bluuebunny/crossref_metadata_2025 huggingface dataset:
#2989 Superposition of atypical hemolytic syndrome and tubulointerstitial nephritis, a case report
Authors: Padilla Manuel Enrique Villalobos , Lopez Daniela Paola Giron , Chacón Melisa Elizalde
Published: May 2024

Background and Aims

Hemolytic uremic syndrome is a heterogeneous group of diseases that have in common the development of thrombotic microangiopathy with diffuse endothelial damage, resulting in the classic triad composed of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury, on the other hand, tubulointerstitial nephritis is characterized by the presence of inflammatory infiltrates and edema and of the interstitial compartment that causes deterioration of renal function.

Method

The following is the case of a patient with acute kidney injury of etiology composed of thrombotic microangiopathy and tubulointerstitial nephritis.

Results

27-year-old female patient without significant history, began 3 weeks prior to admission with fever, chills, asthenia, nausea and vomiting of food content, approximately 5 episodes per day for 3 days, presenting intermittent episodes of jaundice of the mucous membranes and conjunctivae, with progressive increase of the symptoms to the point of preventing daily activities, she was admitted for study, detecting hemolytic anemia, thrombocytopenia and severe acute kidney injury, so she was referred to our center was decided for evaluation by Nephrology and Hematology. In our institution, urinary sediment with dysmorphic erythrocytes was documented, peripheral blood smear without the presence of schistocytes, positive Coombs 4 crosses, renal ultrasound with data compatible with acute kidney injury, and supportive management with hemodialysis was initiated. Due to suspicion of autoimmune glomerulopathy, an autoantibody panel was indicated with negative antinuclear antibodies, anti-double-stranded DNA, anti-Sm, anti-B2 glycoproteins, and lupus anticoagulant, with normal complement values, stool culture, and negative stool Shiga protein assay, angiotomography of the abdomen where the integrity of renal circulation is verified, so renal biopsy with immunohistochemical study is performed, finding data compatible with thrombotic microangiopathy and acute tubulointerstitial nephritis. The patient is maintained with supportive care, steroids and hemodialysis as required with progressive recovery of renal function until renal replacement therapy is weaned, she is discharged with a steroid regimen and clinical nephrology and hematology follow-up.

Conclusion

Acute kidney injury is a complex and multifactorial entity, which requires a comprehensive approach in order to identify the best therapeutic option and to offer a better outcome in the renal function of these patients. The case of our patient presented a sudden deterioration of renal injury composed of two entities with different pathophysiology, demonstrating that, although the approach to these two entities converge in certain etiologies, it is imperative that the clinician does not forget the wide variety of factors that contribute to the development of renal injury.
#2206 Predictors of post-operative acute kidney injury after colorectal cancer surgery
Authors: Larsen Mads Skovsgaard , Munch Philip Vestergaard , Christiansen Christian Fynbo
Published: May 2024

Background and Aims

Post-operative acute kidney injury (PO-AKI) is a common complication of colorectal cancer (CRC) surgery associated with increased morbidity and mortality, and higher hospital costs. Specific treatment of AKI is still limited, supporting the importance of preventing AKI. Identification of patients at high risk may allow early interventions, including closer monitoring and perioperative optimization. This study aimed to identify predictors of PO-AKI by assessing the association between preoperative factors and the occurrence of PO-AKI.

Method

We conducted a nationwide cohort study including adult CRC surgery patients in 2010–2021 using Danish health registries. We defined PO-AKI as AKI within 7 days after the CRC surgery according to the 2012 KDIGO criteria using creatinine measurements. A list of patient characteristics associated with AKI was identified using existing literature. We obtained information on variables using population-based health registries containing data on diagnosis codes, redeemed prescriptions, and laboratory data. We investigated the individual predictive factors by estimating PO-AKI risks and the odds ratios (ORs) with 95% confidence intervals (CIs) adjusting for sex and age.

Results

We identified 35,650 CRC surgery patients, of whom 24,555 had creatinine measurements during the study period, making them eligible for further analysis. Among these patients, we identified 2,694 cases of PO-AKI, corresponding to a 11% risk of PO-AKI.

The risk of PO-AKI was higher for males (13.5% vs. 8.4%, aOR=1.76 [1.62-1.91]), and patients with diabetes (15.4% vs. 10.2%, aOR=1.46 [1.32-1.61]), cardiovascular disease (15.4% vs. 9.9%, aOR=1.38 [1.26-1.52]), CKD (18.9% vs. 9.2%, aOR=1.99 [1.80-2.19]), COPD (16.6% vs. 10.3%, aOR=1.59 [1.42-1.78]), and hypertension (13.6% vs. 7.5%, aOR=1.68 [1.53-1.84]).

When examining potentially nephrotoxic medicine, the risk was higher in ACE-I/ARB users (14.5% vs. 9.6%, aOR=1.44 [1.32-1.56]) and similar in NSAID users and nonusers (10.3% vs. 11.0%, aOR=1.00 [0.84-1.19]).

Conclusion

We found that male gender, diabetes, cardiovascular disease, CKD, COPD, hypertension, and the use of ACE-I/ARB medications were associated with a higher risk of PO-AKI. Interestingly, users and nonusers of NSAIDs had similar risks of AKI. The identification of high-risk groups, such as those with pre-existing comorbidities or users of specific medications, may aid clinicians in identifying patients with a particularly high risk of PO-AKI.
#2237 Preliminary results of Protection of Renal Function after Conversion of fast IR-Tac Metabolizers to Envarsus® study (The Protect RENvarsus study)
Authors: Thölking Gerold , Jehn Ulrich , Sommerer Claudia , Guthoff Martina , Avdiu Alban , Weinmann-Menke Julia , Kommer Andreas , Hesselink Dennis , Schagen Maaike , Kurschat Christine , Miglinas Marius , Reuter Stefan
Published: May 2024

Background and Aims

As shown in a proof-of-concept study, renal function of fast immediate-release tacrolimus (IR-Tac) metabolizers can recover after conversion to prolonged-release tacrolimus (LCP-Tac), whereas slow Tac metabolizers showed no benefit over a 3-year follow-up [1]. The aim of this study is to test this hypothesis in a multi-center trial.

Method

In a multicenter European trial, we aim to enroll 300 renal transplant (RTx) recipients who were switched from IR-Tac to LCP-Tac one month or later after RTx. Metabolizer groups will be defined by calculation of the C/D ratio at one month after RTx: fast IR-Tac metabolizers (<1 ng/mL*1/mg) and slow (≥1) [2]. The development of renal function, acute rejections, infections, and the development of diabetes mellitus will be observed in a 5-year follow-up.

Results

A total of 265 patients have been included in this study to date. Preliminary data confirm that fast metabolizers who were switched to LCP-Tac at a median time of 2.0 months (range: 1.0-253.1 months) showed a recovery of renal function. In contrast, slow metabolizers showed a stable eGFR after switching to LCP-Tac at a median time of 13.2 months (range: 1.2-172.8 months) following RTx. The incidence of complications was low and comparable in both groups.

Conclusion

Preliminary data confirm that early conversion of fast IR-Tac metabolizers to LCP-Tac can improve renal function after RTx. The 5-year follow-up data will provide additional insight.
#2727 Acute kidney in patients with ANCA associated vasculitis
Authors: Dhoha Derbel , Mariem Najjar , Mekki Soumaya , Mariem Hajji , Hmida Fethi Ben , Abderrahim Ezzedine
Published: May 2024

Background and Aims

Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is considered an emergency situation. Early diagnosis and treatment significantly improve prognosis. The aim of this study was to investigate the characteristics of acute kidney injury (AKI) in ANCA-associated vasculitis and assess its developmental aspects.

Method

Our study, conducted in the Internal Medicine Department A of Charles Nicole Hospital over a four-year period (January 2018-August 2022), was retrospective and descriptive. The diagnosis of ANCA vasculitis was made based on the ACR 1990 and/or EULAR 2012 criteria. The severity of AKI was categorized according to the KDIGO AKI classification.

Results

Seventeen patients were included, with a mean age of 51 ± 17.42 years and a sex ratio of 0.42. The primary clinical presentation of AKI was rapidly progressive glomerulonephritis (n=11), followed by acute nephritic syndrome (n=4). Pneumo-renal syndrome was observed in 4 patients. Proteinuria and hematuria were present in all 17 patients, with 4 being oligoanuric on dipstick. The mean creatinine level was 584 μmol/L, ranging from 125 to 1151 μmol/L. Thirteen patients had KDIGO stage 3 AKI on admission. The predominant histological lesion was extracapillary crescentic glomerulonephritis, based on the Berden classification (n=6). Hemodialysis was initiated immediately in 12 cases, and plasma exchange was performed in 10 cases. The average follow-up time was 24 months, ranging from 3 months to 4 years. Evolution was marked by partial remission in 7 cases, with a mean creatinine of 173 μmol/L. Progression to end-stage renal disease (ESRD) occurred in 10 cases. Relapses, presenting as pneumo-renal syndrome, were observed in 4 patients. Seven patients succumbed, with vasculitis being the cause of death in 3 cases.

In univariate analysis, age >70 years was associated with progression to ESRD (p=0.03). No factor studied emerged as a prognostic factor for overall survival.

Conclusion

The presence and severity of AKI in ANCA-associated vasculitis are linked to a poorer prognosis, affecting both patient and renal survival.
#2391 Changes of medical costs and number of uses for continuous renal replacement therapy until recent six years in South Korea
Authors: Kim Hyung-Jong
Published: May 2024

Background and Aims

Continuous renal replacement therapy (CRRT) is a necessary dialysis treatment method applied to patients with acute renal injury at intensive care unit. In South Korea, the use of such CRRT is increasing, and the cost of health insurance used for CRRT is also increasing. In this study, the pattern and medical costs increase of CRRT usage until recent 6 years were investigated.

Method

From 2016 to 2021, the number of CRRT claims was investigated using data from the National Health Insurance Review and Assessment Service. CRRT costs is applied by a resource-based relative value score in Korea. CRRT can be charged as continuous venovenous hemodialysis, continuous venovenous hemofiltration, and continuous venovenous hemodiafiltration depending on the treatment mode. The CRRT cost differs from the very day and the next day's cost, and the cost of the very day includes the femoral hemodialysis catheter insertion cost, which is higher than the next day's cost.

Results

CRRT medical practice is gradually increasing. The number of CRRT the very day increased from 15,640 cases in 2016 to 20,883 cases in 2021, and it continues to increase from 81,649 cases CRRT the next day in 2016 to 121,376 cases CRRT the next day in 2021. The CRRT relative value score is higher than the conventional hemodialysis(HD) and the CRRT relative value score is 9715 points higher than the conventional HD 1065 points. The total cost of CRRT increased by about KRW 52.5 billion (approximately 38,363,171 dollars) in 2021 from about KRW 17.3 billion (approximately 12,641,578 dollars) in 2016. In addition to CRRT medical practice costs, dialysis fluid, anticoagulant costs, and material costs are added, and so actual CRRT-related costs are more expensive.

Conclusion

CRRT medical practice is gradually increasing. The number of CRRT the very day increased from 15,640 cases in 2016 to 20,883 cases in 2021, and it continues to increase from 81,649 cases CRRT the next day in 2016 to 121,376 cases CRRT the next day in 2021. The CRRT relative value score is higher than the conventional hemodialysis (HD) and the CRRT relative value score is 9715 points higher than the conventional HD 1065 points. The total cost of CRRT increased by about KRW 52.5 billion (approximately 38,363,171 dollars) in 2021 from about KRW 17.3 billion (approximately 12,641,578 dollars) in 2016. In addition to CRRT medical practice costs, dialysis fluid, anticoagulant costs, and material costs are added, and so actual CRRT-related costs are more expensive.
#2689 Risk factors for hospitalization for a major acute cardiovascular event after acute kidney injury with full recovery: a single center experience
Authors: Mahmoud Nouha Ben , Hamouda Mouna , Salah Manel Ben , Salem Meriem Ben , Bchir Sirine , Letaief Ahmed , Sabra Aloui , Skhiri Habib
Published: May 2024

Background and Aims

Acute kidney injury (AKI) was found to be associated with an increased risk of major adverse cardiovascular events (MACE) in the general population. We aim to evaluate the risk factors of

Method

We conducted a retrospective single center study including all patients hospitalized in the nephrology ward since 2002 to 2015, which experienced an AKI episode with full recovery. AKI was defined according to KDIGO criteria. Our primary outcome was to identify risk factors in our population exposing them to MACE after AKI.

Results

Our study included 107 men and 107 women with median age was 61 years. KDIGO stage 3 was the major stage (115 patients), 31 of whom required hemodialysis. Hypertension was found to be the major co morbidities in our population with 37.4% of patients followed by diabetes (32.2%). Median creatinine was 3.79 mg/l (1.26–34.57 mg/l). Most patients had anemia (65.4%).

Among 176 patients for whom we have followed up, in the short, medium and long term: 19, 20 and 2 patients had respectively developed a MACE. The characteristics of patients according to the occurrence of MACE or not are illustrated by Table 1. The risk factors found in our population were presence of co morbidities, vascular disease and anemia in univariate analysis and only anemia in multivariate analysis (Table 2). Patients with anemia and vascular disease had 2.4 times more the risk to develop MACE after AKI with full recovery than patients without anemia and no past history of vascular disease.

Conclusion

Patients with anemia, past history of vascular disease are at risk of MACE after AKI with full recovery and those patients should be better monitored in the short, medium and long term. Our aim is to detect the MACE earlier so we decrease the cardiovascular mortality.
#1621 Quantifying ureter smooth muscle electrophysiology from calcium transient images to understand abnormal peristaltic contraction
Authors: Mahapatra Chitaranjan , Pradhan Ashish
Published: May 2024

Background and Aims

Abnormal peristaltic contraction of the ureter smooth muscle (USM) causes acute kidney stone episodes. Intracellular electrical activities like membrane depolarization and action potentials play important roles in modulating the USM contraction by releasing intracellular calcium from the sarcoplasmic reticulum. Therefore, an electrophysiological study will help to assess the USM cell's electrical activities and in diagnosing abnormal USM contraction. The objective of this study is to quantify the contribution of ionic currents in shaping experimental calcium transient profiles using in-silico electrophysiological modeling.

Method

The simultaneous experimental recording of action potential (AP) and intracellular calcium transient images from the mouse ureter is obtained. The single isolated USM cell model comprises several voltage-gated ion channels, such as two voltage-gated calcium (T—type, and L—type) channels, one voltage-gated fast potassium (KA) channel, one calcium-dependent large conductance potassium channel, and an HCN channel. To describe the calcium-dependent gating of Ca2+-dependent potassium channels and to update the equilibrium potential of the Ca2+ ion, the intracellular Ca2+ concentration is updated during the simulation period.

Results

Simulation of simultaneous recordings of AP and cytosolic calcium [Ca2+]i are done on a single isolated cell. The model shows [Ca2+]i as a function of synaptic input-induced AP to simulate extracted experimental data, where Ca2+ transient is recorded simultaneously during AP in mouse USM cells. Fig. 1 shows both experimental and simulation of AP (A) and Calcium transient (B) in the USM cell. In our model, the radius “r” and time constant τ of the shell influence the Ca2+ transient profile. In the USM cell model, the submembrane calcium transient occurs from a depth of 0.1 μm to a depth of 0.6 μm. We have investigated whether Ca2+ current via the L-type Ca2+ channel is responsible for the firing of APs with fast upstroke generation. The AP and calcium transients are demolished with the absence of the L-type Ca2+ channel.

Conclusion

From this study, it is found that inhibition of the L-type Ca2+ channel not only prevented AP generation, it also reduced the cytosolic Ca2+ transient. This study supports the application of L-type Ca2+ channel inhibitor as a potential drug for abnormal peristaltic contraction of the ureter smooth muscle.
#391 Calpain inhibition enhances autophagy-lysosomal pathway and ameliorates tubulointerstitial fibrosis in Nphp1-targeted models
Authors: LI Dantong , Zhang Jinglan , Ye Zhiming , Sun Liangzhong
Published: May 2024

Background and Aims

Nephronophthisis (NPH) belongs to a group of renal ciliopathies and is the most common genetic disease leading to renal failure in children. Mutations in Nphp1 account for the majority of NPH cases, and renal tubulointerstitial fibrosis is one of the most important pathological features. However, the molecular mechanisms of renal tubulointerstitial fibrosis remained unknown.

Method

Previously, we successfully constructed an Nphp1 knockout mice model with renal phenotype of tubulointerstitial fibrosis by CRISPR-Cas9. In this study, we used lentiviral shRNA vectors to construct Nphp1 knockdown HK2 cells. We carried out RNA sequencing in Nphp1-targeted cells and mice kidneys to explore the molecular mechanisms of renal tubulointerstitial fibrosis in NPH. Calpain (CAPN) was found to be upregulated in both models. Western blot and immunofluorescence (IF) were used to verify the expression of CAPN in Nphp1-targeted HK2 cells and mice kidneys, as well as their respective controls. We also detected autophagy activities in NPH models by western bolt, immunofluorescence, lysotracker and transmission electron microscopy (TEM). Epithelial or mesenchymal-specific markers and Masson's trichrome staining were used to detect the status of tubulointerstitial fibrosis. Furthermore, Nphp1-targeted HK2 cells and mice were treated with a CAPN inhibitor to explore the role of CAPN in autophagy-lysosomal pathway and tubulointerstitial fibrosis.

Results

CAPN was verified to be upregulated in both Nphp1-targeted HK2 cells and mice kidneys. We also discovered impaired autophagic flux in NPH models. Furthermore, the impaired autophagic flux induced tubulointerstitial fibrosis in NPH models. However, the autophagic flux was improved and the status of tubulointerstitial fibrosis was ameliorated with CAPN inhibition.

Conclusion

CAPN-mediated autolysosomal pathway disorder may be an important cause of tubulointerstitial fibrosis in NPH. CAPN may be a new target for diagnosis and treatment of NPH.
#2804 Mechanisms of cAMP-induced cyst formation observed in Pkhd1-KO cells
Authors: Ziegler Wolfgang H , Hassan Fatima , Hahnenstein Susanne , Haffner Dieter
Published: May 2024

Background and Aims

Loss of ciliary protein function leads to altered epithelial properties in hereditary polycystic kidney diseases. To address molecular aspects of defective epithelial homeostasis, monolayered epithelial spheroids can be used to analyze lack of protein function and consequences of pharmacological intervention. Here, we employed epithelial cell clones deficient for fibrocystin/polyductin (FPC) protein function, the origin of ARPKD, to study the impact of FPC cytoplasmic domain constructs on cAMP-induced cystogenesis.

Method

We used pl-MDCK, sub-cloned principal-like cell lines, with CRISPR/Cas9-based genetic knockout (KO) of Pkhd1 / FPC, and corresponding controls. Cells were grown in matrigel to allow formation of epithelial spheroids within 3 days. Forskolin (Fsk) treatment was employed to induce cAMP-mediated cyst growth mimicking disease conditions. Measurement of proportional lumen, the ratio of lumen to spheroid area, allowed detection the enhanced water and ion transport across the barrier as characteristic for secretory epithelia. Cystogenic signals were modulated by expression of the FPC C-terminal domain constructs and/or pharmacological inhibitors, and involvement of ion channels was addressed.

Results

In Pkhd1-KO cell lines, enhanced cAMP levels resulted in massive lumen expansion of epithelial spheroids with no increase in cell number. The rise in proportional lumen was sensitive to inhibition of chloride-channels, CFTR and TMEM16A, and Src kinase. Fsk-mediated cyst induction led to activation and increased Y705 phosphorylation of STAT3. To address the impact of FPC on cystogenic signaling, expression of a membrane-bound FPC C-terminal protein domain was studied, and its processing and intracellular localization determined. Controlled expression of the FPC cytoplasmic domain in Pkhd1-KO cell lines suppressed Fsk-induced cyst formation. In addition, the FPC domain reduced activation of Src and STAT3, leading to lower STAT3-dependent transcription.

Conclusion

In FPC-deficient pl-MDCK cells, cyst formation stimulated by high cAMP levels is associated with enhanced Src/STAT3 signaling. Expression of the FPC cytoplasmic domain, leading to a gain-of-function, suppresses Src and STAT3 activity in Pkhd1-KO epithelia and limits cyst growth in vitro. Control of cystogenic Src/STAT3 signaling can be considered a physiologic function of the FPC protein.
#1389 Identification of serum lipidomic profile in nephrotic syndrome patients
Authors: Rother Nils , Rood Ilse , Bekkering Siroon , Riksen Niels , Hilbrands Luuk , Maas Rutger , Nijenhuis Tom , Duivenvoorden Raphaël
Published: May 2024

Background and Aims

Nephrotic syndrome describes a collection of symptoms, mainly heavy proteinuria leading to kidney function loss, that can be caused by different underlying kidney diseases. Common primary causes of nephrotic syndrome include focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and membranous nephropathy (MN). Nephrotic syndrome is often characterized by plasma lipid abnormalities with elevations in cholesterol, triglycerides and lipoproteins. Here we set out to generate a detailed lipidomic analysis of FSGS, MCD and MN patient's plasma to find lipid changes common to nephrotic syndrome or specific for the underlying disease.

Method

For this lipidomic study, we included patients with primary FSGS (2 cohorts with n = 5), genetic FSGS (n = 5), MCD (n = 5) and MN (n = 5) in whom serum had been collected at the time they presented at our center with active nephrotic syndrome. We compared the serum lipidome of nephrotic syndrome patients with age matched healthy controls (n = 5), and with age matched patients with familial hypercholesterolemia (n = 5) who, like patients with nephrotic syndrome, have significantly elevated lipid values. Serum was analyzed using the Shotgun Lipidomics platform by Lipotype GmbH (Dresden, Germany), as previously described [1].

Results

The lipidomic profile of patients with nephrotic syndrome was markedly different compared to control groups (Fig. 1A). In particular, lower levels of lyso-phophatidylcholine (LPC) and higher concentrations of phosphatidylethanolamine (PE) and lyso-PE (LPE) compared to control groups were most prominent (Fig. 1B). Subspecies analysis identified LPC 16:0;0 to be highly downregulated in patients with nephrotic syndrome (Fig. 2A), whereas LPE 18:0;0 and nearly all PE subspecies were increased compared to control groups (Fig. 2B and C). The lipidomic profile was largely comparable between different underlying diseases and we could not identify lipid classes specifically different for certain diseases.

Conclusion

Our lipidomic data show that patients with nephrotic syndrome have a distinct lipid profile compared to healthy controls or other disease controls. We identified LPCs, PEs and LPEs to be changed in nephrotic syndrome. We could not identify lipids specific for certain diseases underlying nephrotic syndrome, but rather identified a general nephrotic syndrome lipid profile. This suggests that lipid changes are rather a consequence of disease manifestation in these patients with various underlying causes. Further research should focus on confirming this lipid profile in larger cohorts and unraveling the mechanisms leading to the observed lipid changes.
#896 Long-term renal outcome in childhood-onset lupus nephritis
Authors: Odone Ludovica , Peyronel Francesco , Calatroni Marta , Pala Chiara , Errichiello Carmela , Doti Federico , Delsante Marco , Conte Emanuele , Emmi Giacomo , Rossi Giovanni Maria , Moroni Gabriella Luisa , Vaglio Augusto
Published: May 2024

Background and Aims

Lupus nephritis (LN) is a common and severe complication of childhood-onset SLE. Little is known about the long-term renal outcome of childhood-onset LN. We investigated predictive factors of end-stage kidney disease (ESKD) and chronic kidney disease (CKD) in a paediatric cohort of patients with LN.

Method

This is a retrospective multicentre study including patients with childhood-onset (<18 years) biopsy-proven LN. Clinical features were analysed at disease onset, time of kidney biopsy, 12 and 24 months after biopsy, and last follow-up. We investigated the prognostic significance of clinical, laboratory and histologic characteristics on the incidence of ESKD and CKD stage 3-5.

Results

We included 73 patients with a median age of 14 years (IQR 11.5-17) . At the time of kidney biopsy, most subjects displayed an aggressive disease: 2 (3%) children required haemodialysis, 27 (38%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The overall median eGFR was 70 mL/min/1.73 m2 (IQR 43-96) . Moreover, the median proteinuria was 4 g/24 h (IQR 1.35-7.41) , with 41 (59%) children displaying a nephrotic range proteinuria (i.e., >3 g/24 h) . The median follow-up was 13.3 years (IQR 4.7-25.4) . A total of 10 patients (13.7%) reached ESKD, the majority of whom (12%) within 10 years from kidney biopsy; during the subsequent follow-up the incidence of ESKD stabilised (Fig. 1). At last follow-up, around 50% of patients displayed an eGFR <90 mL/min/1.73 m2. A younger age at LN onset, a lower eGFR and central nervous system involvement at the time of kidney biopsy were identified as predictors of ESKD by a univariable Cox regression model (Table 1). The same features were significantly associated with the occurrence of CKD stage 3-5 at last follow-up at a univariable logistic regression analysis.

Conclusion

LN often presents with severe kidney function impairment and aggressive systemic involvement in children. In our cohort, whose follow-up was among the longest reported in the literature, 12% of patients reached ESKD within 10 years from kidney biopsy. Significant predictors of poor kidney outcome in the long term were a younger age at LN onset, a lower eGFR and the presence of neurological manifestations at the time of kidney biopsy.
#1793 Association of low serum complement C3 with reduced renal survival in ANCA associated vasculitis
Authors: Khouloud Hafi , Salem Meriem Ben , Mahmoud Nouha Ben , Gana Abir , Letaief Ahmed , Hamouda Mouna , Sabra Aloui , Salah Manel Ben , Skhiri Habib
Published: May 2024

Background and Aims

ANCA-associated vasculitis (AAV) is a condition that remains poorly understood. Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of this disease. And recent studies have correlated low complement levels to unfavourable outcomes. Our study aimed to determine whether low serum C3 levels could be used to estimate the severity of AAV and predict renal survival.

Method

Our study enrolled 26 patients diagnosed with AAV between January 2013 and January 2023. C3 levels were assessed at the time of diagnosis, and patients were categorized into two groups: those with low serum C3 levels and those with normal serum C3 levels (0.9–1.8 g/l). We examined the correlation between serum C3 levels and the severity of AAV at the time of diagnosis, as well as renal survival.

Results

The average age at diagnosis was 52.5 years, with 15 male patients (57.69%). All patients had kidney involvement, 30% of patients had respiratory symptoms (mostly due to diffuse alveolar hemorrhage) 42% had Ear Nose Throat system involvement 15% had nervous symptoms and 38% had skin signs. The mean Birmingham Vasculitis Activity Score (BVAS) at presentation was 20, and the average serum creatinine level was 360 µmol/l. The mean serum C3 and C4 levels were 108.3 and 24.5 mg/dL, respectively. Forty-two percent of the patients (eleven patients) had a low serum C3 level at presentation. Low C3 level was significantly correlated with poor renal survival (p: 0.031) and relapse after 6 months of immunosuppressive treatment (p: 0.02). Furthermore, remission at 6 months was significantly more frequent in patients with normal C3 levels.

Conclusion

The assessment of C3 level in AAV can be a valuable tool to predict the disease severity. Hypocomplementemia can predict worse renal outcome. This phenotype may confer a poor response to usual immunosuppressive approaches. Corresponding patients may greatly benefit from complement-targeting therapy.
#2056 Epigenetic profiles differ by level of kidney function in idiopathic nephrotic syndrome
Authors: Hayward Samantha , Suderman Matthew , Welsh Gavin , Saleem Moin
Published: May 2024

Background and Aims

DNA methylation (DNAm) is an epigenetic mechanism which can therefore induce changes in gene expression without any change to the underlying DNA sequence. Although generally quite stable, DNAm patterns in whole blood do vary across individuals, with DNAm levels associating with age and responding to environmental factors.

We aimed to investigate whether peripheral blood cell DNAm associates with level of kidney function in patients with Idiopathic Nephrotic Syndrome (INS).

Method

Peripheral blood cell DNAm values were generated using the Illumina MethylationEPIC Beadchip (>850,000 CpG sites) for 293 INS patients recruited to the National Unified Renal Translational Research Enterprise–National Study of INS (NURTuRE- INS and NephroS). All patients were younger than 30 years old at INS diagnosis. An Epigenome Wide Association Study (EWAS) was performed using generalised linear models to evaluate associations between DNAm sites and estimated glomerular filtration rate (eGFR). Regions of differentially methylated sites were identified using the ‘dmrff’ R package. Sex chromosomes were excluded from the analyses and all analyses were adjusted for estimated cell type proportions, age, sex and technical variation. A Bonferroni adjusted p value of 5.88 × 10−8 was used as a significance threshold to adjust for multiple tests.

Results

Of the selected 293 INS patients, 173 (59%) were male, 213 (73%) were white and the median age at INS diagnosis was 4 years old (IQR 2-10). One hundred and forty-three (48%) patients were steroid responsive at diagnosis and the remainder were steroid resistant. Sixty-eight of the steroid resistant patients had pathogenic NS variants.

We identified 6 CpG sites associated with eGFR (p < 5.88 × 10−8) in this cohort of INS patients, one replicating a previously reported association. We identified 3 differentially methylated regions, one coinciding with the transcriptional start site of an RNA binding protein which regulates alternative splicing, and another located in the body of a transcription factor regulator containing genetic variants associated with chronic kidney disease.

Conclusion

We have demonstrated variation in peripheral blood DNAm by level of kidney function in children and young adults with INS. Associations between DNAm and eGFR have previously been demonstrated in diabetic kidney disease and heterogenous chronic kidney disease cohorts, including one of the sites which we have identified in our study. Further work is underway to determine if these differences in DNAm are likely to be a cause or consequence of reduced kidney function, which will help to determine their potential clinical utility.
#1283 Rituximab in addition to plasma exchange, cyclophosphamide and steroids for treatment of anti-GBM disease
Authors: Srikantharajah Mukunthan , Cairns Tom , Pusey Charles , Prendecki Maria , Mcadoo Stephen
Published: May 2024

Background and Aims

Anti-GBM disease is a rare antibody-mediated vasculitis, usually treated with plasma exchange (PEX), cyclophosphamide (CYC) and steroids. There are limited data regarding the use of B-cell depleting therapies such as rituximab (RTX). We investigate the use of the addition of rituximab for the treatment of Anti-GBM disease.

Method

Ten-year (2012-2023) single-centre retrospective cohort study of patients with anti-GBM disease treated with or without rituximab, in addition to standard care, as first-line therapy. A Cox-proportional hazards regression model incorporating age, sex, ANCA status, dialysis need at presentation, lung haemorrhage, CYC (oral or IV) and RTX treatment was used to identify disease/treatment factors associated with outcome (death, end-stage kidney disease [ESKD], infection).

Results

Forty-five patients are included; baseline demographics, disease characteristics, treatments and outcomes are summarised in Table 1.

In the Cox regression model, only increasing age was associated with risk of death (HR 1.08 [95% CI 1.02-1.17]). Age (HR 1.04 [1.01-1.08]), female sex (HR 4.93 [1.80-4.87]), and dialysis need at presentation (HR 5.28 [1.54-17.53]) were associated with ESKD-risk. Increasing age (HR 1.04 [1.00-1.09] and ANCA positivity (HR 3.08 [1.14-8.71]) were associated with risk of infection. The addition of rituximab was not significantly associated with risk of death (HR 0.82 (0.24-2.87), ESKD (HR 1.54 [0.64-3.96]) or infection 2.06 [0.67-5.71].

Conclusion

Addition of rituximab to standard treatment for anti-GBM disease was not associated with improved renal outcome or survival benefit. However, rituximab use permitted lower cumulative doses of CYC and reduction in the number of PEX, without an increased risk of infection. Rituximab may have a role as a CYC- and PEX-sparing treatment in patients with anti-GBM disease.
#1293 Endothelial calcification induced by high-phosphate is characterized by mesenchymal and osteoblastic transdifferentiation
Authors: Ciceri Paola , Artioli Luisa , Martinelli Carla , Falleni Monica , Tosi Delfina , Gianelli Umberto , Cozzolino Mario Gennaro
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is a prevalent condition that affects millions of people. Patients with CKD have an increased cardiovascular risk, mostly due to vascular calcification (VC). By now, it's quite clear how, in vitro and in vivo, vascular smooth muscle cells (VSMCs) actively participate to VC. In contrast to the wide studies on VSMCs, the role of endothelial cells (ECs) has been poorly investigated. It's known that ECs have a dynamic nature and following particular stimuli they can trans-differentiate and acquire several different phenotypes through the endothelial-to-mesenchymal transition (EndMT).

Methods

Human aortic ECs (HAECs) were challenged, in an in vitro calcification model, with 2, 2.5, 3, 3.5 mM Pi for up to 7 days. Early morphological changes, gene expression and cell migration were evaluated. Afterwards calcium deposition, genes and protein expression and ultrastructural changes were analyzed.

Results

High-Pi, at a concentration of 3 mM, is able to induce EC calcium deposition. Calcification is dependent on calcium influx without influencing Pit-1 expression. During the first days of high-Pi treatment ECs change their morphology from cobblestone to spindle shape acquiring motility, as demonstrated by the 24% increased closure in the scratch wound test. EndMT master genes such as SNAIL and TWIST resulted up-regulated at day 3 together with an increased protein expression of mesenchymal markers such as N-Cadherin, α-SMA, SM22α, FSP-1 and Fibronectin. Starting from day 5 high-Pi induces osteoblastic differentiation with RUNX2 and BMP2 mRNA up-regulation up to day 7, osteopontin increased protein expression and positive Alcian Blu staining. In calcified ECs mesenchymal and endothelial markers, such as α-SMA, SM22α, FSP-1 and Fibronectin or vWF progressively decrease. Finally, uremic serum is able to exacerbate in vitro calcification, compared to healthy serum characterized by an increase in both mesenchymal and osteoblastic mastergene such as TWIST and RUNX2.

Conclusions

Our data demonstrate that in vitro high-Pi induces the EndMT process and similar osteoblastic trans-differentiation suggesting a potential role of endothelium in VC. The relevancy of endothelial calcification is suggested by the calcification exacerbation induced by uremic compared to healthy sera.
#2421 Kidney injury in scleroderma: serum level of fibroblast growth factor-23, klotho and neutrophil gelatinase-associated lipocalin after iloprost infusion
Authors: De Marco Oriana , Rosato Edoardo , Gigante Antonietta , Pellicano Chiara , Colalillo Amalia , Cianci Rosario
Published: May 2024

Background and Aims

Systemic sclerosis (SSc) is characterized by progressive derangement of the microcirculation leading to a state of chronic tissue hypoxia with release of several inflammatory cytokines such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho.

Renal scleroderma associated-vasculopathy is characterized by vascular damage with normal renal function and increased intrarenal stiffness, assessed by renal resistive index (RRI) Aim of this study was to evaluate at baseline serum levels of FGF-23, Klotho and NGAL in SSc patients and healthy controls (HC) and to correlate the serum levels of these markers with microvascular damage of skin and kidney. Secondary aim was to evaluate the serum levels of FGF-23, Klotho and NGAL after Iloprost infusion.

Method

Twenty-one SSc patients and 20 HC were enrolled. All patients had a 2-months wash-out of Iloprost infusion before of clinical, laboratory and instrumental assessment. Peripheral venous blood was collected at three different time points for SSc patients: t0 immediately before the first Iloprost infusion (after 2-months wash-out period), t1 immediately after the first Iloprost infusion and t2 the day of the next Iloprost infusion (about 14 days from the last infusion).

Results

SSc patients had higher serum level of FGF-23 [18.7 pg/mL (± 6.4) vs 3.6 pg/mL (± 2.2), p < 0.001], Klotho [5.1 pg/mL (±0.8) vs 2.3 pg/mL (±0.6), p < 0.001] and NGAL [20.9 pg/mL (±2.6) vs 14.5 pg/mL (±1.7), p < 0.001] compared to HC. The one-way repeated-measures ANOVA showed that mean FGF-23 [F (2,40) = 71.255, p < 0.001], Klotho [F (1.405, 28.103) = 195.095, p < 0.001] and NGAL [F (2,40) = 48.024, p < 0.001] differed significantly between time points.

Conclusion

SSc patients had higher FGF-23, Klotho and NGAL than HC. Our present data demonstrate that microvascular damage is associated to chronic hypoperfusion with increased circulating markers such as FGF-23, Klotho and NGAL. For the first time, we demonstrated that Iloprost infusion reduces significantly serum level of FGF-23, Klotho and NGAL and it has showed to be a key role in renal vasculopathy in SSc patients. In literature, there are no data about the modification of these serum markers before and after vasoactive treatment, especially of Iloprost infusion.
#2897 Urinary CD44 levels in chronic kidney disease: a validation study
Authors: Gaipov Abduzhappar , Suleimenova Yerke , Makhammajanov Zhalaliddin , Kuspanov Abuali
Published: May 2024

Background and Aims

Proteinuria is the one of the main cause of kidney failure progression. There is inadequate data about protein components in urine and CKD severity. Our recent urinary proteomics study demonstrated the higher expression of CD44 in the urine proteome of healthy participants compared to CKD patients, arguing the protective role of CD44 in kidney health. However, the validation study needed to proof those differences in CD44 levels by ELISA tests in healthy participants and CKD patients. Therefore, we aimed to investigate urinary CD44 levels in our previously studied cohort of healthy controls and CKD patients using ELISA test.

Method

This study included 49 healthy participants and 88 early-stage CKD patients. Along with routine laboratory tests, 24 h collected urine samples were investigated using liquid chromatography-mass spectrometry (HPLC-MS) for proteomic analysis. Exponentially Modified Protein Abundance Index (emPAI) was used to estimate peptide count of proteins. Additionally, urinary CD44 levels were measured using ELISA kit to validate findings from proteomic study.

Results

A brief baseline characteristics of study population presented in Table 1. CKD group represented with lower eGFR, increased creatinine and higher proteinuria compared to healthy controls. Urinary CD44 levels were significantly higher in CKD group compared to healthy controls. Both CD44 levels measured by HPLC-MS and ELISA methods significantly positively correlated with eGFR levels (Table 2).

Conclusion

In this validation study, we compared the levels of CD44 measured by HPLC-MS and ELISA in healthy controls and CKD patients. We demonstrated that CD44 is overexpressed in urine samples of healthy people compared to CKD patients and may play a protective role in the kidney health. Further investigations needed to explain this finding in a different cohort and large number of CKD patients.
#228 APOL1 variants and chronic kidney disease in Morocco: case control study
Authors: Bahadi Abdelaali , Elkabbaj Driss
Published: May 2024

Background and Aims

APOL1 genetic variants account for much of the excess risk of chronic and end stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. These genetic variants were never tested in north African patients and this is the first study aimed to search the existence of this variants in general Moroccan people and patients with chronic kidney disease.

Method

This is a case control multi center study including Moroccan adult with GFR less than 60 ml per min secondary to unknown etiology or nephroangiosclerosis. Patients with known nephropathy or diabetes were excluded. Between July 2014 and June 2017, patients and 100 controls were enrolled for testing APOL1 variants. ADN extraction was done by isolate II Blood DNA kit and nucleic acid concentration by spectrophotometry. The allele frequency was calculated by PCR TaqMan.

Results

During the inclusion period 117 patients with chronic kidney disease from unknown etiology and 8 patients with nephroangiosclerosis were included from all the twelve Moroccan regions. There mean age was 49 years and more than 60% were males. The age of end stage renal disease was 42 years. Testing APOL1 variants did not find G1 or G2 classic mutations but we find a G2 deletion and a new mutation GAT to AAT in two patients. We find also a silent mutation AGA to AGG that we are exploring in a family investigation.

Conclusion

APOL1 genetic variants as described in the literature are not significantly present in Moroccan patient with chronic kidney disease and cannot be yet used as a risk factor in our context. However we find a new mutation needing a wide exploration in a bigger cohort
#1265 Circulating neutrophils in diabetic kidney disease—the relationship with long-term cardiovascular outcomes
Authors: Xie Ruiyan , Zhang Danting , Jason Sher Ka Ho , Yap Desmond
Published: May 2024

Background and Aims

Neutrophils play important roles in the pathogenesis of cardiovascular inflammation and affects cardiovascular disease (CVD) outcomes. The relationship of circulating neutrophil counts with cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) remains unclear.

Method

We retrieved data from 44,494 participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2020, and investigated the associations between circulating neutrophil counts, kidney functions and CVD mortality in T2DM and DKD patients. Clinical predictive models and risk scores for long-term mortality were constructed.

Results

Among the cohort of 44,332 patients (18% with T2DM and 82% without T2DM), a total of 2,220 patients were diagnosed with diabetic kidney disease (DKD) and 775 of them experienced mortality (31.5% related to CVD) during a follow-up of 6.18 (range: 5.94-6.42) years. The weighted mean of peripheral neutrophil count level (×109 /L) in DKD participants was 4.98. DKD patients in the highest quintile of neutrophil count exhibited a positive correlation with urine albumin-creatinine ratio (uACR) and a negative association with estimated glomerular filtration rate (eGFR), when compared to those in the lowest quintile. In the multivariate logistic regression analysis with RCS, circulating neutrophil counts showed a U-shaped association with CVD mortality. Neutrophil counts of 3.68 × 109 /L and 3.69 × 109 /L were associated with the lowest risk of CVD mortality and all-cause mortality respectively in DKD patients. Clinical predictive models showed good diagnostic performance for 5- and 10-year CVD mortality-free survival (all ROC AUC values >0.75).

Conclusion

In this study, higher peripheral neutrophil count was associated with an increased risk of cardiovascular mortality in DKD individuals. Our clinical predictive models may help identify at-risk patients for more aggressive CVD risk factors control.