bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO031: Long-term safety of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease
Authors: Martins Muñoz Judith , Espinel Laura , De Lorenzo Alberto , Tarragon Blanca , Teresa Naya Maria , Cubas Alfonso 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Tolvaptan, a vasopressin antagonist, is a drug that acts by slowing the progression of autosomal dominant polycystic kidney disease (ADPKD). Its administration is not free of side effects. To assess the long-term safety profile of ADPKD patients treated with tolvaptan.

METHOD
Retrospective observational study was undertaken of ADPKD patients on treatment with tolvaptan.

RESULTS
Of the 182 ADPKD patients under follow-up in our hospital, 18% (n = 33) started treatment. Of these, 60.6% (n = 20) were male, with an age of 47.64 ± 8.64 years, a baseline Fg of 65.24 ± 20.14 mL/min, TKVh of 1137.45 ± 667.58 mL and a mean follow-up time of 39.85 ± 10.04 months. A total of 72.7% reached the maximum dose (120 mg), the mean maximum dose reached being 108.18 ± 22.42 mg. At the time of the study, 100% of the patients had reached the maximum dose, the mean time to reach it being 5.8 ± 9.3 weeks. A total of 90.9% (n = 30) presented with side effects: 81.8% (n = 27) aquaretic and 12.1% (n = 4) hepatotoxicity. Others being hypernatremia in 9.1% (n = 3) and hyperuricemia in 24% (n = 8). No other side effects were described. A total of 39.4% (n = 13) of the patients temporarily discontinued treatment after 3.01 ± 2.17 months. The reasons were as follows: aquaretic effects 35.7% (n = 5), hepatotoxicity 35.7% (n = 5), 3.03% desire for pregnancy (n = 1), 3.03% cerebral hemorrhage (n = 1) and 3.03% (n = 1) worsening of renal function. Some 30.76% (n = 4) of the patients restarted treatment at 5.5 ± 6.76 months. Therefore, the treatment discontinuation rate was 27.2%.
The profile of patients with side effects were mostly male (60%) with mean age of 46 ± 8.65 years and TKVh of 1829.93 ± 1172.83 mL .The maximum dose reached in these patients was 107 ± 23.2 mg with a mean time to reach it of 6.19 ± 9.7 ± weeks.
Patients who had more aquaretic side effects were characterized by better baseline prior to renal function and a greater decrease in GFR throughout follow-up. No differences in TRV variations were observed.

CONCLUSION
Tolvaptan treatment is shown to be safe in the long term. However the patient profile to receive treatment must be considered given that a high percentage present aquaretic effects. Regarding hepatotoxicity, although it is another potentially serious effect to consider, it is easily managed and reversible in our studied sample.
MO069: Therapeutic Effects of Semaglutide as Mono and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease
Authors: Christensen Michael , Dalbøge Louise S , Secher Thomas , Gravesen Salinas Casper , Ida Rune , Björk Hansen Henrik , Fink Lisbeth N , Viberg Østergaard Mette 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Obesity, hyperglycemia and hypertension are critical risk factors for the onset and progression of diabetic kidney disease (DKD). Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. We have recently profiled the effects of SGLT2 and angiotensin-converting enzyme (ACE) inhibition in a model of advanced DKD facilitated by adeno-associated virus (AAV)-mediated renin overexpression in uninephrectomized (UNx) diabetic db/db mice (Østergaard et al., AJP Renal Physiol 321: F149–F161, 2021). In the present study, we evaluated the nephroprotective effects of the long-acting GLP1R agonist semaglutide, a long-acting GLP1R agonist currently approved for diabetes and obesity treatment and in clinical development for DKD. Semaglutide was profiled with and without combination treatment with lisinopril, a standard ACE inhibitor, in the db/db UNx-ReninAAV mouse model of DKD.

METHOD
Female db/db mice received a single intravenous injection of reninAAV 1 week prior to UNx. Six weeks post-nephrectomy, mice were randomized into treatment groups based on body weight and blood glucose in the fed state, and received vehicle (SC, QD), semaglutide 30 nmol/kg or semaglutide 30 nmol/kg (SC, QD) in combination with lisinopril 30 mg/kg (PO, QD) for 11 weeks. Treatment endpoints included blood pressure, plasma/urine biochemistry and histomorphometric markers of kidney injury.

RESULTS
Vehicle-dosed db/db UNx-ReninAAV mice developed hallmarks of hypertensive DKD characterized by severe albuminuria and advanced glomerulosclerosis. Compared with vehicle, semaglutide significantly reduced fed blood glucose and hemoglobin A1C levels, whereas no significant effect on plasma insulin was observed. Semaglutide significantly reduced both diastolic and systolic blood pressure as well as albuminuria and urine kidney injury molecule-1 (KIM-1) levels. Semaglutide improved kidney histopathology with notable reductions in glomerulosclerosis severity and percent area of KIM-1 staining. Combined lisinopril treatment led to further improvements in blood pressure, albuminuria and glomerulosclerosis. Semaglutide with and without lisinopril coadministration did not influence plasma urea, cystatin C and kidney CD11 expression.

CONCLUSION
Semaglutide improved disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Further benefits on renal functional and histological markers were obtained by combination with antihypertensive standard-of-care treatment.
MO112: Clinical Features of Allopurinol-Induced DRESS/DIHS in 46 Patients
Authors: Liu Qianling , Zhao Sumei 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Allopurinol is the first-line prescribed agent for hyperuricemia and gout. Allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious and potentially life-threatening drug hypersensitivity syndrome. This study aimed to investigate the clinical features, treatment, outcome and prognostic factors of allopurinol-induced DRESS.

METHOD
Case reports of allopurinol-induced DRESS published by China from January 2000 to August 2021 were retrieved from CNKI, Wan Fang, Wei Pu and PubMed databases for analysis.

RESULTS
This study included 46 patients, consisting of 34 (73.9%) males and 12 (26.1%) females (M: F = 2.8:1). The mean of age was 56.1 ± 17.4 years (range: 23–86 years). The mean of latency periods was 24.0 ± 14.8 days (range:1–60 days). Most patients presented with fever, cutaneous eruption, eosinophilia, lymphadenopathy and facial oedema. All patients showed at least one internal organ injury. A total of 35/46 (76.1%) patients showed two or more internal organs involved. Liver and kidney injury were the most common visceral manifestations. One patient showed central nervous system involved, presenting as leukoencephalopathy. HLA*B 58:01 allele was tested in 19/46 (41.3%) patients. A total of 18/19 (94.7%) patients were positive. A total of 45/46 (97.8%) patients were treated with systemic corticosteroids. Patient outcomes were known for 45 of the 46 patients. A total of 13 (28.9%) patients were cured, 24 (53.3%) patients received partial recovery and 8 (17.8%) patients died. Septic shock and multiple organ failure were the leading causes of death. Patients with older age, underlying cardiovascular disease, chronic kidney disease, infection and internal organ involvement (including kidney, heart and lung) were associated with poorer outcomes.

CONCLUSION
We explored clinical features, treatment, outcome and prognostic factors of 46 allopurinol-induced DRESS cases in China. Early identification and discontinuation of the causative drug are crucial to the management of DRESS. For patients with severe disease, corticosteroids are recommended as the first-line therapy. However, further studies are needed to address diagnostic criteria of DRESS for early diagnosis, as well as to develop standardized corticosteroid treatment regimens.
MO136: Histological Findings in Checkpoint Inhibitor-Induced Nephropathy
Authors: Gerakis Alexander , Kaitantzoglou Christine , Giatras Ioannis , Stauridi Flora , Labropoulos Stefanos , Athanasiadis Ilias , Kosmidis Paraskeuas , Gakiopoulou Harikleia 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Immune checkpoint inhibitors (CPIs)—a landmark in cancer therapy—has been occasionally associated with immune-related nephropathy [1]. Acute interstitial nephritis is considered to be the most common underlying histological entity, according to recent literature [2].

METHOD
We report on six patients, 58–73 years old, three women and three men who presented with acute kidney disease, while on immunotherapy with CPIs. Five of them carried the diagnosis of non-small cell lung carcinoma (NSCLC) and one the diagnosis of renal cell carcinoma. All received proton pump inhibitors and experienced one or more of immune-related adverse events (dermatitis, arthritis, colitis, hepatitis and pneumonitis), prior to nephropathy. All underwent kidney biopsy.

RESULTS
Two female patients, both with NSCLC, developed heavy nephrotic syndrome (serum albumin: 1.7–1.8 mg/dL and 24-h urine protein: 12–16 g), after 23–28 months on pembrolizumab monotherapy, which was withdrawn. In the first patient, kidney biopsy demonstrated histology consistent with a lupus like membranous nephropathy (Figure 1). She received corticosteroids with partial recovery. Rechallenge with pembrolizumab was attempted and well tolerated. Renal biopsy of the second patient demonstrated a secondary AA (+) amyloidosis (Figure 2). She showed increased levels of SAA (114 mg/L) and IL-1b (22.9 pg/mL). She received colchicine and moderate dose of corticosteroids with partial remission.
Two other patients, with NSCLC and clear cell renal carcinoma respectively, demonstrated renal biopsy findings consistent with acute interstitial nephritis (serum creatinine 1.5–1.6 mg/dL). The first one was on pembrolizumab along with cisplatin and pemetrexed, while the second one was on pembrolizumab along with axitinib. Both received prednisolone (10–20 mg for 3 months approximately). Pembrolizumab was restarted thereafter. Their renal function remained stable.
Finally, two patients with NSCLC, both men, disclosed acute renal failure (serum creatinine: 3.6- 5 mg/dL) without considerable albuminuria. Acute tubular injury (ATI) was the predominant histological finding (along with focal and mild interstitial inflammation). Both were on combined chemo- and immune- therapy. One on ipilimumab and nivolumab along with platinum and pemetrexed and the other on pembrolizumab and pemetrexed. ATI was attributed most probably to pemetrexed which was withdrawn. Corticosteroids were promptly stopped in the first patient. The second patient showed gradual improvement of his renal function without corticosteroid therapy.

CONCLUSION
CPIs can induce nephropathy other than acute interstitial nephritis. Renal biopsy showed diverse and unusual histological findings. Renal biopsy along with the clinical setting was helpful in choosing appropriate therapy and deciding on CPI's continuation or withdrawal.
MO208: De Novo Glomerulonephritides Following BNT162B2 COVID-19 Vaccine: A Case Series
Authors: Fornara Laura , Musetti Claudio , Guglielmetti Gabriele , Cantaluppi Vincenzo 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The development and massive use of mRNA COVID-19 vaccine BNT162b2 has raised new concerns on triggering de novo immune-mediated diseases, in particular rare diseases as glomerulonephritis (GN), even if the security profile is excellent and severe reactions have been rare. In literature few similar cases were recently described [1, 2]. We report six cases of newly diagnosed GN after a two-dose regimen of SARS-CoV-2 vaccine, from a single tertiary care institution in Northern Italy.

METHOD
We described six cases of de novo GN occurring after massive use of Pfizer-BioNTech BNT162b2 COVID-19 vaccine from March 2021 to December 2021. All cases were biopsy proven. Baseline characteristics and laboratory findings, treatments and outcomes were based on review of medical records.

RESULTS
From April 2021, we observed two IgA nephropathies (IgA-N), one membranous nephropathy (MN), one membranoprolipherative GN (MPGN), one acute interstitial nephritis (aTIN) and one minimal change disease (MCD). Of note, one IgA-N presented with diffuse purpura as in IgA-vasculitis. The median age at vaccination was 52.8 years (min–max 18–67) and three (50%) were female; arterial hypertension was the most common comorbidity (50%). Only one subject contracted COVID-19 before vaccine (16.6%). None of the points showed any sign of renal disease before vaccine; at the time of disease onset, the median creatinine was 1.49 mg/dL (min–max 0.6–10.5 mg/dL) and proteinuria 3.0 g/24 h (min–max 0.9–13.8 g/24 h). All cases presented after the second dose (1 day to 6 months thereafter) and three (50%) were within 3 weeks from the vaccine. Of note, the aTIN developed after the vaccine during a long-time therapy with statins and relapsed after a rechallenge with a statin few months later. All the nephropathies were treated as per center practice, with an overall good response (four partial remissions and one complete remission). Given a target population of about 100 000–200 000 residents in our area, we could estimate an incidence rate of 4–8 cases/100 000 patient-years.

CONCLUSION
This small series has a lot of limitations including the small number of patients and we probably missed some cases in our area. Furthermore, we could not investigate a causal association, even if the timing of disease onset might be suspicious in three cases and the incidence seemed to be almost twice as the expected in Europe (about 2–4/100.000 patient-years). As for SARS-CoV-2 vaccines, it is likely that the mRNA vaccine will result in a more potent inflammatory stimulus than the one observed after inactivated virus-vaccine: maybe some patients had already a subclinical GN and the vaccine constituted a flare leading to the full-blown disease [3].
MO285: FOSL1 Preserves Klotho Expression and Limits Acute Kidney Injury
Authors: Cuarental Leticia , Ignacia Ceballos Darnaude Mª , Valino Lara , Pintor-Chocano Arancha , Ortiz Alberto , Dolores Sanchez-Nino Maria 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Fosl1 (FRA1, Fos-related-antigen 1) is a transcription factor of the AP-1 complex (activator protein 1) that regulates the expression of genes that regulates processes involved in acute kidney injury (AKI) such differentiation, inflammation, proliferation and cell death. We have now explored the role of Fosl1 in AKI and repair.

METHOD
The function of Fosl1 was explored in murine nephrotoxic AKI induced by folic acid or cisplatin in wild type and genetically modified mice tubular cell Fosl1 deficient mice (Fosl1Δtub). RT-qPCR, western blot, and immunohistochemistry were used to assess gene and protein expression. Direct regulation of Klotho by Fosl1 was explored by chromatin immunoprecipitation (ChIP). Murine tubular cells were cultured in an inflammatory milieu promoted by TWEAK and Fosl1 was targeted by siRNA.

RESULTS
Fosl1 was one of the most upregulated transcription factors in experimental nephrotoxic AKI transcriptomics and also one the transcription factors binding to the Klotho promoter (Panel A). Fosl1 upregulation was confirmed in experimental nephrotoxic AKI and in human AKI and localized to tubular cell nuclei at early times points (panel B). Fosl1 deficient (Fosl1Δtub) mice developed more severe folic acid- or cisplatin-induced AKI and higher proinflammatory cytokine expression and kidney macrophage infiltration (Panel C). Additionally, kidney expression of the nephroprotective and antiaging factor Klotho was more severely depressed in Fosl1Δtub mice (Panel D). Enrichment of AP1 binding sites was found in the Klotho promoter and we confirmed direct Fosl1 binding to the Klotho promoter in a ChIP assay. Moreover, Fosl1Δtub mice had disturbed expression of cell cycle regulators and PCNA expression, suggesting a dysregulation in kidney repair. In tubular cells cultured in an inflammatory milieu, Fosl1 expression was also upregulated. Fosl1 siRNA targeting in cultured tubular cells increased inflammatory gene expression and cell death and decreased Klotho expression.

CONCLUSION
Fosl1 contributes to an adaptive kidney response during AKI that limits kidney injury and includes Klotho expression and Fosl1 deficiency promotes an accelerated loss of klotho and more severe AKI.
MO313: Haematological Ratios as Risk Factor for Acute Kidney Injury in Patients Suspected of an Infection at the Emergency Department
Authors: de Hond Titus , Khairoun Meriem , Haitjema Saskia , Kaasjager Karin A H 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Evidence exists that inflammation plays an important role in the pathogenesis of acute kidney injury (AKI) in sepsis patients. Haematological ratios can be used to measure systemic and silent inflammation. Therefore, we investigated what haematological ratios could be identified as risk factors to predict AKI &lt; 30 days in patients suspected of infection at the emergency department (ED).

METHOD
Data from the SPACE-cohort (SePsis in the Acutely ill patients in the ED) were used. This cohort consists of all patients ≥ 18 years, that present at the ED of the UMC Utrecht for the internal medicine with suspicion of infection. AKI was defined based on the KDIGO criteria. Haematological markers were determined with the Abbott Cell-DYN Sapphire haematology analyser. In total, 7 haematological ratios were included. A Cox regression was performed after the ratios were divided into tertiles. Consequently, Kaplan–Meier curves for 30-day mortality were constructed for the significant predictors from the Cox analysis.

RESULTS
In univariate Cox regression, neutrophil-to-lymphocyte ratio (NLR), segmented neutrophil-to-monocyte ratio (SeMo) and neutrophil-to-lymphocyte-and-platelet ratio (NLPR) were all significant risk factors for the occurrence of AKI &lt; 30 days after ED presentation (Fig. 1). After correction for multiple confounders, NLR, SeMo and NLPR remained significant. There were significant differences in survival for all these three ratios (Fig. 2).

CONCLUSION
In this study, we show that several haematological ratios are risk factors for AKI and mortality in patients suspected of infection at the ED. Using these risk factors in prediction models might enable ED physicians to treat AKI in an early phase and prevent any short- and long-term complications. A limitation of this study is the retrospective character. Because of this, not all patients in the cohort had follow-up creatinine levels, and the occurrence of AKI could not be determined in these patients.
MO371: Should We Systematically Look for Urine Alterations in all Patients With Monoclonal Gammopathy of Undetermined Significance?
Authors: Iturralde Ros Marta , Maiztegi Azpitarte Ainhoa , Ortiz Espejo María , Montes Gaisan Carmen , María Ocio San Miguel Enrique , Carlos Ruiz San Millán Juan , Rodrigo Emilio 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Monoclonal gammopathy of undetermined significance (MGUS) has a high prevalence in the elderly population, being as high as 9% in subjects over 85 years. Population aging leads to an increase in the number of patients with MGUS. In 2012, monoclonal gammopathy of renal significance (MGRS) was described to identify MGUS patients with renal alterations but without overt hematological disorders. Despite an increasing number of cases and case series being reported, the prevalence and natural history of MGRS are not known with precision, in part because a systematic search for kidney damage is not standardized in all patients in whom MGUS is diagnosed. Our objective was to analyze in how many MGUS patients urine has been systematically analyzed and in how many of them any alterations suggestive of MGRS were detected.

METHOD
A retrospective observational study was carried out in our center of all patients in whom a paraprotein had been detected in the blood during the first trimester of 2018 and who did not present a known underlying hematological disorder. Glomerular filtration rate (GFR) was estimated using the CKD-EPI equation. The percentage of patients with a urine test using dipstick and urine sediment was analyzed, as well as the presence or any alteration suggestive of MGRS in them.

RESULTS
Three hundred and sixty patients were recorded, 44% females and with a mean age of 74 ± 12 years. Mean GFR was 69 ± 22 mL/min/1.73 m2 being 32% below 60 mL/min/1.73 m2. Urine dipstick and urine sediment were performed in only 42% and 24% of patients, respectively. Urine dipstick was more frequently performed in patients with worse GFR (72 ± 20 versus 64 ± 24 mL/min/1.73 m2P = 0.001) and in older patients (73 ± 13 versus 76 ± 11, P = 0.027). Similarly, urine sediment was more frequently performed in patients with worse GFR (72 ± 20 versus 59 ± 25 mL/min/1.73 m2 P &lt; 0.001). Significant hemoglobinuria was found in 38% and dipstick albuminuria in 29% of them. Among those patients with urine sediment analysis, significant hematuria was detected in 56% and leukocyturia in 52%. Patients with significant dipstick hemoglobinuria (70 ± 21 versus 55 ± 26 mL/min/1.73 m2 P &lt; 0.001) and albuminuria (68 ± 21 versus 54 ± 28 mL/min/1.73 m2 P = 0.005) showed worse GFR (figure 1).

CONCLUSION
Despite the risk of suffering some pathologic renal conditions included in the term MGRS, in most of our patients with MGUS, a urine dipstick or sediment analysis is not performed. MGUS patients with urine alterations show worse renal function. We advocate that all MGUS patients should have a dipstick and sediment urinalysis to rule out any possible associated kidney damage.
MO373: How to Decide Whether Creatinine or Cystatin C is More Accurate for Kidney Function Assessment in Older Adults
Authors: Potok Alison , Rifkin Dena , IX Joachim , Shlipak Michael , Satish Anita , Schneider Alice , Mielke Nina , Schaeffner Elke , Ebert Natalie 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The gold standard for evaluation of kidney function is measured GFR [mGFR] which is challenging to perform in clinical practice. Serum creatinine and cystatin C are used to estimate GFR clinically, but neither is a perfect marker. Within any given individual, the estimated glomerular filtration rate (eGFR) can be widely different when using serum creatinine [eGFRCr] vs. cystatin C [eGFRCys]. We investigated which was closest to mGFR in elderly outpatients when results between these two eGFRs were discrepant.

METHOD
About 657 older ambulatory participants of the population-based Berlin Initiative Study (BIS) had GFR measured by iohexol plasma clearance (mGFR), as well as serum creatinine and cystatin C levels. eGFRCr and eGFRCys were calculated using the 2009 and 2012 CKD-EPI equations, respectively. The cohort was divided into two groups based on which of these eGFR estimates was lowest. Bias (defined as ‘eGFR-mGFR’), imprecision (standard deviation [interquartile range] of bias), as well as proportion within 30% (P30) were calculated.

RESULTS
Mean (±SD) age was 78 (±6) years, eGFRCys was 59 (±23), mean eGFRCr was 64 (±20) and mGFR was 55 (±20) mL/min/1.73 m2. Mean (±SD) body mass index was 28 (4) kg/m2 58% were men, and 26% had diabetes mellitus. Two-thirds of participants (448/657 = 68%) had eGFRCys &lt; eGFRCr. Regardless of which group participants were in, the lower of the two eGFR estimates was the one less biased compared to mGFR. Among those in whom eGFRCr ≤ eGFRCys, 80% (=168/209) had eGFRCr closer to mGFR than eGFRCys; among those in whom eGFRCys &lt; eGFRCr, 74% (=333/448) had eGFRCys closer to mGFR than eGFRCr (Figure). P30 was 86% for eGFRCr when it was the lower estimate, and was 90% for eGFRCys when it was the lower estimate (Table).

CONCLUSION
In a population of community-dwelling older adults, the lower value between eGFRCys and eGFRCr was closest to mGFR in 76% of participants.