bluuebunny/crossref_metadata_2025 huggingface dataset:
P0098CHANGES OF PERICYTE IN AGING KIDNEY
Authors: Kim Hyung Duk , Kim Eun Nim , JIN YONGJIE , Lim Ji Hee , Kim Yaeni , Ban Tae Hyun , Park Cheol Whee , Choi Bum Soon
Published: June 2020

Background and Aims

In aging kidney, oxidative stress and inflammation lead to a decrease in renal function. Recent studies related to the aging process of the kidneys have shown that pericyte is a progenitor cell of myofibroblast, and the relationship between renal fibrosis and pericyte has been reported. In this study, we investigated the pericytes changes in aging kidneys and mechanism of aging-related pericyte changes.

Method

In vivo study, 2, 24-months-old mice and 18-month-old mice treated with pentoxifylline for 6 months were analyzed with western blot. And renal biopsy from KT donors were analyzed. Donors under age 25 were assigned to young group and donors over age 60 to old group.

Results

Changes of pericytes in mice and human renal tissues were consistent with those in the aging model. In the old age group, pericytes were decreased and interstitial fibrosis was increased. Western blot analysis in mice kidney revealed that IL-1β, IL-6 and TNF-α were significantly increased in old age and significantly decreased in pentoxifylline group. Angiopoietin 2 was increased in old age group and decreased in pentoxifylline group.

Conclusion

In aging kidney, pericytes have been shown to exhibit numerical reduction and loss of perivascular location as in the aging mice model. These changes in pericytes are thought to be induced by angiopoietin 2 excretion.
P0101INHIBITION OF TUMOR NECROSIS FACTOR ALPHA ENHANCED ANTIFIBROTIC EFFECT OF EMPAGLIFLOZIN IN AN ANIMAL MODEL WITH RENAL INSULIN RESISTANCE
Authors: Keshawy Mohammed , Mohammed Hoda
Published: June 2020

Background and Aims

Insulin resistance (IR) has emerged as one of the main risk factors for renal fibrosis (RF) that represents a common stage in almost all chronic kidney disease. The present study aims to investigate the inhibitory effect of empagliflozin (EMPA “a sodium-glucose co-transporter 2 inhibitor”) and infliximab [IFX “a tumor necrosis factor-α (TNF-α) antibody”] on RF in rats with induced IR.

Method

IR was induced by adding 10% fructose in drinking water for 20 weeks. Thereafter, fructose-induced IR rats were concurrently treated with EMPA (30 mg/kg), IFX (1 dose 5 mg/kg), or EMPA + IFX for 4 weeks, in addition to IR control group (received 10% fructose in water) and normal control (NC) group.

Results

Rats with IR displayed hyperglycemia, deterioration in kidney functions, glomerulosclerosis, and collagen fiber deposition in renal tissues as compared to NC. This was associated with downregulation of the renal sirtuin 1 (Sirt 1) expression along with higher renal tissue TNF-α and transforming growth factor-β1 (TGF-β1) levels. Both EMPA and IFX significantly modulated the aforementioned fibrotic cytokines, upregulated the renal Sirt 1 expression, and attenuated RF compared to IR control group. Of note, IFX effect was superior to that of EMPA. However, the combination of EMPA and IFX alleviated RF to a greater extent surpassing the monotherapy. This may be attributed to the further upregulation of renal Sirt 1 in addition to the downregulation of fibrotic cytokines.

Conclusion

These findings suggest that the combination of EMPA and IFX offers additional benefits and may represent a promising therapeutic option for RF.
P0102A REVIEW OF RENAL BIOPSIES IN A LARGE UK RENAL CENTRE- A 20 YEAR EXPERIENCE
Authors: Hudson Amy , Sinha Smeeta
Published: June 2020

Background and Aims

Percutaneous renal biopsy is the mainstay of renal pathological diagnosis. Not only does it secure an accurate diagnosis, but also lends itself to guiding the prognosis of a myriad of renal disorders. An important diagnostic modality for nephrologists, they have contributed greatly to the field of nephrology, both in terms of the classification of diseases and assisting in understanding their pathogenesis. Adequacy of the tissue samples of at least ten to fifteen glomeruli is generally preferred. The aim of our retrospective study was to review the renal biopsies done in one large UK renal centre, namely Salford Royal Foundation Trust, over the last twenty years. This Trust covers a catchment area that serves approximately 1.5 million people.

Method

A list of all renal biopsies performed at Salford Royal Foundation Trust between January 2000 to January 2020 was generated by our pathology department. Following this, each individual biopsy report was reviewed. In addition to this, certain information was collated from individual patient records; namely patient demographics, the indication for biopsy, tissue type (native or transplant), histological diagnosis and outcomes. Our centre has an excellent electronic patient record (EPR). This enabled us to analyse full clinical data retrospectively for each case.

Results

Between January 2000 and January 2020 a total of 3555 renal biopsies were performed at Salford Royal Foundation Trust. These biopsies were performed solely by nephrology specialists and supervised trainees, under ultrasound guidance. 177.5 biopsies were performed on average, per year, ranging between 140 – 203.

90% of biopsies were performed on native kidneys, with 10% being performed on transplanted kidneys.

10% of biopsies had normal histology morphologically when reviewed by light microscopy. There diagnoses of these included entities minimal change disease and thin basement membrane disease most commonly.

IgA nephropathy was the most common glomerular pathology identified, in keeping with the wealth of published literature. There were over 525 biopsies done confirming IgAN as the primary pathology.

7% of biopsies had a crescentic glomerular pathology when examined histologically. The main causes included crescentic IgA nephropathy and anca-associated vasculitis.

Conclusion

Kidney biopsies have long been regarded as safe, minimally invasive procedures are of paramount importance to our diagnostic armamentarium. Our data echoes that of already published pathology series, IgAN being the most common glomerular pathology in our series. We further plan to analyse the various conditions and their outcomes in further detail.
P0105THE ROLE OF PROTEOGLYCANS IN GLOMERULAR PHYSIOLOGY AND PATHOPHYSIOLOGY
Authors: Khramova Alina , Ebefors Kerstin , Nyström Jenny
Published: June 2020

Background and Aims

Damage to the filtration barrier in the kidney may result in proteinuria, a hallmark of kidney disease. The glomerular filtration barrier consist of 3 layers: the endothelial cells with their endothelial surface layer (ESL), the glomerular basement membrane and podocytes. The ESL is rich in negatively charged molecules, such as proteoglycans (PGs). The negatively charged molecules restrain the flow of charged molecules, as albumin, over the barrier. Loss of ESL has been shown to lead to proteinuria without damage to the other structures of the filtration barrier. In order to gain further knowledge about the function and composition of the glomerular ESL we eluted the glomerular ESL from rats and analyzed the PG content as well as the effect of loss of the ESL on the function of the glomerular filtration.

Method

The basic principles of ion exchange chromatography were applied in this study. In order to elute highly negatively charged proteoglycans of the ESL, we used 1 M NaCl solution (HS). 1 M mannitol (HO) was included to evaluate osmotic effects. A control fraction was eluted with normal saline solution (0,15 M NaCl) (NS). Solutions were introduced intraarterially to rat kidneys under anesthesia in vivo. Venous effluent was collected and analyzed using proteomics and mass spectrometry. Fractional clearance of albumin was measured as well as GFR. Electron microscopy (EM) was used to investigate changes to the filtration barrier and the thickness of the glomerular ESL. Immunohistochemistry was used to confirm the presence of identified PGs in human tissue.

Results

We identified 15 PGs and PG candidates in ESL as well as hyaluronan. The most abundant PGs were lumican, glypican-1, syndecan-4, perlecan, podocan, decorin, serglycan, agrin and biglycan. In general, PGs were found in in all HS, NS and HO fractions, but in higher yields in the HS samples. EM demonstrated that the glomerular ESL thickness was significantly reduced in HS perfused rats – 28% (p<0.05) compared to rats perfused with NS. Rats perfused with HS also had increased fractional clearance of albumin compared to NS and HO, and a large reduction of GFR 10 minutes after perfusion.

Conclusion

The ESL itself represents a dynamic structure with significant molecular turnover and is formed by PGs, glycosaminoglycans, glycoproteins and soluble proteins. In our study, we identified several PGs in the glomerular endothelial ESL. We show that loss of ESL leads to increased albumin fractional clearance and reduction in GFR after perfusion, strongly suggesting that the ESL is important for preventing proteinuria. Characterizing the composition of the glomerular ESL is therefore of great importance, and can give new possible targets for treatment of proteinuria.
P0106URINE COMPLEMENT FRAGMENTS ARE ASSOCIATED WITH KIDNEY FUNCTION AND DISEASE ETIOLOGY
Authors: He Tianlin , Beige Joachim , Siwy Justyna , Golovko Igor , Pejchinovski Martin , Metzger Jochen , Mullen William , Vlahou Antonia , Mischak Harald
Published: June 2020

Background and Aims

Changes in complement factors have been associated with chronic kidney disease, most prominently in the context of C3 glomerulopathy. Based on these reports, the hypothesis was generated that specific urine complement fragments are associated with kidney disease etiologies, and progression of the disease may be reflected by changes in these proteins or peptides. In this study, we aimed at investigating the occurrence of complement fragments in urine, and their association with kidney function in general and disease etiology in particular.

Methods

Urine samples from patients with kidney disease of different etiologies and control subjects with normal kidney function were investigated using tandem mass spectrometry coupled with capillary electrophoresis and liquid chromatography to identify complement derived peptides based on their amino acid sequence. Subsequently, distribution of these peptides in the different kidney disease etiologies and normal kidney function was investigated via analysis of datasets recorded in the human proteome/peptidome database. All datasets, where eGFR was available and at least one of the complement peptides detected, were included.

Results

Twenty one different urinary peptides derived from complement could be identified. These peptide fragments originated from the complement factors C3, C4A and C4B, and CFB. Further investigation of 4557 datasets recorded in the urine proteome/peptidome database meeting the aforementioned inclusion requirements (eg available eGFR values and with at least one of the complement peptides detected), revealed, for most C3-derived peptides, an inverse, while for the majority of peptides derived from CFB, a positive association with eGFR.

The table lists the detected complement derived peptides, the parental protein (Complement X), rho and p-value of the association with eGFR, and the number of samples (n) where the peptide was detected.

When investigating the urine complement fragments, as a result of disease etiology, disease-specific distribution was detected, indicating a distinct association of complement factors and associated proteases, depending on disease etiology. As an example, the peptide distribution in AKI, IgA-Nephropathy (IgA-N) and vasculitis is shown in the Figure.

Conclusion

Multiple complement-derived peptides are significantly associated with kidney function, and with certain kidney disease etiologies, such as AKI, IgA-N or vasculitis. Proteomic screening of these complement factors may provide a basis, not only for non-invasively assessing kidney disease, but also for an opportunity to develop novel drugs; the latter, via targeting the associated proteases responsible for the release of these complement-derived peptides, in a specific kidney disease manner, in urine.
P0114BENEFITS AND CHALLENGES OF A RENAL BIOPSY REGISTRY AND NETWORK - FCGG EXPERIENCE
Authors: Laurens Wim , De Meester Johan , Sprangers Ben , Van Laecke Steven , Amélie Dendooven , Evelyne Lerut , Vande Walle Johan , An De Vriese , Pipeleers Lissa , Bart Maes , Mark Helbert , Hellemans Rachel , Tom Dejagere
Published: June 2020

Background and Aims

End December 2016, a renal biopsy network in the Flemish region (Belgium) was founded as a collaboration between the renal pathologists and nephrologists. This FCGG network introduced a uniform renal biopsy request form, a well-structured report form of the renal pathology examination and a comprehensive list of renal pathology diagnoses.

Method

Following informed consent [99.5%] and in compliance with GDPR, the registration of the renal biopsies consists of basic categorical renal data, structured renal pathology information and the final clinical renal disease.

Results

In 2017 and 2018, 1385 renal biopsies were registered – 10.5 per million inhabitants per year; in addition, 28 patients had a repeat biopsy in the same time frame (2%). Of the pediatric patients ( age < 18 years; N=92; 6.6%), 23 had IgA nephropathy, 20 a minimal change disease and 15 another type of glomerulonephritis. The biopsy was reported as normal or non-diagnostic in 15 patients (16%) – the majority was clinically considered as glomerulonephritis. The spectrum of the adult population was quite similar across gender and age groups: 56% glomerulonephritis [= IgA nephropathy [19%] + FSGS [8%] + pauci-immune glomerulonephritis [7%] + other GN [22%] ), 10% tubulo-interstitial nephritis, 7% acute tubular necrosis [ATN], 7% diabetes mellitus, and 7% nephroangiosclerosis. Exceptions are pauci-immune glomerulonephritis as the most important renal disease in women aged 65 years and older, and lupus nephritis as the second most important glomerulonephritis in women aged 18-44 years. Only a small percentage of adult renal biopsies yielded no result (7%), clinically interpreted as glomerulonephritis in 50% of the cases.

Conclusion

The FCGG network has provided a more intense collaboration between renal pathologists and nephrologists mainly by standardizing the renal biopsy reading and reporting across all centers. More precise estimates of the prevalent renal diseases were provided for the first time; however, in order to get full information, renal diseases diagnosed by other techniques ( serology, genetic analysis ) should also be collected in the future. Efforts will be done to coordinate the clinical care of renal diseases, particularly the more rare renal diseases, and to offer access to new therapeutic molecules or new schemes, through this super-regional network.
P0126RENAL TRANSPLANT PATIENTS UNDER CALCINEURIN INHIBITOR THERAPY RAPIDLY ACQUIRE AN ABERRANT LYSOSOMAL LESION IN PROXIMAL TUBULAR CELLS
Authors: Vervaet Benjamin , Kojc Nika , Nast Cynthia , Schreurs Gerd , D'Haese Patrick , De Broe Marc
Published: June 2020

Background and Aims

Calcineurin inhibitor therapy has changed the field of (renal) transplantation by considerably prolonging graft survival. Yet, all immunosuppressive calcineurin inhibitors are nephrotoxic that eventually contribute to complete scarring of the renal allograft. In renal biopsy analysis many histopathological features have been considered indicative of CNI nephrotoxicity, i.e. striped fibrosis, vascular hyalinosis, isometric tubular vacuolization, glomerulosclerosis, cellular infiltration and tubular atrophy, however, all are rather aspecific and can be secondary to many other causes. During the course of evaluating the specificity of a recently discovered proximal epithelial lysosomal lesion (i.e. multiple enlarged (>1,2µm) dysmorphic lysosomes containing dispersed electron dense non-membrane bound aggregates) in patients with Chronic Interstitial Nephropathy in Agricultural Communities (CINAC), we observed it to be present in renal transplant patients treated with cyclosporine or tacrolimus. Here, we test the hypothesis whether this lysosomal lesion is acquired during CNI therapy.

Method

A retrospective transmission electron microscopic analysis was performed to evaluate the presence of the typical lysosomal lesion on the following biopsies from renal transplant patients: 20 deceased donor implantation biopsies; 5 living donor implantation biopsies. For another 10 additional deceased donor renal allograft recipients, we evaluated implantation as well as protocol biopsies taken after 6 and 12 months of CNI treatment that started immediately after transplantation. Also included were 24 indication biopsies of CNI treated renal transplants.

Results

Of the total set of implantation biopsies (n=35), 2 (6%) were positive for the aberrant lysosomal phenotype on EM, whereas in the protocol and indication biopsies prevalence of the lesion was considerably higher ranging between 56% (protocol) and 80% (indication) of cases.

Conclusion

CNI therapy is associated with the fairly rapid appearance of a particular proximal tubular lysosomal phenotype observable on EM, that was not (or rarely) present at implantation. Whether this lesion is related to CNI toxicity and indicative for the outcome for the graft and/or patient survival after renal transplantation has to be investigated in a prospective trial.
P0136COMPARISON OF SECONDARY IGA NEPHROPATHY OF ANKYLOSING SPONDYLITIS AND PRIMARY IGA NEPHROPATHY IN CLINICAL AND PATHOLOGICAL FEATURES
Authors: Xue Qin , Zhang Guang Li , Tian Zebo
Published: June 2020

Background and Aims

Renal involvement is one of the most common extra-articular complications caused by ankylosing spondylitis (AS). The main pathological manifestation is secondary IgA nephropathy(SIgAN) in Chinese AS patients. The difference between SIgAN and primary IgAN (PIgAN) remains unclear due to the lack of cases. Therefore, the aim of this retrospective study was to compare the clinical and pathological features of SIgAN of AS (SIgAN-AS) and PIgAN, to detect the pathogenesis of SIgAN

Method

Clinical characteristics and pathological data were collected in patients who were diagnosed with IgAN by renal biopsy in our hospital from Jan 2008 to Oct 2018. Patients with SIgAN-AS were recruited by the ratio 1:5 of patients with primary IgAN as the control group in the study. Fifteen patients with SIgAN-AS and Seventy-five patients with PIgAN were enrolled in this retrospective study.

Results

There were 15 cases in AS group, including 13 male and 2 female. The cohort of 75 patients with PIgAN included 34 male and 41 female. There were more males in AS group 13/15 (86.7%) vs 37/75(49.3%) ,P < 0.05. Compared with PIgAN patients, SIgAN-AS patients had higher incidences of hematuria( 13/15(86.7%)vs 44/75 (58.7%) , P < 0.05), lower levels of 24-hour urinary protein(0.85±0.68 vs 1.57±1.54g, P < 0.05), but higher levels of eGFR (CKD-MDRD formula) (117.60±37.33 vs 85.35±31.36, P < 0.05),eGFR (CKD-EPI formula) (128.01±41.58 vs 92.75±36.09, P < 0.05), Albumin (44.67±3.48 vs 41.09±7.07 g/L, P < 0.05) ESR (43.20 ±33.94 vs 18.79±16.26mm/h, P < 0.001) , and CRP (21.19±30.61 vs 2.11±4.58mg/L, P < 0.001) . From the perspective of renal pathology of PIgAN, SIgA-AS patients had fewer incidences of renal tubular atrophy / interstitial fibrosis of nephropathy (P <0.05). The immunohistostaining analysis showed higher incidences of dominant deposits of single IgA in mesangial cell area (P < 0.05).

Conclusion

Patients with SIgAN-AS is more common in male and display a milder progression than those with primary IgAN. Majority of the SIgAN-AS can be improved with early intervention.
P0150EFFECT OF SEROTONIN REUPTAKE INHIBITORS (SSRIS) AND SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS) ON BLOOD PRESSURE VARIABILITY USING 24 HOURS AMBULATORY BLOOD PRESSURE MONITORING
Authors: Aslam Nabeel , Memon Sobia , Wadei Hani , Niazi Shehzad
Published: June 2020

Background and Aims

Hypertension (HTN) and psychiatric disorders frequently co-exist in general population. Serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine re-uptake inhibitors (SNRIs) affect serotonin and norepinephrine and may lead to variation in blood pressure (BP). There is paucity of data on blood pressure variations using 24 hours ambulatory blood pressure monitoring (ABPM) with the use of SSRIs/NSRIs.

Method

Subjects who underwent psychiatric evaluation and ABPM within six month of each other between 1/1/2012 to 12/31/2016 at Mayo Clinic Florida were identified using billing data. Demographics, co-morbidities, medications, ABPM, and laboratory results were retrospectively collected from medical records. Subjects were divided into groups – subjects with no psychiatric diagnosis and no psychiatric medicine (Group 1) and subjects with psychiatric diagnosis and on SSRIs/NSRIs (Group 2). BP systolic and diastolic levels (day time, night time) were compared between groups controlling for age, sex, race, presence or absence of HTN, diabetes mellitus (DM) and smoking. Single and multivariable linear regression models were used to analyze group differences.

Results

Total of 367 subjects met inclusion criteria – Group 1=135; Group 2=232. The subjects in group 2 were older (median age 57 yrs vs 47 yrs p<0.001), white (69.8 vs 60% p=0.002), smokers (15.9 vs 3.0% p<0.001), history of HTN (62.5 vs 9.6%), and DM (21.1% vs 0%). ABPM showed that subjects in group 2 had higher median daytime systolic BP (131 vs 124), higher median night time systolic BP (120 vs 110), and higher median night time diastolic BP (68 vs 63). Multivariable linear regression controlling for age, sex, race, presence or absence of HTN, DM, and smoking showed that use of SSRIs/NSRIs (group 2) was significantly associated with higher night time systolic BP (8.36 mm; 95% CI 4.2, 12.5; p <0.0001) and higher night time diastolic BP (4.6 mm, 95% CI 1.9, 7.29, p=0.001). On subgroup analysis comparing subjects with use of SSRIs vs NSRIs, there was no statistically significant difference in the daytime or night time systolic or diastolic BP.

Conclusion

Use of SSRIs and NSRIs are associated with higher nocturnal systolic and diastolic BP, which can potentially increase the risk of adverse cardiovascular outcome in this population. Higher nocturnal BP may be due to ongoing sympathetic activation during sleep with serotonin and norepinephrine with the use of SRRIs and NSRI. Further well designed prospective studies using ABPM are needed to determine the risk of nocturnal hypertension with the use of SSRIs/NSRIs that could have potential adverse cardiovascular outcome.
P0165HYPERTENSION IN OVERWEIGHT AND OBESE CHILDREN: IMPACT ASSESMENT OF ABPM PARAMETERS
Authors: Apuzzo Diletta , Annicchiarico Petruzzelli Luigi , Ascione Serena , Corcione Adele , Pedoto Deianira , Barra Giuseppina , Rocco Maria Chiara , Pecoraro Carmine , Malgieri Gabriele
Published: June 2020

Background and Aims

We describe the relationship between overweight and obesity and Hypertension on ABPM.

Method

We conducted a cross-sectional study using a database of patients aged 6-16 years, who had undergone 24h ABPM from December 2002 through December 2016. ABPM were performed using the validated device Spacelab 90217. Were evaluated the 24h MAP, daytime MAP, nocturnal MAP, systolic and diastolic load, MAP Systolic and Diastolic. Subjects were grouped by BMI Z-score into overweight (>1<2), obese (BMI Z-score >2<3) and severe obese (BMI Z-score >3). A total of 1016 patients were enrolled and recorded n.1210 ABPMs. Obese pts were 202 (19.8%); 126 M;76F;median age 10,2 y. Overweight childrens were 97 (11.9%);52 M;45F;median age 8,4y.

Results

Among overweight childrens (BMI Z-Score >1<2): 12 (12.3%) had hypertension, 22 (22.6%) pre-hypertension, 15 (15.4%) MH; non dipping pattern was recorded in 26 (52%). 48 were normotensive. Among obese childrens, 122 had hypertension (60.3%): 24 pts had Masked Hypertension (19.6%); 72 (59.0%) had severe ambulatory hypertension with BMI z-score >3 (mean 3.8) ,and in this category all pts were both systolic and diastolic non dipping. 32 (64%) obese with BMI z-score >2, <3 were non-dipping. Diastolic load was significantly higher (p>0,0001) in severe obese. 28 pts had ambulatory prehypertension (13.8%), 11 pts had White Coat Hypertension (4.9%).41 pts had normotension (20.2%).

Conclusion

The severity of ambulatory hypertension increased with increased BMI Z-score. The non-dipping status is associated, not only with higher BMI Z-score, but was present in overweight and obese with BMI z-score >2<3 also. ABPM is an effective tool that should become routine in all obese patient, but also in overweight childrens, which may lead to better treatments and prevention methods.
P0170ETHANOL EXTRACT OF LIRIODENDRON CHINENSE(HEMSL.) SARG BARKS ALLEVIATES HYPERURICEMIC NEPHROPATHY VIA MEDIATING RENAL FIBROSIS AND INFLAMMATION
Authors: Pan Jing , Ma Liang , Fu Ping
Published: June 2020

Background and Aims

The barks of Liriodendron Chinense (Hemsl.) Sarg is used in folk for expelling “wind and dampness”, alleviating rheumatic arthralgia in traditional Chinese medicine. The aim of the study was to evaluate the protective effect of ethanol extract of the barks of Liriodendron Chinense (Hemsl.) Sarg (EELC) in a mouse model of hyperuricemic nephropathy (HN) and the mechanisms involved.

Method

EELC at a respective dose of 250 mg/kg/d or 500 mg/kg/d were orally administered to HN mice induced by a mixture of adenine (160 mg/kg/d)/potassium oxonate (2.4 g/kg/d) for 21 days. At the end of the treatment, serum uric acid, kidney functions (serum creatinine, BUN and urine microalbumin), 24-h urine uric acid excretion, as well as kidney pathological changes were investigated by biochemical assay, histopathological score, immunofluorescence and histochemistry, RT-PCR, and western blotting analysis.

Results

Oral administration of EELC to HN mice lowered serum uric acid, improved renal functions and attenuated renal fibrosis, especially the high-dose of EELC. EELC treatment also inhibited the activation of NF-κB, ASK1/JNK/c-Jun, JAK2/STAT3 signaling pathways and reduced the release of pro-inflammatory cytokine TNF-α in the kidneys of HN mice. Furthermore, EELC remarkably increased urine uric acid excretion of HN mice, which may be achieved by the upregulation of organic anion transporter 1 (OAT1), OAT3 and ATP-binding cassette subfamily G member 2 (ABCG2) proteins.

Conclusion

EELC alleviated the progression of HN by suppressing the activation of NF-κB, ASK1/JNK/c-Jun and JAK2/STAT3 signaling pathway, reducing the infiltration of inflammatory factors and uric acid accumulation in the kidney.

Figure

Date are represented as the mean ± SD. *p<0.05,**p<0.01,***p<0.001, ****p<0.0001 vs. control, §p <0.05, §§p<0.01, §§§p<0.001,§§§§p<0.0001 vs. model.
P0172ARE FREQUENT STONE REMOVAL PROCEDURES IN PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 3 (PH 3) RELATED TO DECLINE IN KIDNEY FUNCTION?
Authors: Hoppe Bernd , Martin Higueras Cristina , Beck Bodo B , Zaniew Marcin , Sikora Przemyslaw
Published: June 2020

Background and Aims

PHIII is seen as the less problematic type of autosomal recessive inherited PH. This group of disorders in glyoxylate metabolism is clinically characterized by recurrent urolithiasis and/or progressive nephrocalcinosis, and, in type I and II, end-stage renal failure. The cause of PHIII was identified only in 2010 and unlike in PHI/II a remarkable low prevalence of symptomatic adults was observed, hence long-term clinical data are scarce. This phenomenon is commonly attributed to reduced penetrance of causative hydroxy-oxo-glutarate aldolase 1 gene (HOGA1) variants and a still unexplained tendency for clinical remission with age. Most PHIII patients present in early childhood with recurrent urolithiasis and undergo (repeated) stone removal procedures. We now hypothesized that repeated stone removal procedures may be associated with decline in kidney function.

Method

We retrospectively analyzed clinical and laboratory data of 41 genetically confirmed PHIII patients (0.5-29.3 years of age, with (20 different) biallelic mutations in the HOGA1 gene). Period of follow-up ranged from just diagnosed to 22 years.

Results

Recurrent urolithiasis was most prominently found in the first 3 years of life (>25% of patients). Not all patients experienced clinical remission, 3/6 patients > 20 years of age have ongoing kidney stone development. In addition, patients presented with nephrocalcinosis and/or urolithiasis. A high amount of stone removal procedures during the first years, but also later in life was observed. Urinary oxalate excretion is significantly elevated, and within the range of PHI/II. A decline in kidney function was observed, which is related to a decreased clearance of oxalate (figure). Two patients each post multiple stone removal procedures had CKD stages 2 or 3. Seven further patients had CKD stage 2, which was not related to stone removal.

Conclusion

PHIII is said to be the most favorable PH type, but early diagnosis is mandatory to treat the patients adequately and to avoid repeated stone removal procedures, which may have an influence on decline in kidney function. This decline may also be related to hyperoxaluria per se, as reported for PHI and II.
P0173CHRONIC KIDNEY DISEASE IN PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 3 (PH 3) - A LITERATURE META-ANALYSIS
Authors: Hoppe Bernd , Martin Higueras Cristina
Published: June 2020

Background and Aims

Primary Hyperoxaluria type 3 (PH3) is considered the most benign phenotype of all forms of primary hyperoxaluria. Being it typical that patients with PH type 1 and 2 develop chronic kidney disease (CKD) or end-stage renal disease (ESRD), it appears to be more or less uncommon that patients with PH3 are on risk of CKD and even do not develop ESRD. We now aimed to determine the number of PH3 patients reported to have any kind of CKD.

Method

We performed a literature meta-analysis, searching in PubMed with the following keywords: primary hyperoxaluria, PH, primary hyperoxaluria type III, PH III or PH3.

Results

We found 154 patients in 18 relevant papers published between 2010-2019. The number of patients reported per paper ranged from 1-2 up to 38 patients. Age of diagnosis/disease onset ranged from 1 month to 48 years of life. Most of the patients suffered recurrent urolithiasis, most often during the first years of life, but recurrent kidney stone episodes were also found later in life. In 77 patients no adequate information was provided with regard to renal function. In 14 patients it was only mentioned that they did not have renal failure at time of reporting. Five patients were said to be in stable kidney function without providing eGFR or serum creatinine levels. In 62 patients we were able to assess kidney function at time of paper and only in 41 patients (27%) eGFR values were available (18-232 ml/min/1.73m2). Only one patient in ESRD was reported, however the clear reason for ESRD is not provided in the reference. One patient with CKD stage 4-5 was found with an eGFR of 18 ml/min/ 1.73m2, after heminephrectomy was performed due to renal carcinoma. He was diagnosed at age 78 but has had recurrent kidney stones over a period of 30 years. Other three patients had stage 2-3 kidney disease (eGFR 53-61.8 ml/min/1.73m2). CKD stages 1-2 were found in 17 patients (eGFR from 77-104 ml/min/1.73m2). In six patients follow-up measures were available, as their data were included in two papers (4 years apart from each other). Here, in one patient eGFR significantly declined from 134 to 68.1 ml/min/1.73m2, while in the other 5 it remained stable over time.

Conclusion

Based on this non-comprehensive dataset, the majority of PH3 patients remain in stable kidney function over time. However, there is a massive bias in the data published, as data on kidney function is mostly not adequately reported. Nevertheless, CKD was observed in 13.7% of PH3 patients, and even one patient with ESRD was described. Also, one PH3 patient had died at age 4 months, but because of respiratory failure and not because of PH. Thus, as true long-term follow-up data is still missing, we nevertheless suspect PH3 not being as benign as currently being reported.
P0174NEPHROPROTECTIVE ACTIVITY OF GOSSYPETIN THROUGH INHIBITORY EFFECT ON XANTHINE OXIDASE, NUCLEAR FACTOR KAPPA B (NF-KB) AND SOLUBLE EPOXIDE HYDROLASE (SEH): IN-VITRO AND IN-SILICO EXPERIMENT
Authors: Patel Dinesh Kumar , Patel Kanika
Published: June 2020

Background and Aims

Oxidative stress and inflammation is the major contributor of kidney injury and the drugs which have antioxidant and anti-inflammatory activity could protect kidney against renal damage. Mechanisms involved in renal failure include oxidative stress, inflammation and apoptosis which lead myoglobinemia, myoglobinuria and cast formation. Inflammatory mediators such as IL-1, ICAM-1 and TNFα also play important role in renal failure. Excess production of uric acid can cause serious consequence in hyperuricemia and xanthine oxidase (XO) catalyzes the oxidation of xanthine to uric acid. Protective effects of gossypetin in the management of kidney injury and related disorders have been investigated in the present work through inhibitory potential of gossypetin on nuclear factor kappa B (NF-κB), soluble epoxide hydrolase (sEH) and XO.

Method

Present work described the medicinal importance of gossypetin with their beneficial effect on kidney disorder. In-silico molecular docking and dynamic experiments were carried out with gossypetin against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH). Further docking was also performed to investigate how gossypetin and the active site of XO fit together.

Results

From the analysis of the available data’s in the present work, it was found that gossypetin have protective effect against nephrotoxicity. Gossypetin also showed potent anti-inflammatory activity in kidney mesangial cells which further support application of natural compounds on nephritis treatment. Importance of gossypetin for preventing renal damage has been also emphasized due to its antioxidants potential. In-silico studies showed that, gossypetin exhibited a higher docking score against NF-κB and sEH. Docking studies revealed gossypetin surrounds the active sites of XO and reduces conversion of xanthine to uric acid.

Conclusion

Study revealed their antioxidant, anti-mutagenic, anti-atherosclerotic, anti-microbial and cytoprotective properties. The protective effect of gossypetin in kidney could be due to its antioxidant and anti-inﬂammatory activity through inhibition of NF-κB and sEH upregulation.
P0175DETERMINANTS OF RENAL PAPILLARY APPEARANCE IN RENAL STONE FORMERS: AN IN-DEPTH EXAMINATION
Authors: Bargagli Matteo , De Leonardis Rossella , Ragonese Mauro , Totaro Angelo , Pinto Francesco , Recupero Salvatore , Bassi PierFrancesco , Gambaro Giovanni , Ferraro Pietro Manuel
Published: June 2020

Background and Aims

Nephrolithiasis is a medical condition characterized by high prevalence among the general population both in Europe and in the U.S. and it is responsible for high costs reaching up to $10 billion per year. It is associated with specific comorbidities such as obesity, arterial hypertension, diabetes mellitus, metabolic syndrome and chronic kidney disease.

Kidney stones development is believed to start either from Randall’s plaques or from stone plugs. Both these lesions can be seen on renal papillary surfaces, but what promotes the formation of plaques and plugs is not entirely understood.

The aim of this study is to investigate the association between the urinary metabolic milieu and a published endoscopic papillary evaluation score (PPLA). We also evaluated the correlation of PPLA score with kidney stone recurrence during follow-up.

Method

We prospectively enrolled 31 stone forming patients who undergone retrograde intrarenal surgery procedures. Visual inspection of the accessible renal papillae was performed in order to calculate the PPLA score based on the appearance of ductal plugging, surface pitting, loss of papillary contour and Randall’s plaque extension.

Demographic information, blood samples, 24h urine collections and kidney stone events during follow-up were collected. Stone composition was analyzed using infrared-spectroscopy. Relative urinary supersaturations (RSS) for calcium oxalate (CaOx), calcium phosphate (CaPi) and uric acid (UA) were calculated using the Equil2 software. PPLA score > 3 was defined as high.

Results

Median follow-up period was 11 (min/max 5, 34) months. PPLA score was inversely correlated with BMI (rho = −0.39, p = 0.035) and history of recurrent kidney stones (median PPLA 5.0 vs 2.5, p = 0.029), these results were confirmed when PPLA was considered as a categorical variable (median BMI 27 vs 24, recurrent stone disease 12 vs 62%, p= 0.006). Furthermore, high PPLA score was associated with lower odds of new kidney stone events during follow-up (OR 0.154, 95% confidence interval 0.024, 0.998, p = 0.05). No significant correlations were found between PPLA score, stone composition, blood parameters, 24h urine solute excretions and RSS for CaOx, CaPi and UA.

Conclusion

Different papillary abnormalities seem to be linked to specific mechanisms of stone formation. Although data regarding PPLA score are inconsistent, it may be a valid asset for both medical and surgical management of nephrolithiasis. Larger, long-term prospective clinical studies need to be conducted to assess the validity of PPLA score system in evaluating risk of stone recurrence.
P0177PREVALENCE AND RISK FACTORS OF HYPERURICEMIA IN THE BAI ETHNIC GROUP IN SOUTHWESTERN CHINA
Authors: GAO Chenni , DUAN Yuhua , JIA Liangqin , ZHANG Wen , REN Hong , XIE Jingyuan , CHEN Xiaonong
Published: June 2020

Background and Aims

The Bai ethnic group is one of the officially recognized minorities in the People's Republic of China, with a total population of 1.93 million. More than 80% of the Bai ethnic group live in Dali Bai Autonomous Prefecture in Yunnan Province. Because of their dietary habit and chronic exposure to high altitude, hyperuricemia is not rare among the Bai ethnic group. Hyperuricemia is not only related to the presence of hypertension, obesity and dyslipidemia, but also increases the risks of stroke, heart disease and chronic kidney disease. But the prevalence of hyperuricemia in the Bai ethnic group remains unclear.

Method

We collected the demographic information as well as laboratory test results of 1393 Bai ethnic people undergoing medical examination during Jan 2019 to Dec 2019 in the People's Hospital of Jianchuan County, Yunnan Province (average altitude 2300m). Written informed consent was obtained from all the participants. Hyperuricemia is defined as serum uric acid level superior to 360 μmol/L for female and 420 μmol/L for male. We investigated the prevalence of hyperuricemia and its risk factors in the Bai ethnic group in southwestern China.

Results

Of the 1393 participants enrolled in the study, the prevalence of hyperuricemia was 24.8%, and the prevalence was significantly higher in male gender (33.2% in men vs. 11.0% in women, P<0.001). The prevalence of hyperuricemia increased from 19.2% among participants aged 30-40 years to 30.1% among participants aged 50 years and older (Fig 1). Also, the prevalence of hyperuricemia elevated from 17.2% among participants with normal body mass index (BMI) to 35.5% among those who were overweighed or obese (Fig 2). Interestingly, we found a positive correlation between hemoglobin level and serum uric acid (β=2.19, P<0.01). Logistic regression analysis revealed main risk factors for hyperuricemia in the Bai ethnic group included age, sex, BMI, systolic blood pressure (SBP) and hemoglobin level.

Conclusion

Hyperuricemia is common in the Bai ethnic group. Its prevalence differs in different sex, age and BMI groups. Furthermore, polycythemia secondary to chronic exposure to high altitude may also contribute to the hyperuricemia.
P0183THE USE OF PCSK9 INHIBITORS COULD REDUCE PROTEINURIA IN CHRONIC KIDNEY DISEASE PATIENTS
Authors: Muñoz Ramos Patricia , Gil Giraldo Leydy Yohana , Reque Javier , Quiroga Borja , Alvarez Chiva Vicente
Published: June 2020

Background and Aims

Chronic kidney disease (CKD) is a cardiovascular risk factor per sé and enhances the risk of cardiovascular events. Dyslipidemia is one of the most studied risk factors and current guidelines recommend the universal treatment in CKD patients (not in dialysis) irrespective of low density lipoprotein (LDL) cholesterol level. However, the latest European Cardiology guidelines recommend monitoring LDL cholesterol to achieve levels lower than 70 mg/dl in CKD stage 3 and lower than 55 mg/dl in stages 4 and 5. Proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) have opened a new era leading greater reduction of LDL cholesterol and subsequently cardiovascular events but real-life data is not available in CKD patients. The aim of the present study is analysing the evolution of renal function and proteinuria in a cohort of patients with PCSK9i.

Method

This is a retrospective study that included all the patients treated with PCSK9i in our centre. Inclusion criteria were the presence of CKD and dyslipidemia with indication of the use of PCSK9i (not reaching LDL target with maximum tolerated statin dose or intolerance for the use of statins). At baseline, epidemiological data and comorbidities were collected, as well as renal function using glomerular filtration rate (GFR) estimation with CKD-EPI equation, proteinuria (mg/g of creatinine) and lipid profile. During a one-year follow up, renal function, proteinuria, lipid profile and adverse events were collected and analysed.

Results: . Forty-one patients were included with a mean age of 70±10 years and 26 men (62%). Thirty-four patients (83%) had hypertension, 11 (27%) were diabetic, 19 (44%) had coronary disease, 8 (20%) history of heart failure, 3 (7%) peripheral vascular disease and 6 (15%) history of stroke. Regarding renal function, at baseline mean of creatinine was 1.3±0.5 mg/dl, GFR 54±19 ml/min/1.73m2 and proteinuria 456±215 mg/g. Lipid profile at baseline demonstrated an LDL cholesterol value of 163±58 mg/dl, triglycerides of 255±389 mg/dl and high density lipoprotein (HDL) of 53±14mg/dl.

During follow up, total cholesterol, LDL-cholesterol and triglycerides improved significantly (p<0.001 for all in comparison to baseline values). GFR remained stable during the first year of follow up (CKD-EPI at 1 year 52±20 ml/min/1.73m2). Proteinuria improved at first month (235±71 mg/g), achieving stability at 3 months (124±44 mg/g), 6 months (176±94 mg/g) and 1 year (163±83 mg/g) (p for trend 0.02) (figure 1). No adverse events were registered during follow up, and two patients required hospitalization due to cardiovascular events.

Conclusion

The treatment of dyslipidemia with PCSK9i could decrease proteinuria in CKD patients via controlling lipoid nephrotoxicity. Clinical trials are needed to further investigate this effect.
P0205SYMPTOM BURDEN IN AUSTRALIAN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE AND END-STAGE KIDNEY DISEASE RECEIVING RENAL SUPPORTIVE CARE: A SINGLE CENTRE COHORT STUDY
Authors: Chen Jenny , Ilic Narelle , Mitchell Holly
Published: June 2020

Background and Aims

Renal supportive care (RSC) is a novel multidisciplinary patient-centred model of care that focuses on symptom management and quality of life improvement in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD), including conservative care. Despite an increased interest in embedding RSC into routine nephrology practice, there is limited literature on the effects of symptom improvement in patients attending RSC services. We aimed to examine symptom improvement and symptom progression in patients receiving renal supportive care.

Method

Using Integrated Palliative care Outcome Scale Renal (IPOS-renal) scores collected during routine RSC clinics, we analysed the changes in individual IPOS-renal items and summative scores for symptoms associated with chronic kidney disease, stratified by time from the initial clinic visit (0-6 months, 6-12 months, and >12 months), in all patients attending our RSC service in a tertiary hospital between November 2015 and July 2019.

Results

Of 245 patients referred to our RSC service, 61 patients completed two or more IPOS-renal surveys. At initial visit, majority of the patients were reviewed at hospital outpatient clinic (n=42, 71%), followed by dialysis (n=8, 13%), home visit (n=6, 10%), and inpatient ward (n=4, 7%). The median (IQR) eGFR was 13 (7-16) ml/min/1.73m2 and median Karnofsky score was 70 (60-80). Weakness (n=59, 97%) and poor mobility (n=52, 85%) were the most common initial complaints. For all reported symptoms, dyspnea improved the most for all three time periods (summative IPOS score changes of 28, 17, and 8 points for 0-6, 6-12, >12 months, respectively). Poor mobility was the only symptom that continued to deteriorate between 0-6 months despite attending renal supportive care (without a physiotherapist). For asymptomatic patients, more than half of the symptoms remained quiescent after attending RSC service for more than 12 months. Among newly developed symptoms, nausea, dyspnea, and drowsiness were most common between 0-6 months. In contrast, pruritus, dry mouth, and constipation were the most common complaints after 12 months.

Conclusion

RSC interventions provided symptom improvement in patients with advanced CKD and ESKD, but poor mobility remained a concern in this population. Incorporating physiotherapy to RSC may further improve symptom management.
P0208DIFFERENTIAL ADAPTATION OF RENAL FUNCTION IN TWO TYPES OF INTENSE PHYSICAL EXERCISE
Authors: Coca Armando , Gonzalez Pablo , Rollan Maria Jesus , Toribio Beatriz , Marcos Hortensia , Fidalgo Veronica , Lorenzo Arturo , Andres Melchor , Acosta-Ochoa Isabel , Mendiluce Alicia
Published: June 2020

Background and Aims

Marathon running induces AKI even in adequately prepared and healthy athletes. Heat stress, maintained during more than 2h, has been proposed as one of the leading causes of AKI in marathons runners. Other possible explanations of AKI in this setting could be associated with a reduction of blood supply to the kidneys during the exercise, inadequate hydration or actual structural damage due to microtraumatisms. However, the effect of vigorous exercise of shorter duration on renal function has not been previously described although most risk factors described could also affect kidney function in this type of physical activity.

Method

40 volunteer healthy athletes were enrolled in this study. Subjects participated in two physical tests (10km running, 1.5km swimming) which were separated by at least two weeks from each other. These tests were chosen because of their similar oxygen consumption rate and metabolic load. Vitals, blood and urine samples were collected immediately before and after each test. Informed consent was obtained from all participants. The project was funded by Consejería de Sanidad, Junta de Castilla y León (GRS1732/A/18).

Results

Athletes ranged from 23 to 53 years old. 35% were female. A comparison of hemodynamic and analytical parameters is summarized in Table 1. Running induced a significantly higher rise of serum creatinine and inflammatory markers compared to swimming. Additionally, running caused an increment of serum phosphorus and uric acid levels. Both types of exercise caused a mild increase of urinary albumin/creatinine ratio.

Conclusion

Compared to swimming, running was associated with a greater rise of serum creatinine, possibly linked to a higher degree of acute inflammation and blood flow redistribution to the muscles. The rise of serum uric acid levels may be associated with increased metabolism and reduced elimination of this molecule while running.