidosis. Lightning dietary restrictions in potassium would improve the quality of life of patients with CKD who are often multi-pathological and already subject to multiple dietary constraints.
#5808 EFFECTIVENESS OF ORAL FOSFOMYCIN PROPHYLAXIS IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Morales Nancy Daniela Valencia , Pérez-Flores Isabel , López Rómulo Katsu Loayza , de la Higuera Díaz María Ángeles Moreno , Cubillo Beatriz Rodríguez , Romero Natividad Calvo , Fructuoso Ana Sanchez
Published: June 2023

Background and Aims

Urinary tract infections (UTIs) are one of the most common infectious complications in kidney transplant recipients (KTR), which are of great importance due to their high morbidity and recurrent nature. Our main objective was to evaluate the effectiveness of oral fosfomycin prophylaxis in a group of high-risk patients with recurrent/relapsing urinary tract infections.

Method

Retrospective study of a cohort of 60 KTR with frequent UTIs who had been prescribed daily fosfomycin calcium or fosfomycin trometamol every 7-10 days for prophylactic purposes. Demographic, clinical, analytical and microbiological data were collected during a year before and after prophylaxis.

Results

The median age was 61.8 (55.6-71.2) years, 68.3% were men, with 7.4 (2.8-13.6) years since the transplant. The main etiologies of the underlying renal disease were: autosomal dominant polycystic kidney disease 20%, chronic glomerulonephritis 18.3%, chronic tubulointerstitial nephropathy 10%, and diabetic kidney disease 10%, In 51.7% there was chronic pathology of the urinary tract (mainly vesico-prostatic disease, 24.8% and vesico-ureteral reflux, 15%), with a history of urological surgery in 23.3%. Up to 20% of the KTR had some type of endourological device (permanent/intermittent bladder catheter, percutaneous nephrostomy, Bricker, etc). The most frequently isolated germs were: E. coli and K. pneumoniae, 35.2 and 13.6% pre-prophylaxis and 28.3 and 22.6%, post-prophylaxis, respectively. The median number of UTI pre vs post-prophylaxis was 2 (1-4.75) vs. 1 (0.5-1.6) episode/patient/year (p<0.001), with a reduction in UTI episodes in 69% of patients. Admissions were also reduced, going from 35% in the pre-prophylaxis year to 10% post (p = 0.001). After prophylaxis, the percentage of resistance to fosfomycin increased from 26 to 54%. and a greater number of multi-resistant germs were isolated, 17.7 pre- vs 35% post-. The renal function remained stable during follow-up [CKD-EPI pre- 47.2(20.8) vs 47.2(21.2) ml/min post-].

Conclusion

Oral fosfomycin prophylaxis may be useful in KTR despite the underlying urological pathology, managing to reduce UTI episodes and the need for admission for this reason.
#5819 HAEMODIALYSIS EFFECT ON METABOLIC THERAPY WITH [131INA]: A COMPARATIVE STUDY
Authors: Arias-Camisón Paloma Livianos , Repetto Alessandra , Valeriano Juan Rey , Chamizo Sandra , Talens Antonio Cherino , Viloria María Cristina Peña , Mendez Isabel Garcia
Published: June 2023

Background and Aims

The use of [131INa] therapy in patients undergoing haemodialysis (HD) is still controversial. Considering that the main elimination of 131I is urinary and the sessions of HD take place in wards full of other patients, various modifications should be made in the therapy. Due to the limited bibliography and the lack of consensus in clinical guidelines we developed this comparative study between two patients on HD treated with [131INa]. External dose rate measurement (EDRM), time of hospitalization, timing of dialysis after the administration of [131INa] and the status of contamination of dialysis machine were considered.

Method

Two patients on HD were treated with [131INa] in June 2021. A 74years old women with hyperthyroidism due to a multinodular goitre, resistant to antithyroid drugs (PT1). A 49years old man candidate to ablation treatment with low activity of [131INa] after a total thyroidectomy due to differentiated thyroid cancer (pT2N0) (PT2). The recommended activity was administered according to clinical indication. PT1 received 555MBq and PT2 received 1110 MBq of [131INa] in Metabolic Therapy Unit (MTU) after the first HD session in the nephrology ward. The following HD sessions were in MTU (Wed.-Fri.). High-flux dialysis was performed using a Reverse Osmosis portable system. The hospital stay was 5 days (Mo at Fri) for each patient. EDRM at 1 meter was measured three times a day. Liquid samples from HD machine (dialysis fluid, water wash) were obtained every day at the same time before and after each session and radioactivity was analysed.

Results

EDRM after second HD at discharge was 12 and 7,4mcSv/h in PT1 and PT2 respectively. After first HD both patients reached EDR <40mcSv/h (22 and18 mcSv/h). Red bone marrow dose was 130,76mGy and 110,42mGy respectively. Radioactivity in dialysis fluid was: 0,00999MBq PT1- 0,00259MBq PT2 after first HD; 0,0022MBq PT1- 0,00074MBq PT2 after second HD. No radioactivity was detected in wash water of dialysis equipment in both patients during each HD session. There was no secondary complications due to overhydration or dyslectrolythemias.

Conclusion

External dose rate measurement is key to decide if patients undergoing HD are ready to be discharge. Once EDRM <40mcSv/h at 1 meter has been reached, patients could immediately return to their dialysis centre following the protection radiology rules and so we must always respect the distance between the patients, if that cannot be performed the session will be in the hospital. There is no need to modify radioiodine activities neither timing of HD sessions as red bone marrow dose do not exceed recommended value (2Gy). There is no contamination of HD machine, it could be used after usual decontamination for other patients.
#5826 NEPHROPROTECTIVE EFFECTS OF SEMAGLUTIDE IN A MOUSE MODEL OF HYPERTENSION-ACCELERATED DIABETIC KIDNEY DISEASE
Authors: Christensen Michael , Dalbøge Louise S , Madsen Martin Rønn , Hansen Henrik Björk , Ida Rune , Østergaard Mette Viberg
Published: June 2023

Background and Aims

Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. Here, we characterized the effect of long-acting GLP-1R agonist semaglutide alone and in combination with an ACE inhibitor in a model of hypertension-accelerated, advanced DKD facilitated by adeno-associated virus-mediated renin overexpression (ReninAAV) in uninephrectomized (UNx) female db/db mice.

Method

Seven weeks after ReninAAV administration and six weeks post-UNx, db/db UNx-ReninAAV mice were administered (q.d.) vehicle, semaglutide (30 nmol/kg, s.c.) or semaglutide (30 nmol/kg, s.c.) + lisinopril (30 mg/kg, p.o.) for 11 weeks. Endpoints included tail-cuff blood pressure evaluation at week 1 and 10, plasma/urine biochemistry, kidney histopathology as well as RNA sequencing.

Results

Semaglutide robustly reduced hyperglycemia, hypertension and albuminuria concurrent with notable improvements in glomerulosclerosis severity, urine/renal kidney injury molecule-1 (KIM-1) levels. Furthermore, semaglutide suppressed gene expression markers of extracellular matrix modelling and immune system activation. Co-administration of lisinopril further ameliorated hypertension, glomerulosclerosis as well as markers of fibrogenesis and inflammation.

Conclusion

Semaglutide improves disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Renal outcomes were further improved by combined antihypertensive standard-of-care. These data display the translatability of the db/db UNx-ReninAAV mouse model of DKD.
#5834 ALBUMINURIA AND RENAL RESISTIVE INDEX ARE ASSOCIATED WITH MICROVASCULAR REMODELING IN PATIENTS WITH SEVERE OBESITY
Authors: Moriconi Diego , Mengozzi Alessandro , Nannipieri Monica , Bruno Rosa Maria , Virdis Agostino
Published: June 2023

Background and Aims

Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in severe obesity, its noninvasive assessment with ultrasound still fails to provide pathophysiologic and clinical meaningfulness. The aim of the study is to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity.

Method

We enrolled forty-eight patients affected by severe obesity with an indication for bariatric surgery referring to our Clinic. Patients underwent an extensive renal examination with evaluation of eGFR with EPI-Cr formula, albuminuria and urinary TGF-β as indirect markers of kidney fibrosis, paired with Doppler ultrasound to measure renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L), wall-cross sectional area (WCSA) and vascular response to acetylcholine (ACh), alone or co-incubated with L-NAME, were measured.

Results

Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower eGFR and higher RRI compared to NT. The presence and extent of albuminuria were similar between the two groups, while TGF-β was slightly higher in the HT group (p = 0.059). Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT (p = 0.039). Multivariable analysis showed a relationship between M/L and RRI (p = 0.022, St.β 0.38) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation (p = 0.039, St. β = -0.36). Notably, all these correlations were consistent also after adjustment for confounding factors.

Conclusion

The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal hemodynamics and microcirculatory disruption.
#5835 A LOW DOSE GLUCOCORTICOID, LOW DOSE CYCLOPHOSPHAMIDE, RITUXIMAB TREATMENT PROTOCOL AS INDUCTION THERAPY IN ANCA ASSOCIATED VASCULITIS PATIENTS
Authors: Spanos Georgios , Paschou Styliani , Bakou Marianna , Atalla Alexandros , Bantis Christos , Fragidis Stylianos , Armetzoiou Livia Karmen , Bamichas Gerasimos
Published: June 2023

Background and Aims

There has been a considerable improvement in the survival of patients with ANCA associated vasculitis (AAV) since the introduction of immunosuppressive therapy. Nowadays early deaths are attributable to infection while cardiovascular disease, infection and malignancy are the most common causes in long term mortality in these patients. High-dose glucocorticoids and cyclophosphamide have numerous dose-dependent adverse effects and are associated with those events. The aim of this study is to investigate the efficacy and safety a low dose glucocorticoids, low dose cyclophosphamide, rituximab treatment protocol in AAV patients.

Method

This is a single-centre cohort study of patients on a combination of reduced-dose oral glucocorticoids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of rituximab and tapered steroid for the treatment of AAV (table). Data shown as median (IQR).

Results

Nine patients (3 women) aged 62.4 (55/67.8) years, with serum creatinine (sCre) 2.15 (1.8/2.5) mg/dL, eGFR CKD-EPI 28 (20/39) ml/min/1.73 m2, albuminuria 0.98 (0.57/1.45) gr/24 h and BVAS 14 at baseline were treated with the mentioned protocol. Seven patients had MPO and 2 had double MPO/PR3 positivity. Two were already on dialysis and 4 had pulmonary involvement. The median follow-up was 19 (12.5/39) months. One patient required the addition of plasma exchange and extended treatment due to aggressive disease and one was lost to follow-up after four months. The rest of the 7 patients were dialysis free with a sCre 2.15 (1.8/2.5) mg/dL, eGFR 28 (20/39) ml/min/1.73 m2 at the end of follow-up. Patient and renal survival were 88% and 100% respectively. 85.7% of patients achieved ANCA-negative status and all remained B cell deplete at 6 and 18 months. There were no major relapses, while two patients had infection related hospitalization. No unexpected side effects were observed during follow-up.

Conclusion

These findings confirm the literature that a combined regimen provides early disease control with low relapse rates, without significant adverse effects from immunosuppression. A regimen like this may provide the basis for further refinement of remission induction protocols in AAV, potentially allowing early withdrawal of corticosteroids.
#5842 ULTRASOUND AND 3D IMAGING CHARACTERISATION OF A RAT MODEL OF POLYCYSTIC KIDNEY DISEASE
Authors: Christensen Michael , Porsgaard Trine , Perens Johanne , Sembach Frederikke Emilie , Hansen Henrik Björk , Ougaard Maria
Published: June 2023

Background and Aims

Polycystic kidney disease (PKD) is a congenital fibrocystic disorder where cysts are primarily forming within the kidneys causing enlargement, loss of kidney function and resulting in chronic kidney disease for which there is no curative treatment. Consequently, PKD is classified as a medical condition with high unmet therapeutic need. Animal models with improved clinical translatability can optimally inform about potential clinical efficacy of novel drug candidates for PKD. The polycystic kidney (PCK) rat is an established genetic model of PKD with natural history and renal histologic abnormalities that resemble the human disease. Gubra has established a PCK rat breeding program to enable fast turnaround time of preclinical drug discovery studies for PKD. In this study, we have characterised disease progression in the PCK rat to aid in designing future pharmacological intervention studies.

Method

Male PCK (PCK/CrljCrl-Pkhd1pck/Crl) and control (CRL:CD(SD)) rats (Charles River) were randomised into groups based on body weight at the age of 10 weeks. At the age of 17 and 25 weeks, rats underwent ultrasound assessment of kidney volume, urine collection for quantification of albuminuria, and plasma sampling for analysis of urea and creatinine levels. At termination, whole kidneys were harvested and total kidney volume, cyst number and cyst volume were analysed using quantitative 3D light sheet imaging.

Results

Compared to age-matched control rats, PCK rats displayed marked albuminuria which was significantly increased at week 25 of age. Whereas plasma urea was progressively increased at both time points, plasma creatinine increased at week 25. Ultrasound measurements revealed that total kidney volume progressive increased compared to control rats. 3D Light sheet imaging enabled whole-kidney counting of cysts and quantification of cyst volume as wells as the total kidney volume that closely correlated to kidney ultrasound results.

Conclusion

The PCK rats displays histological hallmarks of PKD, characterized by age-dependent progressive increases in biomarkers of kidney injury, kidney hypertrophy and cyst formation. In vivo ultrasound and ex vivo quantitative whole-kidney 3D light sheet imaging is highly instrumental for detailed assessment of progressive disease in the PCK rat. The renal histopathological markers may serve as key histological endpoints for assessment of therapeutic effects of preclinical drug candidates in this translational rat model of PKD.
#5848 ROLE OF STATINS IN THE CONTRAST-INDUCED ACUTE KIDNEY INJURY PREVENTION AFTER COMPUTED TOMOGRAPHY WITH CONTRAST MEDIA
Authors: Vasin Andrey , Pahlevani Elham , Biryukova Valentina , Mironova Olga , Fomin Victor
Published: June 2023

Background and Aims

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the use of iodinated contrast media (CM). A number of researches have shown that statins have a protective role in the prevention of CI-AKI due to their pleiotropic effects. The aim of the study was to assess the influence of statins on the incidence of CI-AKI after intravenous CM administration.

Method

A randomized controlled open-label prospective study was conducted. Statin naive patients with cardiovascular diseases referred for contrast-enhanced computed tomography (CT) were included. Exclusion criteria were the use of statins and chronic kidney disease (CKD) stages 4-5. Acute kidney injury was defined as an increase in serum creatinine level by more than 44 μmol/L (0.5 mg/dL) or 25% from baseline within 48 hours after CM administration according to KDIGO guidelines. Glomerular filtration rate was calculated using the CKD-EPI formula. Overall, 181 patients were included in the study and divided into two groups. The first group (120 people) received high doses of atorvastatin (80mg or 40mg) 24 hours after and before the CM administration, while the second group (61 people), the control group, did not receive any statin therapy. Low-osmolar solutions in an amount of 100 ml were used. All patients were given intravenous hydration with saline before the study and 24 hours later. The statistical analysis was done using IBM SPSS Statistics v26.0.

Results

The patients in both groups did not significantly differ in age, BMI, coexisting conditions, and medications taken (Table 1). Both groups showed an increase in average creatinine levels after CT with intravenous CM administration, however, in the group of patients receiving high doses of statins, the average level increased less, p = 0.092 (Table 2). AKI developed in 12 individuals (6.7%), 9 of them were in the control group, and 3 were in the group receiving high doses of statins, p = 0.003. The chances of AKI development in the group receiving high doses of statins were 6.95 times lower compared to the control group (OR = 6.05, 95% CI: 1.7-21.5). Most of the patients had preserved kidney function and did not suffer from diabetes mellitus. There were statistically significantly more patients with preserved kidney function in the statin group, p = 0,007, OR: 2,374 (CI 95% 1,258 - 4,479), and fewer patients with CKD 3a stage, p = 0,05, OR: 0,406 (CI 95% 0,195 – 0,844).

Conclusion

Despite the presence of patients at risk, the incidence of CI-AKI was 6.7%, possibly due to additional prevention of this complication with intravenous saline before and after administration of the CM.

In this trial, we observed that periprocedural administration of atorvastatin in high doses for a short duration, reduced the incidence of CI-AKI.
#5852 EFFECT OF DIET ON THE COLLECTOR DUCT BEHAVIOUR: RELEVANCE IN PRECLINICAL DRUG DEVELOPMENT
Authors: Tejedor Marta , Gonzalez-Nicolas Maria Angeles , Uzun Baris , Álvarez-Sala-Walther Luis Antonio , Lázaro Alberto
Published: June 2023

Background and Aims

Drug induced syndrome of inadequate antidiuretic hormone secretion (SIADH) is a common problem in clinical practice. Early detection of this side effect at a preclinical level would improve safety and efficiency. We investigate the role of different diets in preclinical detection of SIADH.

Method

Animals were divided into two groups (n = 4 each), one receiving standard pellet based diet, and the other one a diluted hyposodic gelified liquid diet. After one week, both groups were administered daily intraperitoneal (i.p.) injections of desmopressin acetate (ddAVP; 0.4 μg/kg) and a volume of distilled water equivalent to 2.5% of body weight for 7 days. Animals were placed in metabolic cages for 24h at the end of each period to collect and analyse the urine, and a blood sample from the tail vein was obtained. Weight, water and food intake were measured on a daily basis.

Results

Differences in water and electrolyte balance are shown in Table 1. Pellet fed animals presented an increased water intake and produced a more concentrated urine compared to those on a hyposodic diet. When analysed in detail, urinary osmolality was mainly driven by ionic osmoles in pellet fed animals (42,25 ± 4,72 vs 266,30 ± 17,32 mOsm/kg, p<0,005). Of note, there seems to be an occult osmole, especially prominent in the pellet group (osmol gap 20,40 ± 3,18 vs 99,89 ± 9,81 mOsm/kg, p = 0,017). All of the above suggest there is a net retention of water, sodium and potassium in those animals fed with a conventional pellet diet. Daily administration of ddAVP/water induced a mild transient hyponatremia that was recovered 24h later in both groups; this situation was repeated over a 7 day period. Pellet fed animals did not modify water intake, diuresis, free water clearance or urinary osmolality after ddAVP/water treatment, suggesting that hyperosmolar diets significantly increase urinary osmolality fixating urinary water losses and impairing further urinary concentration. On the contrary, animals on a hyposodic diet did present antiaquaresis, as shown by an increase in water intake, a decrease in diuresis and free water clearance and an increase in urinary osmolality. Animals fed with hyposodic diet progressively lost weight, while pellet fed animals did not. However, this trend was reversed after 4 days of treatment with ddAVP/water, again suggesting a degree of water retention. It is remarkable that we have found signs of water retention despite the fact that the induced hyponatremia is mild and transient.

Conclusion

The antiaquaretic effect of ddAVP is overridden by the amount of urinary osmoles excreted when on a pellet diet, which seem to fixate the amount of water in the urine. Therefore, the use of hyposodic diets in preclinical drug development is essential when SIADH is likely to be expected, as its effects will be unnoticed if a standard diet is used.
#5865 BET INHIBITION DIMINISHES CELLULAR SENESCENCE IN CULTURED TUBULAR EPITHELIAL CELLS
Authors: Basantes Pamela Estefanía , Rayego-Mateos Sandra , Tejedor Lucia , Marquez-Exposito Laura , Díez Raúl Rodrígues , Marchant Vanessa , Tejera Antonio , Ruiz-Ortega Marta
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) can be considered an age-related disorder. Recent studies have shown the involvement of the activation of cellular senescence mechanisms in the kidney and aging. Intensive research to develop pharmacological approaches targeting cellular senescence is under investigation. Among novel therapeutic options, epigenetic drugs, such as bromodomain and extra terminal BET inhibitors, are being widely explored in proliferative, immune and chronic inflammatory diseases, including CKD. These drugs regulate transcription activation of cell cycle control and proinflammatory factors. There are not studies about the potential effect of BET inhibitors on cellular senescence in the kidney despite the fact that tubular epithelial cells are frequently implicated in kidney senescence.

Method

To study this, we evaluate the effect of JQ1, a BET inhibitor, on cellular senescence in primary cell culture of murine tubular epithelial cells (TECs) using Adriamycin as a senescence inducer verified by B-galactosidase assay. Next, we evaluated the effect of JQ1 on gene expression levels of cell cycle markers, components of senescence-associated secretory phenotype (SASP) as well as anti-apoptotic and antioxidant markers, all of them related to senescence program.

Results

Our results indicated that JQ1 significantly decreased Adriamycin-induced p21 gene upregulation, a primordial cell cycle arrest factor. This BET inhibitor also downregulated SAPS genes, such as Tgfb1, Il1b, Ctgf, Ccl2 and Il6 overexpression in Adriamycin-treated tubular cells. Likewise, anti-apoptotic Bcl-xl and antioxidant factors Cat, Hmox-1, Nox-4 and Nrf2 mRNA levels were significantly restored by JQ1.

Conclusion

In conclusion, the present study highlights the use of JQ1 as a therapeutic option to ameliorate tubular cellular senescence-associated markers. These data support the potential use of BET inhibitors in chronic kidney diseases.