bluuebunny/crossref_metadata_2025 huggingface dataset:
P0449SERUM PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) IN NON-DIABETIC ASIANS WITH NEPHROTIC SYNDROME
Authors: Lim Cynthia , Mok Irene , Tan Hui Zhuan , Teng Esther W L , Chue Xiu Ping , Ang Wei Mian , Chin Yok Mooi , Foo Marjorie , Choo Jason
Published: June 2020

Background and Aims

Nephrotic syndrome is associated with hypercholesterolemia, while its treatment, often involving high-dose glucocorticosteroids, may cause hyperglycemia. Proprotein convertase subtilisin /kexin type 9 (PCSK9) regulates plasma cholesterol and is associated with post-transplant diabetes. Although a potential therapeutic target in nephrotic syndrome, the relationships between PCSK9 and lipid parameters are not well established. We aimed to characterize serum PCSK9 and metabolic parameters among individuals with nephrotic syndrome.

Method

Single-center prospective cohort study of non-diabetic adults newly-diagnosed with nephrotic syndrome and subsequently treated with immunosuppressant. Fasting serum PCSK9 was measured using ELISA at diagnosis. Clinical history, blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) and biochemistry (fasting glucose and lipid, HbA1c and fasting serum PCSK9) were obtained at diagnosis and at 3 months during immunosuppression therapy. Spearman’s correlation was used to evaluate for associations between PCSK9 and glycemic and lipid parameters.

Results

Among 15 adults with nephrotic syndrome, the majority was female (60%) and Chinese (80%). Median age was 40 (IQR 26, 51) years. The most frequent diagnoses were minimal change disease or focal segmental nephrosclerosis (n=7) and lupus nephritis (n=5); the minority had IgA nephropathy, membranous nephropathy or vasculitis. At diagnosis, median eGFR was 97.9 (59.5, 120.9) ml/min/1.73 m2, UPCR 7.6 (6.1, 10.4) g/g, LDL-cholesterol 4.6 (3.1, 6.7) mmol/L and fasting serum PCSK9 317.6 (276.8, 470.1) ng/ml. PCSK9 correlated positively with hypertriglyceridemia (r=0.55, p=0.03) at baseline.

Most patients (n=14, 93%) were treated with prednisolone (monotherapy or in combination with other immunosuppressant) and 1 received tacrolimus monotherapy. At 3 months, the majority (n= 11, 73%) had achieved clinical remission.

Fasting serum PCSK9 was higher at 3 months [median 430.6 (283.1, 496.0) ng/ml] compared to baseline, although the difference was not statistically significant. At 3 months, PCSK9 correlated positively with age (r=0.58, p=0.03), LDL-cholesterol (r=0.90, p=0.04) and change in BMI (r=0.72, p=0.01).

Conclusion

PCSK9 is associated with metabolic parameters at diagnosis and during the treatment course in patients with nephrotic syndrome treated with immunosuppressant.
P0452GLYCOSURIA IN MEMBRANOUS NEPHROPATHY: AN UNDERESTIMATED MARKER?
Authors: Ormonde Carolina , Laranjinha Ivo , Gaspar Augusta , Gonçalves Margarida , Gil Célia , Dickson Jorge , Machado Domingos
Published: June 2020

Background and Aims

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. Some studies have suggested that glycosuria is present in the most severe cases of MN and this finding may be associated with tubular injury caused by the overload of filtered proteins. The aim of this study was to evaluate the association between glycosuria in MN and severity and prognosis of the disease.

Method

We conducted a 36-month retrospective cohort study with all patients diagnosed in the last 10 years in our centre with primary MN confirmed by renal biopsy. Data collection was made from patients’ charts. Patients were divided in two groups according to their glycosuric status at the diagnosis. Exclusion criteria: patients with diabetes and glucose intolerance, use of SGLT2 inhibitors, transplant kidney patients and secondary MN.

Results

We studied 27 patients with primary MN. Four patients (14.8%) presented glycosuria at the time of diagnosis. Glycosuric and non-glycosuric groups had comparable demographic data. We found that glycosuric patients had higher baseline albuminuria (10.7±8.6 vs 4.6±4.1 g/g, p=0.029) and lower estimated glomerular filtration rate (eGFR) (39.2±24.6 vs 75.2±30.7 ml/min/1.73m2, p=0.037). We also found that patients with glycosuria had higher interstitial fibrosis and tubular atrophy (IFTA) (33.8%±21.4 vs 10.7%±17.1, p=0.035) but no differences in the percentage of glomerular sclerosis. There were no differences between groups in serum albumin, haemoglobin or therapy. At the end of the follow-up period there was no difference in eGFR decline rate (ml/min/year), 3-year eGFR, 3-year albuminuria and 3-year chronic kidney disease stage 5D incidence.

Conclusion

Prevalence of glycosuria in primary MN is approximately 15%. Its presence at the time of diagnosis was associated with more severe clinical and histological markers: lower eGFR, higher albuminuria and higher IFTA. However, we did not find association between glycosuric status at diagnosis and disease progression. Prospective, bigger and longer studies are needed to evaluate these questions.
P0457MALE LUPUS NEPHRITES: WHAT ABOUT RISK FACTORS FOR RENAL FAILURE ? EXPERIENCE OF ONE DEPARTMENT
Authors: Melek Kharroubi , Trabelsi Raja , Ounissi Mondher , Chargui Soumaya , Jerbi Mouna , Gaid Hanen , Hedri Hafedh , Harzallah Amel , Ben abdallah Taib , Goucha Rim
Published: June 2020

Background and Aims

The occurrence of renal involvement during the clinical course of systemic lupus erythematous (SLE) is generally considered to be the most important factor influencing the prognosis in terms of morbidity and mortality. The factors influencing prognosis in lupus nephritis (LN) are variable in literature. The aim of our study was to analyze the clinicopathological correlations, and risk factors associated with renal failure in male patients with LN.

Method

We retrospectively studied all male patients with kidney biopsy-proven lupus nephritis (LN) treated in our department during the period between 1979 and 2016. Looking for predictive factors related to renal prognosis, we analyzed clinical, biological and histological data by multivariate analysis using the comparison of the survival rates by the log-rank test.

Results

We collected 41 native renal biopsies showing LN. Patients were aged 32.17 years (17-65 years) at the time of diagnosis of LN. Diagnosis of SLE was made according to the criteria of the American College of Rheumatology. The most common clinical presentation was nephrotic syndrome (61%), and the most frequent pathological finding in sediment was proteinuria (85%). At the time of diagnosis, 17% of patients had hypertension and 39 % of patients had an eGFR under than 60 ml/min/1.73 m2. LN was of class I, II, III, IV and V in 7.5%, 12.5%, 27.5%, 47.5% and 41.5% of the cases, respectively. Fourteen patients developed end-stage renal failure. The presence of hematuria, renal failure at the time of diagnosis, nephrotic syndrome, low complement, proliferative glomerulonephritis (class IV), high activity index score of LN and thrombotic microangiopathy were significantly associated with poor renal prognosis with (p=0.0053), (p=0.0002), (p=0.0186), (p=0.0287), (p=0.0005), (p=0.058), (p=0.0117), respectively.

Conclusion

Renal failure at the time of diagnosis and active proliferative lesions should be diagnosed and treated as soon as possible because they influence the renal prognosis in lupus man.
P0461BASELINE SERUM C3 LEVELS IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS AND ITS CLINICAL IMPLICATION
Authors: Maldonado Maria , Santacruz Juan , Afonso Sara , Olea Teresa , León Lina , Santos Carlos , Vega Cristina , Rivas Begoña , Selgas Rafael
Published: June 2020

Background and Aims

The evolution of renal disease and its global impairment in patients diagnosed with ANCA-associated vasculitis (AAV) has been related to baseline C3 serum levels in several studies.

The objective of this study is to evaluate in patients diagnosed with AAV and renal impairment the association between baseline serum C3 levels and the clinical outcomes.

Method

Our cohort included 56 patients diagnosed with AAV diagnosed from January 1986 to January 2018 in Hospital La Paz. According to C3 serum level measurements, patients were divided into low and normal concentration groups at onset. Histological, clinical and laboratory data were compared between groups.

Results

Among the 56 AAV cases, 58.9% were women and 96.5% Caucasian with an age mean and SD of 61.08 ± 15.11 years. Mean follow-up was 10.03 ± 7.02 years. MPO ANCAs were found in 69.8% of the patients and PR3 ANCAs in 22.64%. AAV diagnosis was earlier in PR3 AVV (47.59 ± 13.62 years) compared to MPO AVV (65.66 ± 11.53 years) (p=0.001). At diagnosis, baseline serum C3 was measured in 53 patients (94.6%) being lower in MPO AAV (112.79 ± 33.98) vs PR3 AAV (132.41 ± 20.69) (p=0.023). Low C3 was way more frequent in patients with higher percentage of glomeruli showing >50% of sclerosis (100% vs 32.5%) (p=0.007). Staphylococcus aureus nasal carriers were more frequent in patients with low C3 (27.2% vs 3.1%, p=0.045). 15 patients (27.77%) died during follow-up and patient survival median was 21.75 years (IC 95%: 15.41-28.08). 17 patients (31.48%) reached end-stage renal disease (ESRD) during follow-up and renal survival median was 20.1 years (IC 95%: 19.27-21.05).

There were no statistical differences in the levels of baseline serum C3 according to sex, relapses, extrarenal manifestations, treatment, malignancy, cardiovascular events and time to ESRD or death.

Conclusion

Baseline serum C3 was lower in MPO AV, in Staphylococcus aureus nasal carriers and higher severity histological damage (glomerular sclerosis >50%). Despite previous evidence, in our cohort, time to ESRD and time to death seemed not to be affected.
P0466LUPUS NEPHRITIS IN SOUTH MOROCCO OVER 6 YEARS
Authors: BENHAMOU Ramia , Sara Allibou , Yahioui Mariem , Chettati Meriem , Fadili Wafaa , Essaadouni Lamia , Laouad Inass
Published: June 2020

Background and Aims

Lupus nephritis is one of the most serious manifestation of systemic lupus. The study aimed at assessing the epidemiology and clinical features of systemic lupus erythematosus with lupus nephritis (LN) in south Morocco.

Method

A retrospective study was conducted in the Marrakesh-Tensift region by charts review from 2014 to 2019 (included). Patients with a SLE diagnosed with lupus nephritis over 6 years according to ACR/EULAR criteria were included.

Results

In total, 146 patients met inclusion criteria: 133 were women (94%) and mean age at diagnosis was 31,195 ± 13.5 years. Five percent of all patients had a least one parent with autoimmune disease, and 4,1% with lupus. The main manifestations were musculoskeletal (89%) and mucocutaneous with acute or subacute lesions (68,5%), alopecia (50%), ulcers (3,4%) and discoid lupus (10,27%). Cardiac manifestations in 19,2% and neurological features in 17,9% and psychiatric features in 13,7%. At the moment of diagnosis antinuclear antibodies were positive in 89% (threshold >1/80), and associated to anti-DNA in 91 patients (62,3%), anti-SSA (21,2%), and anti-Sm (34,9%). APL syndrome was diagnosed in 8,2%. Kidney biopsy showed predominantly class IV in 54% and classe I-II in 28%. The average annual standardized incidence of LN between 2014 and 2019 was 2,4 cases per 1,000,000 inhabitants (95% confidence interval [CI]: 5.0–6.0). The prevalence was 21 cases per 1,000,000 inhabitants in 2018 (95% CI: 70–79).

Conclusion

Lupus nephritis in the multi-ethnic population of south moroccan is characterized by high incidence and high rates of diffuse proliferative nephritis.
P0469VALIDATING THE DIAGNOSTIC ACCURACY OF MEMBRANOUS NEPHROPATHY IN THE HEALTH IMPROVEMENT NETWORK (THIN) DATABASE
Authors: Wheatley Roseanna , Hamilton Patrick , Blaikie Kieran , Rao Anirudh , Kanigicherla Durga , Brenchley Paul
Published: June 2020

Background and Aims

Membranous nephropathy (MN) is among the most common causes of nephrotic syndrome in adults worldwide. Despite this, there is currently no robust data on the epidemiology of MN in the UK population. The Health Improvement Network (THIN) is an electronic medical record database that holds longitudinal anonymised patient records for over 17 million patients and has shown to be generalisable to the UK regarding demographics and crude prevalence’s of major conditions. To our knowledge, accuracy of the read codes for glomerular disease is yet to be validated. This will be the first study into MN validating the diagnostic accuracy using the THIN database.

Method

THIN database was interrogated for patients with MN using read codes. Two cohorts were considered: Definite cohort, defined as read codes expected to correspond to a diagnosis of MN, and Probable cohort, defined as read codes that could correspond to a diagnosis of MN. In order to confirm the diagnosis of MN, a short questionnaire was sent to the GP practice of a randomly selected cohort of patients asking if the diagnosis of MN was correct, and that the diagnosis had been confirmed by a specialist renal centre, with or without a renal biopsy.

Results

267 patients with a record of MN were identified from the THIN database. 235 of the patients had Definite cohort read codes, with a mean age at diagnosis of 57 years. There were 155 (66.2%) male and 79 (33.8%) female patients. 32 patients were identified in the Probable cohort. GP questionnaires were sent to 71 randomly selected patients with 61 responses (85.9% response rate). This represented 23% (n=53) of the total Definite cohort and 25% (n=8) of the total Probable cohort. Of the 61 returned questionnaires, an MN diagnosis was confirmed in 96% (n=51) of patients with a definite read code and 25% (n=2) with a probable read code. Amongst the confirmed MN diagnoses in the Definite cohort, 88% (n=45) of the patients had primary MN.

Conclusion

The THIN database is a valid data resource for studying MN in patients with a read code from the Definite cohort list. Read codes from the Probable cohort list cannot be used unless confirmed on a case by case basis such as through the GP. The results of this study will feed into a larger project with an aim to describe accurately the epidemiology of MN in the UK population, and report the incidence and prevalence of specific secondary associations of MN. Once these factors are fully understood, diagnostic and care pathways for MN can be developed.
P0473LONGITUDINAL CHANGES OF IGA1 O-GLYCOFORM IN IGA NEPHROPATHY
Authors: OHYAMA YUKAKO , Yamaguchi Hisateru , Nakajima Kazuki , Inaguma Daijo , Hasegawa Midori , Tsuboi Naotake , Renfrow Matthew B , Novak Jan , Yuzawa Yukio , Takahashi Kazuo
Published: June 2020

Background and Aims

Elevation of circulatory IgA1 with galactose-deficient (Gd) hinge-region (HR) O-glycans (Gd-IgA1) has been detected in most IgA nephropathy (IgAN) patients based on lectin ELISA. However, new approaches are needed for molecular-level characterization of IgA1 HR glycoform(s) in IgAN. We established a high-throughput method for analysis of IgA1 HR O-glycoforms using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). To identify IgAN-associated IgA1 HR O-glycoforms and to assess their changes after therapy (with or without corticosteroids (CS)), we profiled IgA1 HR glycopeptides from sera collected at two time points (before and after therapy) from Japanese IgAN patients.

Method

Of the 10 Japanese IgAN patients recruited, 4 received CS treatment (CS group) and 6 have not (non-CS group). Japanese healthy volunteers (HC, n=10) were recruited as controls. Serum IgA1 was purified by affinity chromatography from HC and IgAN patients before and after therapy. After neuraminidase treatment and trypsin digestion, IgA1 HR glycosylation heterogeneity was analyzed by LC-HRMS. The relative abundance (RA, %) for each glycopeptide was calculated as percentage to the total IgA1 HR glycopeptide. The amount of each glycopeptide was then calculated by multiplying serum IgA concentration (mg/dL) by RA.

Results

Approximately 60% of IgA1 HR O-glycoforms in IgAN patients and HC were Gd O-glycoforms; these glycoforms contained one to three Gd-glycan(s), designated as 1 Gd-glycoform, 2 Gd-glycoform and 3 Gd-glycoform, respectively. In IgAN patients, the RA of non Gd-IgA1 glycoforms was elevated (P=0.002) and correlated with proteinuria (g/gCr) at renal biopsy (P=0.039, R=0.657). The amounts of non Gd- and 1Gd-glycoforms were higher in IgAN patients compared to HC (each P<0.001). After several years of follow up (2.77 years (1.44-3.85)), the RA of non Gd-glycoforms decreased in CS group of IgAN patients (P=0.039) whereas it remained unchanged in the non-CS group (P=0.488). The amount of non Gd-glycoforms exhibited similar trends, i.e., decreased in CS group (P=0.068) whereas it remained unchanged in the non-CS group (P=0.943).

Conclusion

This study profiled serum IgA1 for IgAN-associated IgA1 HR O-glycoforms at the molecular level and assessed their changes in response to CS vs. non-CS therapy. IgA1 HR O-glycoforms altered by treatment may serve as a biomarker(s) for monitoring patients’ responses to therapy.
P0477CLINICOPATHOLOGICAL STUDY OF MIXED CRYOGLOBULINEMIC GLOMERULONEPHRITIS SECONDARY TO HEPATITIS B VIRUS INFECTION
Authors: Li Chao , Li Hang , Su Wei , Wen Yu-bing , Ye Wei , Ye Wen-ling , Qin Xu-zhen , Cai Jian-fang , Li Xuemei , Li Xuewang
Published: June 2020

Background and Aims

To describe the clinical features, renal pathology findings and prognosis in patients with mixed cryoglobulinemic glomerulonephritis (Gn) caused by hepatitis B virus (HBV) infection.

Method

This was a retrospective study including seven Chinese patients with HBV infection associated mixed cryoglobulinemic Gn in a tertiary referral hospital from April, 2016 to March, 2019. The demographic, clinical, pathological characteristics, treatment and follow-up data were collected and analyzed.

Results

Age at renal biopsy was 47±12 years, including three females and four males. 24hUP was 5.6(3.0, 6.6)g/d and five cases presented with nephrotic syndrome. The median baseline eGFR(CKD-EPI) was 23.5(20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations were: purpura (n=6), arthralgia (n=1), peripheral neuropathy (n=1), and cardiomyopathy (n=1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %, rheumatoid factor was 368(117, 733) IU/ml, C3 was 0.48(0.41, 0.57) g/L, C4 was 0.013(0.003, 0.118) g/L. Renal pathologic findings on light microscopy: endocapillary proliferative Gn (n=3), membranoproliferative Gn (n=3), and mesangial proliferative glomerulonephritis(n=1). Hyaline thrombi were seen in four cases, while crescents were found in two cases. On immunofluorescence microscopy, the predominant types of immunoglobulin deposits were: IgM(n=5), IgA(n=1), and codominance of IgG and IgA(n=1). HBsAg and HBcAg deposits were found in only one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and organized microtubules was seen in only one case. All patients received antiviral medication (entecavir, n=6; lamivudine, n=1). They were given corticosteroid alone(n=2) or combined with cyclophosphamide(n=4) or mycophenolate mofetil(n=1). Two patients received plasmapheresis. The median follow-up time were 18 (6, 37) months. One patient died from pneumonia, and one progressed to end stage of renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR (CKD-EPI) was 55.3 (20.7, 111.8) ml/min per 1.73m2.

Conclusion

Mixed cryoglobulinemic Gn should be screened for HBV etiologies, especially in HBV-endemic country. Endocapillary proliferative Gn was the common pathologic type, as well as membranoproliferative Gn. Diagnosis and treatment in early stage benefit patients’ renal outcome. Long-term prognosis should be investigated in further studies.
P0484CLINICAL FEATURES AND OUTCOME OF LUPUS NEPHRITIS IN MOROCCO: A SINGLE CENTER STUDY OF 207 CASES
Authors: Naouaoui Salma , Chettati Meriem , Fadili Wafaa , Laouad Inass
Published: June 2020

Background and Aims

renal involvement is a common and potentially severe complication of systemic lupus erythematosus (SLE). Few data for Lupus nephritis (LN) exist on North Africans, especially those from Morocco. The aim of our study was to report the long-term renal outcome of a cohort of Moroccan patients with LN.

Methods

the records of 207 patients (191 females, 16 males) with LN (American College of Rheumatology criteria) admitted to the departments of nephrology and internal medicine of Marrakesh University Hospital were reviewed and included in a retrospective analysis.

Results

the mean age at the time of renal biopsy was 31,7 ±  15,9 years. Time between diagnosis of SLE and the onset of renal disease was 29 ± 10 months. Renal involvement was observed concomitantly with the onset of SLE in 39 patients (18,8%). At presentation, 65 patients (31,4%) had hypertension. Hematuria was seen in 158 patients (76,3%), nephrotic syndrome in 82 patients ( 39,6%) and renal failure in 76 patients (36,7%). The most frequent extarenal manifestations were skin and joint manifestations in 89,3% and 83,6% respectively. The most common histological finding was type IV LN in 96 patients, followed by type III LN in 51 patients. 191patients (92,3%) received corticosteroids as initial therapy followed by immunosuppressive therapy in 127 patients (61,3%). During the follow-up period, partial or total remission was obtained in 56,5% of cases while 61 patients (29,4%) progressed to end stage renal disease (ESRD) and 29 patients (14%) died. Logistic regression detected that hypertension, high serum creatinine at admission and proliferative histological classes were the main risk factors for poor renal outcome.

Conclusion

Our results showed that LN was particularly severe in our population compared with other published data with predominance of proliferative forms.
P0489URINARY PROTEOMIC MARKERS OF MEMBRANOUS NEPHROPATHY
Authors: Moszczuk Barbara , Krata Natalia , Cysewski Dominik , Perkowska-Ptasinska Agnieszka , Pączek Leszek , Foroncewicz Bartosz , Zagożdżon Radosław , Mucha Krzysztof
Published: June 2020

Background and Aims

Membranous nephropathy (MN) is considered one of the major conditions causing nephrotic-range proteinuria. Last years brought a huge progress in the field of non-invasive diagnostics, mainly due to the PLA2R antibody use in diagnostics and follow-up of primary MN. However, our understanding of MN is far from complete, especially that PLA2R-antibodies are found only in approximately 60-70% of all cases. Urinary proteomics is a promising tool that can help us to improve diagnostics, monitoring and understanding of MN. Our previous studies (Patent No. WO/2017/212463) suggested that specific urinary proteins can be used in the diagnostics of IgA nephropathy, lupus nephritis and ADPKD. The aim of this study was to evaluate with Mass Spectrometry (MS) patients diagnosed with MN in comparison to healthy controls.

Method

This study included patients with biopsy-proven MN (25) and healthy controls (7). Urine samples were obtained from a midstream of the second- or third-morning (SPOT) sample. The samples were processed up to 2 h after collection and stored at -80°C for further measurements with MS. The results were related to demographic data, standard laboratory tests and GFR estimated with use of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Results

The signal intensity of urine protein A, B and C (patent pending and the name of proteins disclosed until the date of ERA-EDTA Congress) was found to be significantly higher (p < 0.05) in MN patients compared to healthy controls (Fig. 1). Mass spectrometry, according to the specific amino-acids fragments of each tested protein, confirmed the differences between tested and control group. Additionally, statistically significant differences exist between patients with different types of glomerulonephritides (comparative MS in progress).

Conclusion

The signal intensity of urine proteins A, B, C is elevated in MN and according to our study, vary depending on types of nephropathies. This observation might suggests their differential roles in the pathophysiology of MN and its’ possible application as a non-invasive diagnostic and prognostic marker. Further studies are desired to establish the role of these urinary proteins.
P0493EPIDEMIOLOGY OF IGA NEPHROPATHY IN THE MALTESE ISLANDS
Authors: Attard Abigail , Vassallo Diana , Swayne John , Buttigieg Jesmar , Grech Edward , Vella Mario Pio , Farrugia Emanuel
Published: June 2020

Background and Aims

IgA nephropathy is the most common cause of glomerular disease worldwide. Natural history and clinical progression of this condition are highly heterogenous and can vary from asymptomatic haematoproteinuria, to a rapidly progressive glomerulonephritis that results in end-stage kidney disease (ESKD). The OXFORD MEST-C score is a set of consensus criteria that have been correlated with renal outcomes independent of baseline clinical features, proteinuria and blood pressure control. This is the first observational study carried out in the Maltese Islands that aims to evaluate the epidemiology and the histopathological distribution in Malta.

Method

All patients with biopsy-proven IgA nephropathy between January 2013 and July 2019 in our centre were recruited into this longitudinal retrospective observational study. Baseline data at time of biopsy included demographics, laboratory data and the MEST-C score. Study end-points included death, doubling of serum creatinine and ESKD. Data was censored on 31/12/2019.

Results

A total of 46 patients were recorded over this 6 year period, with a median follow-up of 2.7 years (Standard deviation 1.9). The median age of our cohort at time of biopsy was 46.1 years (Standard deviation 16.1). In total, 71.7% were males, 34.8% were hypertensive and 6.5% diabetic at baseline. At time of biopsy, 89.1% had an active sediment, 54.3% had established chronic kidney disease (CKD), 17.4% presented with acute kidney injury (AKI), 13% had a history of synpharyngitic haematuria, while 4.3% had a history of Henoch–Schönlein (HSP). In our cohort, 8 patients (17.4%) had progression of CKD. 4 of them had doubling of creatinine with 3 reaching ESKD. 1 patient died. Table 1 shows the distribution of histopathological findings in our cohort:

Conclusion

Despite the limited study sample, short follow-up time, and absence of treatment data, our results demonstrate that the distribution of histopathological variants in our cohort is similar to that reported elsewhere in the literature1.

Barbour SJ, Espino-Hernandez G, Reich HN, Coppo R, Roberts IS, Feehally J, et al. The MEST score provides earlier risk prediction in IgA nephropathy. Kidney Int. 2016 Jan;89(1):167–75.
P0495PAUCI-IMMUNE GLOMERULONEPHRITIS - OUR EXPERIENCE IN A TERTIARY CARE CENTER
Authors: Lingaraj Umesh , Mehta Ricken , SM Shivaprasad , V Leelavathi , A Kishan , C Sreedhara , V MYTHRI
Published: June 2020

Background and Aims

Aims - To study the clinicopathological profile and short-term outcome of patients with Pauci-immune Glomerulonephritis at a tertiary care center

Method

Results

In our study group we found that majority of the patients had RPGN presentation (93.3%).

Conclusion
P0497MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS IN A LMIC : EPIDEMIOLOGIC PROFILE, PROGNOSTIC FACTORS AND IMPACT OF ALPHA SMOOTH MUSCLE ACTIN
Authors: Ikram Agrebi , Khawla Kammoun , Najla Dammak , Soumaya Yaich , Tahya Boudawara , Jarraya Fayçal , Mohamed Ben hmida
Published: June 2020

Background and Aims

Mesangiocapillary glomerulonephritis (MCGN) is a rare kidney disease with a poor prognosis. Several factors have been described associated with poor renal prognosis. The contribution of alpha smooth muscle actin (α-SMA), which is involved in renal fibrogenesis, has been demonstrated in assessing the prognosis of several glomerular diseases, but few studies have concerned the MCGN.

The aim of our study is to determine the epidemiologic profile, to identify prognostic factors and to evaluate the contribution of α-SMA in predicting the prognosis the MCGN.

Method

Our study is retrospective over a period of 16 years (January 1996- December 2011) including all cases of primary MCGN aged more than 15 years, collected at the nephrology department of the university hospital Hedi Chaker Sfax. We reviewed available renal biopsies for the study of the expression of α-SMA by immunohistochemistry.

Results

We collected 118 cases of primary MCGN, with mean age of 45 ± 19 years. The incidence of MCGN has decreased from 10 cases / year between 1996 and 1999 to 5 cases / year between 2008 and 2011. 78.8 % of patients had renal failure at the moment of diagnosis. The study of the expression of α-SMA by immunohistochemistry was made in 16 cases. After a mean follow-up of 51.9 ± 44 months, progression to end stage renal failure (ESRF) was observed in 43.5% of cases. Poor prognostic factors were initial renal failure and sclerotic glomeruli (respectively p at 0,04 and 0,03), but interstitial fibrosis degree was not a prognosis predictor parameter while important interstitial expression of α-SMA was a marker of the evolution to ESRF (p = 0.03).

Conclusion

MCGN has significantly declined over recent years due to improve of socio-economic conditions. The presence of renal failure and sclerotic glomeruli at diagnosis were associated with a poor prognosis. The interstitial expression of α-SMA may be a useful marker to predict the progression of primary MCGN even before the installation of fibrosis.
P0501THE EPIDEMIOLOGICAL FEATURES OF PIRMARY GLOMERULAR DISEASES IN TURKEY: THE MULTICENTER STUDY OF TURKISH SOCIETY OF NEPHROLOGY GLOMERULAR DISEASES (TSN-GOLD) WORKING GROUP
Authors: Turkmen Aydin , Sumnu Abdullah , Cebeci Egemen , Yazici Halil , Eren Necmi , Seyahi Nurhan , Dilek Kamil , Dede Fatih , Derici Ülver , Unsal Abdulkadir , SAHIN Garip , Sipahioglu Murat , Gok Mahmut , Tatar Erhan , Dursun Belda , Sipahi Savaş , Yılmaz Mürvet , Suleymanlar Gultekin , Ulu Memnune Sena , Gungor Ozkan , Kutlay Sim , Bicik Bahçebaşı Zerrin , Sahin İdris , Kurultak Ilhan , Turkmen Kultigin , Yilmaz Zulfikar , Turan Kazancioglu Rumeyza , Cavdar Caner , Candan Ferhan , Aydin Zeki , Oygar Deren , Gul Cuma Bulent , Arici Mustafa , Paydas Saime , Guven Taymez Dilek , Kucuk Mehmet , Trablus Sinan , Turgutalp Kenan , Koc Leyla , Sezer Siren , Duranay Murat , Bardak Simge , Altintepe Luftullah , Arikan Izzet Hakki , Azak Alper , Odabas Ali Riza , Manga Sahin Gulizar , Ozturk Savas
Published: June 2020

Background and Aims

The largest data on the epidemiology of primary glomerular diseases (PGD) are obtained from the databases of countries or centers. Here, we presented the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD)Working Group.

Method

The data of patients who underwent renal biopsy and diagnosed as primary glomerular disease were recorded in the database prepared for the study. Between May 2009 and May 2019, a total of 4399 patients from 47 centers were evaluated. Basal data of 3875 patients were analyzed after exclusion of those lacking light microscopy and immunofluorescence findings.

Results

The mean age was 41.5 ± 14.9 years. Of the patients, 1690 were female (43.6%) and 2180 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGH was IgA nephropathy (25.7%), followed by membranous nephropathy (25.6%) and FSGS (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. Mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. Median proteinuria was 3300 (IQR: 1467-6307) mg / day, mean serum creatinine, estimated GFR and albumin values were 1.4 ± 1.5 mg / dl, 80.7 ± 39.1 ml / min and 3.2 ± 0.9 g / dl, respectively.

Conclusion

In Turkey, the incidence of IgA nephropathy patients have become more common than membranous nephropathy among PGD patients diagnosed with renal biopsy.
P0502BIOBANKING FOR GLOMERULAR DISEASES: A STUDY DESIGN AND PROTOCOL FOR KOREA RENAL BIOBANK NETWORK SYSTEM TOWARD NEXT-GENERATION ANALYSIS (KORNERSTONE)
Authors: Kang Eunjeong , Kim Yaerim , Kim Yong Chul , Lee Soojin , Han Seungyeup , Choe Minsun , Hwang Jin Ho , Lee Sunhwa , Park Ji In , Park Jung Tak , Lim Beom Jin , Lee Jung Pyo , An Jung Nam , Ryu Dong-Ryeol , Kim Jung-Hyun , Kang Hee Gyung , Lee Hyun Soon , Moon Kyung Chul , Joo Kwon Wook , Oh Kook-Hwan , Han Seung Seok , Lee Hajeong , Kim Dong Ki
Published: June 2020

Background and Aims

Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE).

Method

The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every one year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and

connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life.

Disussion

Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases.

Conclusion

In conclusion, we describe the objectives and clinical protocol for the KORNERSTONE. As the first large-scale glomerulonephropathy cohort study with the integration of clinical data, biospecimens and digital pathologic images in Korea, the KORNERSTONE will help to clarify the natural course, complication profiles, and novel treatment targets of the Asian population with glomerular disease.
P0518VNN1 MEDIATES RENAL MALADAPTIVE REPAIR AFTER AKI BY INDUCING PREMATURE SENESCENCE OF RENAL TUBUAR CELLS
Authors: He Yani , Chen Kehong , Chen Jia
Published: June 2020

Background and Aims

Renal maladaptive repair after acute kidney injury (AKI) can easily progress to chronic kidney disease. Sustained renal interstitial damage caused by accelerated senescence of renal tubular cells leads to renal fibrosis. Vanin-1 (VNN1) is an extracellular enzyme with panthenylmethylaminease activity that indirectly reduces the synthesis of glutathione, causing oxidative stress. The purpose of this study was to investigate the expression and of VNN1 in renal tissue and to study its role in senescence of renal tubular cells after ischemia reperfusion (I/R).

Method

hirty male wild BALB/c mice were randomly divided into control group, sham group and I/R group. In the I/R group, the bilateral renal pedicle was ligatured for 35 min followed by reperfusion. The expression of VNN1 and aging markers (P16, P21, SA-b-gal) were detected. Furthermore, wild type mice and VNN1 knockout mice were used to compare the degree of renal tissue and functional damage and the senescence of renal tubular cells after I/R injury.

Results

Compared with sham group, Scr, BUN and renal injury score increased significantly in I/R group at the early stage (3d) of renal injury. Renal fibrosis was observed in the later stage (28-42d). The expression of VNN1 in renal tubular cells of I/R group increased after I/R injury. VNN1 was coexpressed with P16, suggesting that VNN1 might be related to cellular stress senescence. The SCr, BUN of VNN1 KO mice was significantly lower than that of wild type mice at 7-28 d after renal reperfusion. The renal interstitial injury score of VNN1 KO mice was significantly lower than that of wild type mice, and the renal interstitial fibrosis level was significantly higher than that of wild type mice at 42d after reperfusion. The results suggest that VNN1 KO promotes renal repair of AKI. The ratio of P16 positive tubule cells in VNN1 KO mice was significantly higher than that in wild-type mice at 7d after renal reperfusion, suggesting that VNN1 could promote the senescence of renal tubule cells during AKI repair.

Conclusion

VNN1 mediates renal maladaptive repair after AKI by inducing premature senescence of renal tubular cells.
P0522INHIBITING 15-PGDH PREVENTS ISCHEMIC RENAL INJURY BY A PGE2/EP4 SIGNALING PATHWAY MEDIATING VASODILATION, INCREASED RENAL BLOOD FLOW, AND INCREASED ADENOSINE/A2A RECEPTOR
Authors: KIm Byeong Woo , Kim Sun hee , Bae Ki beom
Published: June 2020

Background and Aims

We demonstrate the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia reperfusion injury (IRI). AKI due to ischemic injury represents a significant clinical problem. Prostaglandin E2 (PGE2) is vasodilator in the kidney, but is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI.

Method

10-week aged male C57/BL6 mice were randomly allocated to five groups (n=8 to 15 in each group): the sham-control group, sham-SW033291 group, IRI-vehicle group, IRI-indomethacin group and the IRI-SW033291 group. IRI were induced by clamping bilateral renal artery for 30 min followed by 24 hours of reperfusion. Vehicle, indomethacin, or SW033291 were intraperitoneally administered three times at 1 hour before, immediately after, and 12 hours after IRI. Renal function, histological changes, and renal blood flow were compared and the relevant parameters of oxidative stress and inflammation were detected.

Results

Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI histologic injury score and tubular apoptosis and markedly reduced biomarkers of renal injury that included BUN, creatinine, NGAL and KIM-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high mobility group box 1 (HMGB1), and malondialdehyde (MDA). Protective effects of SW033291 were mediated by PGE2 signaling as they could be blocked by pharmacologic inhibition of PGE2 synthesis or of the EP4 type PGE2 receptor. Consistent with activation of PGE2 signaling, SW033291 induced renal levels of both EP4 and of cyclic adenosine monophosphate (cAMP), along with other vasodilatory effectors including AMP, adenosine, and the adenosine A2A receptor (A2A). Protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug.

Conclusion

Inhibiting 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.
P0524PERICYTE IS ESSENTIAL FOR RENAL TUBULAR CELL REGENERATION AFTER ACUTE KIDNEY INJURY
Authors: Chou Yu-Hsiang , SHAO YU-HAN , LIN SHUEI-LIONG
Published: June 2020

Background and Aims

Pericyte-myofibroblast transition is activated after acute kidney injury (AKI) and is the major mechanism of ensuing chronic kidney disease (CKD). Nevertheless, the role of pericyte in renal regeneration after AKI has not been deeply investigated. Many studies have shown that pericyte can secret growth factors such as fibroblast growth factor 1 and 7 (FGF-1, FGF-7) and is essential for structure support and vascular integrity in normal kidney. We supposed that the ablation or inhibition of pericytes during AKI would retard renal repair.

Method

Our study demonstrated that activated pericytes/myofibroblast was beneficial for renal regeneration after AKI. We here performed pericyte ablation and pericyte inhibition after ischemia-reperfusion renal injury by using transgenic mice such as Gli1-CreERT2;iDTR mice and blockade of platelet-derived growth factor receptor β (PDGFRβ), respectively.

Results

Renal injury was more severe and renal recovery was worse in groups of pericyte ablation or inhibition compared to control groups. Ki67 positive tubular cells which indicated renal regeneration were much more in control groups than that in groups of pericyte ablation or inhibition. We also found higher macrophage number as well as higher inflammatory factor including tumor necrosis factor-α and interleukin-1β which indicated more severe inflammation in groups of pericyte ablation or inhibition.

Conclusion

These studies suggest that pericytes play a beneficial role during renal recovery after AKI. These findings delineate the adequate timing when we target on pericyte/myofibroblast to ameliorate renal fibrosis and avoid to impede renal regeneration at the same time. Further research is still needed to clarify the change of specific gene and signalling pathway after pericyte ablation or inhibition. These are promising findings that provide opportunities to develop new targets to promote AKI recovery and to ameliorate renal fibrosis.
P0526MIR-181D-5P TARGETS KLF6 TO IMPROVE ISCHEMIC/REPERFUSION AKI THROUGH EFFECTS ON RENAL FUNCTION,APOPTOSIS AND INFLAMMATION
Authors: Xu Yan , Zhang Yue
Published: June 2020

Background and Aims

Inflammation and renal tubular cell death is the most crucial pathophysiological changes in acute kidney ischemic/reperfusion injury(IRI). The miR-181d family plays diverse roles in cell proliferation, apoptosis and inflammation, but its renal target and potential role in IRI are unknown.

Method

We built hypoxia/reoxygenation (H/R) renal cell model (HK-2 cells) and renal ischemia/reperfusion (I/R) injury mice model. We used observe the expression location of miR-181d-5p and KLF6 by in situ hybridization and immunohistochemistry, the blood creatinine and urea nitrogen levels through fully automatic biochemical detector, the severity of kidney injury by HE staining, the apoptosis and necrosis of renal tubular epithelial cells by TUNEL and Annexin V-FITC/PI flow cytometry, the concentrations of pro-inflammatory factors in the cell supernatant by ELISA and the mRNA and protein levels of related factors and predicted and verified the relationship between miR-181d-5p and KLF6 via bioinformatics systems and luciferase reporter genes.

Results

We showed that the expression of miR-181d-5p decreased in HK-2 cells of H/R and renal mouse model of I/R injury. Mechanistically, KLF6 was predicted as a new potential target gene of miR-181d-5p through bioinformatics and the Luciferase reporter verification. After renal ischemia/ reperfusion, overexpression of microRNA-181d significantly attenuated the level of KLF6 and inhibited inflammatory mediators such as IL-6, TNF-α, reducing apoptosis and further improving renal function. Critical NF-κB signaling pathways mediated this inflammatory response.

Conclusion

In conclusion, upregulation of microRNA-181d inhibits KLF6 expression, which have protective anti-apoptosis and anti-inflammatory effects against I/R kidney in vivo, and H/R HK-2 cells in vitro, thereby providing novel insights into the molecular mechanisms associated with ischemia/reperfusion injury and a potential novel therapeutic target.
P0527HYPERGLYCEMIA-ASSOCIATED ACUTE KIDNEY INJURY INCREASES THE SUSCEPTIBILITY TOWARDS NEUROLOGICAL DYSFUNCTION: ROLE OF ANGIOTENSIN II TYPE 2 RECEPTOR AND ANGIOTENSIN-CONVERTING ENZYME 2
Authors: Sharma Nisha , Gaikwad Anil Bhanudas
Published: June 2020

Background and Aims

In clinical settings, diabetics remain on higher risk of ischemic renal injury (IRI) than nondiabetic patients. In addition, IRI predisposes distant organs to dysfunction such as neurological impairments via activation of the pressor arm of renin-angiotensin system (RAS). In contrast, the role of depressor arm of RAS on IRI-associated neurological sequalae remains elusive. Hence, this study explored the role of angiotensin II type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) in IRI-associated neurological dysfunctions under nondiabetic (ND) and diabetes mellitus (DM) condition.

Method

Type 1 diabetes was induced by injecting streptozotocin (55 mg/kg i.p.). ND and DM rats with bilateral IRI were treated with AT2R agonist-Compound 21 (C21) (0.3 mg/kg/day, i.p.) or ACE2 activator-Diminazene Aceturate (Dize), (5 mg/kg/day, p.o.) per se or in combination therapy. Behavioural, biochemical, and histopathological analysis were done to assess IRI-induced neurological impairment. Moreover, immunohistochemistry, ELISA and qRT-PCR experiments were conducted for molecular mechanism analysis.

Result

In ND and DM rats, IRI caused hippocampal complications as evidenced by increased MDA and nitrite levels, augmented inflammatory cytokines (granulocyte colony stimulating factor, glial fibrillary acidic protein), altered protein and mRNA expressions of Ang II, Ang-(1-7), AT1R, AT2R and MasR. In contrast, concomitant therapy of C21 and Dize effectively normalised aforementioned hippocampal alterations. The protective effect of combination therapy was exerted due to augmented protein and mRNA levels of depressor arm components.

Conclusion

The current study demonstrated the protective role of AT2R agonist and ACE2 activator in IRI-associated neurological dysfunction through preventing oxidative stress, inflammation and upregulating brain depressor arm of RAS under ND and DM conditions.
P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY
Authors: Li Dan , Li Chenyu , Xu Yan
Published: June 2020

Background and Aims

Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear.

Method

Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR.

Results

The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression.

Conclusion

These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI

Figure

KLF6, AKI, Control Inflammation