MATERNAL PROTEINURIA IN TWIN COMPARED WITH SINGLETON PREGNANCIES

INTRODUCTION: The exact amount of albumin ltered each day by kidneys is controversial. Normal rate of albumin excretion is less than 20 mg/day. The upper limit of the urinary protein excretion is 150 mg/d in normal non–pregnant women. Total protein excretion, however, increases to 150-250 mg daily in normal pregnancy due to increase in blood volume and, therefore, the glomerular ltration rate. This study was conducted to compare 24 hour urinary protein excretion in twin and singleton pregnancies, not complicated by hypertension. MATERIALS AND METHODS: This is a prospective study done in the department of Obstetrics and Gynaecology in R.G.Kar Medical College and Hospital, Kolkata from June, 2015 to May, 2016. A total of 86 women (43 twin and 43 singleton pregnancies) participated in this study. Six collections were inadequate based on creatinine excretion and were excluded. So, 80 women (40 twin and 40 singleton pregnancies) comprised the nal cohort. RESULT: In our study four twin pregnancies (ten percent) were found to have proteinuria ≥ 300 mg/day at the time of the specimen collection but no singleton pregnancy had this level of proteinuria. And only one of these twin pregnancies (who had proteinuria ≥ 300 mg/day ) subsequently developed hypertensive disorder in pregnancy. Rest three twin pregnancies were normotensive, yet they showed proteinuria ≥ 300 mg/day. Though statistical analysis of 24 hour urine protein ≥ 300 mg in singleton and twin pregnancies did not show signicans (P0.1238) in our study. CONCLUSION: Twin pregnancy had signicantly more proteinuria as measured by 24 hour urine protein, than singleton pregnancy. And they are more likely to have proteinuria without hypertension and this value can exceed 300 mg/day. So, a reevaluation of the diagnostic criteria for preeclampsia in twin pregnancies is needed.

MO267HIGHER FRACTIONAL EXCRETION OF TOTAL PROTEIN IS A PREDICTOR OF PROGRESSION IN IDIOPATHIC MEMBRANOUS NEPHROPATHY

Background and Aims Lower estimated glomerular filtration rate (eGFR) and higher proteinuria are the most sensitive predictor of the development of progressive renal insufficiency in various glomerular diseases. On the other hand, the onset of idiopathic membranous nephropathy (iMN) shows insidious progression, and the prognosis varies significantly. Therefore, it is difficult to predict the renal outcome in MN, using only the severity of proteinuria. Fractional excretion of total protein (FETP), which was protein clearance divided by creatinine clearance (Ccr), may be a better indicator of protein leak per functioning nephron. A recent study has also reported that FETP accurately predicted transplant failure and was more sensitive and specific than protein creatine ratio (PCR). Few studies, however, have analyzed the FETP to evaluate their relationship with renal function and histologic lesions in glomerular diseases. Thus, this study aims to assess the relationship between FETP and the clinicopathological findings and whether FETP predicts outcome in iMN. Method This study included patients with iMN that underwent kidney biopsies during the period from 2002 to 2020. We analyzed 24-h urinary protein excretion, FETP, and other clinicopathological findings at the kidney biopsy. The FETP was determined by the standard clearance technique based on 24-h urine collection: FETP = (urinary total protein / serum total protein) / (urinary creatinine / serum creatinine) × 100. A 30% decrease in eGFR or the occurrence of ESRD were the endpoints. The multivariate factors affecting the prognosis were analyzed with the Cox proportional-hazards model, and the cumulative risk of risk factors was analyzed by Kaplan‑Meier curve. Results A total of 153 subjects with MN were identified and were followed up for a median of 5.4 years. (age 64.9±13.6 [mean ± SD] years, male 73.2 %, hypertension 42.5 %, diabetes 10.5 %, nephrotic Syndrome 67.3 %, chronic kidney disease [CKD: eGFR<60ml/min/1.73m2] 51.9 %, eGFR 61.6±22.6 mL/min/1.73m2, urinary protein excretion [u-TP] 4.3±3.6 g/day, PCR 5.4±4.5 g/gCr, FETP 0.12±0.18 %, Selectivity Index [S.I] 0.23±0.39, fractional excretion of IgG [FEIgG] 0.065±0.170 %, glomerulosclerosis [GS] 13.9±13.7 %, interstitial fibrosis and tubular atrophy [IFTA] 12.2±10.0 %). FETP was more significantly associated with clinical parameters than PCR and FEIgG (Table.1). The high FETP group had a significantly worse renal prognosis during the follow-up periods than the low FETP group (Figure.1). Using Cox proportional hazards models, with FETP entered, and age, sex, eGFR,u-TP as covariates, FETP predict the primary endpoint with a hazards ratio of 0.343 (P<0.05). Conclusion These results suggest that FETP would be superior to PCR, the standard measure of proteinuria, in predicting outcome in patients with iMN. FETP could indicate the increased glomerular protein permeability and decreased glomerular filtration function in iMN.

MO538THE SHORT-TERM IMPACT OF HIGH DOSE INTRAVENOUS IRON USE ON RENAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND IRON DEFICIENCY WITHOUT ANAEMIA - A POST-HOC ANALYSIS OF A MULTICENTRE RANDOMIZED CONTROLLED TRIAL*

Background and Aims High dose intravenous (IV) iron is commonly used in patients with chronic kidney disease (CKD) but it remains unclear whether any short or long term impact on renal function exists. Studies using iron sucrose, a second generation IV iron compound suggest effects on proteinuria while evidence with third generation iron products revealed no impact on estimated glomerular filtration rate (eGFR). These newer iron compounds have compact iron-carbohydrate cores, potentially limiting the nephrotoxic effects of labile free iron. As a part of the Iron & Heart study, we examined the impact of high dose ferric derisomaltose (FDI), a third generation IV iron product, in patients with non-dialysis dependent CKD and iron deficiency on markers of renal injury and function using both established (serum creatinine, eGFR, 24-hour excretion of protein) and novel methods (Cystatin C, Neutrophil gelatinase-associated lipocalin (NGAL)). In addition, correlations between the different markers of renal dysfunction were examined alongside the impact of various confounders including age and diabetes mellitus on the reliability of such markers. Method This was a multicentre randomized double-blinded placebo-controlled study involving three tertiary renal centres in the United Kingdom. Patients with CKD stages 3b-5 (non-dialysis), a serum ferritin <100 micrograms/L and/or transferrin saturation <20% and a haemoglobin value of 110 – 150 g/L were enrolled. The participants were randomized 1:1 to receive either 1000 mg of FDI or placebo. Cystatin C, NGAL, serum creatinine eGFR and 24-hour urinary excretion of protein were measured at baseline and then repeated at 1- and 3- months. Changes in the levels of these were analysed both in terms of their absolute values and percentage change from baseline. Pearson’s coefficient (r) was calculated as a measure of correlation between changes in the follow-up values, and the level of statistical significance was set at less than 0.05. Results 54 patients were randomized; 26 to FDI and 28 to placebo. Patients in the two treatment arms were similar in age, gender, the prevalence of diabetes, baseline eGFR and urinary protein excretion (200mg vs 350mg/24hr in the FDI and placebo groups respectively, p = 0.2713). Compared to baseline levels, serum creatinine, cystatin C and NGAL did not change significantly in either arm (figure 1). There were no significant changes in urinary protein excretion both within and between groups (median change in urinary protein excretion: FDI: -10mg and -39mg/24hr; placebo: 0mg and 0mg/24hr at 1- and 3- months respectively, p>0.05) There was a significant correlation between changes in cystatin C levels and serum creatinine (r = 0.6994, p<0.0001) during follow-up. This correlation persisted when patients were stratified by an age of 65 years and presence of diabetes (figure 2). Changes in Cystatin C levels did not correlate well with changes in NGAL. Conclusion This post-hoc analysis of data from the Iron & Heart study indicates that high dose FDI did not cause any significant detriment in the short-term to renal function compared to placebo. This complements the safety profile of high dose third generation IV iron products and improves our understanding of their use in patients with CKD at their approved doses. There was a good correlation between cystatin C and creatinine, which was not affected by various sub-groups such as age or presence of diabetes mellitus. The analysis confirms the role of cystatin C as a robust biomarker of measuring renal function at least when compared to other established methods.

Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury

BackgroundRecent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood.MethodsTo develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20.ResultsAfter recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups.ConclusionsIn this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.

Clinical significance of microRNA-320a and insulin-like growth factor-1 receptor in early-onset preeclampsia patients

Background Currently, there is no reliable method to effectively predict and diagnose early-onset preeclampsia (EOPE). microRNAs (miRs) are powerful and promising biomarkers in multiple diseases, including EOPE. Therefore, the present study investigated the role of miR-320a in EOPE. Methods Expressions of miR-320a and insulin-like growth factor-1 receptor (IGF-1R) in serum of EOPE patients and normal pregnant women were detected. The clinical diagnostic efficacy of miR-320a and IGF-1R for EOPE was analyzed using receiver operating characteristic curve. The correlation between miR-320a expression and EOPE clinical indicators [mean arterial pressure (MAP), 24-h urinary protein excretion, serum creatinine (SCR), uric acid (UA), albumin (ALB) and platelet count] was analyzed. The correlation and binding relationship between miR-320a and IGF-1R was predicted and verified. Results miR-320a was upregulated, and IGF-1R was downregulated in EOPE patients with their differential expressions more obvious in severe EOPE than mild EOPE. miR-320a and IGF-1R possessed potent clinical diagnostic efficacy for EOPE. miR-320a expression showed a positive correlation with MAP, 24-h urinary protein excretion, UA and SCR levels, and a negative correlation with ALB level and platelet count in EOPE patients. Moreover, miR-320a targeted IGF-1R. Conclusion We demonstrated that miR-320a was aberrantly elevated in EOPE and showed powerful clinical diagnostic efficacy for EOPE, which may be achieved by directly targeting IGF-1R. This study provided great reference values for EOPE early diagnosis and novel targets for EOPE treatment.

Abstract P031: Reduced Augmentation Of The Intrarenal Renin-angiotensin System (ras), Lower Systolic Blood Pressure, And Preserved Renal Function In Female Compared To Male Rats With Unilateral Renal Artery Stenosis

Despite growing evidence of sex differences in the progression of hypertension, there are no guidelines that differentiate treatment between men and women. Intrarenal renin-angiotensin system (RAS) activation and tissue injury in 2-kidney, 1-clip (2K1C) hypertensive rats have been characterized in previous studies of male but not female rats. To evaluate possible sex differences in response to renovascular hypertension, urinary angiotensinogen (uAGT) excretion, systolic blood pressure (BP), urinary protein excretion, and renal function were assessed in female rats.Female (n=8) and male (n=6) rats underwent placement of a 0.2 mm clip on the left renal artery to simulate unilateral renal artery stenosis. BP was measured by tail-cuff plethysmography, and clearance studies were conducted in anesthetized rats to assess renal function. Urine protein concentration was determined by pyrogallol red method. uAGT was measured by ELISA as an index of intrarenal RAS activity. Systolic BP increased from 120±1 to 176±8 mmHg, and urinary protein excretion reached 20.2±5.6 mg/day in female rats. Although uAGT excretion increased from 13.2±7.7 ng/day to 74.1±29.9 ng/day in female rats, male rats had a significantly higher uAGT excretion of 1572.6±750 ng/day. Nonclipped kidneys exhibited more uAGT excretion compared to clipped kidneys, consistent with previous findings in males. Although 2K1C female rats demonstrate significantly lower renal function than sham females, they show more preserved renal function than male rats. Female rats also demonstrate significantly lower increases in systolic BP and urinary protein excretion compared to male rats. The data support substantial sex-dependent differences in renal responses to unilateral renal artery stenosis. The results show substantial increases in systolic BP, uAGT, and urinary protein excretion and decreased renal function after renal artery clipping in females, but the magnitude of the changes is markedly lower than in males. Nonclipped kidneys of both sexes exhibit greater uAGT excretion than clipped kidneys. Notably, females show less augmentation of the intrarenal RAS compared to male rats in renovascular hypertension.

Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

Background: Diabetic nephropathy (DN), which affects more than 40% of diabetic patients, is still the main cause of end-stage renal disease in most countries. Prescription containing Astragalus Membranaceus (AM) in the treatment of early stage DN with significant effect, but the mechanism is unclear, which we would explore based on network pharmacology.Method: First, we searched the database of China National Knowledge Internet, Wanfang Database, Chinese Biomedical Literature Database, PubMed, EMBASE, Cochrane database about the randomized, single (double) blind, controlled clinical studies of prescription containing AM in the treatment of DN, determined the effectiveness of prescription containing AM in the treatment of DN. Then, the effective components of AM in Traditional Chinese Medicine systems taxonomy database and analysis platform (TCMSP), Traditional Chinese medicine integrated database (TCMID) and Bioinformatics analysis tool for molecular mechanism of traditio Internal Chinese medicine (BATMAN-TCM) database were searched. According to the oral utilization ≥ 30% and drug-like ≥0.18, the effective components were screened. PubChem and health information technology (HIT) databases were searched for query validation targets and Simplified molecular input line entry specification (SMILES) of the effective ingredients, and Swisstarget prediction database was used to obtain prediction targets (possibility > 0). Drugbank, transient triple differential (TTD), and DisGeNET were searched for the targets related to DN. Finally, the data were integrated by the Cytoscape software, the drug-target-disease network was drawn, the protein interaction network was drawn with String database, and the signal pathway enrichment analysis was carried out with ClueGO.Result: The results showed that prescription containing AM could effectively reduce the urinary protein excretion rate [95% md-43.30 (- 57.00, - 29.61)]. 51 active components, 396 verified targets and 2330 predicted targets were searched. A total of 120 DN related targets were retrieved. 21 targets were found with Cytoscape. The main pathways were Interleukin-4 and 13 signaling, Activation of Matrix Metalloproteinases, EPH-Ephrin signaling.Conclusion: Prescription containing AM could effectively reduce the urinary protein excretion rate of DN patients. We speculated that AM mainly treated DN by regulating Angiotensin-converting enzyme (ACE), Vascular endothelial growth factor A (VEGFA), Janus Kinase 1 (JAK1), and interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, activation of matrix metalloproteins, ephrin signaling and other signaling pathways based on network pharmacology, which would be verified by animal experiments or in vitro experiments in the later.

Chinese Herbal Injections for Primary Nephrotic Syndrome in Adults: A Systematic Review and Network Meta-Analysis

Primary nephrotic syndrome (PNS) is a common renal disease that presents with heavy proteinuria and hypoalbuminemia. Despite notable advances in its treatment, some patients show poor responses and clinical outcomes when treated with conventional Western medicine (WM). Chinese herbal injections (CHIs) have been reported to have beneficial effects for PNS. The aim of the present study was to comprehensively determine the efficacy and safety of CHIs for PNS in adults using a network meta-analysis approach. PubMed, Embase, the Cochrane library, and four Chinese databases were systematically searched to identify randomized controlled trials (RCTs) using CHIs for treatment of PNS published before June 1, 2019. Quality assessment of the identified RCTs was performed according to the Cochrane Handbook. Pooled odds ratios (OR) or mean differences (MD) with corresponding 95% confidence intervals (CI) were calculated for discrete or continuous variables, respectively. The primary outcome was complete/total remission and secondary outcomes were serum albumin and urinary protein excretion. The surface under the cumulative ranking curve (SUCRA) value and cluster analyses were used to rank treatment by probability. Eighty-five studies involving 11 CHIs and 5801 subjects were included. Compared with WM alone, CHI plus WM showed an improved complete/total remission rate as well as higher serum albumin and lower 24-hour urinary protein excretion, except in the following: Yinxingye injection plus WM did not improve the total remission rate, and Dengzhanhua or Xueshuantong injection plus WM did not lower the 24-hour urinary protein excretion. Either Danhong (DH) or Dengzhanhua (DZH) injection plus WM was the preferable treatment for PNS based on SUCRA and cluster analyses of clinical remission and adverse events. However, considering that literature in this area is limited, these results need further validation. CHIs administered as adjuvants to WM showed favourable outcomes for PNS. DH + WM and DZH + WM might be the potential optimal therapies for PNS.