bluuebunny/crossref_metadata_2025 huggingface dataset:
P0435PREDICTORS OF RENAL SURVIVAL IN ELDERLY NEPHROTIC SYNDROME
Authors: Ben ayed Tasnim , Gorsane Imen , Trabelsi Raja , Ounissi Mondher , Ben Abdallah Taieb
Published: June 2020

Background and Aims

With increasing longevity, the numbers of elderly patients presenting with renal diseases including glomerular disease are increasing. Nephrotic syndrome (NS) is a common presentation of glomerular disease in the elderly. We performed this study to assess predictors of renal survival in this population.

Method

A retrospective study including one hundred and six patients aged 65 years or more hospitalized for NS in the Internal Medicine department A of Charles Nicolle hospital at Tunis, between January the 1st, 1975 and December the 31st, 2016.

A multivariate study was carried out, the dependent variable being the evolution towards end-stage renal disease (ESRD).

Results

We studied 106 patients with an average age of 70 ± 4.5years [65-83 years] with a sex ratio (M/F) of 1.7. Twenty-three percent of patients were diabetic. The median proteinuria was 4.6 [3-19.5 g/l], the mean albumin level was 20 ± 5.6g/l and the mean protidemia was 50 ± 6.9 g/l. Nephrotic syndrome was impure in 89.6 % of patients with high blood pressure in 70.5 % of cases, hematuria ≥2 + in 34.7% of cases and renal failure in 88.4 % of cases. The renal biopsy was performed in 41 patients. The most common glomerular lesions were Membranous nephropathy (29 %) followed by amyloidosis (27 %). NS was secondary in 63.2 % of cases mainly to amyloidosis (35.8 %) and diabetes (19.8 %). Idiopathic nephropaty was dominated by membranous nephropathy (11.3 %) and primitive membranoproliferative glomerulonephritis (MPGN) (6.6 %). At the end of follow-up, 35 % of patients achieved complete or partial remission and 58.5 % progressed to ESRD. The multivariate study found as independent risk factors of progression to ESRD uremia ≥ 17 mmol/l (ORa =33.2 [1.3 - 837.7]; p<0.05), phosphoremia ≥ 1.6 mmol/l (ORa=22.1 [1.8-266.5]; p<0.05), potassium concentration ≥ 4.3mmol/l (ORa=24.7 [2.4,251.5]; p<0.01), extra-renal signs (ORa=38,9 [2.4 - 634.3]; p: 0.01), secondary nephropathy (ORa=74 [3.1 - 1788.2]; p<0.01) and MPGN (ORa=48[1.4 - 1675.5]; p<0.05). The protective factors were hemoglobinemia ≥ 9.3g/dl (ORa=0.007 [0 - 0.2]; p<0.01), kidneys well differentiated on ultrasound (ORa=0.032 [0.003 - 0.4]; p<0.01) and treatment with two diuretics (ORa=0.03 [0.003 - 0.4]; p<0.01).

Conclusion

Elderly NS was characterized by a poor prognosis, in particular secondary to delayed and non-uniform treatment strategies, hence the need for rising physician awarness about this decease and consultation on a standardized treatment strategies.
P0445PREVALENCE AND PREDICTORS OF GLYCOSURIA IN PRIMARY GLOMERULOPATHIES
Authors: Ormonde Carolina , Laranjinha Ivo , Gaspar Augusta , Gonçalves Margarida , Gil Célia , Dickson Jorge , Machado Domingos
Published: June 2020

Background and Aims

Albuminuria is a marker of glomerular lesion, however some studies have suggested that proximal tubule (endocytosis of albumin) is also essential to determine the amount of albumin excreted in the urine. It has been hypothesized that patients with glomerulopathies and concomitant tubular damage might present higher levels of albuminuria. Glycosuria is a marker of proximal tubular dysfunction and may be used as an easy and useful marker of tubular lesion in glomerular diseases. The aim of this transversal study was to evaluate the prevalence of glycosuria in primary glomerulopathies (GP) and identify its predictors.

Method

We included all patients diagnosed in the last 10 years in our centre with primary GP confirmed by renal biopsy. Clinical, laboratory and biopsy results were collected 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 GP.

Results

We studied 110 patients – 39 (35.5%) IgA Nephropathy (IgAN), 27 (24.5%) Membranous Nephropathy (MN), 26 (23.6%) Focal Segmental Glomerulosclerosis (FSGS) and 18 (16.4%) Minimal Change Disease (MCD). Demographic data were not different between patients with and without glycosuria. Global prevalence of glycosuria was 9.1% (n=10) – patients with MN had higher prevalence of glycosuria (n=4, 17.4%), followed by FSGS (n=3, 15.5%), MCD (n=1, 5.9%) and IgAN (n=2, 5.4%). We found that patients with glycosuria had higher serum creatinine (3.9±5.1 vs 1.7±1.3 mg/dL, p=0.001), higher albuminuria (7.1±6.3 vs 3.2±3.4 g/g, p=0.002), lower serum albumin (2.3±0.7 vs 3.2±1.1 g/dL, p=0.022) and lower hemoglobin (12.0±2.5 vs 13.4±2.0 g/dL, p=0.050). Nevertheless, we did not find differences between glycosuric and non-glycosuric patients in percentage of glomerular sclerosis (%GS) or interstitial fibrosis and tubular atrophy (IFTA). In a multivariate analysis, glycosuria was positively associated with MN diagnosis, serum creatinine and albuminuria, but not with hematuria, %GS and IFTA.

Conclusion

Glycosuria is not frequent in primary GP. MN is the primary GP that most frequently presents glycosuria. Glycosuria is associated with higher albuminuria and lower serum albumin levels, corroborating the hypothesis that albuminuria as an offender to the tubules will affect the amount of albumin excreted in the urine. We also found that patients with glycosuria presented a more severe renal dysfunction (higher creatinine) at the GP diagnosis.
P0459ADULT MINIMAL CHANGE DISEASE IN TURKEY: THE RESULTS OF TURKISH SOCIETY OF NEPHROLOGY GLOMERULAR DISEASES WORKING GROUP
Authors: Yılmaz Mürvet , Sipahioğlu Murat , Dervişoğlu Erkan , Aydemir Nihal , Uzun Sami , Istemihan Zulal , Unsal Oktay , Tatar Erhan , Berktas Hacı Bayram , Ozdemir Kayalar Arzu , Sumnu Abdullah , Kumru Şahin Gizem , Çetinkaya Hakkı , Kazan Sinan , Kocyigit Ismail , Gokalp Cenk , Hasbal Nuri Baris , Ucar Ayse Serra , Ozelsancak Ruya , Guven Taymez Dilek , Yadigar Serap , Alagoz Selma , Aslan Bilal Burçak , Yaylaci Selcuk , Aydin Zeki , Jabrayilov Jabrayil , Turgutalp Kenan , Dursun Belda , SAHIN Garip
Published: June 2020

Background and Aims

Minimal change disease (MCD) is the most common cause of the nephrotic syndrome (NS) in children. Although there are many data regarding the course, response to treatment, and outcomes in pediatric patients, only a few series have examined these issues in adults. The aim of the study was to delineate the demographic and clinical properties of MCD of adult population in our country.

Method

All over the country, a total of 47 centers entered data between May 2009 and May 2019 to the database created by of Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group. Demographic and clinical characteristics and biopsy findings recorded to the database were analyzed.

Results

In total, 258 patients were compatible with the pathological diagnosis of MCD. Mean age was 36.16±15.44 years and 53.88% were male. At diagnosis, 66.7% patients presented with pretibial edema,15.9% with hypertension. Microscopic hematuria occured in 18.2% patients. Only 24 patients (9.3%) presented with a decrease in renal function (serum creatinine greater than 1.3 mg/dl). The mean daily proteinuria was 6.3 g, and serum albumin was 2.6 mg/dl. The most frequent indication for biopsy was NS (86.4%). On kidney biopsy, the mean number of glomeruli was 18.08±11.11. Mezangial proliferation and mezangial IgM were present in 27.5% and 22.5%, respectively. Only in 3.5% of the included patients, electron microscopic studies were performed.

Conclusion

This study describes the characteristics of a cohort of adult patients with MCD. MCD in adults may sometimes present concurrently with hematuria, hypertension, and acute kidney injury.
P0465NEPHROTIC SYNDROME IN ELDERLY PATIENTS
Authors: Ben ayed Tasnim , Gorsane Imen , Trabelsi Raja , Ounissi Mondher , Ben Abdallah Taieb
Published: June 2020

Background and Aims

Nephrotic syndrome (NS) is one of the manifestations of acute or chronic glomerular nephropathy in the elderly. Our study objective was to determine the particularities of NS in the elderly.

Method

This is a retrospective study, carried out in the Internal Medicine department A of Charles Nicolle hospital at Tunis, between January the 1st, 1975 and December the 31st, 2016. This study included subjects aged 65 years old or over hospitalized for NS.

Results

We studied 115 patients with an average age of 71 ± 5 years [65-83 years] with a sex ratio (M/F) of 1.7. Twenty-three percent of patients were diabetic. The median proteinuria was 4.7 g/l [3-19.5 g/l], the mean albumin level was 20 ± 6g/l and the mean protidemia was 50.6 ± 6.9 g/l. Nephrotic syndrome was impure in 89.5 % of patients with high blood pressure in 54 % of cases, hematuria ≥2 + in 30% of cases and renal failure in 82.7 % of cases. Renal biopsy was performed in 45 patients. The most common glomerular lesions were Membranous nephropathy (29 %) followed by amyloidosis (24.5 %). NS was secondary in 65.2 % of cases mainly to amyloidosis (35.6 %) and diabetes (19 %). Idiopathic nephropaty was dominated by membranous nephropathy (9.5 %) and primitive primitive (MPGN) (4.3 %). The treatment was symptomatic for 84.4% of patients. Corticosteroids and/or immunosuppressive treatment have been used for 15.6% of patients. At the end of follow-up, 35.3 % of patients achieved complete or partial remission and 56.6 % progressed to ESRD.

Conclusion

Elderly NS was characterized by a poor prognosis due to delayed cosultation and non-uniform treatment strategies. Multicentric study in order to identify different action axes could improve the prognosis of this disease. Multicentric study in order to identify different action axes could improve the prognosis of this disease.
P0467THE DIRECT USE OF ORAL ANTI-COAGULANTS IN MEMBRANOUS NEPHROPATHY
Authors: Wills Maximilian , Gupta Sanjana , Gage Alice , Ashman Neil , Forbes Suzanne
Published: June 2020

Background and Aims

Barts Health has a dedicated membranous nephropathy (MN) service with 15-20 incident cases per year. Nephrotic syndrome secondary to MN in particular is associated with arterial and venous thrombosis. There is little evidence to guide optimum pharmacological prophylaxis. In those considered high risk, options include warfarin, heparin or aspirin. The advent of direct oral anti-coagulants (DOACs) offers an alternative, though evidence of efficacy is isolated to case studies.

All patients with an albumin <25g/L are offered anticoagulation. We describe our use of DOACs in a large single centre MN cohort.

Method

Retrospective data MN patients between 2015-2019 was analysed. This included: demographics; frequency, type and timing of thromboembolic and bleeding events; biochemical data at initiation and cessation of agent.

Results

Total number of patients: 26

DOAC treatment courses: 30

Exposure to drug (patient days): 9899

Malignancy was excluded in all cases, with the exception of 1 case of MN secondary to cancer.

There were 3 thromboembolic events in 3 patients; all events occurred on rivaroxaban and in PLA2Rab positive MN.

Thrombotic events were all arterial, with no venous events, 2 cerebral artery infarcts and 1 lower limb arterial thrombosis. These patient’s mean initial presentation PLA2Rab titres were 164 Kunits/L (75-248) and all were nephrotic at the time of the thromboembolic event. Events were 29, 128 and 340 days post DOAC initiation. 2 of these patients had a venous thrombosis prior to DOAC initiation. Event rate: 0.11 per patient year

Safety data also demonstrated 3 bleeds in this patient cohort - all were minor as per ISTH criteria. 2 epistaxes and 1 associated with rectal prolapse, all without a haemoglobin drop.

Conclusion

Our experience is that DOACs are safe and effective in patients with MN and offer a viable anti-coagulant alternative.
P0470IS GLYCOSURIA A MARKER OF TUBULO-INTERSTITITAL FIBROSIS AND PROGNOSIS IN PRIMARY GLOMERULOPATHIES?
Authors: Ormonde Carolina , Laranjinha Ivo , Gaspar Augusta , Gonçalves Margarida , Gil Célia , Dickson Jorge , Machado Domingos
Published: June 2020

Background and Aims

Multiple studies have shown that tubular damage is common in glomerular diseases and that it correlates better with chronic kidney disease (CKD) progression than glomerular lesion itself. The link between glomerular and tubular damage is not entirely established. Glycosuria can be found in (proximal) tubular dysfunction and may be used as a marker of tubular lesion and CKD progression. The aim of this study was to evaluate the association between glycosuria (at the diagnosis) and known histological prognostic markers (glomerular sclerosis (%GS) and interstitial fibrosis/tubular atrophy (IFTA)) and CKD progression, in patients with primary glomerulopathies (GP).

Method

We conducted a 36-month retrospective cohort study with 110 patients with primary GP confirmed by renal biopsy in the last 10 years in our centre – 39 (35.5%) IgA Nephropathy, 27 (24.5%) Membranous Nephropathy, 26 (23.6%) Focal Segmental Glomerulosclerosis and 18 (16.4%) Minimal Change Disease. Patients were divided in two groups according to their glycosuric status at the time of the diagnosis. Data was collected from patients’ charts. Exclusion criteria: patients with diabetes or glucose intolerance, use of SGLT2 inhibitors, secondary GP and transplant kidney patients.

Results

The global prevalence of glycosuria was 9.1% (n=10). Glycosuric patients had, at baseline, higher serum creatinine (3.9±5.1 vs 1.7±1.3mg/dL, p=0.001), higher baseline albuminuria (7.1±6.3 vs 3.2±3.4 g/g, p=0.002) and lower serum albumin (2.3±0.7 vs 3.2±1.1 g/dL, p=0.022). Both groups had similar proportion of patients that underwent immunosuppressive therapy. At the end of the follow-up, in glycosuric patients, only albuminuria was higher (3.3±0.6 vs 0.7±0.8 g/g, p<0.0001); the eGFR decline rate (ml/min/year), 3-year eGFR and 3-year CKD stage 5D incidence were not statistically different. Glomerular sclerosis (%GS) and interstitial fibrosis and tubular atrophy (IFTA) were not different between groups. These results were confirmed by multivariate analysis.

Conclusion

Patients with primary GP with glycosuria at diagnosis had higher baseline creatinine and albuminuria. Even though a worse clinical presentation, glycosuria was not associated with well-known prognostic factors (%GS and IFTA) or CKD progression. We can hypothesize that patients with primary GP with glycosuria have severe diseases at diagnosis, but the lesions may have greater reversibility. Prospective and longer studies are needed to confirm these results.
P0483PREGNANCY OUTCOMES IN PREGNANT WOMEN WITH DIFFERENT TYPES OF GLOMERULONEPHRITIS
Authors: Kirsanova Tatiana , Rumiantseva Elizaveta , Ivanova Olga , Vinogradova Maria , Fedorova Tatiana , Balakireva Alina
Published: June 2020

Background and Aims

Connection between active glomerulonephritis (GN) and adverse pregnancy outcomes is well known. The analysis of pregnancy outcomes for patients with different types of GN in remission has not been performed.

Aim: to investigate pregnancy outcomes in women with inactive lupus nephritis (LN), IgA nephropathy and unspecified types of GN.

Method

A retrospective single-center cohort study 11/2014 – 12/2019: 91 patients with GN in remission > 20 weeks of gestation. Proved IgA-nephropathy was observed in 14 patients, proved LN in 26 patients, 4 patients had proved antiphospholipid syndrome secondary to LN and 51 patients had unspecified types of GN (without morphological confirmation). Morphological class of LN was confirmed in 9 patients: 3rd in 5, 4th in 2, 5th in 2 patients. Renal function at conception, during pregnancy and after delivery, pregnancy outcomes, clinical and laboratory parameters were collected. PE was diagnosed by the 2008 WHO criteria. The sFlt-1/PlGF ratio was used as the main differential marker to exclude GN exacerbation in cases of increased proteinuria.

Results

Rate of preterm birth was significantly higher in patients with LN compared to patients with IgA nephropathy (p = 0.002) and patients with unspecified GN (p < 0.0001), and also in patients with APS plus LN compared to patients with unspecified GN (p < 0.0001) and IgA nephropathy (p = 0.004). PE was observed in 24 patients (25%), type of GN did not affect the incidence of PE. Week of delivery was significantly lower in women with LN compared to IgA-nephropathy (p = 0.013) and unspecified types of GN (p = 0.001) and almost significantly lower in patients with LN plus APS than patients with IgA-nephropathy (p = 0.051) and unspecified types of GN (p = 0.06). Birth weight was significantly higher in babies born to women with unspecified types of GN compared to women with LN (p = 0.018) and LN plus APS (p = 0.047).

Conclusion

Although the rate of PE is similar, the risks of preterm births are high in LN and LN plus APS patients. In this study, laboratory parameters and medical therapy did not significantly affect the pregnancy outcomes.
P0486THROMBOTIC MICROANGIOPATHY IN A PATIENT WITH PERSISTENT CRYOGLOBULINEMIA AFTER HCV ERADICATION AND HETEROZYGOUS DELETION OF CFHR3-CFHR1 REGION: SHOULD WE TREAT WITH RITUXIMAB, ECULIZUMAB OR PLASMAPHERESIS?
Authors: Gallo Pamela , Gallo Pamela , Somma Chiara , Zullo Claudia , Lombardi Marco , Ferro Giuseppe , Dattolo Pietro Claudio
Published: June 2020

Background and Aims

Mixed cryoglobulinemia type II is a systemic vasculitis, caused by deposition of immune complexes in the endothelium of small vessels. Up to 90% are HCV infection related and usually resolve after eradication of the virus.

Method

We report the case of a patient with HCV related type II cryoglobulinemia, persistent despite the eradication of the virus with sofosbuvir and complicated by thrombotic microangiopathy.

Results

Since 2001 patient had cryoglobulinemic vasculitis treated with rituximab in 2002 and in 2011 for a relapse. In 2015 started antiviral therapy with sofosbuvir achieving sustained viral remission.

In December 2018 she admitted to hospital for fever, abdominal pain, diarrhea and oedema.

Blood exams showed acute kidney injury, (scar 3 mg/dl) proteinuria (2,6 g/24h) e microhematuria, haemolytic anaemia and thrombocytopenia, low C4, rheumatoid factor, cryocrit 4% (type II cryoglobulinemia), ANA, ENA e HCV RNA were negatives. On renal biopsy we found a thrombotic microangiopathy (fig.1,2). We rule out a lymphoma through PET total body e immunophenotype.

Conclusion

This report shows persistent cryoglobulinemia with vasculitis relapses, after HCV eradication with direct antiviral therapy (fig. 3), paying attention to complexity of immunological response, causing in this patient a TMA.

Intriguing in our report is the finding of TMA on renal biopsy, without other lesions, contrary to what expected. Cryoglobulinemic vasculitis are usually associated to membranoproliferative glomerulonephritis.

For this reason we search genetic mutation of complement genes, finding a heterozygous deletion on CHFR3-CHFR1 region. A pathogenic role of this deletion, is unknown, but it could mean a different target of therapy.
P0491THE ROUTE TO INDIVIDUALIZED THERAPIES IN PRIMARY MEMBRANOUS NEPHROPATHY: BMI AND KIDNEY OUTCOMES
Authors: Siligato Rossella , Laudani Alfredo , Gembillo Guido , Calabrese Vincenzo , Calderaro Alessandra , Vienna Federica giada , Laurendi Francesco , Cernaro Valeria , Santoro Domenico
Published: June 2020

Background and Aims

A real progress in treating patients more than diseases, would rest on tailored medicine and go beyond the hypothesis that “one size fits all”. Glomerular diseases are not an exception to this consideration, and deserve case-by-case evaluation for choosing both the most suitable therapeutic agent and its appropriate dose, because a standardized treatment may result in worse prognosis.

We analyzed the role of body mass index (BMI) in modifying renal outcomes of patients with nephrotic syndrome due to membranous nephropathy (MN) treated with immunosuppressive drugs.

Method

We performed a retrospective analysis of 29 MN patients related to our center (M 19, F 10), checking their anti PLA2R status at kidney biopsy time and any change in proteinuria, serum creatinine (SCr) and body mass index (BMI) between diagnosis and at last follow-up visit, in search of a correlation with their response to immunosuppressive treatment. Data with non normal distribution are expressed as median and interquartile range [IQR].

Results

The median follow-up of our patients lasted 49 months [IQR 14-80]. At biopsy time, almost half of them was anti-PLA2R positive (n=14 subjects) while the other resulted to be negative and were thus screened for secondary causes of MN (n=15). Irrespective either of anti-PLA2R status or the administration of Ponticelli regimen or Rituximab, complete remission was achieved in 31% of patients, while 34.5% experienced a partial remission and 34.5% resulted non responder to at least a therapeutic protocol. Median proteinuria reduction was of 3.732g/24h [IQR 7.636-1.77 g/24h]. Median rise in SCr was 0.140 mg/dl [IQR -0.11 – 0.4 mg/dl]. Direct association between the proteinuria/BMI ratio at diagnosis and remission of proteinuria at last follow up was statistically significant (r=-0.7506; P<0.0001) (Fig.1).

Conclusion

Albeit remission is not directly correlated with basal BMI, our results appear to confirm that an appropriate drug posology, not only according to patients’ renal or hepatic function but also to their body mass, may result in more effective individualized therapies in MN; nevertheless, this recorded association must be confirmed by large scale randomized clinical trials.
P0496THE IMPORTANCE OF COMPLEMENT LEVELS AND CLINICAL CHARACTERISTICS OF PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS IN TURKEY
Authors: Tatar Erhan , Oygar Deren , Seyahi Nurhan , Eren Necmi , Cantürk Yağmur , Güngör Özkan , Derici Ülver , Sipahioğlu Murat , Yıldız Abdülmecit , Karadağ Serhat , Sumnu Abdullah , Odabas Ali Riza , Turgut Didem , Cavdar Caner , SAHIN Garip , Dursun Belda , Guven Taymez Dilek , Yılmaz Aydın Fatma , Ulu Memnune Sena , Basturk Taner , Yadigar Serap , Bozaci Ilter , Behlül Ahmet , Sipahi Savaş , Bicik Bahçebaşı Zerrin
Published: June 2020

Background and Aims

Membranoproliferative glomerulonephritis (MPGN) may be caused by disturbances in the complement system. Hypocomplementemia is a characteristic of MPGN. Among these patients frequency of hypocomplementemia and their relation with clinical and histopathological findings are still not clearly known. The aim of this study is to evaluate the hypocomplementemia frequency among the primary MPGN patients in Turkey and its relation with histopathological subtypes, findings and demographic characteristics.

Method

The data was obtained from national multicentered (47 centers) records of primary glomerular diseases in Glomerulonephritis Study Group of the Turkish Society of Nephrology database from May 2009 to June 2019. Primary MPGN cases were evaluated and divided into 2 groups with and without hypocomplementemia.

Results

In total, 193 cases were included in the study. The indications for renal biopsy were isolated nephrotic syndrome (55.4%), nephritic syndrome (21.2%), nephrotic syndrome with a nephritic component (6.2%) and asymptomatic urinary findings (17.2%). 34.2% of the cases were reported as immune complex type, another 34.2% of the cases were reported as C3 glomerulopathy. 31.6% of patients were not specified. 82 (42.4%) of the cases presented hypocomplementemia. Hypocomplementemic patients were younger (34±14 vs 41±15, p=0.002) and most frequently female (56% vs 41%, p=0.03). At same time, serum albumin and hemoglobin levels were lower and anemic patient rates were higher (p<0.001). In this group, the nephrotic syndrome rates were higher (72% vs 54%, p=0,01). Hypocomplementemia rate in the C3 glomerulopathy was 52% (in DDD 40%, in C3GN 55% ) whereas in immune complex type 41% and in non specified type 34%. In the pathological evaluation; among the hypocomplementemic group the endocapillary proliferation and glomerular exudative differentiation rates presented significant increase. However the chronicity index were lower in the kidney biopsy (Table 1).

Conclusion

This multicenter study provided important data about the epidemiology of MPGN with importance of hypocomplementemia in Turkey. Hypocomplementemia is associated with both subtypes of MPGN patern, anemia and nephrotic syndrome. At the same time, hypocomplementemia is a valuable parameter for active MPGN pattern in the histopathological evaluation. This may be important in determining the treatment.
P0499SPONTANEOUS REMISSION IN PRIMARY MEMBRANOUS NEPHROPATY WITH POSITIVE ANTIPLA2R ANTIBODIES
Authors: ORTEGO SOFIA , Villacorta Javier , Fernandez Lucas Milagros , Carrasco Angela , RODRIGUEZ MENDIOLA NURIA , CASILLAS ESTHER , Lopes Vanessa , DIAZ MARTA , Rita Claudia , GAÑAN ISRAEL
Published: June 2020

Background and Aims

Patients with primary membranous nephropaty experience a spontaneous remission rate between 30-40%. AntiPLA2R antibodies are involved in the pathogenesis of the disease. Some studies demonstrated that levels of circulating anti-PLA2R in the beginning of the disease revealed a strong correlation with clinical disease activity, and it could help discriminate against those who will make spontaneous remission

Method

The principal objetive was to analize the spontaneous remission rate in patients with membranous nephropaty with positive antiPLA2R antiboidies and study clinical and serological variables associated. A retrospective analysis studied the assocaition between analitis, clinical and serological variables of patients with with spontaneous remission and membranous nephropaty who were diagnosed in between 2015 and 2018 in Ramon y Cajal Hospital.

Results

We included 13 patients with primary positive antiPLA2R antibodies membranous nephropaty. Patients ha a mean age of 61,6 ± 20 and a 64.3% were males. All of them had nephrotic syndrome in the onset disease. Patients were aged 6,6 ± 3.8 gr/24horas, in serum albumine 2.3 ± 0.5 g/L and the serum Creatinine (Cr) was 1 ± 0.5 mg/dl. Medium AntiPLA2R tittle was ±. All the patients were treated at the diagnosis time with ARB/ACE inhibitors . 7 of the 13 (53.8%) patients experienced a spontaneous remission of the nephrotic syndrome. The mean time to spontaneous remission was 4.8 ± 2.4 months. Patients who presented spontaneous remission debuted with lower serum Cr at debut. No significative differences were found in between remisión rate in association with total proteinuria neither PLA2R titles in the beginning.

Conclusion

In our experience, approximately a 50% of patients with membranous nephropaty experienced an spontaneous remission. There was no significative association in between AntiPLA2R titles and spontaneous remission rate in our study. Patients with better renal function in the diagnosis were more frequently associated with spontaneous remission.
P0500RESULTS OF A PHASE 1 TRIAL TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF BION-1301 IN HEALTHY VOLUNTEERS
Authors: Lo Jeannette , Van Zandvoort Peter , Van de Crommert Jos , Endsley Aaron , Müller Thomas , Honarmand Somayeh , Mittan Angelique , Barratt Jonathan , Walling Jackie , Essayan David
Published: June 2020

Background and Aims

IgA nephropathy (IgAN), the leading cause of primary glomerulonephritis, is an autoimmune disease with no approved treatments. Slow progression to end-stage-renal disease occurs in up to 50% of patients with IgAN over approximately 20-25 years, resulting in the need for dialysis or kidney transplant. A critical step in IgAN pathogenesis is the production of galactose-deficient IgA1 (Gd-IgA1) leading to the generation of anti-Gd-IgA autoantibodies and the formation of immune complexes that result in kidney inflammation and damage. Patients with IgAN have elevated levels of A proliferation-inducing ligand (APRIL), which may contribute to IgAN pathogenesis by regulating differentiation and proliferation of B cells. In a study of patients with IgAN, those with high plasma APRIL levels had higher levels of Gd-IgA1 and proteinuria and lower estimated glomerular filtration rates compared to those with lower plasma APRIL levels. BION-1301 is a first-in-class humanized antagonistic antibody targeting APRIL. BION-1301 reduced serum levels of IgA, IgM, and IgG with no drug-related toxicity in nonhuman primates and was well-tolerated with no dose-limiting toxicities in a Phase 1/2 first-in-human clinical study in patients with late-stage multiple myeloma. The Phase 1 trial described here will characterize the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of BION-1301 in healthy volunteers (HV) and patients with IgAN.

Methods

The protocol for this study (NCT03945318) is comprised of 3 parts, of which only Parts 1 and 2 are complete. Parts 1 and 2 assess BION-1301 in HV, and Part 3 will assess BION-1301 in patients with IgAN. Parts 1 and 2 are double-blind, randomized, placebo-controlled single and multiple ascending dose designs, respectively. Part 3 will assess a multiple dose regimen in IgAN patients. Part 1 enrolled 36 HV in 5 dose cohorts, randomized in a 3:1 ratio to receive a single dose of BION-1301 or placebo delivered by IV infusion. Part 2 enrolled 27 HV in 3 dose cohorts, randomized in a 2:1 ratio to receive 3 doses of BION-1301 or placebo delivered by IV infusion once every two weeks over a one month period. Dose escalation decisions were made by a Safety Review Team based on safety, tolerability, and PK-related stopping criteria.

Results

To-date, BION-1301 continues to be well tolerated. Its biological activity in the study is characterized by free APRIL, IgA, IgG, and IgM levels; unblinded safety, PK, and PD results for Parts 1 and 2 in Healthy Volunteers will be presented.

Conclusion

BION-1301, a humanized anti-APRIL antibody, may provide a novel avenue for the potential treatment of IgAN that offers potential advantages compared to currently used antihypertensive or immunosuppressive therapies.
P0509CLINICAL ANALYSIS FOR PROGNOSTIC FACTORS BASED ON RESULTS OF VERY SHORT-TERM TREATMENT IN MEMBRANOUS NRPHROPATHY
Authors: Iwashita Takatsugu , Takayanagi Kaori , Yamasaki Maiko , Aoyagi Mai , Shimizu Taisuke , Hasegawa Hajime
Published: June 2020

Background and Aims

Membranous nephropathy (MN) is known to affect frequently in elderly patients.

Since the duration of MN treatment is likely to be prolonged, it is desirable that the treatment duration would be shortened by the concomitant use of immunosuppressant and prednisolone (PSL). Therefore, we evaluated prognostic factors using the results of treatment in a very short period of time in patients with membrane nephropathy at our hospital.

Method

Biopsy-proven 66 cases with MN, hospitalized between April 2009 and December 2017, were enrolled in this study.

All cases were divided between two groups, high responder and low responder, based on the 50% proteinuria-reduction ratio at a month after the beginning of therapy including sole administration of PSL and concomitant use of immunosuppressants such as Cyclosporin or Mizoribine.

High responder and low responder were comparatively studied.

All biopsy specimens were stained by anti-phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) antibodies by standard protocol.

Results

Estimated glomerular filtration rate (eGFR) was 70.5 vs 60.4 ml/min (p = 0.087), showing no difference.

Baseline urine protein-to-Cr ratio (PCR) and degree of hematuria in high responder were significantly higher than those in low responder; baseline PCR: (6.95 vs 3.86, p = 0.003), degree of hematuria: (1 vs 0, p = 0.036)

There was no difference in intensity of immunofluorescent staining of IgG, A, M, C3 between high responder and low responder. We also studied the difference in immunofluorescent intensity of PLA2R, THSD7A and IgG subclass. Intensity of IgG3 and ratio of PLA2R/IgG4 intensity in low responder were significantly higher than those in high responder; IgG3 intensity: (0 vs 0.5, p = 0.049), PLA2R/IgG4 ratio: (0.58 vs 1.00, p = 0.029)

Conclusion

Obtained results showed that higher baseline PCR and degree of hematuria might be related to the rapid therapeutical response.

On the other hand, higher staining intensity of IgG3 and PLA2R/IgG4 intensity ratio might reduce the response of treatment.
P0510INFLAMMATORY BOWEL DISEASE IN KIDNEY TRANSPLANTATION:CASE REPORT
Authors: Gana Abir
Published: June 2020

Introduction

Kidney transplantation has become the treatment of choice for chronic end-stage renal disease because it improves not only the quality of life of patients but also their survival rate. However, several complications can be observed in transplant patients such as immune rejection, infections and recurrence of initial nephropathy etc.

Case summary

A 21-year-old man diagnosed with chronic end-stage renal failure 5 years ago with a renal biopsy showing an aspect of proliferative glomerulonephritis.

The study of the alternate complementary path show a C3 low level, C4 and CH50 normal level, H factor and I factor was normal too. The patient presented purpuric skin lesions with a biopsy of granular deposits of C3. We started extra renal purification by peritoneal dialysis and the patient had, one year later, a kidney transplant from his mother. Ten month later, we have notice a progressive renal function decline with an aspect of proliferative membranous glomerulonephritis with deposits predominant of c3 in graft biopsy. The diagnosis of the recurrence of the initial nephropathy was made but the treatment was delayed by the onset of cutaneous leishmaniosis. Few months later the patient was presented with diarrhea lasting more than a month, which led us to do a colonoscopy, which objectified an aspect of chronic inflammatory bowel disease evoking earlier a Crohn's disease.

Therefore, we stopped tacrolimus and put the patient on full dose corticosteroid therapy and azathioprine without having a remission, and appearance of skin lesions at the elbow and pelvis evoking pyoderma gangrenosum in skin biopsy. In addition, the patient has presented an ischemic retinal damage probably related to a deregulation of the alternate complement pathway.

Discussion

The complement system is not only a host defense system against microbes, but also a surveillance system that contributes to maintain tissue homeostasis and tissue repair. However, uncontrolled complement activation can induce tissue damage, and inappropriate activation is involved in the pathogenesis of various conditions like autoimmune diseases, sepsis and transplant and extensive inflammation and tissue damage. The impairment of alternative path can explain the extra-renal manifestation of this patient especially the appearance of inflammatory bowel disease witch can be explained by impaired local immune defense in the gut.

Conclusion

Immune system abnormalities can occur after kidney transplantation this leads to the appearance of several inflammatory abnormalities such as chronic inflammatory bowel disease which may in our case be due to an abnormality of the alternate pathway of the complement.
P0534THE EFFECT OF HIGH FAT DIET INTAKE AND FOOD SUPPLY RESTRICTION ON CISPLATIN NEPHROTOXICITY IN MICE
Authors: Kim Ji Su , Kong Min Jung , Park Kwon Moo
Published: June 2020

Background and Aims

Nephrotoxicity is a major side effect of cis-diamminedichloroplatinum (II) (cisplatin), which is widely used for cancer therapy. The nephrotoxicity is associated with the excessive formation of reactive oxygen species (ROS) and oxidation of cell components. Here, we investigate whether cisplatin nephrotoxicity can be controlled by the regulation of food supply which is associated with cellular production of ROS.

Method

Male mice were administered with either cisplatin or saline. Before cisplatin administration, mice were high-fat diet (HFD) feeding for 7 days, no-food supply for 2 days, 2 days no-food supply and refeeding with normal diet (ND), and normal diet. Renal function was analyzed by plasma creatinine (PCr) and blood urea nitrogen (BUN) concentration. Kidney cell damage was evaluated by periodic acid shiff staining and transmission electron microscope analysis.

Results

Cisplatin injection induced the disruption of kidney tubular cells and also increased BUN and PCr concentration. These increases were greatest in the HFD feeding mice, whereas .these increases were lowest in the food restricted mice. Levels of DNA oxidation and lipid peroxidation increased in the kidney after cisplatin injection and these increase were also greatest in the kidney of HFD feeding mice and lowest food restricted mice. Mitochondrial damage was observed in the proximal tubule cells after cisplatin injection and this mitochondria damage was more severe in the HFD feeding mice than ND feeding mice. Cisplatin increased the expression of fission 1 in the kidney, whereas reduced the expression of opa-1 expression. These cisplatin induced changes were greater in the HFD feeding mice than the ND feeding mice.

Conclusion

High fat diet feeding worsens cisplatin-induced nephrotoxicity along with increased oxidative stress and mitochondrial damage, whereas food restriction reduces this cisplatin nephrotoxicity. These data indicate that cisplatin nephrotoxicity is controlled by food supply, suggesting that energy metabolism is associated with cisplatin nephrotoxicity.
P0535ATG5 OVEREXPRESSION IN PACS SIGNIFICANTLY IMPROVES CELL-MEDIATED AKI PROTECTION
Authors: Patschan Daniel , Schwarze Katrin , Ritter Oliver , Patschan Susann , Müller Gerhard Anton
Published: June 2020

Background and Aims

Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. Cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies performed in recent years utilized Pro-angiogenic Cells (PACs). Autophagy (AP) is commonly regarded as process of en-dogenous self-defense. The AP cascade, which may be stimulated by either substrate deprivation or certain exogenous / endogenous stressors, involves the activation of numerous proteins, the so-called Autophagy-related proteins (Atg proteins). Among these, Atg5 has been suggested to play a key role in augmenting AP. The current study evaluated whether selective Atg5 activation in syngeneic murine PACs may result in improved cell-mediated AKI protection.

Method

Cultured murine PACs were selectively transfected for Atg5. Successful transfection was verified by detecting red fluorescing cells. AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI - 40 minutes). Transfected cells were i.v. injected post-ischemia. Mice were analyzed 48 hours and 6 weeks later.

Results

IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels (48 hours and 6 weeks). Cell administration (either native or after transfection) did not improve AKI outcomes at 48 hours. At 6 weeks, injection of native cells resulted in lower serum cystatin C, this effect was even more pronounced if transcfected cells were applied.

Conclusion

Together, our data show that selective Atg5 overexpression in murine PACs sub-stantially augments cell-mediated AKI protection in the long-term. Thus, a new strategy for improving AKI protective effects of PACs has been identified.
P0543NQO1ATTENUATES RENAL INJURY BY RENAL ISCHEMIA REPERFUSION OF MICE
Authors: Lee Kang Wook , Jeong Jin Young , CHOI DAE EUN , Na Ki Ryang , Kim Haeri , Ham Young Rok , Choi Wonjung , Chang Yoon-Kyung , JEON JAE WAN
Published: June 2020

Background and Aims

Ischemia-reperfusion (I-R)-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. We investigate whether NQO1 modulates the renal I-R injury.

Method

C57BL/6N NQO1-deficient mice (NQO1/) were generated. Mice were sacrificed at 4, 12, 24, and 48 h after the surgical procedure. I-R was performed using vascular clamp for 30min. We analyzed renal function, oxidative stress, and tubular apoptosis after I-R injury.

Results

NQO1/ mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1/ mice, the cellular NADPH/NADPþ ratio was significantly higher and NOX activity was markedly higher than in those of NQO1þ/þ mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I-R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADPþ ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I-R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADPþ modulation.

Conclusion

NQO1 activation might be beneficial for ameliorating renal injury induced by I-R.
P0544INHIBITION OF 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE (15-PGDH) PROTECTS MICE AGAINST CONTRAST-INDUCED ACUTE KIDNEY INJURY
Authors: KIm Byeong Woo , Kim Sun hee , Bae Ki beom
Published: June 2020

Background and Aims

Although the mechanism of contrast-induced acute kidney injury (CI-AKI) is not fully known, the imbalance of vasoconstrictive and vasodilative mediators plays a major role. Prostaglandin E2 (PGE2) is one of the vasodilators involved in this process. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) causes elevation of PGE2 level in tissue by delaying the rapid degradation of PGE2 by the enzyme. We tested the hypothesis that the 15-PGE2 inhibitor would protect against CI-AKI in a mouse model and attempted to elucidate the mechanism involved.

Method

10-week aged male C57/BL6 Mice were injected with 10gI/kg of iodixanol by tail vein. Renal blood flow measurement, right nephrectomy, and blood sampling were taken at 48 hours after iodixanol injection. The 15-PGDH inhibitor was injected before and after iodixanol administration. Plasma creatinine, NGAL, KIM-1 were measured as biomarkers for renal function. Histological evaluation was analyzed by the necrosis scoring system and TUNEL assay. Arteriolar area of outer medulla was analyzed by α-smooth muscle actin stain. Renal blood flow was measured by the non-invasive laser doppler.

Results

Plasma creatinine (1.94±0.75 vs 1.11±0.44 mg/dL, p=0.005), NGAL (299.7±115.87 vs 140.4±76.56 ng/mL, p=0.004), and KIM-1 (2.09±2.34 vs 0.43±0.89 ng/mL, p=0.024) levels were significantly lower when the 15-PGDH inhibitor was injected before and after iodixanol administration than the vehicle group. But no significant renal protective effect was shown when the 15-PGDH inhibitor was injected before or after iodixanol administration. The 15-PGDH inhibitor administration before and after iodixanol injection showed a significantly wider renal arteriolar area (683.63±248.46 vs 1132.97±357.46 μm2, p=0.039) and larger renal blood flow (360.0±49.72 vs 635.1±27.20, p=0.011) than vehicle administration.

Conclusion

The 15-PGDH inhibitor has a renal protective effect against CI-AKI in mice by increasing renal blood flow when injected intravenously before and after iodine contrast media administration.
P0553PROTECTIVE EFFECT OF (-)-ALPHA-BISABOLOL OVER RENAL CYTOTOXICITY INDUCED BY AMPHOTERICIN B
Authors: Paula Magalhães Emanuel , Pinheiro Silva Brenna , Paula Pessoa Bezerra de Menezes Ramon , Lima Sampaio Tiago , Bandeira Lima Danya , Bezerra da Silva Junior Geraldo , De Francesco Daher Elizabeth , Costa Martins Alice Maria
Published: June 2020

Background and Aims

Drug-induced acute kidney injury (AKI) is a health problem that increases morbidity and mortality rates as well as costs to health systems. Amphotericin B (AnB) is a widely used antifungal, which its therapy is closely associated with nephrotoxicity. The mechanisms of nephrotoxicity are not yet fully understood and there is a need to search for substances that prevent and / or reverse the associated renal damage. (-) - α-Bisabolol (BIS) has been demonstrated nephroprotective effect due to its antioxidant action. Thus, the aim of this study was to evaluated the effect of BIS as a protective substance on renal cell injury induced by amphotericin B.

Method

LLC-MK2 tubular renal cells were treated with different concentrations of BIS and AnB and its viability was measured by MTT assay to define the working concentrations of BIS and AnB. Then, cells were pretreated or post treated with BIS (31.25 - 125 μM) and AnB (13.97 μM) for 24 hours to evaluate the protective effect of BIS. Control (CT) was treated with sterile PBS. The experimental groups were further submitted to flow cytometry assays for membrane integrity evaluation using 7-AAD and measurement of cytoplasmic ROS production using DCFH-DA. The experiments were performed in triplicate (n = 3), and the data analyzed by One-Way ANOVA with Bonferroni post-test.

Results

BIS concentrations from 31.25 to 125 μM were selected, as well as the IC50 for AnB (13.97 ± 1.45 μM) for the furthers assays. Pretreatment with BIS increased cell viability by about 10% (31.25 – 63.31 ± 2.04%; 62.5 – 64.75 ± 2.10%; 125 – 63.92 ± 2.72%) compared to the AnB-only group (49.79 ± 1.25%), which had its cell viability reduced by about 50% (CT – 100.70 ± 0.83%). BIS was also able to increase the whole cell population at concentrations of 62.5 (83.10 ± 1.10%) and 125 μM (84.67 ± 0.98%) when compared to the AnB group (76.54 ± 1.18%). In DCF labeling, it was observed that AnB increased the production of ROS in 20% (IFR = 1.21 ± 0.02) when compared to the control (IFR = 1.00 ± 0.01), and BIS (31.25 μM) was able to reduce in 41% (IFR = 0.79 ± 0.01) when compared to the AnB group.

Conclusion

The (-)-α-bisabolol was able to prevent the renal cytotoxicity induced by amphotericin.
P0554IN VITRO ASSESSMENT OF HA330 CARTRIDGE ADSORPTION CAPACITY REALTED TO VANCOMYCIN
Authors: Lorenzin Anna , Godi Llaria , De Cal Massimo , Ronco Claudio
Published: June 2020

Background and Aims

The rationale for blood purification as adjunctive therapy during sepsis involved the capacity in removing endogenous and exogenous toxins, but currently no recommendations exists [1]. A critical point may be the potential interaction with antimicrobial therapy, which remains the mainstay of sepsis treatment. HA330 cartridge (Jafron, Zhuhai City, China), widely used in China and actually available in Europe, is used in hemoperfusion for blood purification in septic patients.The aim of this in vitro study was to investigate the adsorptive capacity of HA330 related to vancomycin (VAN).

Reference: 1. Rhodes A et al. Crit Care Med 45:486-552. 2017

Method

This is an experimental study, simulating an hemoperfusion treatment with HA330. We circulated (250 ml/min) in a closed loop 500 ml of normal saline solution enriched with VAN, stirred and maintained at 37°C. We spiked 100 mg of VAN every 15 minutes to increase the antibiotic load until reaching 1500 mg, the last injection was 500 mg to get a total amount of 2 g. Samples were collected from the inlet line at each VAN adjunct, after system stabilization. Measured VAN concentrations were used to get the adsorption isotherm: for each VAN load, the adsorbed amount of VAN was obtained by multiplying VAN reduction ratio and the quantity of VAN injected.

Results

Figure 1 shows VAN adsorption isotherm obtained with HA330 cartridge. We observed that, at each injection, after 15 minutes VAN was almost entirely adsorbed by the cartridge, with an average reduction ratio of 0.96. Interestingly, this was confirmed even adding 500 mg at once. Even increasing the VAN load to 500 mg at once, the reduction ratio was maintained.

Conclusion

In our study, simulating hemoperfusion using HA330, a rapid and clinically relevant removal of VAN has been shown. A significant amount of VAN (2g) was adsorbed without reaching membrane saturation nor reducing its adsorptive capacity.

In a clinical setting, we recommend a therapeutic drug monitoring to optimize VAN levels during blood purification with HA330 and a VAN loading dose may be considered. Further in vivo studies are warranted to confirm these findings.