bluuebunny/crossref_metadata_2025 huggingface dataset:
#2907 Characterization of patients needing red blood cell transfusion after kidney transplant
Authors: de Hilla Nerea Ormaetxe Ruiz , Etxarri Neike Murua , Martín María Fernández , De Juan Oihane Abaunza , Davis Mónica Paola Rodríguez , Noguer Raquel Vila I , Castaño Isabel Benito , Mendia Iñigo Yañez , Montes Amaia Begoña Osorio , Berastegui Begoña Bralo , Álvarez Quintana Eva María , Larrondo Sofia Zarraga
Published: May 2024

Background and Aims

After kidney transplant there is often need of red blood cell (RBC) transfusion because acute bleeding associated with surgery; or because multifactorial progressive anemization the days after. The aim of this work is to describe the characteristics of transfused kidney transplant recipients (KTR) and compare them to nontransfused controls.

Method

Retrospective observational study, reviewing the data from electronic medical records of patients receiving a kidney transplant in our hospital during 2022.

Results

During 2022, 160 kidney transplants were performed in adult people in our hospital and 66 (41.25%) KTR were transfused; some of them receiving the first red blood cell concentration (RBCC) during surgery (19.7%), the rest after surgery hospitalization because acute (10.6%) or progressive (69.7%) anemization. The total number of RBCC received was 1 in the 15% of transfused KTR, 2 in the 48%, 3 in the 8% and ≥ 4CH in the 29%.

Among transfused KTR, the 13.6% kidney grafts came from living donors, 48.5% from Maastricht III, 36.4% from brain death and 1.5% from Maastricht II, whereas the kidney grafts of nontransfunded controls came from living donors (11.7%), Maastricht III (54.26%), encephalic death (32.98%) and Maastricht II (1.06%).

The mean age of the transfused KTR was 62 years, 63.6% were males, 14.1% with ischemic heart disease, 6.3% with heart failure, moderate-severe valvular heart disease. The 12.12% were treated with acenocoumarol and the 25.7% with acetylsalicylic acid before the transplant hospitalization (whereas in nontransfunded controls the percentages were 10.6% and 21.3% respectively).

Haemoglobin (Hb) levels previous to the surgery was lower in transfused KTR, presenting Hb <10 g/dl in the 10.6% of the recipients, whereas in nontransfunded controls was 2.1%. Moreover, ferritin levels were <100 ng/ml in 13.6% and transferrin saturation index was <20% in the 30.3% (whereas in nontransfunded controls it was 25.53% and 38.29% respectively).

The mean of Hb before the transplant surgery in transfused KTR was 11.7 ± 1.4 g/dl, and before RBCC transfusion the median was 7.8 g/dl [7.6-8.1].

Conclusion

Although more studies are needed, it is interesting to know the characteristics of the KTR that need RBC transfusion in order to asses measures (such us for example, Hb, iron … pretransplant adequate thresholds), in order to avoid if it is possible, unnecessary RBC transfusions.
#1274 Post kidney transplant parvovirus disease presenting as refractory anemia—case series of 21 patients
Authors: Mittal Ankur , Hegde Umapati , Gang Sishir , Konnur Abhijit , Patel Hardik
Published: May 2024

Background and Aims

Kidney transplant recipients (KTRs) are susceptible to a wide range of infections, one of which includes Parvovirus B19 (PVB19). It usually presents in the first year after transplant, with anemia and causes increased morbidity and risk of graft dysfunction.

Method

Charts of patients undergoing kidney transplant between May 2013 and March 2022 were reviewed. 21 patients had PVB19. Their clinical presentation, laboratory parameters and outcome was studied. The diagnosis of PVB19 was established by PVB19 polymerase chain reaction (PCR) and by bone marrow examination(BME) in 6 patients.

Results

Prevalence of PVB19 disease was 1.9% (21/1164) with a median time to onset was 39 days post-transplantation. Clinical presentation included fever, generalized weakness, dyspnea, and myalgia in 47%, 76%, 23%, and 33% of patients respectively. Anemia, leukopenia, and thrombocytopenia were present in 100%, 14%, and 9.5% of patients respectively. Graft dysfunction was observed in 61.9% (13/21) patients. 20/21 (95%) patients had a positive PVB19 PCR and one patient had a typical viral inclusion on BME. Immunosuppression especially antiproliferative was reduced in all patients. 8 patients received IVIG, 8 received packed cell blood transfusion and 7 received Erythropoietin therapy. All patients recovered with median time to normalization of hemoglobin was 30 days. One patient had graft loss secondary to non-responsive graft rejection.

Conclusion

PVB19 is a rare but clinically significant cause of refractory anemia during the early post-transplantation. Any kidney transplant patient in first 4 months who has unexplained normocytic normochromic refractory anemia with or without graft dysfunction should be screened for PVB19 by DNA PCR or BME to rule out PVB19 infection. The use of PCR for diagnosis and reduction in immunosuppressants particularly antiproliferative drugs is the mainstay of treatment.
#983 Identification of gut microbiome signatures associated with albuminuria in diabetes mellitus
Authors: Lin Yi-Ting , Sayols-Baixeras Sergi , Dekkers Koen , Baldanzi Gabriel , Larsson Anders , Orho-Melander Marju , Fall Tove , Ärnlöv Johan
Published: May 2024

Background and Aims

Diabetes is a growing global problem with serious complications, including kidney impairment and cardiovascular morbidity and mortality. Monitoring albuminuria, which is associated with these complications, is crucial in optimal diabetes management. Recent research suggests a link between the gut microbiome, plasma metabolites and albuminuria development in diabetes patients, highlighting the need for further investigation using deep metagenomic sequencing.

Method

We investigated the relationship between 1002 gut microbial species, 1308 metabolites and albuminuria in 752 participants with diabetes from the Swedish CArdioPulmonary BioImage Study. To determine the relative abundance of species, we employed deep shotgun metagenomic sequencing of fecal samples. Plasma metabolites were analyzed using mass spectrometry-based methods.

Results

Shannon diversity index was inversely associated with albuminuria after adjusting for confounding factors (Fig. 1). Our multivariable-adjusted models revealed seven metagenomic species that were associated with albuminuria (Fig. 2). Furthermore, employing a global metabolomics approach, we identified phenyl sulfate, among 98 annotated metabolites (Fig. 3), as linked to the species Clostridium sp. AT4 and Eggerthella lenta. Notably, phenyl sulfate is involved in tyrosine metabolism, and we also observed an association between the gut metabolic module of Tyrosine degradation II and albuminuria.

Conclusion

In the present study, we identified seven gut microbial species linked to albuminuria and established a connection between these species and phenyl sulfate, which previously has been associated with podocyte damage and the development of albuminuria. These findings provided additional evidence of the impact of microbial species and contribute to our understanding of the complex relationship between the gut microbiome, plasma metabolites, and albuminuria in patients with diabetes.
#803 Identification and validation of immune and cuproptosis-related genes for diabetic nephropathy by WGCNA and machine learning
Authors: Chen Yubing , Wu Zhan
Published: May 2024

Background and Aims

As the leading cause of chronic kidney disease, diabetic kidney disease (DKD) is an enormous burden for all healthcare systems around the world. However, its early diagnosis has no effective methods.

Method

First, gene expression data in GEO database were extracted, and the differential genes of diabetic tubulopathy were obtained. Immune-related gene sets were generated by WGCNA and immune cell infiltration analyses. Then, differentially expressed immune-related cuproptosis genes (DEICGs) were derived by the intersection of differential genes and genes related to cuproptosis and immune. To investigate the functions of DEICGs, volcano plots and GO term enrichment analysis was performed. Machine learning and protein-protein interaction (PPI) network analysis helped to finally screen out hub genes. The diagnostic efficacy of them was evaluated by GSEA analysis, receiver operating characteristic (ROC) curve, single-cell RNA sequencing and the Nephroseq website. The expression of hub genes at the animal level by STZ -induced and db/db DKD mouse models was further verified.

Results

Finally, three hub genes, including FSTL1, CX3CR1 and AGR2 that were up-regulated in both the test set GSE30122 and the validation set GSE30529, were screened. The areas under the curve (AUCs) of ROC curves of hub genes were 0.911, 0.935 and 0.922, respectively, and 0.946 when taking as a whole. Correlation analysis showed that the expression level of three hub genes demonstrated their negative relationship with GFR, while those of FSTL1 displayed a positive correlation with the level of serum creatinine. GSEA was enriched in inflammatory and immune-related pathways. Single-nucleus RNA sequencing indicated the main distribution of FSTL1 in podocyte and mesangial cells, the high expression of CX3CR1 in leukocytes and the main localization of AGR2 in the loop of Henle. In mouse models, all three hub genes were increased in both STZ-induced and db/db DKD models.

Conclusion

Machine learning was combined with WGCNA, immune cell infiltration and PPI analyses to identify three hub genes associated with cuproptosis, immunity and diabetic nephropathy, which all have great potential as diagnostic markers for DKD and even predict disease progression.
#707 Effectiveness of a personalized approach to the treatment of patients with chronic coronary syndrome with type 2 diabetes and renal dysfunction
Authors: Alyavi Bakhromxon , Rasulev Yorkin , Abdullayev Akbar
Published: May 2024

Background and Aims

To evaluate the effectiveness of complex personalized treatment of patients with chronic coronary syndrome (CCS) with type 2 diabetes mellitus (T2DM).

Method

We observed patients with chronic stable angina pectoris III (FC) (Group I, 16) and CV IV FC (Group II, 18) with T2DM who underwent planned stenting of the coronary arteries (SCA). At baseline and after 3 and 6 months, we studied cholesterol, LDL cholesterol and HDL cholesterol, triglycerides (TG), ALT and AST, total bilirubin (TB), polymorphism of the CYP2C19 and 9p21 genes (rs 2383206 and rs 10757272), assessed myocardial viability (ECHOCG, MSCT), an ultrasound of the liver was performed. Against the background of basic therapy (antiplatelet agents, statins, beta blockers, ACE inhibitors), patients received a herbal hepatoprotector.

Results

Initial lipid parameters in patients with CCS and T2DM: cholesterol—6.9 mmol/l; LDL cholesterol –3.6; HDL cholesterol –1.1; TG –2.5 mmol/l. Parameters of global and regional systolic function were reduced. At the end of observation, lipid content: cholesterol—5.0; LDL cholesterol—2.3; HDL cholesterol –1.18; TG—1.61 mmol/l. Statins and antiplatelet agents were well tolerated, and there were no cases of withdrawal. Enzyme activity (ALT, AST), OB content were within normal values. The genetic studies carried out helped to select the most effective and safe doses of antiplatelet drugs and statins and significantly reduced the risk of complications and drug resistance. The hepatoprotector had a beneficial effect on the condition and function of the liver and improved the tolerability of medications. A personalized approach to the treatment of CCS was carried out taking into account the results of genetic testing with the selection of optimal doses of drugs. When the genotypes of CYP2C19*17 (rs 12248560) CC, ST and TT were distributed, the dose of antiplatelet agents was increased, and when the genotypes of the CYP2C19 gene (rs 4244285) GG, AG and AA were distributed, they were reduced. Assessment of myocardial viability, selection of doses of statins and antiplatelet agents according to individual characteristics, as well as a hepatoprotector increased the effectiveness and safety of treatment. SCA and basic treatment had an impact on the pathogenetic links of CCS, which is especially important in the treatment of patients with concomitant T2DM.

Conclusion

A personalized approach to the treatment of patients with CCS with T2DM who require SCA, taking into account the functional state and viability of the myocardium, the pharmacogenetic characteristics of the drugs, increases the effectiveness of revascularization, prevents the development of resistance, side effects and complications.
#2630 Current perceptions and interests of Spanish Nephrology Fellows
Authors: Lozano Claudia Yuste , Cabrera Maria Sagrario Soriano , Sanchez-Alvarez Jose Emilio
Published: May 2024

Background and Aims

The Spanish Peritoneal Dialysis Support Group (GADDPE) aim to enhance peritoneal dialysis (PD) education among young nephrologists to increase the incidence and prevalence of PD in Spain.

Method

Aiming to develop initiatives to make PD a more attractive and suitable for nephrologist, we conducted a 22-item survey targeting Spanish nephrology fellows (NF) sought to explore their areas of interest, experiences, and perceptions across their training in various nephrology subspecialties.

Results

51 survey answers where received, mainly from women (69%) during their last two years of training in tertiary hospitals (76%). Clinical nephrology was the preferred subespeciality of nephrology among NF (61.5%), and so the most frequently chosed as their free rotation (36.5%). As expected, interventional nephrology held the second place in NF preferences (25%) and the second-one selected as their free rotation (30.8%), since the 36.5% of NF consider interventional nephology as their least well-trained subespeciality. Sadly, most of the NF believe they will end up working in hemodialysis (63.5%), even though is favorite area of just the 11.5%. Regarding PD, is favorite area of just one fellow (1.9%), none believe they will end up working in it, and 28.8% thinks it is the area where they are least well-trained. On the other hand, 41.2% of residents perceive that clinical nephrology is the most renowned subespecility in their training hospital, while 31.4% believe that transplant is the least renowned area, followed by PD in the 21.6%. Finally, the 66% of the residents have participated in some research mainly related to Clinical nephrology (75.7%), followed by far from hemodialysis (16.2%).

Conclusion

Clinical nephrology is the preferred nephrology subespeciality for nephrology fellows, likely due to their greater involvement in research and the feeling that is the most renowned subespeciality on their hospital. To enhance the appeal of Peritoneal Dialysis for residents it is essential to promote innovation and research.
#748 Association between systemic inflammation biomarkers and mortality in patients with SA-AKI receiving CKRT
Authors: Jung Chan-Young , Jung Jiyun , Lim Jeong-Hoon , Paek Jin Hyuk , Kim Kipyo , Ban Tae Hyun , Park Jae Yoon , Kim Hyosang , Kim Yong Chul , Back Chung Hee
Published: May 2024

Background and Aims

Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT.

Method

This multi-centre, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, KRT dependence at discharge, and lengths of ICU and hospital stays.

Results

When added to the widely accepted Acute Physiology and Chronic Health Evaluation-II score, platelet-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% CI, 0.00-0.02) and 0.02 (95% CI, 0.01-0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models.

Conclusion

Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.
#1301 Orellanine intoxication—a case report
Authors: Ahmad Irma , Sundstedt Amanda , Tenerz Linnea , Mörtberg Lina Josefin Gisela , Haraldsson Boerje
Published: May 2024

Background and Aims

This is a case report presenting a patient with orellanine-caused acute kidney failure. Cortinarius rubellus is a mushroom containing orellanine which is a selective nephrotoxin that destroys the proximal tubule cells of the kidney. Intake of just a few mushrooms is enough to cause irreversible damage and furthermore lead to severe kidney failure. Symptoms as gastrointestinal irritation usually occur 3-7 days after intake. Anti-oxidative medication and steroids have been evaluated but have not shown any effect on the kidney damage.

The aim of this case report was to raise awareness about the clinical manifestations of orellanine poisoning, diagnostic challenges, and potentially severe consequences.

Method

The junior doctors (IA, LT, AS) and the senior doctor (JM) took care of the patient at the ED, the internal medicine ward and the dialysis clinic. All data was extracted from the medical record. Informed consent was obtained from the patient. An attempt to analyze orellanine in the kidney biopsy was made.

Results

A 40-year-old male entered the emergency department with abdominal pain, fever, nausea and vomiting. The creatinine concentration was 278 µmol/L (3.14 mg/dl) where acute kidney failure due to prerenal cause was suspected. The patient was recommended to stay but declined due to personal reasons, and instead a follow-up next day was planned.

The following day, the creatinine concentration was increased to 477 µmol/L (5.39 mg/dl). The junior doctor specifically asked for mushroom intake. The patient confirmed that three days before, he had been in the forest picking mushrooms, of which he consumed two raw and the rest in a stew. Acute renal failure from mushroom poisoning was now suspected. The patient was admitted, and serum creatinine increased to 817 µmol/L (9.24 mg/dl) the following day. The urine production decreased, and the patient was anuric 7 days after intake. Hemodialysis was initiated due to uremic symptoms and volume overload. After showing the patient different photos of mushrooms it was suspected that he had consumed Cortinarius Rubellus. A renal biopsy was performed 12 days after the mushroom intake, which showed a fulminant acute tubular necrosis, no sign of glomerulonephritis, vasculitis, or interstitial nephritis. The attempt to analyze orellanine in the kidney biopsy material was not successful. Orellanine would not be detected in the urine or blood samples because they were collected 72 hours after intake. The half-life of orellanine in otherwise healthy humans is considered to be around 2-4 hours.

The patient stayed at the hospital for a total of 14 days. He was on hemodialysis for 14 months and was then successfully kidney transplanted.

Conclusion

Orellanine is a very potent toxin leading to severe damage of the kidney tubules. Due to the diagnostic challenges, it is important to keep this in mind when managing a patient with acute renal failure.
#2921 The SOFA score: predictive factor of nephrotoxicity post injection of iodized PDC in the emergency room
Authors: Othmani Safia , Jouini Sarra , Hedhli Hana , Bouarada Ghada , Jendoubi Asma , Hosni Dhekra , Jemai Mouna
Published: May 2024

Background and Aims

Nephrotoxicity following injection of iodinated contrast media is the leading cause of iatrogenic acute renal failure. Its incidence is variable taking into account the study population as well as associated factors.

The aim: To study the contribution of the SOFA score in the prediction of nephrotoxicity post injection of iodized PDCs in septic patients.

Method

This was a prospective, single-center study over a six-month period. Patients aged over 14 years and having undergone an injection of iodinated contrast products were included. Nephropathy in this context is defined by an elevation in plasma creatinine of more than 25% within 48 to 72 hours following injection and in the absence of other etiologies.

Results

During the study period, 135 patients were collected with a mean age of 46 ± 18 years and range of 16 to 97 years. The gender ratio was 3.2 with a male predominance. Hypertension and diabetes were the most noted comorbidities (20.7%, 20%).

Clinical examination revealed polypnea in 26% of cases, desaturation in 11.8%, tachycardia (27%) and oliguria (5.2%). Fourteen patients had an altered state of consciousness with coma in 10.4% of cases. Twenty-one patients (15.6%) were febrile on admission.

The incidence of nephropathy post injection of iodized PDCs was 15.6%. 111 patients (82.8%) benefited from per-procedure hydration. Emergency mortality was 4.4% (n=6).

The SOFA score was calculated in 24 patients with a median score of three. Nineteen patients (14.1%) had a score ranging from two to six, which predicts an intra-hospital mortality risk of 10%. Four patients (2.9%) had a score between 7 and 9, which reflects a risk of death of 15 to 20%. In univariate analysis, the SOFA score was calculated in six patients with nephrotoxicity and in 18 patients who did not develop nephrotoxicity. A score between seven and nine was significantly associated with the risk of developing nephrotoxicity (14.3% vs 0.9%) with p=0.012 and ORb=19.2, 95% CI [1.8-196.8].

Conclusion

The incidence of post-iodized PDC injection nephropathy was high in emergency rooms. Among the independent factors associated with nephrotoxicity, the SOFA score was found to be.
#1378 A single-center retrospective study on clinical characteristics and outcomes of extended-spectrum beta-lactamases positive acute pyelonephritis
Authors: Bae Eunjin , Lee Tae Won , Park Dong Jun
Published: May 2024

Background and Aims

The increase of extended-spectrum beta-lactamases (ESBL) releasing bacteria in acute pyelonephritis (APN) is a growing problem world-wide. Recently, little is known about the incidence, clinical features and outcomes of ESBL positive APN. This study intends to describe the epidemiology and clinical outcomes of ESBL positive APN.

Method

A retrospective study of 1631 culture positive patients with APN admitted from Jan, 2011 to Dec, 2019 in a single-center was performed. Adults over 18 years of age were included, and outpatient treatment, pregnant women, and transplant patients were excluded.

Result

A total of 2818 patients were diagnosed as APN during this period and causative bacteria was confirmed in1631 patients among them (57.9%). ESBL positive bacteria were found in 553 patients (33.9%). There were no differences in baseline characteristics between ESBL positive and negative groups. Most common strain was Escherichia coli, followed by Klebsiella and Pseudomonas species. The proportion of ESBL positive APN increased when evaluated at one-year intervals for 8 years (from 4.9% in 2011 to 20.9% in 2019). The rate of positive blood culture was higher in ESBL positive patients (39.2% vs 21.1%, p<0.001). Hospital stay was longer in ESBL positive patients (12.3 ± 2.2 vs. 5.4 ± 5.2, p<0.001) and the number of re-admission is higher (1.7 ± 1.3 vs. 1.2 ± 0.6, p<0.001). The incidence of acute kidney injury according to KDIGO was higher in ESBL positive groups (25.4% vs 12.3%, p<0.001). There was no hospital mortality between two groups.

Conclusion

We should attempt to detect ESBL positive bacteria through timely performing blood and urine culture and administer appropriate antibiotics if APN is clinically suspected because of poor clinical courses.
#2561 Association of acute kidney injury stage with in-hospital mortality in elderly patients with hip fractures
Authors: Kwon Soon Hyo , Lee Haekyung , Kim Hyoungnae , Noh Hyunjin , Jeon Jin Seok
Published: May 2024

Background and Aims

Elderly individuals often experience hip fractures and acute kidney injury (AKI), both of which are associated with higher rates of morbidity and mortality. This study aimed to evaluate whether the severity of AKI is associated with higher mortality rates in elderly patients with hip fractures.

Method

Patients aged 65 years and older, who underwent surgery for hip fracture between October 2015 and October 2020, were retrospectively evaluated. Those with known chronic kidney disease stages 4, 5, or end-stage kidney disease were excluded. AKI was defined and categorized into stages 1, 2, and 3 according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines.

Results

In the study, 780 elderly patients with hip fractures were included, with a median age of 82.0 years (interquartile range 77.0–87.0) and 22.4% of them being men. Of these, 172 patients (22.1%) experienced AKI, with 125 (72.7%), 26 (15.1%), and 21 (12.2%) of these patients categorized as having stage 1, 2, and 3 AKI, respectively. Higher AKI stages were independently associated with increased in-hospital mortality compared to patients without AKI (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.18–6.55, P=0.940 for AKI stage 1; OR 14.09, 95% CI 1.47–135.52, P=0.022 for AKI stage 2; and OR 413.79, 95% CI 45.84–3735.28, P<0.001 for AKI stage 3). Furthermore, compared to patients without AKI, those with AKI stage 3 had a significantly increased risk of mortality (hazard ratio 15.30, 95% CI 2.65–88.48, P=0.002).

Conclusion

A higher stage of AKI is independently associated with increased in-hospital mortality in elderly patients with hip fractures. Prevention and prompt treatment of AKI, especially higher AKI stages, is important in elderly patients with hip fractures.
#927 Assessment of kidney function recovery post discharge in patients with acute kidney injury requiring dialysis during hospitalization
Authors: Elshirbeny Mostafa Fottoh , Elesnawi Mohamed , Abdellatif Tarek , Abdulrahman Rasha , Khater Iman , Hamad Abdulla , Alkadi Mohamad , Al-Ali Fadwa , Almalki Hassan
Published: May 2024

Background and Aims

Acute kidney injury requiring dialysis (AKI-D) is a serious medical condition that becomes increasingly common and associated with high rate of mortality. Identifying modifiable predictors of AKI-D patients’ outcomes will lead to better care and improve kidney and patient survival. This study aimed to assess long-term outcomes (ESRD, HD-independence, or death) of AKI-D patients after hospital discharge as well as to identify the clinical predictors of their outcomes.

Method

We followed 64 AKI-D patients who survived till hospital discharge and continued receiving dialysis treatment in outpatient dialysis center. Follow up continued for 6 months between January 2016 and December 2022 for patients discharged from Hamad General Hospital to receive dialysis in Fahd Ben Jassim Kidney center. All demographic data, patients’ comorbidities, hospital course, laboratory values and outpatient dialysis details were collected and analysed. Follow up of recovered patient was continued for 2 years either in nephrology or low clearance clinic.

Results

During follow up, 20 patients (31.3%) recovered enough kidney function to stop dialysis while 44 patients (68.7%) were declared as ESRD. The average time to recovery was 106 ± 81 days. No significant difference was noticed between both groups regard to patients’ age, gender or comorbidities. Recovered patients had more ICU admission rate compared to non-recovered patients (60% and 29.5% of patients respectively, p 0.028) and more use of vasopressors (p 0.002). Moreover, the recovered patients received significantly more dialysis sessions during hospital stay than non-recovered patients (p 0.009).

Conclusion

Close monitoring of AKI-D patients during ICU admission, use of vasopressors, and frequent dialysis sessions may facilitate recovery of kidney function. More research is needed to identify the modifiable predictors of AKI-D patients’ outcomes.
#75 Extracorporeal membrane oxygenation (ECMO) in patients with acute kidney injury (AKI): a prospective, observational, multi-center study
Authors: Alsahow Ali , Alkandari Omar , Alyousef Anas , Alhelal Bassam , Bahbahani Yousif , Alsharekh Monther , Alkandari Abdulrahman , Mazroue Ahmed Mohamed Eltaher Eliwa Bayoumi , Abdallah Emad , Abdelzaher Ali , Mashal Basem , Nessim Gamal
Published: May 2024

Background and Aims

Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for patients with severe respiratory and/or cardiovascular failure. Acute kidney injury (AKI) is a frequent complication in ECMO, resulting in increased morbidity and mortality. We aim to evaluate impact of ECMO on AKI outcome in Kuwait.

Method

Demographics, comorbidities, management, and 30-day kidney and patient outcome data for adult inpatients with native kidneys with AKI who received ECMO in seven public hospitals in Kuwait from 1/January to 31/December 2021, were prospectively collected and analyzed.

Results

Total number of AKI cases during study period was 3744, but only 121 patients received ECMO, or only 3.2%, with mean age of 56.3 years; and mean baseline eGFR of 81.6 ml/min. Males were 62.8% of the cohort, and 91.7% of cases were hospital-acquired AKI. Only 21.5% had pre-existing CKD (mainly diabetic kidney disease), and only 26.5% were older than 65, however, 58.7% were diabetics, and 48% were hypertensive. COVID-19 infection was a cause for AKI in 69% of patients. ECMO was veno-venous in 90% of cases, and AKI developed before ECMO initiation in 62.8% of cases. Dialysis was provided for 92% with continuous kidney replacement therapy (CKRT) accounting for 97%, and 93% of patients were in ICU (all on inotropic support). At 30 days, 86.8% of the whole group died (91% of those died on dialysis), six patients remained alive on dialysis, and only four patients recovered kidney function completely.

Conclusion

Although ECMO utilization in patients with AKI is limited in our AKI cohort, and despite relatively young age and reasonable baseline eGFR for the cohort, ECMO is associated with high need for ICU admission, high incidence of AKI, high need for dialysis, and high mortality rates.
#2500 Renal perfusion and SGLT2i
Authors: Nielsen Steffen Flindt , Duus Camilla , Buus Niels Henrik , Bech Jesper Noergaard , Mose Frank
Published: May 2024

Background and Aims

Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) have revolutionized treatment of type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), improving cardiovascular and renal endpoints. This improvement could be due to a decrease in renal perfusion (RP), attenuating glomerular hyperfiltration thus leading to kidney protection. This has been demonstrated in patients with type 1 diabetes and in animal studies, but not in patients with DM2 and it has never before been investigated in patients with CKD. Our aim was to examine the effects of the SGLT2i empagliflozin on RP in patients with DM2, DM2 and CKD and non-diabetic CKD, respectively.

Methods

We conducted three randomized, double-blind placebo controlled cross-over studies, including patients with:

Participants were randomized to four weeks' treatment with empagliflozin 10 mg or matching placebo and were, after a washout period of at least two weeks, crossed over to four weeks of the opposite treatment. At the end of each treatment period we measured RP using 82Rb-PET/CT and standardized GFR using 99mTc-DTPA-clearence. We also measured 24-hour ambulatory blood pressure (BP), urinary albumin/creatinine ratio (UACR) and Hb1Ac.

Results

A total of 49 patients completed the studies, 16 in the DM2-group, 17 in the DM2-CKD-group and 16 in the CKD-group. In the combined study-population empagliflozin reduced RP compared to placebo by 4% (geometric mean ratio: 0.96, 95% CI: 0.94; 0.99, p = 0.0171). This change was most pronounced in the DM2-CKD-group, with a reduction of 6% (geometric mean ratio: 0.94, 95% CI: 0.91; 0.97), p < 0.001). There was a decrease of 4% in the DM2-group and 1% in the CKD-group, though these changes were not statistically significant (p = 0.29 and 0.72, respectively, see Fig. 1). In the 29 patients with a UACR > 30 mg/g, empagliflozin treatment led to a significant decrease in UACR in the combined study-population (geometric mean ratio: 0.61, 95% CI: 0.46; 0.80, p = 0.001), again primarily driven by a decrease in the DM2-CKD-group (geometric mean ratio: 0.51, 95% CI: 0.31; 0.85, p = 0.014), with non-significant decreases in the remaining groups. Empagliflozin decreased standardized GFR and BP in the combined population as well as in all sub-groups, while we found no change in Hb1Ac. For further details, see Table 1.

Conclusion

Short-term empagliflozin treatment reduces RP, GFR, BP and albumin excretion. Relative changes in RP and UACR were most pronounced in patients with concomitant DM2 and CKD, whereas changes in BP and GFR were seen in all groups.
#2743 Impact of fatty acid-binding protein 4 on SUMOylation balance and renal tubular epithelial cell senescence in acute kidney injury
Authors: Liu Jing , Wu Qimei , LI Lingzhi , MA Liang , Fu Ping
Published: May 2024

Background and Aims

Dysregulated lipid metabolism and cellular senescence intricately interact in the context of acute kidney injury (AKI). Fatty acid-binding protein 4 (FABP4), a critical enzyme regulating lipid metabolism, potentially induces cell senescence through lipotoxicity in AKI. However, the specific mechanisms remain unclear.

Method

We established an ischemia-reperfusion-induced AKI (IRI-AKI) model in C57 mice and quantified and localized FABP4 expression in renal tissues using Western blotting (WB), qPCR, and immunofluorescence (IF). Oil Red O staining and beta-galactosidase staining were employed to assess lipid deposition and cellular senescence in tubular cells. The same measurements were repeated in IRI-AKI by knocking out Fabp4. Additionally, bulk mRNA sequencing and single-cell sequencing were conducted on renal tissues to analyze key molecules and related mechanisms.

Results

In vivo, we observed a significant decline in renal function, severe tubular epithelial damage, and abundant inflammation in the IRI-AKI group, which was noticeably alleviated in the Fabp4 knockout group (Fig. 1). Furthermore, we detected upregulation of FABP4 expression in the kidneys of IRI-AKI, primarily localized in the tubular epithelial cells. Fabp4 knockout effectively reduced tubular lipid accumulation and cellular senescence (Fig. 3). Through integrating mRNA and single-cell sequencing data, UBC9, an E2 enzyme involved in protein SUMOylation, emerged as a potential key regulator of cell senescence and AKI. WB and qPCR both confirmed the upregulation of UBC9 expression in IRI-AKI and its downregulation after Fabp4 knockout. Conversely, we observed that downregulated SUMOylation in IRI-AKI was upregulated in the Fabp4 knockout group (Fig. 4).

Conclusion

In conclusion, FABP4 modulates the expression of UBC9 and SUMOylation, thereby mediating cellular senescence and causing renal tubular cell damage in IRI-AKI. The mechanisms underlying FABP4’s regulation of UBC9 and the opposing trend between UBC9 and SUMOylation require further elucidation.
#1437 Renal expression pattern of the relaxin receptor, RXFP1, and effects of the RXFP1 agonist, AZD5462, on renin in non-human primates and humans
Authors: Lal Mark , Ryberg Erik , Althage Magnus , Bergström Fredrik , Hansen Pernille B L , Pettersen Daniel , Connolly Kat , Rosenmeier Jaya
Published: May 2024

Background and Aims

RXFP1 is a G protein-coupled receptor (GPCR) for the pregnancy hormone, relaxin. While preclinical studies, performed primarily in rodent, describe beneficial effects of this pleiotropic peptide across several organ systems, there has been a disappointing lack of success in translating these observations into clinical benefit. To provide a potential pharmacological explanation accounting for this translational gap, the aim of this study was thus to thoroughly evaluate RXFP1 expression across species and tissues as well as to evaluate the renal-intrinsic effects of the RXFP1 agonist, AZD5462.

Method

Unbiased bioinformatic analysis of several gene expression databases was used as a first approach to compare RXFP1 tissue-level expression between rodent and human. Experimental validation was subsequently performed using scRNAseq, RNAscope and immunohistochemistry on mouse, rat, non-human primate (NHP) and human kidney. The putative renal target engagement effects of RXFP1 agonism were assessed by determining the acute and chronic effects of the RXFP1-selective small molecule agonist, AZD5462, on plasma renin concentrations in both NHPs and in a Phase 1 randomized, single-blind, placebo-controlled study in healthy humans.

Results

RXFP1 was identified as one of the most highly expressed GPCRs in human and NHP kidney glomeruli. Specifically, by multiple assays, we identified glomerular endothelial cells as the principal cell type expressing RXFP1. This observation is in stark contrast to mouse and rat kidney, where RXFP1 was not readily detected. AZD5462 administered orally to NHPs and healthy human participants elicited an early and sustained dose-dependent increase in plasma renin concentration, and in humans an additional decline in serum creatinine.

Conclusion

Human RXFP1 kidney glomerular expression is conserved with NHPs but not rodent, thus highlighting the translational and pharmacological challenges in studying RXFP1/relaxin biology across species. The concordant ability of AZD5462 to induce elevations in renin and reduction in serum creatinine, together with relaxin's reported renal-hemodynamic activity in humans, may underlie a previously unappreciated renal-intrinsic RXFP1 target engagement mechanism driving its hemodynamic and renal effects. The potential therapeutic benefits of RXFP1 agonism are the subject of on-going clinical trials in heart failure patients.
#1343 Microfluidic kidney tubuloids-on-a-chip for improved drug translation
Authors: Kurek Dorota , Torregrosa Manuel Caro , Admiraal Jade , Gijzen Linda , Grasegger Julia , Lanz Henriëtte
Published: May 2024

Background and Aims

Current 2D in vitro models of renal epithelium lack key features of the in vivo setting, such as tubular structure and perfusion, resulting in low translatability to human situations and failure in clinical translation. Advanced renal in vitro models are of great importance to study kidney function under healthy and diseased conditions. Kidney tubular epithelial organoids, called tubuloids, are three-dimensional multicellular structures that recapitulate tubular function and have been used to model genetic, metabolic, and infectious renal diseases. To increase physiological relevance of the tubuloids, they can be integrated into an organ-on-a-chip system. This microfluidic technique is becoming increasingly recognized as a valuable tool for adding physiologically relevant cues to traditional cell culture including long-term gradient stability, continuous perfusion, and interaction with other cell types such as vasculature.

Method

Here, we introduce the OrganoPlate microfluidic platform, which can accommodate up to 64 independent microfluidic chips in a microtiter plate format, allowing the growth of 64 independent kidney tubuloid-derived barrier tissues in the form of perfused tubules. To this end, tubuloids derived from adult kidney tissue were plated as single cells in the OrganoPlate against an extracellular matrix (ECM). These renal tubules can be formed in just four days of culture in the device showing rapid and reproducible cell polarization, tight junction formation, proper expression of renal markers and functional transport.

Results

When integrated into an OrganoPlate system, kidney tubuloids form leak-tight, perfusable tubes with stable Trans Epithelial Electrical Resistance (TEER) and are suitable for high-throughput screening of compound effects through assessment of barrier integrity by use of OrganoTEER and by real-time imaging of transport. OrganoPlate grown kidney tubes treated with Pgp inhibitor Verapamil show significant reduction of Rhodamine123 transport through kidney tubule barrier which confirms show stable activity of Pgp transporter and usability of the model in studying renal drug clearance.

Conclusion

Our results demonstrate the suitability of our in vitro microfluidic kidney tubuloid-on-a-chip model in mimicking key physiological aspects of the kidney and offer new ways for studying organ physiology and renal disease mechanisms, toxicity screening, and personalized medicine. Additionally, the use of animal models, as well as the costs of drug development, can be reduced.
#1949 Comparison of two commercial available primary human mesangial cell clones reveal differences
Authors: Johansson Alva , Boi Roberto , Narasimhan Gayathri , Ebefors Kerstin
Published: May 2024

Background and Aims

Mesangial cells and their matrix form the central stalk of the glomerulus but is often overlooked when studying glomerular function. The cells are however highly involved in glomerular function and crosstalk between the different cell types of the glomerulus. They are important in onset and progression of several glomerular diseases, such as IgA nephropathy and diabetic kidney disease.

As mesangial cells have several functions and are involved in glomerular disease they are often used for in vitro work studying response to various stimuli and downstream signaling. This includes changes in the production and regulation or their matrix, proliferation, contractility, protein expression and release of different inflammatory mediators such as cytokines and growth factors [1]. Using primary cells when doing in vitro work is usually considered the best option, but there might be differences between origin of cells in their response and physiology.

For this study, our aim was to compare two types of commercially available primary human mesangial cells from Cell systems (CS) and Novabiosis (NBS).

Method

For characterization of the CS and NBS mesangial cells, gene expression of commonly used mesangial cell markers, including KRT19, ACTA2, PDGFRA and PDGFRB, was analyzed with real time qPCR. Staining of smooth muscle actin was done in order to compare the phenotype of CS and NBS. To compare the cells, differences in protein expression were determined using proteomics. CS and NBS Cells were cultured in the same way and were also treated with PDGF-BB for 24 h to compare with untreated control. For further comparison, proliferation assay was used to compare proliferation after treating cells with PDGF-BB for 24 h.

Results

Both sources of cells expressed all markers, but there was a difference in level of gene expression. CS cells showed higher expression than NBS cells for all markers, apart from ACTA2. NBS cells had a more stellate phenotype whereas the CS cells were more elongated. There was a difference in proteins expressed by CS and NBS mesangial cells from our proteomics. The level of upregulation of proteins seen with proteomics was stronger for CS than NBS cells when treated with PDGF-BB. The number of proteins upregulated was also higher for CS than NBS cells. Both mesangial cell types had increased proliferation when treated with PDGF-BB, however CS cells were seen to grow faster in cell culture and seemed to be more responsive to the treatment with PDGF-BB.

Conclusion

In conclusion, this study compares two commercially available primary human mesangial cells and show that there is a difference between the two. The cell types react differently when treated with PDGF-BB and has some difference in what proteins they express. This needs to be considered when conducting cell culture experiments with mesangial cells, depending on what the aim and focus for the study is.
#2327 Extent of proteinuria in autosomal dominant Alport syndrome compared to X linked Alport syndrome
Authors: Gonçalves Pedro Lisboa , de Faria Vitoria Paes , Furlano Monica , Almeida Catarina , Sampani Erasmia , Teran Melissa Pilco , Viera Elisabet , Fayos Leonor , Pybus Marc , Aza Miriam , Ars Elisabet , Torra Roser
Published: May 2024

Background and Aims

Alport syndrome (AS), as first described by Arthur Cecil Alport in late XIX century, encompasses a clinical picture of neurosensorial hypoacusia, ocular abnormalities, hematuria and proteinuric kidney disease progressing to end-stage kidney disease in the young adulthood. Differently from X-linked and autosomal recessive AS, autosomal dominant AS (ADAS), a more recently recognized entity, whose prevalence based on populational studies may be near to 1%, generally presents with a milder kidney involvement and with negligible extrarenal features. Nevertheless, some of these patients progress to chronic kidney disease (CKD) category G5, with marked intra and interfamilial variability.

Although hematuria is almost universally present all three inheritance patterns, the magnitude of proteinuria, a reliable prognostic marker of the X-linked form has not been thoroughly studied in ADAS.

We aimed to compare the extent of proteinuria between patients with X-Linked and autosomal dominant AS.

Method

Retrospective registry data on type of Alport hereditary pattern and spot urine protein to creatinine ratio per CKD category were collected. The 2021 CKD-EPI formula for calculation of glomerular filtration rate (eGFR) was used. Non-parametric test was used to analyze variables that did not follow normal distribution.

Results

We analyzed proteinuria and eGFR of 127 patients with Alport Syndrome. Information on patient gender, hereditary pattern and gene involved is illustrated it Table 1. Increased proteinuria was observed with CKD progression in all categories (p < 0.05). Within each CKD category, X-linked males had greater median proteinuria followed by, X-linked females and autosomal dominant patients (Table 2 and Fig. 1).

No difference in median proteinuria was observed between X-linked females and those with autosomal dominant inheritance throughout CKD categories G1, G2, G4 and G5 (p = 0.142, 0.878, 0.327, 0.909 respectively). Difference in median proteinuria between X-linked females and autosomal dominant inheritance revealed statistical significance in CKD category G3 (p = 0.034), however the small sample size in this group must be taken into account.

Conclusion

Pathogenic variants in COL4A3, COL4A4, and COL4A5 are all causes of CKD, and proteinuria serves as a hallmark of disease progression. However, the extent of proteinuria in ADAS is significantly lower than that observed in XLAS. Additionally, some ADAS patients develop CKD with only albuminuria. While there is still much to be understood about this common condition, the renal mechanism of damage in ADAS appears to differ definitively from that in XLAS or ARAS.