bluuebunny/crossref_metadata_2025 huggingface dataset:
P0306ACUTE KIDNEY INJURY AFTER CHECKPOINT INHIBITOR TREATMENT: FACING THE FUTURE
Authors: Garcã­a Carro Clara , Bolufer Mónica , Oleas Diana , Azancot María A , Agraz Irene , Ramos Terrada Natalia , Espinel Eugenia , Seron Micas Daniel , Soler María José
Published: June 2020

Background and Aims

Checkpoint inhibitors (CPI) are used to treat solid organ metastatic malignancies. They act on by triggering a vigorous immune response against tumoral cells, preventing their proliferation. CPIs reinvigorate antitumor immune responses by interrupting co-inhibitory signaling pathways and promote immune-mediated elimination of tumor cells.This is not a selective response, deriving in immune related adverse events (irAEs). The kidney can potentially be damaged with an incidence of 13-29%. The most frequent type of toxicity is acute interstitial nephritis (AIN).

Method

We evaluated all the patients with solid organ metastatic malignancies treated with immunotherapy that developed acute renal injury (AKI) and underwent to kidney biopsy from March 2018 to November 2019 at Vall d’Hebron University Hospital.

Results

11 patients with solid organ metastatic malignancies treated with immunotherapy developed AKI and underwent to kidney biopsy during the study period. The most frequent malignancy was lung cancer - in 6 patients-, followed by 3 patients with melanoma. 8 patients (72%) had already received previous oncological therapy, and for the remaining 3 patients (27%), CPI was the first line therapy. 8 patients (72%) were treated with anti-PD1 (programmed cell death protein 1), 4 patients (36 %) received anti PDL-1 (programmed death-ligand 1) 1 of these patients in combination with an anti CTLA-4 (cytotoxic T-lymphocyte antigen 4) and another patient received both anti PD1 and anti PDL-1. The time between the start of CPI and the onset of the AKI ranged between 2-11 months. The most frequent urine findings were subnephrotic range proteinuria with a mean protein/creatinine (mg/g creatinine) 503.6 ± 190.5 and leukocyturia in 9 of 11 patients. Mean creatinine (mg/dl) at diagnosis was 3.4 ± 1.3. 10 out of the 11 patients were diagnosed of AIN after performing a kidney biopsy. The remaining patient presented chronic changes (IFTA and glomerulosclerosis) in the biopsy, performed after receiving steroids for a month. 3 patients who presented AIN received pulses of methylprednisolone 250-500mg as induction treatment and 7 patients received prednisone 1mg/kg/day. Mean prednisone accumulated dose (mg) during the first month of treatment was 1387.5 ± 540. 9 patients experienced complete recovery of kidney function and two patients progressed to CKD.

Conclusion

We reported 11 patients who presented AKI associated to CPI treatment and underwent to kidney biopsy in the last 20 months at our center. 10 out of 11 presented biopsy confirmed CPI related AIN. In our experience, CPI related AIN is the most frequent renal lesion associated to the novel immunotherapy treatments. This entity seems to have good renal prognosis as long as steroid treatment is early started.
P0324SODIUM ZIRCONIUM CYCLOSILICATE TO PREVENT HYPERKALAEMIA IF HAEMODIALYSIS IS POSTPONED DUE TO VASCULAR ACCESS COMPLICATIONS: EXPERIENCE FROM CLINICAL PRACTICE
Authors: Brooks Owain , Mikhail Ashraf , Brown Chris , Gumbleton Mark , Jenkins Justine , Boyle Kaitlin
Published: June 2020

Background and Aims

Vascular access is a fundamental aspect of haemodialysis (HD) treatment. Vascular access may be compromised due to central venous catheter (CVC) thrombosis, arterio-venous fistula (AVF) or graft (AVG) stenosis, infections or perioperative complications that require urgent resolution or the formation of alternative emergency or definitive access. Sodium zirconium cyclosilicate (SZC) (Lokelma®) is a new oral potassium binder. We offer an insight into SZC treatment to prevent hyperkalaemia in patients where HD is postponed due to vascular access complications.

Method

Adult prevalent HD patients were included for analysis. Each patient was unable to receive their full scheduled HD treatment due to a vascular access complication. SZC was prescribed on the day HD was not possible (D1) until the vascular access issue was resolved and HD could recommence. The primary efficacy measures were the prevention of increases in serum potassium (sK+), the safe postponement of HD and the avoidance of emergency hospital admission.

Results

Four patients receiving thrice-weekly HD (mean age 69 years, all male) received SZC for a mean duration of 3.5 days (min 2 days, max 6 days). No patients were admitted during these acute episodes. The mean pre-dialysis sK+ on D1 was 6.0mmol/L (K1). No post-dialysis sK+ values were obtained on D1 because HD was not possible or cut-short (Table 1).

For patients 2 and 3, one and 10 HD treatments preceded the next sK+ (K2) respectively. sK+ reduced from 5.8mmol/L (K1) to 4.8mmol/L (K2) for patients 1 and 4 (Table 1). No statistical analyses were undertaken due to the low patient numbers.

HD was delayed beyond the scheduled treatment date for 3 of the 4 patients, with a mean delay of 1.75 days (min 0 days, max 3 days) (Table 2). There was no delay between HD treatments for patient 2, who only received 1 hour HD treatment on D1. The last full HD treatment for patient 2 was 3 days prior to D1. A gap between SZC initiation (D1) and the next HD treatment was seen for all four patients, with a mean gap of 2 days (min 1 day, max 3 days) (Table 2).

Conclusion

Sodium zirconium cyclosilicate can be used to successfully reduce, or avoid an increase in sK+ in mild to moderate hyperkalaemia, avoid emergency hospital admission and allow HD to be postponed for a valuable short period until HD vascular access can be re-established.
P0326EFFECT OF PRAVASTATIN ON ERYTHROCYTE MEMBRANE FATTY ACID CONTENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Lee Sumi , Choi DongHo , Jeong Yu In , Son Young Ki , Kim Seong Eun , An Won Suk
Published: June 2020

Background and Aims

Treatment with statin has been decreased the risk of cardiovascular events in patients with chronic kidney disease (CKD). Erythrocyte membrane oleic acid contents are significantly higher in patients with acute coronary syndrome than control subjects. Still, there is no report about the effect of statin on erythrocyte membrane fatty acid (FA) including oleic acid. The aim of this study was to evaluate the effect of pravastatin on the erythrocyte membrane FA in patients with CKD.

Method

Sixty two CKD patients were enrolled in this single arm randomized clinical trial and this trial was conducted at two centers from Jan 2017 to March 2019 (NCT02992548). Pravastatin with dose of 20mg was initially treated for 24 weeks. Pravastatin dose was increased to 40mg after 12 weeks, if it is necessary to control dyslipidemia. The primary outcome of this study was the change of erythrocyte membrane FA including oleic acid after pravastatin treatment for 24 weeks. We checked total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol and adiponectin for secondary outcome at baseline and after 24 weeks. Erythrocyte membrane FA contents were measured by gas chromatography at baseline and after 24 weeks.

Results

Forty-five patients finished this study (age: 59.2±12.4 years, male: 42.2%, diabetes: 48.9%). There was no adverse effect related with pravastatin. Baseline serum creatinine was 1.5±0.7 mg/dL and estimated glomerular filtration rate was 54.2±27.3 ml/min/1.73 m2. Compared to baseline, total cholesterol (223.1±50.8 mg/dL vs. 168.4±32.5 mg/dL), LDL-cholesterol (149.1±35.3mg/dL vs. 100.1±25.4 mg/dL) and C-reactive protein were significantly decreased after pravastatin treatment. There were no significant changes in triglyceride, HDL-cholesterol, serum creatinine, amounts of proteinuria and adiponectin levels. Saturated FA, oleic acid and arachidonic acid contents of erythrocyte membrane were significantly increased after pravastatin treatment compared to baseline levels. Polyunsaturated FA (PUFA) and linoleic acid were significantly decreased after pravastatin treatment compared to baseline. Decreased tendency of eicosapentaenoic acid and omega-3 index were found after pravastatin treatment.

Conclusion

Linoleic acid or omega-3 FA supplementations may be necessary to recover erythrocyte membrane FA changes, when pravastatin is used for dyslipidemia treatment in CKD patients. Further study for reducing cardiovascular events are necessary by using combined PUFA and pravastatin treatment.
P0335PULMONARY HEMORRAHGE IN IG A NEPHROPATHY: A RARE MANIFESTATION
Authors: Hanen Abid , Amel Harzallah , Chifaa Trigui , Soumaya Chargui , Rim Goucha , Fathi Ben Hamida , Mondher Ounissi , Taieb Ben Abdallah
Published: June 2020

Background and Aims

Ig A nephropathy is the most frequent cause of glomerulonephritis worldwide. Renal-limited disease is the habitual clinical form of the disease. Pulmonary involvement may also be seen in rare cases. Capillaritis with pulmonary hemorrhage is the most frequent pulmonary involvement and is lifethreatening. We reported the case of patient presenting a rapidly progressive glomerulonephritis with pulmonary hemorrhage revealing Ig A nephropathy.

Method

A case report

Results

A 23 year-old man admitted for a rapidly progressesive glomerulonephritis with sever hypertension. He presented a respiratory distress with hemoptysis. At biology serum creatinine was at 2200µmol/l (eGFR = 2.4 ml/min) and Hemoglobin was at 5g/dl. Immunoassays of anti-glomerular basement antibodies and antineutrophil cytoplasmic autoantibodies were negatives.

Computed tomography scan showed diffuse intra alveolar hemorrhage associated with pleural effusion. Bronchoalveolar lavage confirms this diagnosis. Renal histology showed Ig A nephropathy.

Treatment consisted of daily depleted haemodialysis with blood transfusion and corticosteroids associated with monthly pulses of cyclophosphamide. His hemoptysis gradually resolved with a stable hemoglobin at 11 g/dL. However, renal failure persisted requiring maintenance hemodialysis regularly.

Conclusion

Pulmonary hemorrhage is a rare but serious complication of Ig A Nephropathy which is associated with significant morbidity and mortality. The exact cause for this “extra renal bleed” in Ig A Nephropathy is not known but it possibly represents IgA capillaritis. Though no evidence-based treatment protocol exists, therapeutic options includes steroids, plasmapheresis, cyclophosphamide and rituximab.
P0348THE DUAL ENDOTHELIN ETA AND ANGIOTENSIN AT1 RECEPTOR BLOCKER SPARSENTAN PROTECTS AGAINST THE DEVELOPMENT OF ALBUMINURIA AND GLOMERULOSCLEROSIS IN THE GDDY MOUSE MODEL OF IGA
Authors: Nagasawa Hajime , Suzuki Hitoshi , Jenkinson Celia , Ueda Seiji , Fukao Yusuke , Nakayama Maiko , Otsuka Tomoyuki , Liu Kai , Komers Radko , Suzuki Yusuke
Published: June 2020

Background and Aims

gddY mice are an IgA nephropathy (IgAN)-prone mouse model that develops albuminuria by 8 weeks (wks) of age with glomerular IgA, IgG, and C3 deposits and progressive mesangioproliferative glomerulonephritis. A previous study in the ddY mouse model, the more genetically heterogeneous predecessor of gddY mice, using the endothelin type A receptor (ETAR) antagonist FR139317 resulted in amelioration of proteinuria and preservation of kidney function. Treatment of ddY mice with the angiotensin II type 1 receptor (AT1R) blocker valsartan resulted in significant protection from glomerulosclerosis (GS) without a significant prevention in proteinuria. Here we examined the effect of sparsentan (SP), a dual ETAR and AT1R blocker, currently in phase 3 trials for focal segmental glomerulosclerosis and IgAN, on the development of albuminuria and GS in gddY mice.

Method

gddY mice at 4 wks of age were fed with control (C) chow (n=5) or chow containing 900 ppm (n=10) or 1800 ppm (n=10) SP (approximately 180 and 360 mg/kg/day) for 8 wks. Albuminuria (U-Alb) was assessed at 4, 6, 8, and 12 wks of age and plasma levels of SP were determined at 8 am and 4 pm at wks 6, 8, and 12. Kidney biopsies were taken at the end of the study at 12 wks of age for processing and 30 glomeruli per animal were scored for the percentage of GS.

Results

gddY mice fed SP in the diet for 8 wks from 4 wks of age demonstrated significantly (*P<0.05) decreased U-Alb compared to mice fed the C diet in a dose-dependent manner (Figure 1). The development of GS in mice fed the diet containing 1800 ppm SP was significantly (*P<0.05) attenuated compared to C diet (Figure 2). Plasma levels of SP taken at 8 am and 4 pm after 8 wks of treatment were (mean±SD) 281±107 and 105±62 ng/ml for 900 ppm SP respectively, and 774±674 and 304±176 ng/ml for 1800 ppm SP, respectively. Weight gain in mice fed SP was not different from mice that received C diet.

Conclusion

Eight weeks of treatment with SP attenuated increases in albuminuria and GS associated with the development of IgAN in gddY mice. If translated to the clinic, these data support SP as a new approach to the treatment of IgAN.
P0349A MISSPROCESSED FORM OF APOLIPOPROTEIN A-I IS SPECIFICALLY ASSOCIATED TO RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Authors: Jacobs Cachá Conxita , Puig Gay Natàlia , Helm Dominic , Rettel Mandy , Sellares Joana , Meseguer Anna , Savitski Mikhail M , Moreso Francesc , Soler María José , Seron Micas Daniel , López Hellín Joan
Published: June 2020

Background and Aims

Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation. There are no accurate means to diagnose the relapses or to detect the patients at risk. In an exploratory study we detected Apolipoprotein A-Ib (ApoA-Ib), a high molecular weight form of ApoA-I, specifically in urine of kidney transplanted patients that relapsed of FSGS. The diagnostic performance of ApoA-Ib has been assessed in two independent cohorts obtaining high specificity (94,1 %) and sensitivity (87,5 %) to detect FSGS relapses. It has also a potential to detect patients at risk of relapse as ApoA-Ib predates the recurrence episodes in most of the cases. As urinary ApoA-Ib is strongly associated to primary FSGS we aimed to unravel the nature of the modification present in ApoA-Ib.

Method

The whole APOA1 gene was sequenced in ApoA-Ib positive and negative patients and the protein structure was studied using 2D electrophoresis followed by mass spectrometry.

Results

No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in the molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I). These results suggest that proApoA-I is miss-cleaved producing ApoA-Ib probably due to an altered protease activity in recurrent FSGS patients

Conclusion

ApoA-Ib, found specifically in urine of recurrent FSGS patients, is a misprocessed form of ApoA-I that retains three aminoacids of the six-aminoacid N-terminal propeptide of proApoA-I. The description of ApoA-Ib could be relevant not only to allow the automated analysis of this biomarker in the clinical laboratory but also to shed light into the molecular mechanism of idiopathic FSGS.
P0353EFFECT OF RITUXIMAB IN PATIENTS WITH RELAPSED OR REFRACTORY PRIMARY MEMBRANOUS NEPHROPATHY
Authors: Akyildiz Arif , Uludag Omer , Mirioglu Safak , Ucar Ali Riza , Demir Erol , Caliskan Yasar Kerem , Ozluk Yasemin , Turkmen Aydin , Sever Mehmet Sukru , Yazici Halil
Published: June 2020

Background and Aims

Membranous nephropathy (MN) is the most common cause of glomerulonephritis in non-diabetic adults. B-cell dysfunction is an important pathway involved in pathogenesis. We, therefore, investigated effects of rituximab (RTX) on the outcome of patients with relapsed or refractory primary MN.

Method

In this retrospective analysis, 48 patients with primary MN were evaluated. Patients, who had relapsed or refractory biopsy-proven disease, with a nephrotic-range proteinuria despite at least six months of prior immunosuppressive therapy using corticosteroids, calcineurin inhibitors or mycophenolic acid derivatives, which were used according to KDIGO guidelines. All patients received at least 2 doses of 375 mg/m2 of RTX. Proteinuria and serum albumin levels of the patients were recorded at baseline, and 3,6,12,18 and 24 months.

Results

Of 48 patients who participated in this study, 27(56.3%) were male. Mean age was 45.3±17.2 years. Results of serum anti-phospholipase-A2-receptor (PLA2R) were available in 31 patients, 23 of whom (74%) were positive. Proteinuria levels at 3, 6, 12, 18, and 24 months after treatment with RTX showed a significant decrease when compared to baseline (p<0.05) (Figure 1): From 7±3.5 g/24h at baseline to 2.6±2.4 g/24h at 12 months. Serum albumin levels at 3, 6, 12, 18, and 24 months after RTX significantly increased compared to baseline values (p<0.05) (Figure 2): From 2.97±0.76 g/dl at baseline to 3.88±0.67 g/dl at 12 months.

Conclusion

Treatment with RTXiseffective in patients suffering from relapsed or refractory primary MN.
P0365INCREASED LIFETIME RISK OF END-STAGE RENAL DISEASE IN FAMILIAL IGA NEPHROLOGY
Authors: Xie Jingyuan
Published: June 2020

Background and Aims

Familial IgA nephropathy (IgAN) has been widely reported around the world. However, it's clinico-histological characteristics and long-term prognosis are not clear.

Method

In this study, 348 familial IgAN cases from167 independent IgAN families were recruited and their clinico-histological characteristics were compared to 1,116 sporadic IgAN patients from the same geographic region. Inheritance patterns, clinical features, and treatment regimens of all recruited patients were recorded and lifetime risk of end-stage renal disease (ESRD) was compared between familial and sporadic cases.

Results

Of all familial IgAN patients, 60 (17%) came from 32 single-generation (SG, defined as all affected individuals are siblings) families, while 286 (82%) came from 134 multiple-generation (MG, affected individuals were present in at least two consecutive generations) families. There’re totally 178 transmissions, 79 of which (44%) were paternal transmission and 99 (56%) were maternal transmissions. We observed evidence for incomplete penetrance in 30 (22%) MG families. The lifetime risk of progression to ESRD was significantly higher in familial IgAN patients than sporadic patients after adjusted by gender [HR=1.40, 95%CI: 1.12-1.74, P=0.004], with 5-year younger in median ESRD onset age [median ESRD-free survival of 60 years vs. 65 years in familial and sporadic cases separately]. As expected, compared to the ones without progressive renal failure at disease onset (eGFR≥60ml/min), familial cases with progressive renal failure (eGFR<60ml/min) had higher risk of lifetime ESRD [HR=6.32, 95%CI: 3.73-10.72, P<0.001]. Interestingly, among familial cases, we found cases from SG families [vs MG families: HR=2.62, 95%CI: 1.59-4.31, P<0.001] or with early onset (onset age <30yrs) [vs late onset: HR=4.79, 95%CI: 3.16-7.26, P<0.001] had higher lifetime risk of ESRD. Furthermore, among sporadic patients, compared to females, males had lower eGFR, higher urine protein, higher Oxford T score and resulted in a higher risk for lifespan ESRD (male vs female, 25% vs 17%, P=0.003) while these gender difference was not seen in familial patients.

Conclusion

In conclusion, familial IgAN cases had poorer renal outcomes and less gender differences compared to sporadic cases. These findings provide evidence that familial disease represent a distinct subtype of more progressive IgAN.
P0367STATIN THERAPY AS A PROTECTOR FACTOR OF VENOUS THROMBOEMBOLIC EVENTS IN PATIENTS WITH ANCA-GLOMERULONEPHRITIS ?
Authors: HENRY NICOLAS , Renaud GANSEY , Assia DJEMA , Giorgina PICCOLI , Jean François SUBRA , Jean François AUGUSTO
Published: June 2020

Background and Aims

The incidence of venous thromboembolisms (VTE) is greatly increased in patients with anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV). However, its incidence and risk factors in patients with ANCA-glomerulonephritis (ANCA-GN) has been poorly analyzed. Thus, the aim of the present study was to assess the frequency, the risk factors and outcomes of patients with VTE after ANCA-GN diagnosis.

Method

Patients from the Maine-Anjou AAV registry with a biopsy showing pauci-immune glomerulonephritis between 01/01/2000 and 01/01/2019, were included. VTE events, the site and delay from AAV diagnosis were retrieved from patient’s medical records.

Results

Among the 165 patients, 133 fulfilled the inclusion criteria and were analyzed. After exclusion of arterio-venous fistulae thrombotic events, VTE episodes were diagnosed in 23/133 (17.3%) at a median delay of 3 months from ANCA-GN diagnosis or relapse. As compared to patients that did not developed VTE, patients with VTE had less frequently PR3 ANCAs (p=0.05), tended to be older (p=0.081), had lower serum albumin at AAV diagnosis (p=0.040) and were less frequently on statin therapy (p=0.028). Univariate cox analysis identified age (HR 1.49 for each 10-year increase, p=0.028), serum albumin at diagnosis (HR 2.21 for each 10g/L decrease, p=0.045), lack of statin therapy (HR 5.26, p=0.008) and rituximab treatment (HR 4.10, p=0.026) to be significantly associated with VTE occurrence. However, after adjustment in the multivariate model, only lack of statin therapy (HR 4.80; p=0.039) was significantly associated with VTE, while serum albumin was borderline (HR 2.20 for each 10 g/L decrease, p=0.067). Patients with VTE developed more frequently end-stage renal disease (p=0.040), but AAV relapse rate and mortality were not significantly different as compared to patients without VTE.

Conclusion

Patients with ANCA-GN are at high risk of VTE, especially within the first months following AAV diagnosis. We identified the lack of statin therapy as an independent risk factors of VTE development in our cohort. Thus, our results suggest that statins may have anti-thrombotic properties in ANCA-GN, which opens new therapeutic perspectives.
P0371DENTAL CARIES INDUCED BY CNM-POSITIVE STREPTOCOCCUS MUTANS DERIVED FROM IGA NEPHROPATHY PATIETNS IN RATS INDUCED GLOPERULONEPHRITIS LIKE IGA NEPHROPATHY
Authors: Nagasawa Yasuyuki , Naka Shuhei , Wato Kaoruko , Nomura Ryota , Misaki Taro , Ito Seigo , Kida Aritoshi , Nanami Yoshimasa , Hasuike Yukiko , Takahiro Kuragano , Matsumoto-Nakano Michiyo , Nakano Kazuhiko
Published: June 2020

Background and Aims

IgA nephropathy (IgAN) is one of most common primary glomerulonephritis, whose pathogenesis had remained unclear. We had reported that Cnm-(+)Streptococcus mutans, a kinds of major dental caries bacteria. Cnm-(+)S. mutans had strong collagen binding ability, resulting in high pathogenicity. We reported that the prevalence of Cnm-(+)S. mutans in IgA nephropathy is significantly higher than that in control (Misaki-T et al, Clin Exp Nephrol 2015; 19:844-50), and that Cnm-(+)S. mutans in IgA nephropathy was associated with proteinuria (Misaki-T et al, Sci Rep 2016). We also reported C.rectus and S. mutans increased proteinuria synergistically (Misaki-T et al, Nephron, 2018). In this point, there is no direct evidence that Cnm-(+)S. mutans could induce IgA nephropathy. In this study, we evaluated the renal lesions in rats which had dental caries induced by Cnm-(+)S. mutans derived from IgA nephropathy patient to confirm the pathogenesis of IgA nephropathy like lesions induced by Cnm-(+)S mutans.

Method

Cmn-(+)S. mutans from saliva of IgA nephropathy patients was orally administrated into 4 weeks old male Sprague-Dawley rats. Addition of sugar to water had been kept during study period to develop dental carits. At week 34 after the infection, blood, urine, and kidney samples were evaluated. Kidney samples were stained by Periodic Acid-Schiff (PAS), IgA, C3. Historical evaluation by electron microscope analysis was also performed.

Results

At week 34, plaque score and dental caries score in infectious rats significantly elevated, compared with control rats (P<0.001) (Figure 1). These findings suggested Cmn-(+)S. mutans from IgA nephropathy patients induced dental caries in rats. PAS staining revealed the significant mesangial proliferation. At week 34, the prevalence of IgA deposition in infections rats was higher than that in control rats (52.4% vs 4%), and the prevalence of C3 deposition in infectious rats was also higher than that in control rats (42% vs 11%) (Figure 2). Incidence of hematuria was also significantly higher in dental caries group than control. Electron microscopy analysis revealed high dense deposit in mesangial areas.

Conclusion

Cmn-(+)S. mutans from saliva of IgA nephropathy patients could induce IgA-dominant infection-associated glomerulonephritis, or IgA nephropathy.
P0376EFFECTS OF HYPERURICEMIA ON THE PROGNOSIS OF IGA NEPHROPATHY AND ITS SEX DIFFERENCE
Authors: Oh Tae Ryon , Choi Hong Sang , Kim Chang Seong , Ma Seong Kwon , Kim Soo Wan , Bae Eun Hui
Published: June 2020

Background and Aims

Hyperuricemia is a potential risk factor for immunoglobulin A nephropathy (IgAN) progression, but its sex-specific effects on IgAN progression remain unclear. This study aimed to determine the effect of serum uric acid on IgAN progression and whether its effect varied according to sex.

Method

A total of 4339 patients were retrospectively analyzed at a university medical school. We assessed the effect of serum uric acid on IgAN progression using Kaplan–Meier survival analyses and Cox proportional hazards models. The study’s primary end point was IgAN progression that was defined as a 50% decline in the estimated glomerular filtration rate or the initiation of dialysis.

Results

On average, the serum uric acid levels were higher in the men than in the women. In the fully adjusted Cox proportional hazards model that considered all subjects, the risk of IgAN progression increased by about 25.6% for every 1 mg/dL increase in the baseline uric acid level. The serum uric acid level was an independent risk factor for IgAN progression in both sexes, but its effect was more pronounced in the women (hazard ratio [HR], 1.383; confidence interval [CI],1.263 to 1.514; P<0.001) than in the men (HR, 1.181; CI, 1.097 to 1.272; P<0.001) (Pinteraction <0.001). A sensitivity analysis involving serum uric acid quartiles generated consistent and robust results.

Conclusion

The serum uric acid level was an independent risk factor for IgAN progression, and its effect was more pronounced among the women compared with that among the men.
P0378SERUM URIC ACID IS ASSOCIATED WITH PROGNOSIS OF LUPUS NEPHRITIS IN FEMALE BUT NOT IN MALE
Authors: Oh Tae Ryon , Choi Hong Sang , Kim Chang Seong , Kim Soo Wan , Bae Eun Hui , Ma Seong Kwon
Published: June 2020

Background and Aims

Lupus nephritis (LN) is one of the major complications of systemic lupus erythematosus. Early intervention in lupus nephritis is known to benefit patients' prognosis. Recent studies have found an association between hyperuricemia and lupus nephritis, but the sex-specific role of uric acid in lupus nephritis remains unclear. The purpose of this study is to elucidate the relationship between lupus nephritis and hyperuricemia, and to investigate sex differences.

Method

We retrospectively analyzed 394 patients who diagnosed with LN by renal biopsy. We assessed the effect of serum uric acid on progression of LN using Kaplan–Meier survival analyses and Cox proportional hazards models. The study’s primary end point was LN progression that was defined as the initiation of dialysis.

Results

The male had a higher mean of serum uric acid level than female. In the overall patient analysis, every 1 mg / dL increase in baseline uric acid level increased the risk of LN progression by about 16.9%. The serum uric acid level was an independent risk factor for LN progression in female (hazard ratio [HR], 1.177; confidence interval [CI],1.024 to 1.353; P<0.001) but not in male (HR, 1.0351; CI, 0.661 to 1.622; P = 0.880). A sensitivity analysis involving serum uric acid tertile generated consistent and robust results.

Conclusion

The serum uric acid level was an independent risk factor for LN progression in female but no in male.
P0384PROTEINURIA SELECTIVITY INDEX MAY PREDICT RITUXIMAB RESPONSE IN MCD AND FSGS
Authors: Allinovi Marco , Trivioli Giorgio , Lugli Gianmarco , Caroti Leonardo , Antognoli Giulia , Cirami Calogero
Published: June 2020

Background and Aims

Proteinuria selectivity index (PSI) predicts steroid responsiveness in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Rituximab, a monoclonal antibody targeting CD20, has increasingly recognized as a potential therapy of idiopathic podocytopathies, such as MCD and FSGS, although the mechanism of action is still unrecognized and randomized controlled studies are still lacking. Currently, no tools are available to predict responsiveness to RTX. We explored the role of PSI as a potential predictor of RTX responsiveness in MCD and FSGS.

Method

We analysed cases of biopsy-proven MCD and FSGS followed at one single centre, who received RTX therapy. Baseline data, including proteinuria and PSI, were collected. Proteinuria was considered selective with PSI (clearance of urinary IgG/transferrin ratio) <0.20. Complete remission (CR) was resolution of proteinuria and clinical symptoms, while partial remission (PR) was proteinuria decrease (>50%) and substantial improvement of clinical symptoms.

Results

RTX was administered to 14 patients with MCD and 16 patients with FSGS and, of them, PSI was available before treatment for 10 and 14 patients, respectively. Baseline characteristics of the patients are shown in Table 1. Among the 24 cases with available PSI, CR was reported in 12 and PR in 5, while 9 did not respond to RTX. All patients who achieved CR and PR had selective proteinuria at baseline, while all patients with PSI >0.20 did not respond to RTX (Figure 2). Median relapse-free survival was 25.4 months. Among responders, in 10 out of 19 patients (53%) the relapse occurred between 4 and 60 months from initial treatment. No potentially life-threatening adverse events have been observed.

Conclusion

Selective proteinuria before treatment can predict the response to RTX in adult patients with steroid-dependent and refractory forms of MCD and FSGS.
P0387PATHOLOGICAL FEATURES AND CLINICAL COURSE OF LATE-ONSET LUPUS NEPHRITIS
Authors: Shabaka Amir , Sanchez Alamo Beatriz , Gatius Serena , Cases Corona Clara Maria , Valdes Elena , Dominguez Torres Patricia , Diaz Enamorado Yunayka , Fernandez Juarez Gema Maria
Published: June 2020

Background and Aims

It has been described that the early onset of lupus nephritis (LN) at a young age can determine the clinical course and outcome of the disease, being more aggressive with a higher mortality rate. However, no studies have explored the influence of age at onset of the disease in European cohorts of LN patients, neither have they analyzed treatment outcomes depending on age at presentation. Therefore, the aim of our study was to compare the clinical and histological characteristics of patients with late-onset LN compared to those with an onset at a younger age.

Method

We performed a retrospective observational study of biopsy-proven LN diagnosed between 1981 and 2018. Patients were stratified according to their age at presentation of LN, considering an onset with >50 years old as late-onset. Demographic, clinical and serological data at presentation of systemic lupus and LN, during and at the end of follow-up, as well as extrarenal manifestations, histological characteristics of the kidney biopsy, clinical course, received treatment regimens and related adverse effects were registered.

Results

85 LN patients were included in the study, 10 of whom had late-onset LN (11.7%). Late-onset LN patients presented significantly higher serum C3 and C4 levels at the time of kidney biopsy (92.8 ± 22.4 mg/dl vs 62.5 ± 25.7 mg/dl, p=0.002, and 18.6 ± 5.0 vs. 9.3±5.8 mg/dl, p<0.001 respectively), and had lower eGFR measured by CKD-EPI (58.50±19.79 vs 90.41±30.53,p=0.003), a higher frequency of serositis manifestations (53.45% vs 17.46%, p=0.034), predominantly pleuritis (79.37% vs 51.75% p=0.013). Early-onset LN had predominantly Class IV LN (50% vs 10%, p=0.017), whereas in late-onset LN the most frequent type was Class V LN (50% vs 21.3%, p=0.048). Tubular atrophy was more common in late-onset LN (75% vs 34.9%, p=0.035). The group of patients with late-onset LN achieved complete clinical remission more frequently (87.5% vs 57.1%), but there were no differences in relapses between the groups. No differences were found in treatment regimens among the groups. Late-onset LN patients were more seronegative (100% vs 61.3%, p=0.015) at the end of follow-up. Severe infectious complications related to immunosuppression were significantly higher in late-onset LN patients (62.5% vs 22.2%, p=0.027)

Conclusion

Late-onset LN has a milder complement consumption at presentation compared to early-onset, and Class V LN is its most frequent form of presentation. Complete renal remission is more frequently achieved in late-onset LN compared to those with an early-onset, but present more adverse events associated with immunosuppression, particularly infectious complications.
P0389THE PREVALENCE, CLINICAL AND PATHOLOGICAL CHARACTERISTICS OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN TURKISH ADULTS: THE DATA FROM TSN-GOLD ( TURKISH SOCIETY OF NEPHROLOGY GLOMERULAR DISEASES) WORKING GROUP
Authors: Kurultak Ilhan , Gungor Ozkan , Ozturk Savas , Dirim Ahmet Burak , Eren Necmi , Yenigun Ezgi , Ahbap Dal Elbis , Dincer Mevlut Tamer , Bora Feyza , Akgur Suat , Sumnu Abdullah , Dursun Belda , Sipahi Savaş , Çetinkaya Hakkı , Sahin İdris , SAHIN Garip , Yılmaz Mürvet , Vatansever Bulent , Aydin Emre , Ulu Memnune Sena , Gundogan Ali , Üstündağ Sedat , Sayarlioglu Hayriye , Kumru Şahin Gizem , Elcioglu Omer Celal , Aydin Zeki , Selcuk Nedim Yılmaz , Onal Ceren , Oruc Meric , Kucuk Mehmet , Aktas Nimet , Derici Ülver , Suleymanlar Gultekin
Published: June 2020

Background and Aims

Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerulopathies which is the most common cause of end-stage renal disease among all primary glomerular diseases. In adults, nephrotic syndrome develops 10-35% due to FSGS. However, its frequency has been increasing in recent years. This study was aimed to present the data and the prevalence of primary FSGS patients in Turkey.

Method

These data were obtained from the National Multicenter (47 centers) Primary Glomerular Diseases registry system, which was entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The presented data in this study is cross-sectional and includes the recorded data of the patients in the hospitalization period for the kidney biopsy. These demographic, clinic and pathological data of patients were evaluated with using statistically.

Results

Of the 3875 patients enrolled in the Primary Glomerular Diseases database, 850 (21.9%) had FSGS. The mean age of the patients was 47.1 ± 13.7 and 435 (52%) of patients were male. Two hundred and eighty one (33.1%) had hypertension and 93 (11%) had diabetes. Five hundred and four patients (59.3%) were diagnosed as nephrotic syndrome. At the time of diagnosis, the mean systolic blood pressure was 13.8 ± 18.6 mm Hg and the mean diastolic blood pressure was 81.4± 11.4 mm Hg. The laboratory findings at the time of diagnosis on following; serum creatinine 1.2 ± 0.04 mg / dl, albumin 3.3 ± 0.03 g / dl, and 24 hours urinary proteinuria amounts to 4743 ± 181 mg / day. Demographical and clinical data of the patients at the time of diagnosis were presented on Table 1. In pathological examination; the mean number of glomeruli was 16.8 ± 0.3, global sclerotic glomeruli were 3.1 ± 0.1, and segmental sclerotic glomeruli were 2.4 ± 0.1. Summary of Pathological Findings were presented on Table 2

Conclusion

It is very difficult to determine the absolute incidence and prevalence of primary FSGS. Incidence rates have been reported to range from 0.2 to 1.8 / 100,000 per year in the literature. In a United States study, the most common diagnosis in 2501 kidney biopsies was FSGS (35.9%). According to this database, the prevalence of FSGS in primary glomerular diseases in our country is 21.9%.
P0391STUDY OF ANTI COMPLEMENT FACTOR H MEDIATED DISEASE AT A TERTIARY CARE CENTRE
Authors: Lingaraj Umesh
Published: June 2020

Background and Aims

To study the clinical profile and outcome of patients with anti complement factor H mediated disease at our centre.

Method

We conducted a prospective study over 24 months ( August 2016 to July 2018) to assess the clinical profile and outcome of patients with anti complement factor H mediated disease at our tertiary care centre. We had a total of 18 cases during the study period. All patients were followed up to assess their response to therapy.

Results

A total of 28 cases of atypical HUS were seen during the study period of which anti factor H antibody was elevated in 18 (64.2%). All patients presented with hypertension with active urinary sediments and rapidly progressive renal failure. Mean serum creatinine at presentation was 6.8 +/- 1.2 mg/dl and all patients were oliguric at presentation and required haemodialysis. Anti complement factor H antibody was elevated in all patients with a mean of 549 +/- 90 AU/ml. (normal - 0 to 100 AU/ml).Renal biopsy showed thrombotic microangiopathy in 12 patients (66.6%) while features were suggestive of C3 glomerulopathy in 6 patients (33.3%). All patients received induction with plasmapheresis and pulse steroids followed by oral steroids at 1mg / kg with IV cyclophosphamide 500mg/ m 2 monthly for 6 months . This was followed by maintenance immunosuppression with azathioprine +/- oral steroids. 10 patients (55.5%) attained complete remission. Patients with anti complement factor H mediated disease presenting with TMA had better prognosis compared to patients presenting with C3 glomerulopathy. Also patients in the paediatric age group showed good response to treatment

Conclusion

Our study shows that anti complement factor H mediated disease is more common in the paediatric age group with good response to plasmapheresis and immunosuppression in the form of oral steroids and cyclophosphamide. Patients presenting with TMA have better prognosis compared to C3 glomerulopathy
P0398PREVALENCE OF RED COMPLEX OF PERIODONTAL DISEASE BACTERIA IN TONSILS OF IGA NEPHROPATHY PATIENTS
Authors: Nagasawa Yasuyuki , Nomura Ryota , Misaki Taro , Ito Seigo , Naka Shuhei , Wato Kaoruko , Kida Aritoshi , Nanami Yoshimasa , Hasuike Yukiko , Matsumoto-Nakano Michiyo , Nakano Kazuhiko
Published: June 2020

Background and Aims

IgA nephropathy (IgAN) is one of most common primary glomerulonephritis, whose pathogenesis had remained unclear. We had reported that C.rectus and T.denticola, kinds of major periodontal disease bacteria, in tonsils with IgA nephropathy patients were specific to IgAN patients compared with chronic tonsillitis (Nagasawa-Y et al, Plos One, 2014). We also reported C.rectus and S.mutans increased proteinuria synergistically (Misaki-T et al, Nephron, 2018). Red complex of bacteria related with periodontal disease consists of P.gingivalis, T.denticola, and Tannerella forsythia, which has strongest pathogenicity of periodontal disease (Figure 1). But, in this point there were no report of prevalence of red complex of periodontal bacteria in IgA nephropathy. In this study, we evaluated the periodontal disease bacteria including P.gingivalis, T.denticola, and Tannerella forsythia in tonsils of IgAN patients, and the relationship between these periodontal bacteria clinical features in IgAN patients.

Method

Tonsils were obtained from 23 IgAN patients and 63 chronic tonsillitis patients when the tonsillectomy was operated. mRNAs were extracted from tonsils and the prevalences of P.gingivalis, T.denticola, and Tannerella forsythia were evaluated by RT-PCR using bacteria specific primers. All patients gave the written informed consent which was approved by Hyogo College of medicine.

Results

Average age was 33+-14 in IgAN patients, and the age in control patients was 27+-7. The average proteinuria in IgAN patietns was 0.9+-1.1g/gcre, and average hematuria was (2+). The prevalence of T.denticola was very low in both groups (0%, 1.6% respectively). The prevalence of P.gingivalis in IgA patients was significantly higher than that in control patients (33% vs 3.2%, respectively, P<0.0001), and the prevalence of Tannerella forsythia in IgAN patients was also significantly higher than that in control (28% vs 6.4%, respectively, P<0.05) which had not been reported (Figure 2). The types of cilia of P.gingivalis (fim A types) were also evaluated. Obviously untypeable of fim A, which is usually minor type, was dominant in IgAN patients.

Conclusion

Prevalence of red complex of periodontal disease bacteria, especially P.gingivalis, Tannerella forsythia in IgAN patient was higher than that in control. Red complex of periodontal disease bacteria might have some relationship with pathogenesis of IgAN
P0400DECREASED REGULATORY B CELLS AND THEIR ASSOCIATION WITH CLINICAL RESPONSE IN PATIENTS WITH NEW ONSET LUPUS NEPHRITIS
Authors: Gupta Krishan Lal , Girimaji Ivedita , Rakha Aruna , Kaundal Urvashi , Ramachandran Raja , Rathi Manish , Sharma Aman
Published: June 2020

Background and Aims

Studies in lupus nephritis (LN) have shown impairment in both T regulatory (Treg) number and function. However, the data on B regulatory (Breg) is limited in LN. Our objective was to study Breg and Treg populations in newly diagnosed treatment naïve LN and study their change after initiation of immunosuppression.

Method

Study included 25 patients of newly diagnosed LN of Class III (+V), IV (+V), V and 10 healthy controls (HC). Immunophenotyping was performed for peripheral blood mononuclear cell (PBMCs) samples using fluorochrome labelled monoclonal antibodies for Tregs (CD3+CD4+CD25hiCD127loFoxP3+) and Bregs (CD19+CD5+CD1dhi IL-10+). The cells were expressed as percentage of T and B cells. Each lymphocyte population was analysed at baseline, 2 and 6 months after initiation of immunosuppression which was given as per unit protocol.

Results

Bregs were significantly decreased compared to HC at baseline (p=0.002). With immunosuppression, Bregs showed significant increase at 2 and 6 months (p=0.008) and from baseline to 6 months (p=0.005). Bregs in responders significantly increased from 2 to 6 months (p= 0.017) and from baseline to 6 month (p=0.020), while they did not in non-responders. Tregs did not differ significantly from HC and did not show significant increase at 2 and 6 months, in both responders and non-responders.

Conclusion

Breg population in newly diagnosed LN was significantly reduced and increased significantly with immunosuppression. Bregs had an association with renal remission. This underscores the potential role of Bregs in the pathophysiology of LN and their association with clinical response. This could aid in the design of new immunotherapies for treatment of lupus nephritis.
P0403INNATE DEFECTS OF COMPLEMENT ALTERNATIVE PATHWAY AMONG LUPUS PATIENTS WITH AND WITHOUT THROMBOTIC MICROANGIOPATHY
Authors: Yue Cai , Cui Quexian , Li Xuemei
Published: June 2020

Background and Aims

Thrombotic microangiopathy (TMA) is a rare and severe complication of systemic lupus erythematosus (SLE). The pathogenesis of TMA among lupus patients is not fully understood yet. The aim of the study was to evaluated innate complement alternative pathway (AP) defects among patients with SLE-TMA.

Method

15 consecutive lupus patients with clinically or pathologically diagnosed TMA from Peking Union Medical College Hospital through Jan 2017 to Dec 2019 were enrolled. Lupus patients with TMA secondary to antiphospholipid antibodies, ADAMTS13 inhibitor, overlap syndrome, infection, malignant hypertension and medications were excluded. The exonic regions of 13 genes including CFH, CFI, CFB, C3, CFHR1-5, MCP, THBD, DGKE, PLG were analysed with next generation sequencing. Mutations were interpreted according to ACMG 2015 guideline. Patients with atypical hemolytic uremic syndrome (aHUS) (n=2), lupus nephritis (LN) without TMA (n=8), and malignant hypertension (n=6) were set as control.

Results

Six AP mutations rated as VUS or likely pathogenic were detected among 5/15 (33.3%) patients with SLE-TMA, while three were detected among 3/8 (37.5%) of patients with LN, one among 1/6 (16.7%) patients with malignant hypertension, and three among 2/2 (100%) of patients with aHUS. There was no significant difference regarding mutation rate among the groups.

Conclusion

There is no significant difference regarding AP mutations among lupus patients with and without TMA. Mechanisms other than innate AP abnormality may be involved in the pathogenesis of TMA among lupus patients.
P0410SIGNIFICANT BURDEN OF DISEASE DURING MAINTENANCE TREATMENT OF ANCA-ASSOCIATED VASCULITIS (AAV) PATIENTS IN REAL WORLD PRACTICE IN EUROPE
Authors: Rutherford Peter , Götte Dieter
Published: June 2020

Background and Aims

ANCA associated vasculitis (AAV) is a relapsing remitting long term condition and patients are at risk of organ damage from both active AAV and its therapy in particular high dose and/or prolonged glucocorticoids (GC). The remission maintenance phase of AAV is critical for good long term outcomes including renal preservation as well as preventing AAV relapse. This retrospective study aimed to examine the definition of maintenance, therapy and clinical outcomes in patients managed in routine practice.

Method

1478 AAV patients (France, Germany, Italy, Spain and UK) managed by 493 physicians (61% Nephrologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance therapy between 2014-16 were studied. Data were collected retrospectively at the time maintenance was determined to begin by the physician and then at 6, 12, 18 and 36 months.

Results

49% had granulomatosis with polyangiitis,; mean age 54.2 years with 56% male. 49% had incident AAV and 51% were studied from the time of a relapse requiring remission induction therapy. 70% received cyclophosphamide and GC and 30% received rituximab and GC as induction treatment with 28% receiving plasma exchange. Physicians defined time of the start of maintenance from induction treatment start with mean of 5.7 months on the basis of fixed time point 40%, starting new drug for maintenance 26%, reaching full remission 26% and no specific criteria 8%. At this time of maintenance start 43% were in full remission vs 50% in partial and 7% refractory. Various maintenance regimes were used, 21% received rituximab (88% 6 monthly and 8% 12 monthly, 4% other) at varying planned doses 34% 1g, 40% 500 mg and 23% 375 mg/m2, 4% other regime. Remission rates varied with patients experiencing disease relapse and many patients experienced adverse events (AE) and infections with prolonged GC use being common. Renal function was relatively unchanged and some patients had worsening eGFR, protein excretion or blood pressure. At the most recent clinical review patients had been followed for a mean of 50.7 months – 6% had died, 38% had relapsed at least once, and 11% required renal replacement therapy. 54% had no vasculitis activity, 26% were ANCA positive without active disease and 19% were still experiencing active disease. 32% were still receiving GCs - 22% of them receiving > 5mg/ day.

Conclusion

Maintenance therapy is variably defined but typically at 6 months from start of remission induction therapy. Achieving full remission and preventing relapse are still clinical problems and many patients require ongoing GC therapy to maintain remission. Infectious complications and adverse events are common and renal disease remains an ongoing clinical problem.