bluuebunny/crossref_metadata_2025_split huggingface dataset:
#817 Genetic analysis in a group of patients with persistent isolated microscopic hematuria
Authors: Sevillano Angel , Bada Teresa , Trujillo Hernando , Alonso Marina , Corona Clara Cases , Shabaka Amir , Gutiérrez Eduardo , Juarez Gema Maria Fernandez , Caravaca-Fontán Fernando , Praga Manuel 
Published: May 2024

Abstract

Background and Aims
Autosomal dominant Alport syndrome (ADAS) is a genetic disease caused by pathogenic variants in COL4A3 and COL4A4 genes. ADAS is the main cause of isolated persistent microscopic hematuria (PMH). However, other diseases like IgA nephropathy (IgAN) can present with PMH. Establishing a precise genetic diagnosis in this type of patients would avoid invasive studies like kidney biopsies. In this study we performed a comprehensive genetic test in a cohort of patients with isolated PMH to evaluate the frequency of ADAS or other genetic abnormalities and compare the clinical characteristics of patients with or without ADAS

Method
Fifty-two patients with PMH were included in the study. PMH was defined by the presence of 3 or more dysmorphic red blood cells per field in at least 5 consecutive urine sediments and a time-averaged proteinuria &lt;1 gr/day. Average proteinuria was determined for every 6 months of follow-up and time-averaged (TA) proteinuria represented an average of the mean proteinuria measurements in each 6-month period. A comprehensive genetic study using whole exome next-generation sequencing was performed. One hundred and one genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney diseases were analyzed. Patients with known secondary causes of hematuria were excluded. The baseline clinical characteristics of patients with and without ADAS were compared. Patients with pathogenic variants in COL4A5 gene were excluded of this analysis.

Results
Thirty-one (60%) patients were diagnosed with ADAS (16 patients with pathogenic variants in COL4A3, 15 in COL4A4), 3 (6%) patients (2 women, 1 man) presented pathogenic variant in COL4A5 gene, and the genetic study was negative in the remaining 18 patients (variants of unknown significance in COL4A3 or COL4A4 were found in 3 of the latter). No other genetic abnormalities were detected in the panel of 101 genes. Table 1 shows the baseline clinical characteristics of patients with and without ADAS. Patients with ADAS presented a higher TA proteinuria [0.23 (0.11-0.6) vs 0.08 (0.05-0.16), p = 0.01], and a more frequent familial history of isolated microscopic hematuria (76% vs 40%, p = 0.01) chronic kidney disease (CKD) (44% vs 0%, p = 0.01) or end stage kidney disease (32% vs 0%, p = 0.02). In the multivariate analysis, only a family history of microscopic hematuria was associated with ADAS: OR 5.62 (1.25-25.49, p = 0.02).

Conclusion
ADAS is the most common cause of PMH. A genetic study should be the first diagnostic step in order to obtain a precise cause of the disease and avoid invasive procedures. A family history of microscopic hematuria and of CKD increases the likelihood of ADAS prior to the performance of genetic test.
#1460 Targeting cyst progression: evaluation of anthelmintic and proton pump inhibitor in a rodent PKD model
Authors: Clanget Tilmann , Heigwer Jana , Bierhoff Kim , Tabatabaeifar Mansoureh , Schaefer Franz 
Published: May 2024

Abstract

Background and Aims
In polycystic kidney disease (PKD) cyst formation and growth leads to progressive kidney damage. Recognizing the need for effective cyst-inhibitory drugs, we previously performed high-content screening of approved, repurposable drugs in a zebrafish model and identified several compounds with cyst-inhibitory activity and low toxicity. Here, we further tested two of the identified compounds, an anthelmintic agent and proton pump inhibitor, in a rodent model of PKD (PCK rat) for their cyst inhibitory and GFR-preserving capacity in mammals.

Method
The identified compounds were administered to 3-week-old male and female PCK rats for a total of 10 weeks to evaluate early drug effects on kidney function. Untreated PCK rats fed a normal ROD16 diet served as controls. After 5 weeks of treatment, total kidney and cystic volume and number of cysts were assessed in vivo by ultrasound. Following 10 weeks of treatment, kidney function was assessed by transcutaneous measurement of FITC-Sinistrin. After perfusion fixation in the same week, the kidneys, liver, heart, and pancreas were harvested for subsequent histological and molecular biological analyses.

Results
In male rats, 5-week proton pump inhibitor treatment was associated with a 50% reduction in the number of cysts (p &lt; 0.05) and a nominal 22% reduction of fractional cystic kidney volume (CKV). Females showed a 16% reduction in cyst count and a modest reduction in fractional CKV. Treatment with the anthelmintic tended to reduce fractional CKV and cyst count in female animals whereas fractional cyst volume in males increased. After 10 weeks of treatment, a trend towards better preservation of GFR was observed for both therapies.

Conclusion
In conclusion, our study demonstrates a potential therapeutic benefit of a proton pump inhibitor and an anthelmintic agent in attenuating the progression of polycystic kidney disease (PKD) in a PCK rat model. The observed reductions in fractional cystic kidney volume and cyst count, coupled with marginal improvements in renal function, document a potential therapeutic effect of these compounds. Our preliminary findings justify further exploration of novel treatment modalities targeting cyst progression and renal dysfunction in this challenging clinical condition.
#1504 Performance evaluation of MicroVue sC5b-9 for analysis of urine samples
Authors: Hulsebus Holly , Gorzkowski Eric , Galvan Manuel 
Published: May 2024

Abstract

Background and Aims
Complement mediated kidney diseases including C3 glomerulopathy (C3G), atypical uremic syndrome (aHUS), lupus nephritis (LN), and immunoglobulin A nephropathy (IgAN) are chronic inflammatory conditions characterized by dysregulated complement activation. Traditionally, complement activation is measured in plasma. However, patients with kidney disease often have an abundance of complement activation fragments in their urine—including soluble C5b-9 (sC5b-9), a marker of terminal pathway activation—highlighting the potential value of sC5b-9 measurement in urine for diagnosis and risk management in patients with C3G, aHUS, LN, IgAN, and other kidney diseases. Herein we evaluated the analytical performance of the Quidel MicroVue sC5b-9 Plus EIA for measurement of sC5b-9 in urine.

Method
The Quidel MicroVue sC5b-9 Plus EIA was evaluated using randomly collected healthy urine samples or healthy urine samples spiked with a known concentration of sC5b-9, as well as chronic kidney disease (CKD) urine samples.

Results
The analytical performance of the Quidel MicroVue sC5b-9 Plus EIA for measurement of sC5b-9 in urine met acceptability criteria for accuracy and precision. Assay accuracy was (100 ± 20%) and intra-assay precision as well as inter-assay precision was ≤ 11% coefficient of variability (CV). sC5b-9 was not detected in healthy urine samples (N = 40), but sC5b-9 was detected in a subset of urine samples from patients with CKD (N = 10). Positive linearity was observed over a wide range of concentrations. sC5b-9 measured in urine was not affected by hemoglobin or triglyceride, and was stable following three freeze-thaw cycles. Lastly, sC5b-9 measured in urine was stable when stored at −20°C and –80°C for 4 weeks. Long term stability testing at –80°C is underway.

Conclusion
Quidel MicroVue sC5b-9 Plus EIA is an accurate, reliable assay for detection of sC5b-9 in urine samples.
#1355 Albuminuria after Induction Treatment and Kidney Prognosis in ANCA-associated Glomerulonephritis
Authors: Chalkia Aglaia , Jones Rachel B , Smith Rona M , Willcocks Lisa , Jayne David R W 
Published: May 2024

Abstract

Background and Aims
Persisting proteinuria has been associated with worse kidney outcomes in ANCA-associated glomerulonephritis (AAGN). However, it remains unclear whether this reflects damage from the initial injury or ongoing inflammation.

Method
A retrospective, single centre study of biopsy-proven AAGN. The group “albuminuria” was defined as urine albumin-to-creatinine ratio (ACR) more than 300 mg/g and the group “no albuminuria”, defined as ACR less than or equal to 300 mg/g at 6 months. We sought the clinical and histopathological characteristics from both the initial and any subsequent biopsies, and long-term kidney outcomes stratified by albuminuria levels.

Results
218 patients were included. Within the first six months, 28 (13%) had either died or progressed to end-stage kidney disease (ESKD). Among the remaining 190 patients, 37% had an ACR&gt;300 mg/g at 6 months. The albuminuria group more frequently presented with a Berden mixed or crescentic class and had higher glomerular activity on the initial biopsy. They were also more often male [odds ratio (OR) 2.69; 95% CI 1.13-6.41], of younger age (OR 0.96; 95% CI, 0.93 to 0.99) and had fewer normal glomeruli in the biopsy (OR 0.96; 95% CI, 0.93 to 0.99) compared to the group without albuminuria. Over the initial 5-year period, the recovery in glomerular filtration rate (GFR) was lower in the albuminuria group (adjusted mean difference in delta GFR −12.5 ml/min per 1.73 m2; 95% CI, −15.8 to −9.1). In multivariable analysis, ACR greater than 300 mg/g was associated with a higher risk of ESKD, even after adjusting for age, Berden classification and GFR at diagnosis (Hazard ratio 7.25; 95% CI, 1.62 to 32.47).

Conclusion
In a well-defined cohort of AAGN, one third of the patients, primarily younger males with a lower percentage of normal glomeruli, had persisting albuminuria after induction treatment which was associated with worse kidney outcomes independent of Berden class and GFR at diagnosis.
#1774 ANCA vasculitis with renal involvement: age as a prognostic factor
Authors: Talavera Andrea Cifuentes , Subiela José Enrique Ruiz-Cabello , Wang Yali Chen , Galindo-Izquierdo María , González Javier García , Ruiz Enrique Morales 
Published: May 2024

Abstract

Background and Aims
Older patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognosis. The European Vasculitis Study Group trials showed that approximately 16.7% and 22.5% of older patients with AAV suffered from end-stage renal disease (ESRD) in 5- and 10-year durations. The aim of this study was to analyze differences in course and outcome of patients with AAV with respect to age.

Method
This retrospective observational study included patients with diagnosis of AAV and biopsy proven renal involvement between 2000-2021. Patients were divided into two groups according to age: ≥65 or &lt;65 years old. We recorded baseline characteristics and clinical data during follow-up. Response was defined as a BVAS reduction of at least 50% or BVAS of 0, while receiving prednisone dose higher than 4 mg; and remission as BVAS of 0 while receiving prednisone dose of 4 mg or less.

Results
We included 42 patients with AAV diagnosis, 47.6% of which were 65 years-old or older. Mean age of the older age group was 77 ± 8 years. No differences were found between older and younger patients at baseline (BVAS, FFS extra-renal symptoms, serum creatinine at diagnosis, hematuria), Patients &gt; 65 years were significantly more likely to present p-ANCA positive MPA, as shown in Table 1.
There was no difference in initial or maintenance immunosuppressive therapy between the two groups. No differences were found between older and younger patients with regard to treatment response. Although we found no statistical differences, older patients had worse renal outcomes. The older adult group had a higher mortality rate, p 0.01. The average time to death was 27 months for patients over 65 years and 34.5 in those who were younger (p 0.71).

Conclusion
No differences were found between older and younger patients with regard to treatment response. However, mortality was higher during follow-up in the group of older patients. Our results suggest that more attention should be paid to older patients with severe renal impairment.
#326 Features of intrarenal hemodynamics in patients with chronic glomerulonephritis on the background of taking anticoagulants
Authors: Abduvakhitova Asalya 
Published: May 2024

Abstract

Background and Aims
Chronic glomerulonephritis (CGN)-glomerular, autoimmune kidney disease, where baseline therapy is clinically proven to be successful. The study evaluates hemodynamic disorders of renal blood flow in patients with CGN on the background of baseline treatment with the inclusion of rivaroxaban.

Method
We researched108 patients CGN against the background of 3-month basic therapy with the inclusion of rivaroxaban (group AC+, 55 patients) and without anticoagulant (group AC-, 53 patients). Initial and after 3 months evaluation in the mode of color Doppler mapping and pulse-wave doppler.

Results
In the course of 3-month therapy, the performance of dopplerography of renal arteries in patients with CGN did not change reliably. But there was a credible and clinically significant increase in the systolic blood flow rate at the level of the Interregional Artery (IA), both compared to the baseline data and towards the end of hospitalization (by 9.27 2.58% p &lt; 0.001 the validity of the difference with the raw data, by 8.60 2.53%, p &lt; 0.01 with the 10th day of therapy), remaining reliably lower than in control group (p &lt; 0.001). The speed at the arc artery (АА) also increased slightly (by 2.46 1.03%, p &lt; 0.05 reliability of the difference with the original data and the end of hospitalization), but although statistical reliability was achieved, the dynamics was clinically insignificant and was less than 2.5%. The resistivity index (RI) at both IA and AA levels did not change reliably.

Conclusion
In CGN patients, intrarenal hemodynamics change with decreased blood flow rates in IA and AA. In the future, against the background of 3-month basic HGH therapy, there was some improvement in blood flow at the IA level but not AA, but no qualitative changes in intrarenal hemodynamics were achieved. The supplementation of long-term anticoagulation therapy with rivaroxaban has increased the effect of therapy on hemodynamic rates, resulting in some improvement in blood flow at both IA and AA levels, but no qualitative improvement has been achieved, possible due to pronounced structural remodeling of kidney vessels in patients with CGN.
#1864 Phosphorilation of SHP-1 switch does not indicate lupus nephritis activity
Authors: Vajgel Gisele , Nascimento Denise Queiroga Do , Junior Braziliano Silva , Oliveira Camila , Castoldi Ângela , Lima Camilla , Souto Fabricio Oliveira , Valente Lucila , Salama Alan , Sandrin-Garcia Paula 
Published: May 2024

Abstract

Background and Aims
Protein tyrosine kinases (PTKs) are enzymes responsible for the phosphorylation of tyrosine residues in lymphocytes. In 2017, Mkaddem et al. suggested that unique PTK signatures in peripheral leukocytes (PBMC) are associated with lupus nephritis (LN) activity [1]. Lymphocytes express two important PTKs, Lyn and Fyn, that modulate inhibitory or activatory signals depending on ligand avidity or phosphorylation status. SHP-1 tyrosine 536 phosphorylation (pSHP1-Y536) by Lyn activates inhibitory signaling and Fyn-dependent phosphorylation of SHP-1 serine 591 (pSHP1-S591) inactivates the phosphatase, enabling activatory immunoreceptor signaling. We hypothesized that active and refractory patients with proliferative LN have a different PTK profile in PBMC, with lower expression of pSHP1-Y536 and greater expression of pSHP1-S591, in comparison with those who have responded to treatment.

Method
In a cohort from the Royal Free Hospital, UCL (London, UK) we performed western blotting of PBMC lysates for SHP1-phospho-S591 and-Y536 from healthy individuals (HC; n = 19), LN patients in remission (n = 11) and with ongoing disease activity (n = 4). Densitometry of bands was carried out and a ratio of S591:Y536 expression was calculated (both normalized to actin). For the flow cytometry analysis, we followed up a Brazilian cohort of LN (n = 24) from Hospital das Clinicas, UFPE (Recife, Brazil). All patients had ongoing active LN with initial renal biopsy (class III, IV or/and V). PBMC samples were collected at 0, 3, 6, 9, 12, 18, and 24 months after biopsy. Isolated PBMC samples were stored at −80°C. PBMC samples were stained with antibodies against pSHP1 S591 and p-SHP1 Y536 and cell viability was checked using zombie red dye. Samples were acquired on the Accuri C6 cytometer (BD) and analyzed using the FLOJO software (BD).

Results
The western blotting relative expression of pSHP-1 S591:Y536 in PBMC was not significantly different when we compared HC with active LN (p = 0.098) and active with remission LN (p = 0.10), Fig. 1. The results obtained by flow cytometry expression ratio of pSHP1-S591:Y536 did not show a significant correlation with the median of proteinuria (Fig. 2), C3, C4, or SLEDAI from time of active kidney biopsy during LN flare throughout induction treatment.

Conclusion
There was no expression pattern of pSHP-1 Y536 and S591 in PBMC of LN patients, regardless of their renal activity or inflammatory status. Therefore, we cannot state those markers as a potential “liquid biopsy” for LN.
#1644 Prognostic significance of hematuria on kidney survival in podocytopathies
Authors: Stefan Gabriel , Simona-Mihaela Cinca , Zugravu Adrian Dorin , Petre Nicoleta , Stancu Simona 
Published: May 2024

Abstract

Background and Aims
Hematuria is common in podocytopathies, but its prognostic impact on kidney survival in these proteinuric diseases is not well-established. Our study examines the prevalence of hematuria at podocytopathy diagnosis and its association with renal survival.

Method
In our retrospective study, we analyzed 236 patients (median age 50 years, 60% male, median eGFR 65.5 mL/min/1.73 m2, median proteinuria 3.9g/g) with biopsy proven podocytopathies—48% membranous nephropathy (MN), 32% minimal change disease (MCD), 20% focal and segmental glomerulosclerosis (FSGS)—diagnosed at a tertiary center from 2010 to 2015.
Hematuria was defined as the presence of 5 or more red blood cells (RBCs) per high-power field in 3 of 3 consecutive centrifuged urine specimens obtained at least 1 week apart.
The follow-up period extended until the onset of end-stage kidney disease (ESKD: start of kidney replacement therapy or renal transplantation), death, or January 2022, with a median duration of 8.5 (95% CI: 8.1, 8.8) years.

Results
In our patient cohort, 31% (n = 73) presented with hematuria, having a median of 120 (IQR: 40-220) red blood cells (RBCs). Those with hematuria more frequently exhibited arterial hypertension (55% vs 36%, p 0.007) and had higher levels of proteinuria (5.3 vs 3.2g/g, p 0.01). However, no significant differences were noted in terms of age (53 vs 48 years, p 0.08), Charlson comorbidity score (2 vs 2, p 0.9), type of podocytopathy (MN 52 vs 47%, MCD 27 vs 34%, FSGS 21 vs 19%, p 0.5), eGFR (62.1 vs 68.8 mL/min, p 0.08), serum albumin levels (3.3 vs 3.4g/dL, p 0.6), total renal chronicity score on histology (0 vs 0, p 0.6), and treatment with ACE inhibitors/angiotensin receptor blockers (43% vs 50%, p 0.4) or immunosuppression (81% vs 74%, p 0.4).
Thirty-two percent of the patients with hematuria reached ESKD versus 9% in the group without hematuria (p 0.001); there were no differences regarding mortality between the two groups.
Mean kidney survival time for the entire cohort was 10.3 (95% CI: 9.9, 10.8) years; renal survival at 1, 3, 5 and 10 years were 97%, 92%, 88% and 82%, respectively. Patients with hematuria at diagnosis had a significant shorter kidney survival time (9.0 (95% CI: 8.0, 10.0) vs 11.0 (95% CI: 10.6, 11.4) years, p 0.001).
In a multivariate Cox proportional hazard model (backward Wald), presence of hematuria at diagnosis (HR 3.64, 95% CI: 1.87, 7.07), lower eGFR (HR 0.96, 95% CI: 0.94, 0.97) and higher total renal chronicity score on histology (HR 1.10, 95% CI: 1.00, 1.22) were independent predictors of reduced kidney survival.

Conclusion
Hematuria is prevalent in the three podocytopathies and independently correlates with poorer kidney survival outcomes. This underscores the possible need for personalized treatment strategies in patients with podocytopathies presenting with hematuria.
#2161 Phosphodiesterase V inhibitor attenuates the fibrotic gene expression of human renal fibroblast derived from IgA nephropathy: an in-vitro study
Authors: Behera Manas Ranjan , Singh Mantabya , Rai Mohit , Kaul Anupma , Prasad Narayan , Bhadauria Dharmandr , Misra Durga Prasanna , Agarwal Vikas 
Published: May 2024

Abstract

Background and Aims
Renal fibrosis (RF) is the final common pathway that determines the progression of many glomerular disease including IgA nephropathy (IgAN). Till date there is no definite therapy available to retard RF. Being the key mediator of fibrosis, TGF-β is being targeted in many studies. Phosphodiesterase V inhibitor (PDE5i) is known to inhibit TGF-β but its role in RF is yet to be established. Hence, in the current in-vitro study we wish to establish the role of PDE5 inhibitor as an inhibitor of TGF-β and hence the RF.

Method
This is a pilot study to evaluate the efficacy of ‘Phosphodiesterase V inhibitor’ on TGFβ1 induced fibrosis on fibroblasts derived from biopsy specimen of IgA nephropathy patients. Renal fibroblasts were cultured from six IgA patients. The fibroblasts cells were treated with PDE5i inhibitor (tadalafil) (at different doses of 1 µm, 5 µm, 10 µm and 15 µm), both before and after stimulation with transforming growth factor beta-1 (TGF-b1) (at doses of 5 ng/ml, 10 ng/ml, 15 ng/ml and 20 ng/ml). Gene expression was studied by real-time polymerase chain reaction (RT-PCR) for messenger ribonucleic acid (mRNA) of pro-fibrotic genes Col1a1, Col1a2, FN1, CTGF, ASMA, TIMP1, and anti-fibrotic MMP2.

Objectives

Results
Our results shows that TGFβ significantly increased the expression of profibrotic gene (Col1a1, Col1a2, ASMA, CTGF, FN and TIMP1) at concentration of 10 ng/ml in the fibroblast cells derived from IgAN patients. Treatment of fibroblast cells with Tadalafil (PDE5 inhibitor) significantly decreased the pro-fibrotic gene mRNA expression (Col1a1, Col1a2, ASMA, CTGF, FN and TIMP1) with increased anti-fibrotic gene expression (MMP2) at the dose of 5 µm and 10 µm concentration in the fibroblast cells (Fig. 1).

Conclusion
This study may provide potential therapeutic target for prevention of renal fibrosis in IgAN patients. Till date PDE5 inhibitors were not used for IgAN. We found that, PDE5 inhibitor reduces the fibrosis in this in vitro study, this drug may be proposed as a potential therapy for IgAN.