bluuebunny/crossref_metadata_2025_split huggingface dataset:
#657 Obinutuzumab is effective for the treatment of frequently-relapsing/steroid-dependent minimal change disease in adults
Authors: Jin L I , Lu Wanhong , LI Xueying 
Published: May 2024

Abstract

Background and Aims
Higher relapse rates and steroid dependency are challenges in the treatment of minimal change disease (MCD). The aim of this study was to evaluate the efficacy and safety of obinutuzumab, a humanised type II anti-CD20 monoclonal antibody, in adults with frequently relapsing (FR) or steroid-dependent (SD) minimal change disease (MCD).

Method
Patients with FR/SD MCD receiving obinutuzumab at our center between September 2022 and February 2023 were enrolled. Complete remission was defined as the reduction of proteinuria to 0.3g/d. The time to remission, the relapse rate, and adverse events were evaluated.

Results
Six patients with FR/SD MCD were included in the present study. The median age of the patients was 30.44 years (range 18.80-72.09 years) and 3 of them were male. Prior to treatment with obinutuzumab, five patients remained in nephrotic syndrome and one patient was in partial remission after previous treatment. One or two doses of 1g obinutuzumab were given. All six patients achieved a complete remission. Five patients with nephrotic syndrome achieved complete recovery within a range of 14 to 57 days. The patient, who initially achieved partial remission, reached complete remission within 27 days after receiving the first obinutuzumab dose. The average follow-up duration was 12.53 ± 1.97 months, during which there was no observed relapse. Furthermore, None of the patients experienced infusion-related adverse effects, serious infectious complications or neutropenia following treatment with obinutuzumab.

Conclusion
Obinutuzumab is an effective and safe treatment option for adult patients with FR/SD minimal change disease. Further randomized trials are needed to confirm these findings.
#1170 Efficacy and safety of telitacicept in IgA nephropathy: a real-world study
Authors: Dong Lingqiu , Qin Wei 
Published: May 2024

Abstract

Background and Aims
IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and the specific therapeutic methods are limited in IgAN. Telitacicept is a humanized fusion protein composed of a transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor and human IgG. This study was designed to evaluate the efficacy and safety of telitacicept in adult patients with IgAN in a real-world study.

Method
Biopsy-proven IgAN patients with 24-hour proteinuria greater than 0.5 g/day who received telitacicept 240 mg once a week were recruited in this study and 1:1 matched with patients who received supportive treatment only or immunosuppressive treatment by propensity score matching. The primary outcome was the change from baseline in 24-hour proteinuria over the 3-month follow-up.

Results
Twenty-one patients in each group were enrolled. The mean eGFR was 80.1 ml/min/1.73 m2, and the median 24-hour urine protein level was 1.48 g/day. At the end of the 3-month follow-up period, telitacicept reduced median proteinuria by 0.72 g/d (54.6%) from baseline, compared with a reduction of 0.18 g/d (20%) in the supportive treatment group (P &lt; 0.001), and 1.12 g/d (72.1%) in the immunosuppressive treatment group (P = 0.814). Preserved eGFR levels were observed in the telitacicept group (1.9 ml/min/1.73 m2 [4.3%]), while the eGFR level declined in the supportive treatment group (- 2.9 ml/min/1.73 m2 [- 5.8%]) and immunosuppression group (- 6.1 ml/min/1.73 m2 [- 8.4%]). No serious adverse events were observed in the telitacicept treatment group. Injection site reactions were more prevalent in the telitacicept group (8/21 [38.1%]), meanwhile immunosuppression group had more respiratory tract infections (7/21, [33.3%]).

Conclusion
Telitacicept can reduce proteinuria in patients with IgAN and showed a favourable safety profile in patients with IgAN.
#2840 Early tolerance of SGLT2i therapy in patients with ATTR V30M amyloidosis: staging the disease to establish standard of care
Authors: de Bessa e Silva João Pedro Peixoto , Campos Andreia , Pereira Sandra , Santos Josefina , Lobato Luísa 
Published: May 2024

Abstract

Background and Aims
Studies of sodium-glucose co-transporter 2 inhibitors (SGLT2i) therapy on ATTR cardiomyopathy are scarce and focus wild-type and V122I. In ATTRv, namely V30M, SGLT2i introduction to preserve kidney function or improve cardiorenal syndrome is not an outlined practice. Our aim was to assess the clinical evolution and difficulties with SGLT2i therapy in ATTR V30M amyloidosis, a population with neurogenic bladder, dysautonomia and prone to dehydration.

Methods
Patients with ATTR V30M amyloidosis and criteria for SGLT2i started standard dosages. Gillmore score (GS) for ATTR cardiomyopathy, kidney failure risk equation (KFRE) and the renal system score (RSS) of the FASTEX model (Fabry disease) were calculated. Estimation of heart amyloid load was based on Tc-99-DPD scintigraphy.

Results
Eight patients were followed on median of 7 months [IQR 5.6-9.4]; 7 treated with dapagliflozin, 1 with empagliflozin. 6 had type-2 diabetes. 4 were treated with tafamidis, 1 inotersen and 1 patisiran. 3/7 had positive DPD scintigraphy. Heart failure decompensation, new arrhythmias and renal adverse events were absent. Neurogenic bladder was present in 4 patients, 2 had urinary tract infections. 1 had symptomatic hypotension, leading to discontinuation of therapy. EGFR and RSS improved in 5 and 3 patients, respectively; NT-proBNP/albuminuria/proteinuria and KFRE at 2 and 5 years decreased. In terms of cardiomyopathy, 1 patient improved to GSI; 2 using CKD-EPI creatinine and none using CKD-EPI cystatin C. 1 progressed to GSII in all equations.

Conclusion
In this pilot study, we evidenced that ATTR V30M patients meet the criteria for SGLT2i therapy. Dysautonomia and neurogenic bladder were not an impediment for therapy. In addition to disease modifying drugs, SGLT2i may improve kidney and cardiovascular outcomes in ATTR V30M amyloidosis.
#1150 Neutrophil rich infiltrate in immunotherapy induced acute interstitial nephritis
Authors: Glezerman Ilya , Gutgarts Victoria , Salvatore Steven 
Published: May 2024

Abstract

Background and Aims
Acute interstitial nephritis (AIN) is a well-recognized cause of acute kidney injury (AKI) in patients treated with Immune checkpoint inhibitors (ICI). Kidney biopsy typically shows tubular interstitial infiltration with well-differentiated mononuclear cells with occasional granulomas and eosinophils. Neutrophil rich tubular interstitial infiltration is typically associated with pyelonephritis. We report a case series of neutrophil rich ICI induced AIN.

Method
After obtaining approval from the institutional review board, medical records of the nephrology service at a large cancer center were reviewed. Patients were included in the study if they underwent a kidney biopsy for the diagnosis of ICI associated AKI, the biopsy was consistent with atypical AIN with neutrophil rich infiltrate, there was no glomerular involvement, they exhibited no symptoms of pyelonephritis including but not limited to fever, nausea, vomiting, flank pain and dysuria and had a negative urine culture.

Results
Forty eight patients who had a biopsy proven ICI associated AIN were identified from the medical records. Four (8.3%) patients met the study criteria (Table 1). There were three males and one female. The mean age was 75.5 years. One patient had a history of pre-existing CKD stage 3. Mean number of ICI therapy cycles prior to the development of AIN was seven with two patients treated with pembrolizumab (2 and 14 cycles), one patient treated with nivolumab (1 cycle) and one patient treated with the combination of nivolumab and ipilimumab (2 cycles). All patients presented with asymptomatic rise in serum creatinine (sCr). Kidney biopsy showed neutrophil rich infiltrate and neutrophilic tubulitis in all patients. Neutrophilic casts were present in three biopsies. One patient had evidence of granulomatous inflammation. All patients had mild to moderate interstitial fibrosis. Three patients were initially treated with flat dose prednisone 60 mg daily and one was treated with weight adjusted dose of prednisone 1 mg/kg at 75 mg/day. Three patients had complete renal recovery (sCr &lt; 0.5 mg/dl above baseline) after steroid taper. One patient developed a relapse but achieved partial recovery (sCr &lt; 2x baseline) after the second taper. Two patients remain alive three and 12 months after the kidney biopsy. Two patients died due to the progression of cancer two and 10 months after the biopsy.

Conclusion
AIN with neutrophil rich infiltrate likely represents a subset of ICI induced AIN. In the absence of clinical signs of pyelonephritis and with evidence of negative urine cultures the treatment should be geared towards addressing inflammation with systemic corticosteroids which have been shown to be effective in management of ICU induced AIN. Avoidance of antibiotics in this setting would lead to better antibiotic stewardship.
#2487 Deleterious renal outcome in patients with thrombotic microangiopathy after lung transplantation: the lung TMA trial
Authors: Rosseels Wouter , Claes Kathleen , Godinas Laurent , Kuypers Dirk 
Published: May 2024

Abstract

Background and Aims
Thrombotic microangiopathy (TMA) is a rare but severe complication following lung transplantation. The pathogenesis is poorly understood, involving endothelial damage and various risk factors, including calcineurin inhibitor (CNI) toxicity. We aimed to evaluate diagnostic accuracy, identify risk factors for and assess the renal and overall survival of TMA in this patient group.

Method
We performed a retrospective study of patients with TMA after lung transplant between 01/01/2000-01/01/2021. Matching controls were selected based on underlying lung disease, age, gender, CMV risk, and immunosuppressive regimen. Overall survival and baseline data (age, gender) were collected for the whole lung transplant group.

Results
A total of 29 TMA cases (2.9%) were identified out of 1025 lung transplantations. 48% of patients had a complete hematological assessment with Coombs testing as the most frequent (52%) missing test. The median time from transplantation to TMA was 5.9 months. 76% of the episodes occurred before 12 months. 77% of patients had organ damage with acute kidney injury in 72%. At the time of TMA 38% of patients had a cytomegalovirus (CMV) infection. Arterial hypertension was found in 31% and acute rejection in 11%. The immunosuppressive scheme consisted of tacrolimus/mycophenolate mofetil and corticosteroids in the majority of cases (56%). Tacrolimus (n = 22) and cyclosporine (n = 7) trough levels were respectively 11.8 and 207 µg/l at the time of TMA. Treatment consisted of change in immunosuppressive regimen (72%), 31% received plasmapheresis. When comparing the TMA patients with the control group a higher rate of donor specific antibodies were found (11% vs 1%), a lower median time till chronic lung allograft dysfunction (37 m vs 91 m) and a higher prevalence of end-stage renal disease (24% vs 6%) and overall death (97% vs 44%) with mortality being significantly higher (p &lt; 0.01). Fig. 1 illustrates the overall outcome.

Conclusion
This study illustrates the clinical characteristics and outcomes of TMA after lung transplantation. Even though the prevalence is low the effects are deleterious with acute kidney injury in the majority of cases and higher risk of end-stage renal disease and mortality. Our study emphasizes the need for higher further research into risk factors, and therapeutic strategies to prevent and improve patient outcomes. Furthermore, the findings underscore the importance of vigilant monitoring and tailored interventions for TMA in lung transplant patients.
#1289 The effect of desmopressin in reducing post-kidney biopsy bleeding complication in patients with reduced renal function: a randomised control trial
Authors: Chaturvedy Manish , Jhorawat Rajesh , Chakrabarti Uttayan , Bajpai Nitin Kumar , Nalwa Aasma , Khera Pushpinder 
Published: May 2024

Abstract

Background and Aims
Percutaneous kidney biopsy remains the gold standard for diagnosis of kidney disease. The incidence of bleeding complications following kidney biopsy ranges from 13 to 34%. This study aimed to evaluate the effect of prebiopsy administration of intranasal desmopressin on the incidence of post-biopsy bleeding complications in patients undergoing ultrasound-guided percutaneous native kidney biopsy with an estimated GFR of 60 ml/min/1.73 m2.

Method
It was a single-centre, double-blind, randomized controlled trial. Patients undergoing percutaneous ultrasound-guided biopsy of the native kidney in the department with age &gt;18 years, BP before biopsy ≤140/90 mm Hg, and eGFR &lt; 60 mL/min/1.73 m2. The patients were divided into experimental (intranasal desmopressin) and control group (intranasal normal saline), and block randomization was done by a computer-generated random number list prepared by an investigator with no clinical involvement in the study into an experimental and control group. The experimental group was treated using intranasal desmopressin acetate (dosage of 3 mcg/kg, each puff delivering 10 mcg) 1 hour before the kidney biopsy. The control group was treated with a placebo (equivalent dose of intranasal saline)(CTRI/2023/01/048812)

Results
A total of 152 patients were included (78 male and 74 female), the experimental group had 74 patients, and the control group had 78 patients. The mean age was 39.08 ± 15.03 yrs and 38.83 ± 15.67 yrs., respectively (p = 0.921). The experimental group had significantly less hematoma formation at 24 hrs. post kidney biopsy compared to the control group (p = 0.019). The hematoma volume at six hrs. (p = 0.342) and 24 hrs. (p = 0.698); post-kidney biopsy was not different between the two groups.

Conclusion
Intranasal desmopressin administration effectively reduces post-biopsy native kidney peri-renal hematoma formation at 24 hrs post-procedure. However, other bleeding complications were not different in the two groups of our studies.
#684 Safety and Tolerability of adipose-derived mesenchymal stem cell “ADR-001” in the treatment of immunoglobulin A nephropathy
Authors: Maruyama Shoichi , Tanaka Akihito , Furuhashi Kazuhiro , Fujieda Kumiko , Maeda Kayaho , Mimura Tetsushi , Saka Yosuke , Naruse Tomohiko , Ishimoto Takuji , Kosugi Tomoki 
Published: May 2024

Abstract

Background and Aims
Immunoglobulin A (IgA) nephropathy is one of the most frequent glomerular diseases and is sometimes refractory, requiring kidney replacement therapy. Although corticosteroids are mainly used for treatment, infection is a serious adverse event, and evidence for therapeutic efficacy is insufficient; therefore, new therapeutic options are highly desired. Mesenchymal stem cells (MSCs) contribute to the amelioration of inflammation and recovery of organ function. Due to these properties of MSCs, they have been clinically applied to various inflammatory diseases. Therefore, we decided to conduct the world's first investigator-initiated clinical trial to administer MSCs for refractory IgA nephropathy.

Method
This trial was a phase 1, open-label, multiple-center, dose-escalation study of adult patients with refractory IgA nephropathy resistant to or difficult to treat with existing therapies. This trial was registered and assigned the number, jRCT2043200002 and NCT04342325. ADR-001 was administered intravenously from three to six patients at a dose of 1 × 108 cells once in the first cohort and to six patients twice at two-week intervals in the second cohort (Fig. 1A). When MSCs were administered, heparin was also administered. The observational period continued until 52 weeks. The primary endpoint was the safety up to 6 weeks after ADR-001 administration. Secondary endpoints will be the respective percentages of patients with adverse events and efficacy, such as clinical remission, partial remission, remission of urine protein, remission of hematuria, time to remission, changes in urine protein, hematuria, and estimated glomerular filtration rate.

Results
First, regarding the primary endpoint, three patients in the first cohort received single dose of ADR-001, and the data safety monitoring board determined that the safety of the ADR-001 was well controlled because no adverse clinical events occurred. Therefore, the trial shifted the second cohort, and six patients received two doses of ADR-001. In the second cohort, the data safety monitoring board determined that safety was well controlled and that ADR-001 was safe and well tolerated for clinical use. Next, regarding the secondary endpoint, especially regarding to efficacy, kidney damage marker (Fig. 1B) and urinary protein were drastically reduced immediately after administration of ADR-001.

Conclusion
The safety and tolerability of ADR-001, an adipose-derived MSC, were confirmed. Furthermore, the efficacy of ADR-001 is strongly expected.
#1950 Burosumab activity on osteomalacia—a TIO case report
Authors: Foligno Nadia Edvige , Kato Hajime , Hoshino Yoshitomo , Kimura Soichiro , Sunouchi Takashi , Hidaka Naoko , Watanabe So , Vezzoli Giuseppe , Ito Nobuaki 
Published: May 2024

Abstract

Background and Aims
Tumor-Induced Osteomalacia (TIO) is a rare paraneoplastic disorder caused by a tumor (PMT), usually of small size and benign, secreting FGF23.
FGF23 suppresses the reabsorption of phosphate and the synthesis of 1,25(OH)2 vitamin D in the proximal tubular cells of the kidney; consequently, affected patients develop hypophosphatemia and osteomalacia, resulting in bone pain and pathological fractures.
The treatment of choice is the surgical resection of the tumor, but when the latter is not detected or cannot be removed, phosphate salts and active vitamin D can be employed to improve TIO symptoms.
Burosumab, a monoclonal antibody directed against FGF23 introduced for the treatment of X-linked hypophosphatemic rickets, has recently been tested for the treatment of TIO non-surgical patients with encouraging results, even if few data are currently available.

Method
Starting from January 2021, a 56M patient affected by TIO without identified PMT has been treated with burosumab at the dosage of 1 mg/kg s.c. every 4 weeks.

Results
Before the introduction of burosumab, his blood exams showed hypophosphatemia (1.9 mg/dL), low 1,25(OH)2 vitamin D levels (15 pg/mL) and hyperparathyroidism (81 pg/mL) secondary to previous administrations of phosphate salts.
He also reported widespread bone pain, suspect of multiple fractures and pseudofractures, confirmed by whole skeleton bone scintigraphy (BS) as numerous areas of pathological accumulation in the ribs, sacrum, bilateral femur, right proximal tibia, sternoclavicular joint and vertebral bodies.
After the initiation of burosumab, serum phosphate, PTH and 1,25(OH)2 vitamin D levels gradually normalized. The patient also reported an improvement in bone pain, and later BS described a notable and continuous reduction in pathological accumulations, which almost completely disappeared after 24 months, confirming the absence of new fractures and the improvement of existing ones.

Conclusion
Therefore, burosumab is suggested as an alternative treatment for non-surgical TIO patients, especially since, unlike conventional therapy with phosphate salts and active vitamin D, its therapeutic action seems to contribute to the further improvement of osteomalacia.
#2776 Monoclonal gammopathies and amyloidosis unit (UGAM-A): importance of the nephrologist in the multidisciplinary approach
Authors: Moreno Fernando Bertomeu , Almenara-Tejederas Marina , Garcia Fabiola Alonso , Millán Rafael Duro , Lazo Mercedes Salguiera 
Published: May 2024

Abstract

Background and Aims
The Monoclonal Gammopathies and Amyloidosis Unit (UGAM-A) is a multidisciplinary hospital subcommittee that discusses complex cases in relation to the diagnosis and treatment of patients with blood dyscrasia and amyloidosis.

Method
Retrospective observational study of the cohort of patients presented at UGAM-A
The data were extracted from the minutes of the UGAM-A for the period Jan/18-Dec/22.

Results
81 patients were assessed with a median age of 69 years, 52 men (64.2%). HT 58 (71.6%), DM 22 (27.2%), cardiovascular disease 14 (17.3%), Neoplasm 12 (14.8%).
56 patients (69.1%) had renal damage at the time of assessment, 54 with CKD criteria, with a mean creatinine of 1.7 ± 1.0 mg/dl and proteinuria of 1.3 ± 1.7 g/mg. Cardiac involvement was found in 19 patients.
There were 37 (45.7%) diagnostic changes after assessment by the UGAM.
A total of 22 (27.2%) therapeutic modifications, initiation or change were made. 17 (77.3%) occurred in patients with renal involvement.
There were 10 (12.3%) treatment changes, with 22.7% of them improving renal function vs. 7% in the group with no change in treatment (p = 0.04).
8 (9.9%) patients required SDB, with a median time to onset of 452d.
A total of 25 (30.9%) patients died, with a median time of 370d, with 12 being the most common cardiac cause, followed by infectious 8.

Conclusion
Nephrologists should be involved in the complex clinical cases that accompany hematologic diagnoses. In our study, almost 80% of patients had renal involvement concomitant with haematological pathology.
The role of the nephrologist is fundamental in clarifying mechanisms of kidney damage and enhancing the initiation of treatment even when they do not meet criteria from the haematological point of view, so that more than 77% of the therapeutic actions took place in patients with renal involvement.