24-h Proteinuria Research Articles

Diagnostic utility of protein excretion in 24-hour urine and the protein to creatinine ratio for adverse perinatal outcomes and time of delivery

Objective Our study aimed to evaluate the perinatal and neonatal outcomes of hypertensive pregnant women with or without proteinuria. We compared the predictivity of spot urinary protein to creatinine (P/C) ratio and 24-hour protein excretions on outcomes. Methods We retrospectively enrolled 230 pregnant women with a new diagnosis of hypertension between 20 and 37 weeks of gestation. We divided the patients into two groups according to the protein level determined by 24-hour urine collection and P/C ratio. The presence and level of proteinuria, its relationship with the P/C ratio, and the relationship between these findings and perinatal outcomes were evaluated. Results Gestational age at delivery weeks and latency period (duration between diagnosis of hypertension and delivery) were significantly earlier in pregnant women with ≥300 mg/24-h and P/C ratio ≥0.3. Adverse neonatal outcomes were significant in patients with proteinuria ≥300 mg/24-hour and P/C ratio ≥0.3. Urinary protein levels in 24-hour urine were significantly higher in pregnant women with P/C ratio ≥0.3 and a significantly positive correlation was found between 24-h proteinuria and P/C (r=0.382, p<0.001). Conclusion Our study demonstrated that a protein loss of ≥300 mg in 24-h and a P/C ratio in spot urine ≥0.3 in hypertensive pregnant women is associated with adverse perinatal outcomes. Furthermore, we have identified that proteinuria ≥300 mg/day and spot urine P/C ratio ≥0.3 in hypertensive pregnant women make them prone to early delivery risk.

Graded Renal Response Criteria for Light Chain (AL) Amyloidosis

Graded Renal Response Criteria for Light Chain (AL) Amyloidosis

Predictive Factors of Overall Survival in Patients with Relapsed AL Amyloidosis Treated with Single Agent Daratumumab

Predictive Factors of Overall Survival in Patients with Relapsed AL Amyloidosis Treated with Single Agent Daratumumab

A study on the relationship between morphological lesions of lupus nephritis with demographic and biochemical findings

Introduction: Lupus nephritis is one of the important aspects of systemic lupus erythematosus (SLE). Objectives: This study aimed to investigate possible relationship between pathological lesions of lupus nephritis classes and demographic and biochemical findings among patients. Patients and Methods: This is a cross-sectional study that was conducted on a group of renal biopsy proven lupus nephritis patients using lupus nephritis classification of ISN/RPS 2003. We collected demographic data of all patients including age, gender serum creatinine and 24h proteinuria. Results: Data of 101 patients, of whom 78 (77.23%) were females and mean age of 33.54±13.15 years. The mean serum creatinine and proteinuria were 1.54±0.88 mg/dL 2502.5±1495.05 mg/d. Based on our data, IV-G (class IV, diffuse lupus nephritis-global) lupus nephritis class was the most common (39.6%) followed by class III (23.8%). The mean crescent and sclerotic glomeruli were 1.66±3.32 and 2.27±5.32, respectively. In this study, 24 hours proteinuria, serum creatinine, activity percent, chronicity percent, crescent and glomerular sclerosis between genders showed no significant differences (P>0.05). The correlation between plasma creatinine and activity was directly positive and significant (r=0.381, P=0.001). In addition, a significant correlation between C1q deposits and glomerular sclerosis (P=0.031) was detected. Accordingly, a significant correlation between IgG deposits and lupus nephritis classification (P=0.025) was seen. Conclusion: Lupus nephritis of IV-G and III classes of lupus nephritis were most common among patients and higher IgG deposits were observed in patients with IV-G classification. We found a significant correlation between glomerular sclerosis and C1q deposits that could be an indicator of lupus nephritis activity and severity. However, we recommend further studies in this regard.

Association of the chronic kidney disease urinary proteomic predictor CKD273 with clinical risk factors of graft failure in kidney allograft recipients.

Kidney transplantation is the best treatment option for end-stage kidney disease but is still associated with long-term graft failure. In this study, we evaluated the application of urinary proteomics to identify grafts with high failure risk before initial decline of estimated glomerular filtration rate (eGFR) with irreversible graft changes. Fifty-two living donor kidney transplant recipients (KTR) with 8-year follow-up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24-hproteinuria. Graft function was estimated according to Nankivell. Urine samples at Month 24 were analysed by capillary electrophoresis coupled mass spectrometry followed by classification with the chronic kidney disease classifier CKD273. CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = -0.29, P=0.05). Receiver operating characteristics analysis for graft loss and death within the next 6 years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273-positive and -negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity. Using a representative KTR cohort with 8-year follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as a prognostic tool for long-term graft function risk stratification by large prospective clinical trials.

OAB-036: Graded renal response criteria and revised renal progression criteria for light chain (AL) amyloidosis

<h3>Background</h3> Renal light chain (AL) amyloidosis manifests as proteinuria with or without renal failure and is associated with a risk of progression to renal replacement therapy (RRT). A significant reduction in circulating amyloidogenic light chain is needed to achieve a renal response. Current renal response criteria are binary defining a renal response as >30% reduction in 24-h proteinuria without worsening estimated glomerular filtration rate (eGFR). Several studies suggest that greater reduction in proteinuria following successful therapy improves renal and overall survival. <h3>Methods</h3> AL amyloidosis patients diagnosed between 2010 to 2015, achieving at least hematological partial response to therapy and with renal involvement were included. Four renal response categories were formulated based on reduction level in pretreatment 24-h proteinuria in the absence of renal progression: renal complete response (renCR, 24-h proteinuria ≤200 mg/24-h); renal very good partial response (renVGPR, >60% reduction in 24-h proteinuria); renal partial response (renPR, 31-60% reduction in 24-proteinuria); and renal no response (renNR, 30% or less reduction). Renal response was assessed at landmark (6-, 12-, and 24 months from treatment initiation) and as best renal response. Graded renal responses were assessed as predictors for time from diagnosis to RRT and overall survival. <h3>Results</h3> Seven hundred and thirty-seven patients were included. The median age was 63. Renal stage I, II and III were assigned to 34%, 52% and 14% of patients, respectively. Reduction in 24-h proteinuria from baseline improved over time with a median reduction of 34%, 50% and 71%, at 6-month, 12-month and 24-months, respectively. At best response, renCR, renVGPR, renPR and renNR were achieved in 27%, 34%, 15% and 24% of patients, respectively. A renal response as early as 6 months after therapy initiation was able to predict time to RRT with an increase in RRT risk with lower level of renal response at that time point (5-year RRT 0%, 3%, 9% and 16% for renCR, renVGPR, renPR and renNR, respectively, P<0.001). Prediction of risk for RRT based on renal response depth improved at 12- and 24-months and at best renal response. Overall survival discrimination based on renal response depth was noted as early as 12 months from therapy initiation and improved with time. eGFR progression (≥25% decrease in eGFR) and proteinuria progression (at least 50% increase to ≥3g/day) were predictive for time to RRT. <h3>Conclusions</h3> We validated new graded renal response criteria based on reduction in 24-h proteinuria. These 4-level renal response criteria highlight the importance of achieving a deep renal response to improve renal and overall survival. These findings will allow clinicians to make decision on therapy changes or augmentation based on response depth as early as 6-month before irreversible renal failure has developed.

Clinical and Histological Predictors of Renal Survival in Patients with Biopsy-Proven Diabetic Nephropathy

Introduction: Clinical indicators or pathological features alone cannot reliably predict renal survival in patients with biopsy-confirmed diabetic nephropathy (DN). Therefore, this analysis sought to develop and validate a predictive model incorporating both clinical and pathological markers to predict renal outcomes in patients with biopsy-confirmed DN. Methods: A predictive nomogram was developed based upon data pertaining to 194 patients with biopsy-confirmed DN. The prognostic relevance of individual clinicopathological variables was assessed through univariate and multivariate Cox regression analyses. A prognostic nomogram was then developed and validated based upon concordance (C)-index values and calibration curves. Internal validation was conducted through bootstrap resampling, while the clinical utility of this model was assessed via a decision curve analysis (DCA) approach. Results: Nephrotic-range 24-h proteinuria, late-stage CKD, glomerular classification III–IV, and IFTA score 2–3 were all identified as independent predictors of poor renal outcomes in DN patients and were incorporated into our final nomogram. Calibration curves revealed good agreement between predicted and actual 3- and 5-year renal survival in DN patients with the C-index value for this nomogram at 0.845 (95% CI: 0.826–0.864). DCA revealed that our nomogram was superior to models based solely upon clinical indicators. Conclusion: A predictive nomogram incorporating clinical and pathological indicators was developed and validated for the prediction of renal survival outcomes in patients with biopsy-confirmed DN. This model will be of value to clinicians, as it can serve as an easy-to-use and reliable tool for physicians to guide patient management based on individualized risk.

Nephrological factors may cause kidney dysfunction in patients with common variable immunodeficiency

Background/aimCommon variable immunodeficiency (CVID) is a heterogeneous primary deficiency characterized by hypogammaglobulinemia, recurrent infections, an increased risk of autoimmune disease, malignancy, and chronic inflammation. Proteinuria is one of the most important prognostic factors causing progression in kidney disease. Proteinuria causes tubulotoxicity, activates inflammatory markers that cause fibrosis, and consequently nephropathy progression. The data is scant in the literature regarding the inflammation and nephropathy in CVID. Hence, in the present study, we aimed to investigate the relationship between tubular dysfunction, proteinuria, and inflammation in patients with CVID.Materials and methodsThis was a cross-sectional study involving 27 patients with CVID (15 females, 12 males; mean age, 39.88 ± 13.47 years) and 18 control subjects (10 females, 8 males; mean age, 33.83 ± 7.97 years). Patients were evaluated for kidney functions including glomerular filtration rate, fractional excretion of sodium, metabolic acidosis, serum/urine anion gap, 24-h urine proteinuria and, were grouped in terms of proteinuria. Blood samples obtained from the patients with CVID were taken into 2 mL EDTA tube to evaluate peripheral NK cell subgroups according to CD56 and CD16 expression and CD3, CD4, CD 8 expression to determine subtypes T cells. These cells were evaluated by flow cytometry technique.ResultsUrinary density, fractional excretion of sodium, proteinuria, and metabolic acidosis are found to be higher in patients with CVID when compared to healthy controls. In the bivariate correlation analysis, proteinuria was positively correlated with age (r = 0.496, p = < 0.001), CD8+T cells percentage (r = 0.427, p = 0.02). Albumin, CRP, and CD8+T cell percentage were found to be independent variables of proteinuria.ConclusionIncreased chronic ongoing inflammation was found to be associated with proteinuria in patients with CVID. Hence, in routine outpatient clinics, proteinuria should not be overlooked in this group of patients.

Resistive index of ophthalmic artery as animaging biomarker of hypertension-related vascular and kidney damage.

Aim: Resistive index of ophthalmic artery (RI-OA) is associated with atherosclerotic diseases. The aim of this study was to evaluate the association of RI-OA and hypertension-related vascular and kidney damage. Materials and methods: Two-hundred and eighty hypertensive patients underwent evaluation of RI-OA, carotid atherosclerosis and level of 24h albuminuria. Results: Albuminuria and carotid atherosclerosis were positively associated with RI-OA independently of other cardiovascular risk factors. Receiver-operating characteristic curve analysis allowed us to calculate a cut-off value of RI-OA >0.625, which would be suspicious about the existence of atherosclerotic disease. Conclusion: The ophthalmic vascular circulation allows to study connections between macro-and microcirculation in vivo. RI-OA could be a useful marker for a better stratification of the risk of developing kidney and cardiovascular disease.

Lenalidomide and dexamethasone in relapsed/refractory immunoglobulin light chain (AL) amyloidosis: results from alarge cohort of patients with long follow-up.

Lenalidomide and dexamethasone (RD) is a standard treatment in relapsed/refractory immunoglobulin light chain (AL) amyloidosis (RRAL). We retrospectively investigated toxicity, efficacy and prognostic markers in 260 patients with RRAL. Patients received a median of two prior treatment lines (68% had been bortezomib-refractory; 33% had received high-dose melphalan). The median treatment duration was four cycles. The 3-month haematological response rate was 31% [very good haematological response (VGHR) in 18%]. The median follow-up was 56·5months and the median overall survival (OS) and haematological event-free survival (haemEFS) were 32 and 9months. The 2-year dialysis rate was 15%. VGHR resulted in better OS (62 vs. 26months, P<0·001). Cardiac progression predicted worse survival (22 vs. 40months, P=0·027), although N-terminal prohormone of brain natriuretic peptide (NT-proBNP) increase was frequently observed. Multivariable analysis identified these prognostic factors: NT-proBNP for OS [hazard ratio (HR) 1·71; P<0·001]; gain 1q21 for haemEFS (HR 1·68, P=0·014), with a trend for OS (HR 1·47, P=0·084); difference between involved and uninvolved free light chains (dFLC) and light chain isotype for OS (HR 2·22, P<0·001; HR 1·62, P=0·016) and haemEFS (HR 1·88, P<0·001; HR 1·59, P=0·008). Estimated glomerular filtration rate (HR 0·71, P=0·004) and 24-h proteinuria (HR 1·10, P=0·004) were prognostic for renal survival. In conclusion, clonal and organ biomarkers at baseline identify patients with favourable outcome, while VGHR and cardiac progression define prognosis during RD treatment.

Biotechnological Agents for Patients With Tumor Necrosis Factor Receptor Associated Periodic Syndrome-Therapeutic Outcome and Predictors of Response: Real-Life Data From the AIDA Network.

Objective: To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response.Methods: Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers.Results: A total of 55 biological courses with anakinra (n = 26), canakinumab (n = 16), anti-TNF-α agents (n = 10), and tocilizumab (n = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbations was 458.2 flare/100 patients-year during the 12 months prior to the start of biologic treatment and 65.7 flare/100 patients-years during the first 12 months of therapy (p < 0.0001). The median duration of attacks was 5.00 (IQR = 10.50) days at the start of biologics and 1.00 (IQR = 0.00) days at the 12-month assessment (p < 0.0001). Likewise, a significant reduction was observed in the Autoinflammatory Disease Activity Index during the study period (p < 0.0001). A significant corticosteroid sparing effect was observed as early as the first 12 months of treatment both in the number of patients requiring corticosteroids (p = 0.025) and in the dosages employed (p < 0.0001). A significant reduction was identified in the erythrocyte sedimentation rate (p < 0.0001), C reactive protein (p < 0.0001), serum amyloid A (p < 0.0001), and in the 24-h proteinuria dosage during follow-up (p = 0.001). A relapsing-remitting disease course (OR = 0.027, C.I. 0.001–0.841, p = 0.040) and the frequency of relapses at the start of biologics (OR = 0.363, C.I. 0.301–0.953, p = 0.034) were significantly associated with a complete response. No serious adverse events were observed.Conclusions: Treatment with biologic agents is highly effective in controlling clinical and laboratory TRAPS manifestations. Patients with a relapsing-remitting course and a lower frequency of flares at the start of treatment show more likely a complete response to biologic agents.

MO648SERUM SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR IN PATIENTS WITH DIABETIC KIDNEY DISEASE

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide, associated with significant cardiovascular morbidity and mortality. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with inflammation, endothelial dysfunction and kidney disease. There is a lack of studies that investigate the role of suPAR in patients with DKD. Our aim was to assess the level of serum suPAR and to evaluate its association with kidney function, proteinuria and histological lesions in patients with DKD. Method We performed a cross-sectional study on 75 patients with DKD evaluated in our department between 2019 and 2020. Inclusion criteria were: age&amp;gt; 18 years, diagnosis of type 1 or type 2 diabetes mellitus, DKD and absence of malignancy, autoimmune disease, infectious disease and liver disease. Demographical, clinical and laboratory parameters were collected at the time of admission. A subset analysis was performed on 28 patients with biopsy- proven diabetic nephropathy (DN) to investigate the association of serum suPAR with histological lesions. Kidney function was evaluated based on serum creatinine and estimated with CKD-EPI formula, proteinuria was reported as 24h proteinuria and albumin/creatinine ratio (ACR) and serum suPAR levels were measured with a solid-phase ELISA kit. The detection range of the kit was 12 -360 pg/ml (7.8- 500). Results Among the 75 patients, mean age was 57.9±12.2 years, male was the dominant gender (65.3%), mean BMI was 30.7±5.5 kg/m2, most patients had hypertension (97.3%) and 22.7% were active smokers. Sixty six out of 75 patients (88%) had type 2 diabetes and the median duration of diabetes was 180 months (120- 240). Median values of estimated glomerular filtration rate (eGFR), 24h proteinuria and ACR were 24.3 ml/min (15- 36), 4.8 g/24h (1.9- 7.1) and 2000 mg/g, respectively. Median serum level of suPAR at the time of evaluation was 2857.2 pg/ml (1916.4- 3700.1). Its level was positively correlated with duration of diabetes (r= 0.278, p= 0.01), eGFR (r= 0.634, p&amp;lt; 0.001), 24h proteinuria (r= 0.490, p&amp;lt; 0.001), ACR (r= 0.524, p&amp;lt; 0.001) and negatively correlated with urine specific gravity (r= -0.284, p= 0.01). In the subset analysis on 28 patients with biopsy-proven DN, median suPAR level was 2474 pg/ml (1782-3745) and was positively correlated with DN class (r= 0.493, p=0.008) and interstitial fibrosis and tubular atrophy (IFTA) score (r= 506, p=0.006), but not with interstitial inflammation, arteriolar hyalinosis or arteriolosclerosis. Conclusion Our study showed a high serum level of suPAR in patients with DKD and its association with duration of diabetes, urinary specific gravity, kidney function and proteinuria. We also found a positive correlation with severity of glomerular lesions and IFTA.

MO252PLA2R -VE MEMBRANOUS GLOMERULONEPHRITIS PATIENTS SHOWS MORE EFFECTIVE RESPONSE THAN PLA2R +VE ON TACROLIMUS PLUS LOW DOSE PREDNISOLONE THERAPY*

Abstract Background and Aims PLA2R is an autoantigen present in glomerular podocytes of Membranous Nephropathy (MN) patients. Several drugs have been tried which included nonspecific anti-proteinuric agents; corticosteroids, alone or with alkylating agents; cyclosporine; intravenous Ig; mycophenolate mofetil; and rituximab. There is no standard therapy for patients with frequent relapsing or steroid-dependent MN. We propose the efficacy of low dose Tacrolimus (TAC) plus prednisolone and associated changes in anti-PLA2R in adult IMN. Method Total 101 membranous nephropathy patients were treated with combination of prednisolone 1mg/kg alt-day) and Tac 0.1mg/kg/day (trough 6-10 ng/ml first 6M and 4-6 ng/ml for next 3M) then both taper by 1/3 every month up to 12M. Out of 101 patients; 15 diabetic; 7 lupus; 1HBV and 1 ankylosing spondylitis patients were excluded. Finally; 77 Patients were followed and evaluated for the anti-PLA2R level at baseline; 3M; 6M; 12M and end of follow-up (17-61 ; median 38 months). CR; PR; relapse; and side-effects were recorded.Of the 77 patients; at 3M 60(77.92%; CR-37; PR-23); at 6M 61(79.22%; CR-53; PR-8); at 12M 53(68.86%; CR-47; PR-6) achieved remission. Eight (10.38%) relapsed and 16(20.77%) showed no response at 12M. At end of follow-up; out of 54 responsive patients 37(68.51%; CR-36; PR-1) remained in remission and 17(31.48%) patients relapsed. Results Out of 77 patients; 51 (66.3%) were anti-PLA2R positive. Remission rate was significantly low in PLA2R+ve than PLA2R-ve (36/51 vs 24/26; p=0.03) at 3M; (36/51 vs 25/26; p=0.009) at 6M and (31/51 vs 22/26; p=0.03) at 12M. PLA2R level was decreased by 60.38% and 77.56% at 3M and 6M respectively (1A &amp; 1B). There were significant correlations between PLA2R level and 24h proteinuria at baseline; 3M and at 6M (1C). During therapy 4 patients develop cutaneous tenia; 1 osteonecrosis of the femur head; 1 corpus tunnel syndrome; 4 onset diabetes; 3 tremor; and 14 patients experienced GI symptoms. The eGFR was decreased significantly (p=0.003) by 26.5% at the end of therapy and was normalized after stopping Tac; and 5 non-responsive patients had doubling of serum creatinine and progressively deteriorated eGFR. To note; 4 females had pregnancy and successful delivery in our cohort of patients. Conclusion PLA2R+ve patients showed poor response compare to PLA2R-ve patients. Remission with Tacrolimus and prednisolone therapy is comparable to historical Ponticelli (Pred plus CYP) regimen. Successful pregnency was ovserved on Tac based regimen.

MO227RELATIONSHIP BETWEEN KIDNEY DAMAGE AND COGNITIVE FUNCTIONS IN PATIENTS WITH GLOMERULOPATHIES

Abstract Background and Aims Mild Cognitive Impairment (MCI) has been found to be highly prevalent amongst patients with Chronic Kidney Disease (CKD). In this cohort, the prevalence of MCI was estimated to be between 30% and 63%. Mild cognitive impairment is an intermediate state between normal aging and dementia. An individual suffering from MCI has difficulty in remembering, sustaining attention, or decision making which can negatively affect their daily lives. The aim of this study was to verify the role of different glomerular diseases diagnosed by kidney biopsy on the MCI through a retrospective study. Method We recruited 45 patients with bioptic diagnosis of the following glomerular diseases: Focal Segmental Glomerulo Sclerosis (FSGS), minimal change disease (MCD), membranous glomerular disease (MG), IgA nephropathy. The renal function was analyzed using clinical variables, while Cognitive functions using the MoCA test. Patients were divided into two groups based on 24h proteinuria. Results The MoCA score was directly correlated to the uric acid levels (R=0.13; p=0.03). The MoCa score in the group with higher proteinuria levels was significantly lower than those of the group with lower proteinuria levels (p = 0.03). Finally, the MoCA score in subjects with FSGS or MCD is significantly higher compared the other groups (p&amp;lt;0.05). Conclusion Our data suggest that serum uric acid and proteinuria in glomerular diseases influence cognitive functions. Interestingly, uric acid plays a neuroprotective role, as low levels of uric acid reduce the MoCA score. This result agrees with previous observations of a protective role of uric acid on dopamine neurons. Conversely, the extent proteinuria seems to negatively affect cognitive functions, suggesting a role of the endothelial dysfunction. Finally, glomerulopathies with a lower degree of inflammation (FSGS, MCD) have minor impact on cognitive functions.

MO109CHARACTERIZATION OF RESISTANT HYPERTENSION IN CKD PATIENTS

Abstract Background and Aims Hypertension resistant to drug treatment is common among CKD patients. However, the phenotype of resistant hypertension in the CKD population is still loosely defined and scarcely characterized. Method In a cohort of 759 stage 2-5 CKD patients, we identified a subgroup of 647 patients with &amp;gt;4 longitudinal visits (range 4-7 visits) over a median follow-up time of 36 months. These patients did not differ from the original study population as for age (62±11 years vs 62±11), gender (59% vs 60%), diabetes (34% vs 35%) and eGFR (36±13 versus 36±13 ml/min/1.73m2). We adopted a conservative definition of resistant hypertension i.e. as a BP above the 2020 KDIGO guideline threshold (130/80 mmHg) in spite of concurrent use of 3 antihypertensive agents (at maximum tolerated doses) of different classes including a diuretic or BP controlled with four or more medications in at least 75% of visits. Adherence to drug treatment in this cohort was systematically checked by attending physicians across all visits. Data are given as mean ± SD or as median and interquartile range (IQR). Results Across the 36 months follow-up, 131 out of 647 patients (20%) had resistant hypertension in &amp;gt;75% of visits. Resistant hypertensive patients were older (64±8 years vs 61±11), more frequently diabetics (53% vs 29%) and with background cardiovascular comorbidities (38% vs 29%) , higher body mass index (BMI) (30±5 kg/m2 vs 28±4 kg/m2), serum phosphate (3.9±0.7 mg/dL vs 3.7±0.8 mg/dL), CRP (median: 3.2 mg/L, IQR: 1.6-6.5 vs 3.2 mg/L, IQR: 1.6-6.5 vs 2.1 mg/L, 0.9-5.1 mg/L), 24h urinary protein (median: 1.0 g/24h, IQR: 0.4-2.3 vs median: 0.5 g/24h, IQR: 0.2-1.0 g/24h) and lower serum albumin (4.1±0.5 g/dL vs 4.2±0.5 g/dL) and eGFR (34±13 ml/min/1.73m2 vs 37±14 ml/min/1.73m2 as compared to remaining patients (all P&amp;lt;0.03). In a multiple logistic regression model, 24h proteinuria [odds ratio (OR): 1.31, 95% CI: 1.13-1.53, P&amp;lt;0.001] and BMI [OR: 1.08, 95% CI: 1.03-1.13, P=0.001] resulted to be the first factors in rank explaining resistant hypertension followed by diabetes (OR: 1.83, 95% CI: 1.18-2.85, P=0.008). Age, background CV comorbidities, serum phosphate, serum CRP, albumin, and eGFR failed to be associated with resistant hypertension after multiple data adjustment (P ranging from: 0.14 to 0.61). Of note, the combination of 24h proteinuria, BMI and diabetes had a relevant discriminatory power for resistant hypertension because the area under the ROC curve area of these risk factors was 0.71 (95% CI: 0.66-0.76) (P&amp;lt;0.001). Conclusion A rigorously defined phenotype of resistant hypertension has a 20% prevalence in the CKD population. Proteinuria, high BMI and obesity are the main risk factors associated with this phenotype. Optimization of diabetes control, weight loss and pharmacotherapy targeting proteinuria may mitigate resistant hypertension in the CKD population.

MO223MEMBRANOUS NEPHROPATHY ASSOCIATED TO ANKYLOSING SPONDYLITIS: CASE REPORT

Abstract Background and Aims Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic disease diagnosed by the presence of the HLA-B27 antigen with joint and extra-articular manifestations. Its pathogenesis was initially based on auto-inflammatory phenomena, mainly involving innate immunity. However, many studies carried out in the recent years focus on its adaptive immunity aspect, especially autoimmune. These mechanisms seem to interact with each other, resulting in a complex pathophysiology. The general autoimmune characteristics of AS were investigated by Yuan and al, who reviewed recent reports of autoantibodies levels in AS patients. Their analysis shows that none of the autoantibodies considered in the study meet the criteria to be considered as a biomarker for the disease (including antibodies Anti- :CD74; beta2-Microglobulin; mutated Citrullinated Vimentin (MCV); Heat Shock Protein 65 (HSP65); 14-3-3 eta autoantibodies (14-3-3η); 1A-dependent autoantibody magnesium anti-protein phosphatase (PPM1A); sclerostin (SOST); and Anti-microbial antibodies). Renal involvement in AS is dominated by amyloidosis and IgA nephropathy. In rare cases, this disease has been associated with Membranous Nephropathy (MN). The pathogenetic link between the two disorders remains obscure. However, the recent connection of AS to autoantibodies potentially indicates the involvement of immune complexes formed from these autoantibodies in the development of MN. Method We report the case of a 36-years-old woman with a 7 years history of sacroiliitis, who also developed a pedal edema in May 2020. AS was diagnosed in 2014 by the presence of positive HLA-B27, and clinical and radiological manifestations of bilateral sacroiliitis without extra renal manifestations treated by indometacin during periods of pain . A pure nephrotic syndrome was revealed with a 24h proteinuria of 12g / 24h.The patient’s Albumin levels were at 16g/l, without HTA or hematuria, and with a correct renal function (Creatinine at 60mmol/l). A renal biopsy showed a MN with type I polytypical. Light microscopy showed a thickening of capillary loops, while IF staining revealed granular deposits of IgG along the capillary wall. Investigations of further secondary MNs were negative, and the patient was aPLA2R-negative. Results A treatment by corticosteroids was initiated prior biopsy to her referral , which resulted in pain relief and urinary protein reduction (prot 24h 1.5g/24h). Given her good response to this initial treatment, corticotherapy was maintained. As the levels of inflammation and discomfort were low, the patient did not wish to be treated by biotherapy. Conclusion This case suggests a secondary MN in association with AS.The discovery of new autoantibodies associated with AS opens up promising perspectives, and could potentially lead to the characterization of biomarkers for screening and monitoring this disease. However, more studies are needed in order to improve our understanding of the role played by possible immune complex diseases, (in particular MN), in relation to this Ankylosing spondilitis.

FC 039RENAL OUTCOME AFTER RITUXIMAB IN ADULT-ONSET IGA VASCULITIS AND CRESCENTIC IGA NEPHROPATHY: A MULTICENTRE STUDY

Abstract Background and Aims Glucocorticoids (GC) and/or immunosuppressive agents are the mainstay of therapy for adult-onset IgA Vasculitis (IgAV), but their efficacy is often partial while their toxicity is relevant. Recently, rituximab (RTX) has been reported as a safe and effective option but only few data on renal outcome are available.1 RTX has also been used in a few cases of crescentic IgA Nephropathy (cIgAN), an IgAN subset with vasculitic lesions and poor response to conventional immunosuppressive regimens.2 We present the results of a multicentre cohort of patients with IgAV and cIgAN treated with RTX. Method The databases of 16 consorted European centres were investigated to screen for patients with adult-onset, biopsy-proven IgAV and cIgAN (crescents in ≥25% glomeruli and rapid eGFR worsening at presentation), who received RTX as induction therapy. We selected patients with active renal manifestations at the time of RTX. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS)=0 or &amp;lt;5 if it was due to persistent proteinuria and relapse as an increase in BVAS requiring change in immunosuppressive therapy. Results We identified 38 patients with IgAV and 12 patients with cIgAN who received RTX and had active renal involvement at the time of treatment. The median age at onset was 40 years (interquartile range, IQR, 25-53) and more than two-thirds of patients were male (Table 1). The median follow-up after RTX was 41 months (IQR 18-60). Renal outcomes are reported in Table 2. At the time of treatment, 24 patients (48%) had eGFR ≥60 mL/min/1.73 m2. All had IgAV and their median BVAS was 17 (IQR 10-22). Furthermore, all had microhaematuria and proteinuria. Renal histology showed mesangial or focal endocapillary proliferation in 12/17 (71%) patients who underwent biopsy (class II-IIIA according to Pillebout3). Twenty patients (83%) achieved remission; after a median of 12 months (range 9-14), four experienced a minor relapse and one had a major relapse with significant renal disease progression. Renal function remained stable in all but two patients who developed end-stage renal disease (ESRD). Micro-haematuria subsided in 14/24 (58%) and median 24h proteinuria decreased from 1750 mg (IQR 865-3275) to 175 mg (IQR 100-800) at last follow-up (p=0.029). Of the 26 patients with eGFR &amp;lt;60 mL/min/1.73 m2, 14 had IgAV and 12 had cIgAN. All were biopsied and 20 (77%) had diffuse endo/extra-capillary proliferation (classes IIIB-IV). Five patients required dialysis but recovered soon after treatment start. Remission was achieved by 16/26 (61%); eight (50%) subsequently relapsed and two (12%) reached ESRD. At last follow-up, eGFR was ≥60 mL/min/1.73 m2 in 8/26 (31%), 10/26 (48%) had stable renal function as compared to the time of RTX, while 8/26 (31%) had developed ESRD. Median 24h proteinuria decreased from 3400 mg (IQR 2150-6500) to 770 mg (177-1315) (p=0.016). Remission rate and ESRD-free survival were respectively 86% and 92% in patients with IgAV, while they were respectively 42% and 42% in cIgAN patients. Furthermore, 21/24 (87%) patients who received RTX alone or combined to glucocorticoids but not to immunosuppressive agents achieved remission and 22/24 (92%) were ESRD-free at last follow-up. Of the 26 patients receiving immunosuppressive agents, 17 (65%) obtained remission and 18 (69%) were ESRD-free at last assessment. Over the whole follow-up, only one patient reported a severe adverse effect related to RTX (pneumonia). Conclusion Renal involvement in adult-onset IgAV and cIgAN is frequently severe. RTX, combined or not with other immunosuppressive agents, may improve renal manifestations and is well tolerated. IgAV patients show higher remission rates and a longer ESRD-free survival as compared to cIgAN patients.

MO300PHOSPHOLIPASE A2 RECEPTOR ANTIBODY SCREENING IN NEPHROTIC SYNDROME MAY IDENTIFY A DISTINCT SUBSET OF PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY

Abstract Background and Aims Primary membranous nephropathy (MN) is a glomerulus-specific autoimmune disorder caused by anti-phospholipase A2 receptor (anti-PLA2R) antibodies in 70-80% of cases. We sought to investigate the utility of anti-PLA2R antibody as a non-invasive screening method for the diagnosis of primary MN in patients with nephrotic syndrome (NS). Method A total of 203 consecutive patients with NS admitted in the Nephrology Department of Fundeni Clinical Institute, Bucharest, Romania, between January 2015 and December 2019 were screened for anti-PLA2R antibodies by an ELISA assay (Euroimmun, Lubeck, DE). A positive anti-PLA2R serology was defined as an ELISA value over 2 RU/ml. Subsequently, all patients underwent kidney biopsy to confirm the histological diagnosis. Results Of the 203 patients with NS, 113 (55.7%) patients tested negative for anti-PLA2R antibodies, while 23 (11.3%) and 67 (33%) patients had an anti-PLA2R antibody titer of 2-20 RU/ml and &amp;gt;20 RU/ml, respectively. Mean age and serum creatinine of the entire cohort were 53 ± 13 years and 1.84 ± 1.63 mg/dl, respectively, while median 24-h proteinuria was 6.8 g/day (IQR: 4.8 – 10.6). Thirty patients (14.7%) were identified to have a potential secondary cause of NS. Ninety-five patients (46.8%) had a histological diagnosis of MN, while 108 patients were diagnosed with other glomerular disorders. In patients with anti-PLA2R antibody titer &amp;gt; 20 RU/ml, the most frequent histological diagnosis was MN (n=61, 91%) with 6 patients having other glomerular patterns of injury (two FSGS, one minimal-change disease, one membrano-proliferative glomerulonephritis, one diabetic nephropathy and one postinfectious glomerulonephritis) (Figure 1). Of patients with intermediate anti-PLA2R antibody titer (2-20 RU/ml), 39% had MN and 61% had other glomerular disorders (Figure 1). Eighteen patients with MN had a positive work-up for secondary causes, eight patients (44%) having an anti-PLA2R antibody titer &amp;gt; 20 RU/ml. Additionally, patients with anti-PLA2R antibody titer &amp;gt; 20 RU/ml had a lower serum creatinine (1.5 ± 0.89 mg/dl) than patients with intermediate titer (1.89 ± 1.21 mg/dl) and those with negative titer (2.03 ± 1.98 mg/dl) (Figure 2). When analyzing the diagnostic performance of anti-PLA2R antibodies in the entire cohort we identified an AUC of 0.83 (95%CI, 0.78-0.89; p&amp;lt;0.001), the cut-off titer of 20 RU/ml having a sensibility, specificity, positive predictive value (PPV) and negative predictive value of 65%, 94%, 91% and 75%, respectively. The accuracy of anti-PLA2R antibodies for non-invasive diagnosis of primary MN was improved in the subgroup of patients that were younger than 60 years (AUC=0.88; 95%CI, 0.82-0.95; p&amp;lt;0.001, with a PPV and NPV of 91% and 80%), had an estimated glomerular filtration rate over 60 ml/min (AUC=0.85; 95%CI, 0.77-0.93; p&amp;lt;0.001, with a PPV and NPV of 95% and 69%) or had a negative work-up for secondary causes of NS (AUC=0.88; 95%CI, 0.82-0.93; p&amp;lt;0.001, with a PPV and NPV of 93% and 80%). Conclusion Serum anti-PLA2R antibody screening in patients with NS is a useful method for the diagnosis of primary MN. In younger patients (less than 60 years-old) that have a preserved renal function and a negative work-up for secondary causes a positive anti-PLA2R antibody test highly predicts a diagnosis of primary MN.

FC 044THE LONG-TERM EFFECTS OF ACUTE KIDNEY INJURY ON INTESTINAL OXALATE-DEGRADING BACTERIA IN RATS

Abstract Background and Aims Gut microbiota is considered an important factor affecting oxalate handling in the intestine. It has been demonstrated that intestinal oxalate secretion provides a complementary route of excretion, and it becomes more evident when kidney function declines. A diversity of gut oxalate-degrading bacteria (ODB) has been hypothesized to play a role in this process. However, there is a general lack of research on the long-term effects of acute kidney injury (AKI) on ODB and their total oxalate-degrading activity (ODA) in fecal microbiota. In this study, we evaluated whether renal dysfunction could affect intestinal ODB and their total ODA in a rat model of glycerol-induced AKI. Method The Male Wistar rats (200-300 g, n=20) on oxalate-free diet were randomly divided into 2 groups. After 24-h of water deprivation, Group 1 (n=10) received an intramuscular injection of 50% glycerol (10 ml/kg of body weight), and Group 2 (n=10) served as control. The numbers of ODB (incubated in a highly selective Oxalate Medium and determined using culture method) and total fecal ODA were measured after injection on days 7 and 70. The method of redoximetric titration with a KMnO4 solution was adopted to evaluate total ODA in fecal microbiota; the results were expressed as % of oxalate degradation per 0.01 g of feces. Renal injury was assessed by histopathological examination, serum creatinine and daily proteinuria levels after removing the animals from the experiment on day 70. Cortical interstitial fibrosis was measured by computerized image analysis on sections stained with picrosirius red. The median (Me) and the interquartile ranges (Q25; Q75) were calculated and compared using the nonparametric Mann-Whitney test. The Spearman correlation coefficient was used to evaluate association between the examined parameters. Results The obtained results demonstrated: 1) after glycerol injection on day 7, no differences were found in the numbers of ODB and total fecal ODA between the experimental and control groups: 5.9 (5.4-6.0) vs 6.0 (5.4-6.4) CFU/g, p=0.65 and 2.0 (0.1-5.0) vs 2.5 (2.0-9.0) %/0.01g, p=0.24, respectively; 2) after AKI initiation on day 70, the numbers of ODB and total fecal ODA were significantly lower in Group I compared with control Group II (Fig. 1); 3) the higher percentage of renal interstitial fibrosis was, the higher total fecal ODA occurred in the experimental rats (Fig. 2). In addition, the number of ODB in feces in Group 1 had an inverse association with serum creatinine (r=-0.52, p=0.006) and 24-h proteinuria levels (r=-0.86, p&amp;lt;0.0001). Conclusion AKI had the long-term negative effects on the quantitative and qualitative characteristics of ODB in fecal microbiota in rats. Moreover, the results of our study confirmed an increasing trend in total fecal ODA according to the aggravation of renal interstitial fibrosis in rats.

First and second morning spot urine protein measurements for the assessment of proteinuria: a diagnostic accuracy study in kidney transplant recipients

BackgroundQuantification of proteinuria in kidney transplant recipients is important for diagnostic and prognostic purposes. Apart from correlation tests, there have been few evaluations of spot urine protein measurements in kidney transplantation.MethodsIn this cross-sectional study involving 151 transplanted patients, we investigated measures of agreement (bias and accuracy) between the estimated protein excretion rate (ePER), determined from the protein-to-creatinine ratio in the first and second morning urine, and 24-h proteinuria and studied their performance at different levels of proteinuria. Measures of agreement were reanalyzed in relation to allograft histology in 76 patients with kidney biopsies performed for cause before enrolment in the study.ResultsFor ePER in the first morning urine, percent bias ranged from 1 to 28% and accuracy (within 30% of 24-h collection) ranged from 56 to 73%. For the second morning urine, percent bias ranged from 2 to 11%, and accuracy ranged from 71 to 78%. The accuracy of ePER (within 30%) in first and second morning urine progressively increased from 56 and 71% for low-grade proteinuria (150–299 mg/day) to 60 and 74% for moderate proteinuria (300–999 mg/day), and to 73 and 78% for high-grade proteinuria (≥1000 mg/day). Measures of agreement were similar across histologic phenotypes of allograft injury.ConclusionsThe ability of ePER to accurately predict 24-h proteinuria in kidney transplant recipients is modest. However, accuracy improves with an increase in proteinuria. Given the similar accuracy of ePER measurements in first and second morning urine, second morning urine can be used to monitor protein excretion.