bluuebunny/crossref_metadata_2025 huggingface dataset:
#2978 Formative usability test of a novel device for peritoneal dialysis (WEAKID)
Authors: de Vries Joost , Mathijssen Elke , Trappenburg Jaap , de Lange Wendela , Simonis Frank , Dolmans Helma , Donati Gabriele , Cappelli Gianni , Ligabue Giulia , Rubio María Auxiliadora Bajo , Gilsanz Gloria del Peso , Gerritsen Karin
Published: May 2024

Background and Aims

Chronic kidney disease is a growing problem worldwide with a growing number of patients requiring kidney replacement therapy. In recent years we have developed a novel device for peritoneal dialysis (PD), the WEarable Artificial KIDney (WEAKID); composed of a wearable device connected to a dialysate reservoir. WEAKID uses both sorbent technology and continuous flow PD to improve dialysis efficacy. Formative usability testing aids to the identification of design issues that may interfere with a device's safe and effective use and thus may influence decisions made in the design process. Here, we present the results of an international, multicentre, formative usability study of WEAKID among nurses and patients.

Method

This study used a mixed-methods design and was conducted in hospitals in Italy (Modena University Hospital), Spain (La Paz University Hospital, Madrid), and the Netherlands (University Medical Center Utrecht) between November 2021 and December 2022. An individual, formative usability testing session was conducted with each participant (nurse or patient) under the conditions of simulated use. Participants were asked to perform basic operational procedures (i.e. turning the device on/off, input of dialysis settings, handling an alarm) with the device according to a usability task list. Their performance was observed and use errors (i.e., something that a participant does or fails to do that results in an unexpected or unintended outcome) were noted. Furthermore, participants were asked for feedback, both verbally and by means of completing the system usability scale (SUS), reflecting perceived usability on a scale from 0 (worst) to 100 (best).

Results

We included 14 participants (n = 6 nurses, n = 8 patients) in three participating centres. All nurses were female and had a median experience with PD of 20.5 years (range 0.5-32). Patients were generally highly educated (n = 5, 63%). In total, 22 use errors occurred, 10 in nurses and 12 in patients. These use errors included factors not related to the device, e.g. not taking appropriate hygiene measures. In particular, use errors occurred during the priming/connection of catheter and handling the alarm. Participants’ feedback mainly concerned the small screen (and thus font) size, user interface (e.g. lack of colour-coded soft buttons), and (short) length of the patient line. The mean SUS score was 70 (range 57.5–85) for nurses, and 71.9 (range 55–87.5) for patients.

Conclusion

Despite the slightly above-average perceived usability of the device's current design stage, participants made a lot of suggestions for improvements, and usability must be improved to make the device ready for market introduction.
#2096 A randomized controlled study of telemonitoring in kidney transplantation: interim results of the Ap'TX trial
Authors: Mariat Christophe , Dinic Miriana , Thibaudin Damien , Maillard Nicolas
Published: May 2024

Background and Aims

Telemedicine is a matter of growing interest in transplantation. However, its real added value is uncertain. In 2018, we have started to study the medico-economic impact of a less stringent on-site follow-up of our kidney transplant recipients (KTR) using Ap'Telecare®. We present here a preliminary report focusing on 500 KTR with a 2 years follow-up.

Method

The Ap'Tx study (NCT03750331) is a controlled randomized trial testing the hypothesis that monitoring stable KTR (at least 3 months after transplantation) with Ap'Telecare® is non inferior to a conventional follow-up in terms of the occurrence of graft dysfunction (defined as a decrease in eGFR of 20% or more). On-site consultation scheduling was 2 times less frequent for KTR followed by Ap'Telecare®. Secondary endpoints were the impact of a remote follow-up by Ap'Telecare® on medical workload, economic saving and quality of life.

Results

688 KTR have been randomized so far with 500 of them having completed the 2 years follow-up. Among all KTR approached to participate in the study, 37% were not included mainly due to difficulties with accessing internet (44%) or to masterize the app (36%). After randomization, 27% of KTR were considered as non compliant in adequately using Ap'Telecare®. Over the 2 years study duration, graft dysfunction occurred in 16% and 18% of KTR in the Ap'telecare® and conventional arm, respectively (RR of 0.87 (0.56; 1.39), non-inferiority confirmed, superiority not significant). Medical time dedicated to handling daily lab results was decreased by a factor 3 for KTR using Ap'Telecare®. Rates of unplanned consultations and hospitalisations were reduced by 26% and 32% for patients using Ap'Telecare®,  respectively (P < .05).

Conclusion

This preliminary report of Ap'Tx suggest that a partial and reasonable remote follow-up of selected KTR is feasible, safe and logistically beneficial. Determining the nature of factors associated with a wider implementation of Ap'Telecare® is underway.
#1776 Distinct changes in gut microbiota of patients with kidney graft rejection
Authors: Visconti Vanessa , Müller-Deile Janina , Schiffer Mario , Wirtz Stefan
Published: May 2024

Background and Aims

Kidney graft rejection still represents the major cause of graft loss in kidney transplant recipients. Of growing interest is the bidirectional relationship between gut microbiome and immune system suggesting that gut microbiota can affect allograft outcome.

Method

In this cross-sectional case control study, we characterized the gut microbial profile of adult renal transplant recipients with and without graft rejection in order to define a cohort-specific microbial fingerprint through 16S rRNA gene sequencing. We used very strict inclusion and exclusion criteria to address confounder of microbiota composition.

Results

Different relative abundances in several gut microbial taxa were detectable in control patients compared to patients with kidney allograft rejection. Alpha diversity was lower in the rejection group and beta diversity revealed dissimilarity between patients with and without kidney graft rejection (P < .01). When the rejection group was stratified according to different types of allograft rejection, major changes were identified between patients with chronic T cell mediated rejection (cTCMR) and controls. Changes in alpha diversity within the gut microbiome were related to the probability of cTCMR (P < .05). Kidney transplant patients without rejection showed significant enrichment of rather anti-inflammatory taxa whereas in the rejection group bacteria well known for their role in chronic inflammation were increased. For example, ASV 362 belonging to the genus Bacteroides and ASV 312 belonging to Tanerrelaceae were enriched in no rejection (P < .001 and P < .01) whereas ASV 365 was enriched in patients with allograft rejection (P = .04). Looking at metagenomic functions, a higher abundance of genes coding for enzymes involved in bacterial multidrug resistance and processing of short chain fatty acids was found in patients without rejection but an increase in enzymes involved in NADPH production was seen in patients with allograft rejection.

Conclusion

A distinct microbial fingerprint of patients with allograft rejection might serve as non-invasive biomarker in the future.
#1731 Clinico-epidemiological characteristics of early versus late onset cytomegalovirus disease among renal transplant recipients: two decade experience
Authors: Kaul Anupma , Roy Shuvam , Prasad Narayan
Published: May 2024

Background and Aims

The epidemiology of the Cytomegalo virus (CMV) disease among renal transplant recipients has changed with the advent of effective antiviral prophylaxis usually occurs in the later part of the post transplant period. To study the difference between CMV infections occurring in early versus late post renal transplant period with respect to nature of immunosuppressive medications (induction agents, maintenance agents and heightening of immunosuppression), type of CMV infection and occurrence of biopsy proven rejection post CMV infection.

Method

A single centre retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between 1st January, 2002 and 31st December, 2021. CMV disease was classified as early or late depending on detection before or after 90 days post transplant. The differences in clinical presentation between early and late onset CMV disease, use of immunosuppression, and the impact on graft outcomes were studied.

Results

Total number of recipients with CMV disease was 156 (7.2%) out of total 2164 renal transplant recipients. Twenty-five (16%) patients had early CMV while one hundred and thirty one (84%) had late CMV. The two groups did not differ with respect to induction or use of maintenance immunosuppressive agents. Proportion of CMV syndrome was more among early CMV group (56.0% vs 26.7%, p = 0.01) while tissue invasive disease was more frequent among late CMV group (44.0% vs. 73.3%, p = 0.01). Diarrhoea was more frequent in late (63.4%) versus early CMV (36%) (p = 0.01). Graft loss occurred in 4.0% of early and 25.2% of late CMV cases (p = 0.03). However, both groups did not differ with respect to occurrence of biopsy proven rejection post infection.

Conclusion

Early CMV presents more frequently as CMV syndrome while late CMV usually manifests as tissue invasive disease. Graft loss is more common in patients with late onset disease.
#2867 Is there an interrelationship between the SARS-CoV-2 virus and the BK polyomavirus in kidney transplant recipients?
Authors: Alonso Marta , Villanego Florentino , Vigara Luis Alberto , Orellana Cristhian , García Ana , Lopez Juan Manuel Cazorla , Amaro José Manuel , Montiel Natalia , Garcia Teresa , Rodriguez-Iglesias Manuel , Mazuecos Auxiliadora
Published: May 2024

Background and Aims

Several viral co-infections following SARS-CoV-2 infection have been described. However, there is very limited and inconclusive data on the relationship between COVID-19 and BK polyomavirus (BKV) in kidney transplant (KT) recipients.

Method

Retrospective analysis of KT recipients with BK infection (BKi) in our centre from March 2020 (first cases of COVID-19) to March 2023. BK viremia is periodically determined prospectively in all KTs performed in our hospital. We carried out a case-control study, choosing two controls without BKi for each case (closest transplant date and similar donor and recipient age). We analyzed clinical characteristics and evolution, as well as previous history of COVID-19 in both groups. A composite outcome including de novo BKi and/or significant increase in BK viremia (increase > 50% in at least 2 consecutive samples) was analyzed. Multivariate analysis was performed using logistic regression for de novo BKi and/or significant increase in BK viremia risk factors.

Results

During this period 235 KTs were performed in our center, of which 37 were diagnosed with BKi (16.1%). The median time from the date of KT to BKi was 73 days.

When comparing cases versus controls, demographic characteristics and donor type were similar in both groups, except for a higher proportion of males in the BKi group (76.3% vs. 55.3%; p = 0.029). The incidence of SARS-CoV-2 infection was significantly higher in patients with de novo/increased viremia BKi than in the control group (44.7% vs. 26.3% p = 0.048). During follow-up, one patient in the BKi group died and one patient in the control group lost the graft due to causes other than viral infections.

In multivariate analysis, male gender and SARS-CoV-2 infection were risk factors for the composite outcome.

Conclusion

As has been described with other viruses, there may be an interrelationship between SARS-CoV-2 and BKV. Our experience suggests that close monitoring for BKV after episodes of COVID-19 may be appropriate.
#3087 Phenotype of extracellular vesicles in diabetic kidney disease with albuminuria
Authors: Mora-Gutiérrez José María , Fernández Alfonso Jiménez , Andueza Saioa Echeverria , Fernandez-Seara Maria A , Garcia-Fernandez Nuria
Published: May 2024

Background and Aims

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) and affects more than 40% of patients with type 2 diabetes mellitus (T2D). The pathogenesis of CKD is multifactorial and leads to a clinical presentation with diverse phenotypes characterised by proteinuria and/or progressive deterioration of renal function, thus urging the search for new non-invasive biomarkers that allow early diagnosis and the development of new therapeutic targets. Urinary extracellular vesicles (EVs) have emerged as an alternative, as changes in their number and composition have been described in clinical conditions associated with DM and kidney disease. EVs are able to interact with neighbouring and/or distant cells by transferring their cargo, rich in proteins, lipids or nucleic acids, from progenitor cells to recipient cells, thus participating in cell-to-cell communication processes. The aim of the present study was to analyse the different phenotypes of EVs in T2D patients with different degrees of albuminuria compared to healthy controls, as well as their correlation with the degree of albuminuria.

Method

A cohort of 69 subjects (49 patients with T2DM and 20 healthy volunteers) was analysed. The phenotype of EVu present between the two groups was assessed, as well as the association between the different cell lines and the presence of albuminuria. Statistical analysis was performed using Spearman correlations. Analyses were performed with R software.

Results

A positive correlation was observed between EVu from podocytes (PODO+) and those from macrophagocytes (R = 0.3180, p-value = 0.0082), as well as a positive association between PODO+ and neutrophil EVu, both in the whole cohort and when analysing only patients with diabetes (R = 0.3225, p-value:0.0254). When assessing the association of EVu with the degree of albuminuria, we observed a direct association with proximal tubule EVu (R: 0.3158, p-value 0.0271) both in all subjects (T2D and HV) and only in those with T2D (R = 0.4200, p-value = 0.0056). When stratifying according to the degree of albuminuria (A1, A2 and A3), we still observed a dependent association of the degree of glomerular involvement with the number of EVu of TCP (A1: mean 5.5 (SD 4.1); A2: mean 12.3 (SD 30.9); A3: mean 132.5 (SD 322.8)) p-value: 0.0609.

Conclusion

The results presented suggest a relevant role of TCP in the glomerular involvement of patients with DKD, in line with the emergence of new therapeutic lines such as iSGLT2. The study suggests new lines of research aimed at developing therapeutic targets that assess the cellular expression of EVu.
#993 The molecular effects of SGLT2i (Empagliflozin) on α-Klotho and Nephrin/Podocin proteins in type II diabetic mice model
Authors: Ertracht Offir , Nakhoul Farid
Published: May 2024

Background and Aims

Type 2 diabetes mellitus (T2DM), especially hyperglycemia, is associated with increased glucose cell toxicity and oxidative stress that can lead to irreversible damage in the kidney such as diabetic nephropathy (DN). DN is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy. Several works in the setting of early experimental diabetic nephropathy using the recent anti-diabetic drugs such as sodium-glucose transporter type 2 inhibitors in the prevention, development or amelioration of renal injury. The exact mechanisms, by which these drugs ameliorate glomerular injury from hyperglycemia, had not been clarified well.

Klotho and Podocin-Nephrin proteins are an important proteins involved in the tubule-glomerular injury. The Klotho is a circulating anti-ageing hormone with anti-oxidative and anti-inflammatory properties with vascular protective effects in animal studies. Podocin & Nephrin are important component of the glomerular foot-process membrane, the slit-diaphragm. Recently, several experimental reports showed decreased α-Klotho, Nephrin and Podocin expression in different models of diabetic nephropathy.

Method

We used BTBR mouse strain with the ob/ob leptin-deficiency mutation, which develops T2DM with hyperglycemia and DN; C57/BL mice were the control (CON). EMPA was administrated to T2DM mice (T2DM+EMPA) via drinking water for 12 weeks. Blood parameters were measured repeatedly, and at sacrifice, mice kidneys were harvested for histological and biochemical analyses. We evaluated renal glomerular structure of Nephrin, Podocin and α-Klotho proteins expression.

Results

EMPA treatment reduced T2DM blood glucose vs C57 group (P < 0:01), and increase urine glucose in EMPA+DM group (P < 0:001) EMPA vs. C57BL/6 and DM). Histological analyses in kidney sections, revealed decreased α-Klotho expression in glomeruli of DM mice vs Control mice (15.95 ± 0.64 vs 36 ± 2.42, (P < 0:01), and restored back in DM+ EMPA mice vs control mice (27.64 ± 0.94 vs 15.95 ± 0.64, P < 0:01). Podocin expression in glomeruli: control mice 31.3 ± 3.7 VS DM mice 21.26 ± 1.22 and DM + EMPA mice 28.22 ± 0.50 VS DM mice 21.26 ± 1.22

Conclusion

Hyperglycemia (DM type II) reduces Podocin-Nephrin and α-Klotho proteins expression in the glomeruli kidney and upregulated by EMPA treatment. SGLT2i (EMPA) treatment in DM patients can significantly reduce progression of DN and onset of ESRD probably through its effect on α-Klotho/Podocin-Nephrin proteins.
#909 Role of cystatin C in the development and progression of chronic heart failure in patients with diabetes
Authors: Vasilkova Volha , Mokhort Tatsiana , Naumenka Elena , Yarets Yulia
Published: May 2024

Background and Aims

It has been known that cystatin C is a marker for early prediction of renal function. In recent years, studies have shown that cystatin C plays an important role in predicting new or worsening cardiovascular diseases. The aim of our study was to investigate the role of cystatin C in the development and progression of chronic heart failure (CHF) in patients with diabetes.

Method

A total of 499 patients with DT1 and DT2, aged 34 to 84 years (60 [60; 72]), were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of the natriuretic peptides (BNP and NTproBNP) in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine and cystatin C. Patients were divided into quartiles according to cystatin C levels: Q1 <0.78 mg/l, Q2 0.78-0.92 mg/l, Q3 0.93-1.38 mg/l, Q4 >1.38 mg/l.

Results

Significant differences in the levels of BNP and NTproBNP were observed in patients with diabetes with cystine C levels ≥0.93 mg/l (32.20 [19.85; 69.35] pg/ml and 104.25 [57.70; 210.08] ng/l, respectively). There were significant correlations between cystatin C and the levels of BNP (r = 0.56, p < 0.05) and NTproBNP (r = 0.58, p < 0.05). Logistic regression analysis showed the prognostic value of cystatin C, and not creatinine, as a predictor of heart failure in patients with diabetes and GFR>60 ml/min/1.73 m2 (1 mg/l increase of cystatin C was associated with 7.085 times increase in CHF odds). ROC analysis revealed that the level of cystatin C ≥0.96 mg/l with a sensitivity of 84% and specificity of 75% predicted increased BNP and NTproBNP in patients with diabetes (ROC AUC = 0.844).

Conclusion

Cystatin C level could be used as a predictive indicator of CHF in patients with diabetes and GFR>60 ml/min/1.73 m2.
#411 Magnesium deficiency abrogates the activation of Insulin-like growth factor-1 signaling pathway in the kidney induced by DPP4 inhibitor
Authors: Iwakura Takamasa , Ema Chiemi , Yasuda Hideo
Published: May 2024

Background and Aims

Dipeptidyl peptidase-4 (DPP-4) inhibitor could attenuate cisplatin nephrotoxicity dependent on the glucagon-like peptide-1 (GLP-1) signaling pathway [1]. We had previously reported that the use of a DPP-4 inhibitor might also attenuate cisplatin nephrotoxicity in diabetic cancer patients [2], and its renoprotective effect was lost under magnesium (Mg) deficiency [3]. However, it remains to be investigated how the GLP-1 signaling pathway changes after the treatment of a DPP-4 inhibitor under Mg deficiency. The purpose of this study was to examine the changes in the downstream pathway of the GLP-1 signaling pathway after the treatment of DPP-4 inhibitor under Mg deficiency.

Method

Sprague Dawley rats received a Mg-deficient diet for 7 days to induce Mg deficiency (low Mg group). Control diet was given to the normal Mg group. Oral administration of a DPP-4 inhibitor was injected 1 day before sacrifice. The changes in serum active GLP-1, insulin, insulin-like growth factor (IGF-1), and the expression of their receptor in the kidney were examined. In addition, the phosphorylation of insulin/IGF-1 receptors in the kidney were investigated.

Results

Serum active GLP-1 increased equally in both groups with DPP-4 inhibitor administration. Renal GLP-1 receptor expression was not observed in the renal tubules. Serum IGF-1 did not change with DPP-4 inhibitor administration in the normal Mg group but increased in the low Mg group. In normal Mg group, renal IGF-1 receptor expression tended to increase with DPP-4 inhibitor administration, and its phosphorylation increased significantly. In contrast, the expression and phosphorylation of the IGF-1 receptor did not change with DPP-4 inhibitor administration in the low Mg group. The increase in serum insulin with the DPP-4 inhibitor was enhanced in the low Mg group, compared to the normal Mg group. The expression and phosphorylation of the insulin receptor did not change with DPP-4 inhibitor administration in both groups.

Conclusion

DPP-4 inhibitor activated the renal IGF-1 signaling pathway, but this effect disappeared under Mg deficiency. Further investigation is needed to determine whether the renal protective effect of DPP-4 inhibitor is dependent on the IGF-1 signaling pathway.
#2977 Pregnancy-related acute kidney injury in a second level care hospital in Merida, Yucatan, Mexico
Authors: Cruz Julio Ismael Pech , Alejandra Álvarez Zapata Naomi , Yah Anhialy Yaniré Collí
Published: May 2024

Background and Aims

Pregnancy-related acute kidney injury (PRAKI) is a public health problem associated with an increased risk of adverse maternal and fetal outcomes. The causes of PRAKI varies according to the age of gestation. Mexico lacks a national acute kidney injury (AKI) registry, and the access to AKI treatment is limited due to lack of financial coverage, lack of nephrologists, and poor infrastructure. The General Hospital Dr. Agustín O'Horán is a second level unit that attends to the uninsured pregnant population from the southeast of Mexico. The aim of this study was to investigate the prevalence, clinical characteristics, and outcomes of PRAKI in a Mexican population.

Method

This was a retrospective study in an obstetric intensive care unit (OICU) in the General Hospital Dr. Agustín O'Horán in Merida, Yucatan, Mexico. Women during pregnancy and postpartum periods admitted to the OICU between January to December 2023 were included. Demographical, clinical and laboratory data were collected from medical records, and AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. We evaluated the prevalence, clinical characteristics, and outcomes of PRAKI.

Results

During the study period, 188 women were admitted to the OICU, and the mean age was 24.9 years. Eight women presented in the first trimester, 19 in the second trimester, 21 in the third trimester, and 140 in the postpartum period. Fifty-five women met AKI creatinine criteria: 31 (56.3%) had stage 1, 15 (27.3%) had stage 2, and 9 (16.4%) had stage 3. The most common causes of PRAKI were obstetric hemorrhage (27.3%), eclampsia (21.8%), and preeclampsia (18.2%) (Table 1). There was no difference in vital signs on admission and baseline creatinine level between both groups. Women who developed PRAKI had a longer stay in the OICU (4.2 days vs 2.3 days, p < 0.001), and greater use of vasopressor (30.9% vs 9.0%, p < 0.001), and mechanical ventilation (34.5% vs 11.3%, p < 0.001). Women with AKI had higher mortality (9.1% vs 1.5%, p = 0.012), and perinatal mortality (9.1% vs 2.3%, p = 0.035) (Table 2).

Conclusion

Women during pregnancy and postpartum periods who developed PRAKI had more adverse clinical and obstetric outcomes (maternal and perinatal mortality). Hence, women in pregnancy and postpartum periods admitted to an intensive care unit should be closely monitored and implement strategies for early diagnosis and aggressive therapy of PRAKI regardless of KDIGO stage.
#557 Seraph® 100 affinity blood cartridge as a potential adjunctive blood purification strategy for S. aureus-induced septic shock
Authors: De Rosa Silvia , de Cal Massimo , Lorenzin Anna , Ronco Claudio , Zanella Monica
Published: May 2024

Background and Aims

S. aureus infections, particularly methicillin-resistant strains, can induce severe conditions, provoking an overwhelming immune response and contributing to systemic inflammation and organ failure. Effective antibiotic therapy and meticulous supportive care are crucial in the ICU to manage S. aureus-induced septic shock. In this context, blood purification strategies aim to target the microorganism and associated toxins, contributing to the systemic inflammatory cascade. The objective of this in-vitro study was to analyze the potential removal, through adsorption, by the Seraph100 Affinity Blood Cartridge (S100ABC) against S. aureus. Subsequently, the study assessed whether the adsorptive capabilities toward bacteria were maintained, and if so, whether the bacteria retained its bactericidal activity.

Method

The study employed an in vitro model of hemoadsorption to characterize the adsorption performed by the S100ABC on a circulating bacterial load inoculated in blood. A volume of 150 ml of blood served as a negative control (CTR-). The remaining 650 mL were enriched with a concentration of S. aureus bacteria equal to 1×106 and incubated for 4 h at 37°C. At 4 h, the blood was divided into 2 glass bowls and stirred at 37°C: 500 mL were circulated at a speed of 120 mL/min via a dedicated test platform (Galileo) with Seraph100, while another 150 mL was stirred and used as a positive control (CTR+). The experiment was performed twice. Samples were taken from circulating blood and the two controls for blood cultures and placement on CNA agar.

Results

This study demonstrated that the S100ABC reduces the circulating bacterial load (from 1x106 at T0 to 0.25x106 at T6 h), leading to the adsorption of bacteria onto the cartridge. Bacteria were found adhering to the beads contained in the cartridge.

Conclusion

Our preliminary data show that the S100ABC effectively reduces the circulating bacterial load. The S100ABC could be an adjunct sorbent for reducing S. aureus in human blood, supporting antibiotic therapy in patients with S. aureus-induced septic shock.
#102 Increased expression of carbonic anhydrase 4 in megalin deficiency
Authors: Klahn Peter Andreasen , Berg Peder Matzen , Svendsen Samuel Levi Svinth , Tan Yifan , Sørensen Mads Vaarby , Weyer Kathrin , Damkier Helle Hasager , Rinschen Markus , Leipziger Jens , Nielsen Rikke
Published: May 2024

Background and Aims

Megalin is an endocytic receptor located in the apical membrane of proximal tubule (PT) cells. It prevents low molecular-weight proteinuria by reuptake of a variety of proteins from the filtrate. Megalin is required for normal uptake of Cubilin-bound proteins, but it is unknown if the receptor is important for other apical PT proteins. Carbonic anhydrase 4 (CA4) is an enzyme crucial for PT bicarbonate reuptake. Our aim was to investigate the relationship between the expression patterns of these two proteins.

Method

A mouse model of kidney-specific mosaic megalin-knockout (M-KO). Liquid chromatography-mass spectrometry (LC-MS) on mouse kidney cortex. Immunohistochemistry (IHC), electron microscopy (EM) and Western blotting (WB) of mouse kidney. Biochemical analysis of mouse blood and urine.

Results

LC-MS revealed a 4.23-fold increase in CA4 abundance in M-KO mice together with smaller but also statistically significant alterations in other acid-base-associated proteins. IHC shows that the increase in CA4 abundance specifically was in the cells lacking megalin, while cells with megalin retained normal abundance. The same pattern was observed in a biopsy from a patient lacking megalin. WB revealed increased shedding of CA4 in urine from M-KO mice and EM showed mislocalization of CA4.

Conclusion

We show a hitherto unknown relationship where the expression and subcellular localization of CA4 is altered in PT-cells lacking megalin and show that M-KO mice have altered acid-base handling. Comparable blood parameters at baseline are maintained despite differences in urinary excretion and when challenged with acetazolamide the urinary excretion of the groups becomes alike, however blood parameters become different. While the mechanisms and full extend are unknown, this links megalin to the acid-base regulating systems of the PT.
#1715 Role of T cell profile (Th1/Th2/Th17/Treg) and podocyturia in the peripheral blood of patients with preeclampsia versus normal pregnancy
Authors: Kaul Anupma , Agarwal Vikas , Pandey Amita
Published: May 2024

Background and Aims

The concept of the balance between Th17/Treg cell immunity plays important role in determining pregnancy outcomes. Does Treg/TH17 play a role in pathogenesis of preeclampsia associated proteinuria and its implication on irreversible renal damage was the research question. 

Method

This hospital based prospective study conducted in the Department of obstetrics and gynecology at a tertiary care medical college between October 2018 till October 2020 and assessment of T cell profiling and urinary podocyturia among all pregnancies with clinical evidence of preeclampsia and compared it with normal pregnancy monitoring for maternal and foetal outcomes. Repeat assessment of Th profiling and podocyturia was done after 3 months post partum to look for any residual effect.

Results

A total of 40 patients of preeclampsia and 40 control were enrolled in the study with median age group (24.58 ± 1.22 vs 25.16 ± 1.01). The percentage of Th1 and Th2 were higher for the preeclampsia group as compared to the control group with no change in the percentage of Th17 subsets while Th17 1 were found higher and percentage of Treg (8.1 ± 3.19 vs 2.3 ± 1,05, p = 0.001) lower in the peripheral blood of the preeclampsia group at time of delivery however the ratio of Th1/Treg, Th2/Treg, Th17/Treg and Th17.1/Treg were found significantly lowered after 6 weeks of delivery among those with preeclampsia nearly comparable to the normal pregnancy group The quantitative assessment of podocyte in urine using antinephrin showed increase numbers among preeclamptic pregnancies compared to normal yet it settled within 6 weeks of delivery.

Conclusion

Women with preeclampsia per se does not increase the risk to exacerbation of kidney disease however greater research mandates to assess the women at greatest risk of kidney disease after pre-eclampsia to have good maternal and foetal outcomes.
#2003 Genetic association in patients with chronic kidney disease of unknown etiology: an observational study
Authors: Tiwari Vaibhav , Shikarwar Tarun , Bhalla A K
Published: May 2024

Background and Aims

Chronic kidney disease (CKD), impacting over 850 million people worldwide, is a diverse group of inherited and acquired nephropathies. While only about 10% of adult CKD is hereditary, predominantly due to mutations in genes like PKD1, PKD2, and PKHD1, the etiology often remains unidentified, leading to challenges in management, especially in transplantation and genetic counseling contexts. This study used whole exome sequencing to investigate CKD of unknown origin, aiming to improve diagnostic yields and establish genetic associations. Our objective was to find the diagnostic yield of Whole exome sequencing in patients with CKD of unknown etiology and to establish genetic association for same.

Method

The study was conducted in the Department of Nephrology and the Institute of Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi. It was an observational cross-sectional analysis.

All patients, both male and female of all age groups with Chronic Kidney Disease of unknown etiology who were willing to participate.

All patients, both male and female of all age groups with Chronic Kidney Disease of known etiology were excluded as following:

Results

In the investigation of 56 chronic kidney disease samples with unknown etiology, genetic testing yielded 45 mutated gene variants in 37 subjects. The variants comprised 32 missense mutations, 8 deletions, 3 nonsense mutations, and 1 splice site mutation. Variant zygosity was as follows: 34 heterozygous, 6 homozygous, and 2 hemizygous. Pathogenic variants were detected in 9 patients (20%), likely pathogenic in 6 (13.33%), and variants of uncertain significance in 29 (64.44%). Eighteen subjects (32.14%) demonstrated no genetic mutations.

A genetic diagnosis was established in 15 patients, representing a diagnostic yield of 26.78%. Stratified by disorder, the yield was 40% for glomerular, 100% for tubular, 50% for renal calculi, and 18.42% for undetermined CKD. Genetic testing facilitated a novel diagnosis or an alteration of the existing diagnosis in 6 patients (10.71%).

Conclusion

The results affirm the efficacy of genetic testing in elucidating the etiologies of chronic kidney disease where traditional diagnostic methods do not yield definitive causation. Genetic alterations were identified in a significant proportion of the patient population, indicating the presence of underlying genetic contributors to the disease. The identification of pathogenic and likely pathogenic variants highlights the potential of genetic testing to impact clinical decision-making and patient care.
#646 SGLT2 inhibitor alleviates hypomagnesemia in patients with chronic kidney disease: a retrospective observational study
Authors: Osawa Kosuke , Ohya Masaki , Yamamoto Shuto , Nakashima Yuri , Tanaka Yusuke , Yamano Yukiko , Takatsuka Taisuke , Araki Shin-Ichi
Published: May 2024

Background and Aims

Magnesium (Mg2+) is a critical component in numerous biological processes. Hypomagnesemia is associated with an increased risk of cardiovascular events and vascular calcification in individuals with and without chronic kidney disease (CKD). Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed for treating CKD, based on their reported benefits to the kidney and cardiovascular system and in increasing serum Mg2+ levels in patients with type 2 diabetes mellitus. However, the underlying mechanisms remain unclear. In this retrospective observational study, we aimed to investigate the changes in serum Mg2+ levels after administering SGLT2 inhibitors and to identify factors contributing to these changes.

Method

We retrospectively examined 57 patients with CKD who received treatment at Wakayama Medical University between January 1, 2017, and December 31, 2022. We assessed changes in serum Mg2+ levels at baseline and 1, 3, and 6 months post-treatment. Patients were stratified into tertiles based on baseline Mg2+ levels. Multivariate regression analyses were conducted to identify factors associated with changes in Mg2+ levels.

Results

SGLT2 inhibitor treatment was associated with a significant increase in serum Mg2+ levels in the low and intermediate tertiles but not in the high tertile. Multivariate analysis revealed that gender, baseline serum Mg2+, and sodium-chloride difference were independent predictors of the increase in serum Mg2+ levels.

Conclusion

SGLT2 inhibitor treatment in CKD patients is associated with an increase in serum Mg2+ levels, particularly in those with lower baseline levels. The serum Mg2+-improving effect of SGLT2 inhibitors is influenced by baseline serum Mg2+ levels, sodium-chloride difference, and gender. These findings suggest the potential utility of SGLT2 inhibitors for treating hypomagnesemia in CKD.
#2725 Chronic kidney disease is a risk factor for hyperchloremic metabolic acidosis after plasma exchange
Authors: Simon Sanédy , van Sandwijk Marit , Engberink Rik Olde
Published: May 2024

Background and Aims

Observational studies have demonstrated that metabolic acidosis due to hyperchloremia is an often encountered metabolic disorder following plasma exchange (PE) with an albumin-saline solution. Because of the reduced capacity for acid and chloride excretion, we hypothesized that patients with chronic kidney disease have the highest risk for hyperchloremic metabolic acidosis, in particular when multiple PE sessions are performed in a limited period.

Method

We prospectively collected data from all patients who received PE at Amsterdam UMC, between February 2023, and January 2024. We collected data on demographics, exchanged plasma volume, replacement fluids, and collected blood for analysis of sodium, chloride and bicarbonate before and after plasma exchange. We selected patients who received ≥5 plasma exchanges in an intensive cycle (≥4.2 sessions/week). We excluded patients who received Omniplasma, intravenous sodium bicarbonate or dialysis during the PE period. We assessed the effect of PE and kidney function on plasma bicarbonate and chloride concentration throughout the PE period with repeated measures mixed ANOVA, corrected for baseline plasma bicarbonate concentration, volume of exchanged plasma and PE intensity.

Results

Data from 26 patients, corresponding to 130 plasma exchanges, were included in the analysis. The mean age was 56 ± 14 years and 46% was female. Mean eGFR was 45 ± 14 ml/min/1.73 m2. Patients with an eGFR ≤59 ml/min/1.73 m2 (n = 17) had a significantly lower baseline plasma bicarbonate concentration (19.0 ± 2.8 versus 24.0 ± 1.9 mmol/L; p < 0.001) and used oral bicarbonate supplements (29% versus 0%; p = 0.02) more often than patients with an eGFR ≥60 ml/min/1.73 m2 (n = 9). Despite the lower baseline plasma bicarbonate and more frequent use of oral bicarbonate supplements, the plasma bicarbonate levels decreased the most in subjects with an eGFR ≤59 ml/min/1.73 m2 (mean difference −4.2; 95% CI −7.1 to −1.3; p = 0.006; Fig. 1A) during a cycle of 5 PE sessions. Baseline plasma chloride concentration was similar in both groups (103 ± 7 vs 103 ± 4 mmol/L) and increased the most in patients with an eGFR ≤59 ml/min/1.73 m2 (mean difference −1.4; 95% CI −2.2 to 5.0; p = 0.426; Fig. 1B).

Conclusion

Repeated plasma exchange with albumin-saline as a replacement fluid is associated with a significant decrease in plasma bicarbonate concentration in patients with impaired kidney function. Future studies should determine whether this hyperchloremic metabolic acidosis has impact on the patients’ symptoms or long-term outcome.
#212 The clinical significance of circulating piRNAs in extracellular vesicles in patients with idiopathic membranous nephropathy
Authors: Sun In O , Cho A Young , Kwon Soon Hyo
Published: May 2024

Background and Aims

Of various small RNAs, many miRNAs have been studied as potential biomarkers for various renal diseases. However, there are few literatures about P-element-induced wimpy testis-interacting RNAs (piRNAs), which are the most recently discovered class of small RNAs. Therefore, we investigated the clinical significance of piRNAs in idiopathic membranous (IMN) patients.

Method

We prospectively enrolled 60 participants, including those with IMN (n = 19) and idiopathic nephrotic syndrome (INS; n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum extracellular vesicle (EV)-piRNA profiles of all participants. We investigated whether the piRNAs could be helpful to discriminate IMN from INS and predict the treatment response of patients with IMN. Based on achievement of clinical remission, IMN patients were divided in to two groups: a well-responding (IMN-W) and refractory (IMN-R) group [IMN-W (n = 9) vs IMN-R (n = 10)].

Results

We found 11 piRNAs that were upregulated and 6 that were downregulated in patients with IMN when compared to HVs. There were 22 miRNAs that were upregulated and 23 that were downregulated in patients with IMN when compared to the INS. Among these miRNAs, we found 5 piRNAs, whose levels were significantly up- or downregulated in patients with IMN compared to HVs and patients with INS. There were 50 upregulated and 11 downregulated piRNAs in patients with IMN-R when compared to patients with IMN-W. Of these piRNAs, the expression level of piRNA-42775 and piRNA-36743 were found to be inversely correlated with proteinuria on kidney biopsy. Meanwhile, a positive correlation was observed between renal function and expression of piRNA-43108.

Conclusion

Patients with IMN have a distinct EV-piRNA expression profile compared with INS and HVs. In addition, circulating EV-piRNAs could be useful to predict the treatment response of IMN patients.
#1307 Glomerular galactose-deficient IgA1 (KM55) positive may be associated with poor prognosis in DKD patients
Authors: Xu Xiaoyi , Guo Weiyi , Cheng Hong , Sun Lijun , Wang Guoqin , Cheng Wenrong , Dong Hongrui
Published: May 2024

Background and Aims

Diabetic kidney disease (DKD) and IgA nephropathy (IgAN) are prevalent renal diseases with a high incidence rate, and the prognosis is notably poorer when these two diseases coexist. However, it remains uncertain whether the pathological changes associated with DKD combined with IgA deposition (DKD-IgA deposition) are linked to a worsened prognosis.

Method

To address this question, we conducted an analysis comparing the clinicopathological characteristics and prognosis of DKD-IgA deposition patients to DKD patients as controls (Fig. 1).

Results

The results revealed that DKD-IgA patients exhibited higher cholesterol levels compared to DKD patients (6.2 ± 2.0 vs. 5.4 ± 1.9 mmol/L, p = 0.042). The group with DKD-IgA deposition had a significantly shorter follow-up duration (10.9 ± 10.6 months) compared to the control group (20.4 ± 18.7 months, p = 0.029). However, they exhibited higher levels of serum creatinine at the end of the follow-up period (343.8 ± 328.0 μ mol/L vs. 182.1 ± 124.6 μmol/L, p = 0.031). Kaplan-Meier analysis showed a higher cumulative incidence of poor events in the DKD-IgA deposition group (p = 0.036) (Fig. 2). In addition, we also detected galactose deficient IgA1 (KM55) in the kidneys and serum of patients with DKD-IgA deposition. Of the 24 patients with DKD-IgA deposition, 54.5% (24/44) showed positive glomerular KM55 results. Immunofluorescence analysis revealed that KM55 and IgA were predominantly colocalized in the mesangial and capillary regions (Fig. 3). Furthermore, the subgroup with KM55 positivity had a shorter disease duration compared to the KM55 negative subgroup (66.0 vs. 120.0 months, p = 0.048). The serum levels of galactose-deficient IgA1 (Gd-IgA1) (6296.4 ± 1535.4 vs. 4057.4 ± 1082.0 ng/mL, p = 0.010) and C4 (0.4 ± 0.1 vs. 0.3 ± 0.1 g/L, p = 0.020) were significantly higher in the KM55 positive subgroup than in the KM55 negative subgroup. Furthermore, it was observed that the KM55 positive subgroup exhibited a considerably higher incidence of reaching the renal endpoint compared to the control group (64.3% vs. 20.0%, p = 0.047).

Conclusion

These study results suggest that individuals with DKD who display glomerular IgA deposition alongside KM55 positivity may experience a more unfavorable prognosis.
#2389 Enhancing immunoglobulin A nephropathy management: insights from the IGAN-MIC project
Authors: Jiang Gengru , Chen Qinkai , Zhang Qinghong , MA Tean , Chen Chaosheng , Bi Guangyu , Xing Changying
Published: May 2024

Background and Aims

Immunoglobulin A nephropathy (IgAN) comprises a substantial proportion of primary glomerulonephritis cases in China, yet comprehensive nationwide data regarding its diagnosis and treatment are lacking. The Immunoglobulin A Nephropathy Management Quality Improvement Initiative Project in China (IGAN-MIC) seeks to establish an IgAN cohort collaboration network to comprehend real-world IgAN management practices in China.

Method

The IGAN-MIC project convened 15 Chinese experts from 14 regions to form an expert committee to develop a registry of IgAN patients to evaluate regional differences in IgAN management from 2015 to 2024. The registry will involve comprehensive data collection from electronic medical records, encompassing key aspects including demographic and clinical characteristics, renal biopsies, diagnoses, comorbidities, laboratory findings, and treatment modalities, facilitating a detailed analysis of disease progression and changes in treatment strategies from initial diagnosis through subsequent follow-up periods.

Results

The IGAN-MIC project has garnered applications from 78 healthcare institutions, with 7 of them already incorporated into the initiative and initiated data collection. As of January 1, 2024, the project has enrolled 543 pathologically confirmed IgAN patients diagnosed between 2015 and 2023 from these 7 centers. At the time of diagnosis, the median (IQR) of age was 38.00 (30.00, 48.00) years; 54.51% were females; the median (IQR) of eGFR was 75.41 (51.93, 104.09) mL/min/1.73 m2 and the median (IQR) 24-hour urinary protein was 1263.50 (645.30, 2362.64) mg/day. For these patients, the utilization rates of RAS inhibitors (RASi), SGLT2 inhibitors (SGLT2i) and glucocorticoids at initial treatment were 53.41%, 3.51%, and 42.73% respectively. The utilization rate of SGLT2i from 2022 to 2023 was 9.90%, as the first indication for SGLT2i in CKD was approved in China in September 2022. A detailed outline of patient baseline characteristics is presented in Table 1 below.

Conclusion

These initial findings in the registry showed that the Chinese IgAN patients were young, had mildly reduced renal function, and with massive proteinuria at the time of initial diagnosis. For initial treatment, only half of the patients received RASi, and only one tenth received SGLT2i. More education needs to be focused on promoting guideline-directed medical therapies in the future. Given that nationwide data on Chinese IgAN patients are limited, the IGAN-MIC project is anticipated to broaden its registry to include more healthcare institutions and Chinese IgAN patients in the future, with the aim of providing a more in-depth understanding of the changing clinical presentations and ongoing follow-up scenarios among IgAN patients, contributing crucial insights to the clinical management of IgAN.