24-hour Proteinuria Research Articles

MON-006 RISK FACTORS FOR PROGRESSION TO END-STAGE RENAL DISEASE IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS-EXPERIENCES FROM A CHINESE SINGLE CENTRE

Although ANCA associated vasculitis (AAV) is not a common disease, AAV renal damage is the leading rapidly progressive glomerulonephritis leading to end-stage renal disease (ESRD). If we can screen out the risk factors for progression to ESRD, it will be valuable for the treatment. 498 AAV patients diagnosed from October 23, 1999 to February 15, 2017 were enrolled, the latest follow up date was February 21, 2018. The general conditions, clinical manifestations, laboratory investigations, renal biopsy results, treatment regimens and prognosis (renal/patient survival) were analyzed. Among the 498 cases, there were 283 females and 215 males. The average onset age was 60.9±14.5 years old (10-90). MPO-AAV was more than PR3-AAV (91% vs 9%). 486 patients (97.6%) had renal impairment. 216 patients (44.4%) received renal biopsy. 54 patients (11.1%) received dialysis at the onset and 11 of them get rid of dialysis. Apart from 56 patients (11.2%) lost to follow up and 53 patients (10.6%) died, we divided patients to ESRD group (n=145) and Stable group (n=302). We compared the baseline data of the two groups (age, sex, onset to diagnosis time, clinical presentation, BVAS score and lab investigation) and treatment regimen (whether plasma replacement, whether or not glucocorticoid pulse therapy). The results showed that the parameters associated with the progression of the patients to ESRD included the type of vasculitis (P=0.016), the combination of hypertension (P<0.001), the combination of fever (P=0.048), hemoglobin level, platelet level, 24-hour proteinuria, serum creatinine level, eGFR level and the need for dialysis (P<0.001). Multiple factor Cox regression analysis showed that daily urine protein (3.21±2.46 vs 1.71±1.61g, 95% CI 0.67-0.99, P=0.041) and eGFR level (9.25±6.10 vs 44.37±40.76ml/min, 95% CI 1.018-1.159, P=0.013) were independent risk factors for the patient's progression to ESRD. During the past 18 years, 554 AAV patients in our centre were female predominant (56% vs 44%）and MPO-AAV dominant (91% vs 9%); The average onset age was 61 years. The overall patient mortality was 10%，renal involvement incidence was 97%，and nearly 30% progressed into ESRD. The prognosis of renal function was poor in patients with heavier proteinuria or lower eGFR level. The long term survival was superior in patients with stable renal function (P<0.001). Due to the low rate of renal biopsy (45%), we found that the segmental crescentic ratio and fibrinous necrosis were associated with deterioration of renal function, but not independent risk factors.

MON-256 RELATIONSHIP OF RANDOM URINARY PROTEIN AND CREATININE RATIO WITH 24 HOUR URINARY PROTEIN IN THE PROTEINURIC INDIAN PATIENTS

The gold standard test for the assessment of proteinuria is 24-hour urinary collection. However, 24-hour urinary collection is cumbersome, time consuming and inconvenient. Urinary protein creatinine ratio is used as surrogate for the 24-hour urinary proteinuria. There are scant studies which have validated this ratio in the Indian population. The aim of the study was to evaluate the relationship between 24-hour urinary protein and spot urinary protein to creatinine ratio (P/C) in patients with proteinuria diagnosed using dipstick test.

SUN-330 RELATIONSHIP BETWEEN THE PRESENCE OF FOAM IN URINE AND THE DIAGNOSIS OF PROTEINURIA IN 24-HOURS URINE

The presence of foam in the urine has been related to the diagnosis of proteinuria, which consists of the abnormal presence of proteins in the urine. Objectives: 1) To determine sensitivity, specificity and positive predictive values (PPV) of the presence of foam in the urine as a marker of proteinuria; 2) Correlate 24-hour proteinuria with the amount of foam assigned by the patient according to a visual analogue scale (VAS).

Relationship Between PNPLA3 rs738409 Polymorphism and Decreased Kidney Function in Children With NAFLD.

Emerging evidence suggests that patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the major genetic variant associated with susceptibility to nonalcoholic fatty liver disease [NAFLD]) is associated with decreased kidney function in adults. Currently, it is uncertain whether this association also occurs in children/adolescents and whether any association is independent of liver disease severity. We enrolled a sample of 142 Caucasian children and adolescents with biopsy-proven NAFLD, presenting to the Liver Unit of the "Bambino Gesù" Children's Hospital. The glomerular filtration rate (e-GFR) was estimated using the Bedside Schwartz equation, whereas 24-hour proteinuria was measured using a radioimmunoassay method. Genotyping for the PNPLA3 rs738409 genotype was undertaken using the single-nucleotide polymorphism genotyping allelic discrimination method. Overall, 45 children had G/G, 56 had G/C, and 41 had C/C PNPLA3 rs738409 genotype, respectively. Children with G/G genotype had significantly lower e-GFR (107.5±20 versus 112.8±18 versus 125.3±23 mL/min/1.73 m2 , P=0.002) and higher 24-hour proteinuria (58.5±21 versus 53.9±22 versus 42.9±20 mg/day, P=0.012) compared with those with either G/C or C/C genotypes. After adjustment for age, sex, systolic blood pressure, measures of adiposity, homeostasis model assessment-estimated insulin resistance and biopsy-confirmed nonalcoholic steatohepatitis and stage of liver fibrosis, the presence of rs738409 G/G genotype was independently associated with both lower e-GFR (β coefficient: -23.6; 95% confidence interval [CI]: -36.3 to -10.8; P<0.001) and higher 24-hour proteinuria (β coefficient: 15.3; 95% CI: 1.12 to 30.5; P=0.046). Conclusion: Regardless of established renal risk factors and the histological severity of NAFLD, the PNPLA3 G/G genotype was strongly associated with decreasing kidney function and increasing 24-hour proteinuria in children/adolescents with histologically confirmed NAFLD.

Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial

Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. Phase 2, randomized, controlled, open-label, crossover trial. Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs)>15mL/min/1.73m2 and residual proteinuria with protein excretion≥0.5g/24h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. After stratification by serum phosphate level,≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. Short treatment duration, lower pretreatment proteinuria than expected. 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. Sanofi (Milan, Italy). Registered at ClinicalTrials.gov with study number NCT01968759.

C5 Convertase Blockade in Membranoproliferative Glomerulonephritis: A Single-Arm Clinical Trial

Primary membranoproliferative glomerulonephritis (MPGN) is a rare glomerulopathy characterized by complement dysregulation. MPGN progresses rapidly tokidney failure when it is associated with nephrotic syndrome. We assessed the effects of C5 convertase blockade in patients with MPGN and terminal complement activation. Prospective off-on-off-on open-label clinical trial. Consenting patients with immune complex-mediated MPGN (n=6) or C3 glomerulonephritis (n=4) with sC5b-9(serum complement membrane attack complex) plasma levels>1,000ng/mL and 24-hour proteinuria with protein excretion>3.5g identified from the Italian Registry of MPGN and followed up at theIstituto di Ricerche Farmacologiche Mario Negri IRCCS (Bergamo, Italy) between March 4, 2014, and January 7,2015. Anti-C5 monoclonal antibody eculizumabadministered during 2 sequential 48-week treatment periods separated by one 12-week washout period. Primary outcome was change in 24-hour proteinuria (median of 3 consecutive measurements) at 24 and 48 weeks. Median proteinuria decreased from protein excretion of 6.03 (interquartile range [IQR], 4.8-12.4) g/d at baseline to 3.74 (IQR, 3.2-4.4) g/d at 24 weeks (P=0.01) and to 5.06 (IQR, 3.1-5.8) g/d (P=0.006) at 48 weeks of treatment, recovered toward baseline during the washout period, and did not significantly decrease thereafter. Hypoalbuminemia, dyslipidemia, and glomerular sieving function improved during the first treatment period. 3 patients achieved partial remission of nephrotic syndrome and all had undetectable C3 nephritic factors before treatment. Mean measured glomerular filtration rate was 69.7±35.2 versus 87.4±55.1 and 75.8±42.7 versus 76.6±44.1mL/min/1.73m2 at the start versus the end of the first and second treatment periods, respectively, among all 10 study participants. Unlike C3, sC5b-9 plasma levels normalized during both treatment periods and recovered toward baseline during the washout in all patients. Single-arm design, small sample size. Eculizumab blunted terminal complementactivation in all patients with immunecomplex-mediated MPGN or C3 glomerulonephritis and nephrotic syndrome, but persistently reduced proteinuria in just a subgroup. Registered in the EU Clinical Trials Register with study no. 2013-003826-10.

Evaluation of Renal Function in Obese Children and Adolescents Using Serum Cystatin C Levels, Estimated Glomerular Filtration Rate Formulae and Proteinuria: Which is most Useful?

Objective:There is a growing interest in the relationship between obesity and renal damage. The effect of obesity on renal function in children and adolescents has not been adequately investigated. In addition, there is no complete consensus on the reliability of various renal function parameters. The primary goal of this study was to evaluate renal function in obese children and adolescents using glomerular filtration rate (GFR), cystatin C, and creatinine (Cr)-derived formulas. We also compared classical GFR measurement methods with methods based on bioimpedance analysis-derived body cell mass (BCM).Methods:We enrolled 108 obese and 46 healthy subjects aged 6-18 years. Serum cystatin C, serum Cr, 24-hour proteinuria, Cr clearance, and GFR were evaluated in both groups. Estimated GFR was measured with Cr-based, cystatin C-based, combined (cystatin C and Cr) and BCM-based formulae. Both actual and fat-free mass body surface areas (BSA) were used when required. Metabolic parameters (blood glucose, insulin, and lipids) were analyzed in the obese subjects. International Diabetes Federation criteria were used to identify metabolic syndrome (MetS).Results:We did not detect statistically significant differences between the obese and control groups for mean Cr (p=0.658) and mean cystatin C (p=0.126). Mean cystatin C levels of MetS patients were significantly higher than those of non-MetS obese participants (p<0.001). Cr-based GFR measurements, BCM-based measurements and a combined Cr and cystatin C measurement showed a statistically significant increase in the GFR of obese subjects compared to controls (p=0.002 and p<0.001). This increase was negatively correlated with duration of obesity. Estimations based on actual or fat-free mass BSA did not differ either. Only the Filler equation showed a statistically significant decrease in eGFR in MetS patients. There were no statistically significant differences between the obese and control groups for proteinuria (p=0.994) and fat-free mass proteinuria (p=0.476).Conclusion:We conclude that cystatin C could be used as an earlier biomarker than Cr in the detection of impaired renal function in obese children, especially those with MetS. Cr-based formulae reveal hyperfiltration as the first change in renal function. Decreasing eGFR seen in MetS patients with cystatin C-based formulae, but not Cr-based formulae, may represent the early stages of renal damage. Using fat-free mass or BCM for eGFR formulae in obese children seems to provide no additional information.

Serum Metabolomic Alterations Associated with Proteinuria in CKD.

Data are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria with serum metabolites identified using untargeted profiling in populations with CKD. Using stored serum samples from the African American Study of Kidney Disease and Hypertension (AASK; n=962) and the Modification of Diet in Renal Disease (MDRD) study (n=620), two rigorously conducted clinical trials with per-protocol measures of 24-hour proteinuria and GFR, we evaluated cross-sectional associations between urine protein-to-creatinine ratio and 637 known, nondrug metabolites, adjusting for key clinical covariables. Metabolites significantly associated with proteinuria were tested for associations with CKD progression. In the AASK and the MDRD study, respectively, the median urine protein-to-creatinine ratio was 80 (interquartile range [IQR], 28-359) and 188 (IQR, 54-894) mg/g, mean age was 56 and 52 years, 39% and 38% were women, 100% and 7% were black, and median measured GFR was 48 (IQR, 35-57) and 28 (IQR, 18-39) ml/min per 1.73 m2. Linear regression identified 66 serum metabolites associated with proteinuria in one or both studies after Bonferroni correction (P<7.8×10-5), 58 of which were statistically significant in a meta-analysis (P<7.8×10-4). The metabolites with the lowest P values (P<10-27) were 4-hydroxychlorthalonil and 1,5-anhydroglucitol; all six quantified metabolites in the phosphatidylethanolamine pathway were also significant. Of the 58 metabolites associated with proteinuria, four were associated with ESKD in both the AASK and the MDRD study. We identified 58 serum metabolites with cross-sectional associations with proteinuria, some of which were also associated with CKD progression. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_02_07_CJASNPodcast_19_03_.mp3.

Association of serum high mobility group box 1 levels with disease activity and renal involvement in patients with systemic vasculitis.

High mobility group box 1 (HMGB1) is a kind of proinflammatory mediator that acts as an alarmin when released by dying, injured or activated cells. Previous studies have reported that HMGB1 are closely linked to antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The present study aimed to evaluate whether serum HMGB1 levels were associated with systemic vasculitis (VAs).The study population consisted of 51 patients with VAs, 46 patients with essential hypertension (EH) and 46 healthy controls (HC). Thirty-five patients with VAs had in active stage and 16 patients with VAs in an inactive stage. Furthermore, 31 patients with VAs had renal involvement, the other 20 patients were selected for without renal involvement. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. Associations between serum HMGB1 levels with clinical and laboratory parameters were analyzed.Serum HMGB1 levels in patients with VAs were significantly higher than in EH and HC (all P < .05), and no difference regarding serum HMGB1 levels could be found between EH and HC (P = .208). Serum HMGB1 levels in VAs patients with active stage were significantly higher than those in HC and VAs patients with inactive stage (all P < .05). Patients with renal involvement and non-renal involvement had increased HMGB1 levels compared with HC (all P < .05). In addition, serum HMGB1 levels were significantly higher in patients with renal involvement compared with non-renal involvement patients (P = .001). Correlation analysis showed that serum HMGB1 levels were positive significant correlated with the Birmingham Vasculitis Activity Score, hypersensitive C reactive protein (Hs-CRP), serum creatinine (Scr) and 24-hour proteinuria (all P < .05). Among the subsets of VAs, serum HMGB1 levels were significantly higher in AAV, polyarteritis nodosa (PAN) and takayasu arteritis (TA) than in HC (all P < .05). More interestingly, serum HMGB1 were significantly higher in patients with PAN compared with AAV and TA patients (all P < .05). Furthermore, there was positive correlation between serum HMGB1 levels and Hs-CRP, Scr, and 24-hour proteinuria in patients with PAN (all P < .05).Serum HMGB1 levels are increased in patients with VAs compared with HC and EH and can reflect the disease activity and renal involvement.

Influence of the Klotho/FGF23/Egr1 signaling pathway on calcium-phosphorus metabolism in diabetic nephropathy and the intervention of Shenyuan granules.

This study aimed to explore the effects of Shenyuan granules on the Klotho/FGFR23/Egr1 signaling pathway and calcium-phosphorus metabolism in diabetic mice models with impairment of renal function. Streptozotocin-induced diabetic nephropathy (DN) mice models were randomly divided into three groups: Shenyuan granules group (n=10), model control group (n=10), and blank control group (n=10). Corresponding drugs were given by gavage for 8 weeks. Blood glucose and serum creatinine (SCr), urea nitrogen (BUN), calcium (Ca), phosphorus (P) and mLAB were detected before and after administration. Moreover, RT-qPCR was performed to detect the expression of CYP24 and CYP27 mRNA in kidney tissue. Blood FGF23 was detected by ELISA. Western-blot and immunohistochemistry were performed to detect the expressions of Klotho, FGFR1, Egr1, CYP24, CYP27, ERK1/2 and p-ERK1/2. Compared with the blank control group, in the model control group serum FGF23,P, SCr and 24-hour proteinuria levels increased (P<0.05), serum Ca significantly decreased (P<0.05), expressionss of Egr1, CYP24, CYP27 and p-ERK1/2 were up-regulated (P<0.05), and the expressions of Klotho and FGFR1 were down-regulated (P<0.05). After treatment, compared with the model control group, in the Shenyuan granule group serum FGF23, P, SCr levels decreased (P<0.05), serum Ca increased (P<0.05), expressions of Egr-1, CYP24, CYP27 and p-ERK1/2 were down-regulated (P<0.05), and the expressions of Klotho and FGFR1 were up-regulated (P<0.05). Shenyuan granules may partly intervene in the expressions of CYP24 and CYP27 through the Klotho/FGF23/Egr1 signaling pathway, thereby improving calcium and phosphorus metabolism and alleviating renal injury in diabetic nephropathy.

An unresolved issue: The relationship between spot urine protein-to-creatinine ratio and 24-hour proteinuria.

ObjectiveTo investigate the relationship between spot urine protein-to-creatinine (sP/Cr) ratio and 24-h protein excretion in patients with different diagnoses.MethodsThis retrospective study analysed data from the medical records of patients admitted for24-h proteinuria determination who also had sP/Cr ratio data for the same day.ResultsA total of 1222 urine samples obtained from 694 adult outpatients were analysed. The mean ± SD age of the patients was 53.6 ± 15.9 years. The mean ± SD 24-h proteinuria and sP/Cr were 1.7 ± 2.4 g/day and 1.8 ± 2.4, respectively. The correlation between the sP/Cr and 24-h protein excretion was high (R2 = 0.89). The sP/Cr ratio accounted for 72% of the variability in 24-h proteinuria in the entire study population. Areas under the curve for 24-h proteinuria at 0.3 g/day, 1.0 g/day and 3.0 g/day were 0.940, 0.966, and 0.949, respectively. The mean + 2SD limits of agreement were between +2.99 and –2.73 g/day according to the Bland Altman analysis.ConclusionThis current study found a clinically unacceptable deviation between 24-h proteinuria and sP/Cr ratio. Therefore, the sP/Cr ratio cannot replace 24-h proteinuria. A new method using spot urine protein and creatinine values that is able to minimize under or over estimation is still warranted.

The effects of bitter gourd saponins on the expression of podocin and nephrin in renal tissues of rats with renal damage induced by salt-sensitive hypertension

Objective To study the therapeutic effect of bitter gourd saponins on salt-sensitive kidney injury induced by high salt diet and its possible mechanism. Methods 50 Sprague Dawley (SD) rats were randomly divided into normal group, model group and low-dose, middle-dose and high-dose treatment group after 10 days of adaptive feeding. Each group had 10 rats. Except the normal group, the other four groups were given high salt diet (4.0% high salt diet) to induce salt-sensitive kidney damage in rats. The normal group and the model group were given 1.0 m/(kg·d) normal saline, and the three dosage groups of total saponins of balsam pear were given 10 mg/(kg·d), 20 mg/(kg·d) and 40 mg/(kg·d) respectively. After 8 weeks of treatment, rats were sacrificed and collect the 24-hour proteinuria, creatinine. Serum creatinine, serum aldosterone, serum sodium and serum potassium were measured, and renal histopathology and the expression of podocin and nephrin were detected. Results Pathological examination of model group showed obvious glomerular sclerosis and renal interstitial fibrosis, and glomerular sclerosis in the treatment group was obviously improved by bitter gourd saponins; The systolic pressure in the model gr-oup was 170 mmHg, significantly higher than that of the normal and treatment groups, the systolic blood pressure of the treatment groups were obvious decreased when treated by bitter gourd saponins (P<0.05); Compared with normal group, serum creatinine and 24 h proteinuria / urine creatinine in model group were significantly increased (P<0.05), while creatinine clearance rate and aldosterone were significantly decreased (P<0.05), and the above indexes in bitter gourd saponins treatment group were significantly improved; Compared with the model group, the protein and mRNA expression of podocin and nephrin were significantly decreased (P<0.05), while the two indexes can be revered by bitter gourd saponins in treatment group (P<0.05). Conclusions The bitter gourd saponins can significantly improve the symptoms of salt-induced hypertensive nephropathy in rats, which may be related with the expression of podocin and nephrin in renal tissue, thereby inhibiting glomerulosclerosis and improving renal interstitial fibrosis. Key words: Momordica charantia; Saponins/AD; Hypertension/CO; Kidney diseases/ET/DT; Kidney/PA; Intracellular signaling peptides and proteins/ME; Membrane proteins/ME; Rats

A10216 Serum MCP-1 levels are increased in systemic vasculitis of pations with hypertension with renal involvement

Objectives: Monocyte chemotactic protein 1 (MCP-1), which is able to adjust the migration of monocytes/macrophages, osmosis and raise monocytes and T lymphocyte cells to participate in a variety of inflammation, are closely linked to various types of systematic vasculitis. However, serum MCP-1 levels have not been evaluated in patients with small and medium vessel vasculitis (SMVV), especially in those with PAN. The study was performed to investigate the level of serum MCP-1 in determining the SMVV. Methods: We reviewed all patients admitted to our center for the etiology screening of hypertension between January 2013 and December 2016. All vasculitis are diagnosed by a rheumatologist and fulfilled the American College of Rheumatology (ACR) 1990 criteria. Serum samples were collected in 43 patients with systemic vasculitis with hypertension and 43 healthy controls (HC). Serums MCP-1 were measured using commercially available ELISA kits. Results: The serum MCP-1 levels were significantly higher in patients with systemic vasculitis, compared with healthy controls (p < 0.001). Furthermore, it was significantly increasing in patients with renal than non-renal involvement (p = 0.001) and HC (p < 0.001). However, there was no significant statistical differences between active and inactive phase. Serum MCP-1 levels with patients in systemic vasculitis were positive correlation with serum creatinine levels (r = 0.387, p < 0.010). Furthermore, there was a closely correlation between 24-hour proteinuria and MCP-1 levels (r = 0.404, p < 0.014). Conclusion: Serums MCP-1 were significantly higher in patients with systemic vasculitis compared with HC, especially in patients with renal involvement. Serum MCP-1 might be as a potential biomarker tools in the systemic vasculitis with renal involvement.

Using plasma circRNA_002453 as a novel biomarker in the diagnosis of lupus nephritis

This study aimed to determine the expression of circRNAs in plasma from lupus nephritis (LN) patients to identify novel biomarkers for LN screening. We initially performed microarray screening of circRNA changes in plasma from 5 L N patients, 5 systemic lupus erythematosus (SLE) patients without LN, and 5 healthy controls. We then confirmed the selected circRNA changes in plasma from 59 SLE patients (30 with LN and 29 without LN), 26 rheumatoid arthritis (RA) patients, and 27 age- and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction. Spearman’s correlation test was performed to assess the correlation of circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. We confirmed that plasma circRNA_002453 was significantly elevated in LN patients when compared with SLE patients without LN, RA patients, and healthy controls. Plasma circRNA_002453 was also found to be upregulated in SLE patients when compared with RA patients and healthy controls. Among these LN patients, we detected no significant correlation between plasma circRNA_002453 and disease activity, including complement 3 (C3), complement 4 (C4), and SLE disease activity index 2000 (SLEDAI-2 K) score. However, its expression level was significantly and positively correlated with 24-hour proteinuria (r = 0.571, p = 0.001) and renal SLEDAI score (r = 0.640, p < 0.001). ROC analysis showed that plasma circRNA_002453 had an area under the curve of 0.906 (95% CI 0.838–0.974, p < 0.001) to discriminate LN patients from controls (SLE patients without LN, RA patients, and healthy controls) with sensitivity of 0.900 and specificity of 0.841. The highest Youden index was 0.741 and the corresponding optimal cut-off value was 0.001. This study suggests that upregulated plasma circRNA_002453 level in LN patients is associated with the severity of renal involvement and may also serve as a potential biomarker for LN patient diagnosis.

Histological predictors of renal outcome in lupus nephritis: the importance of tubulointerstitial lesions and scoring of glomerular lesions.

Introduction Lupus nephritis (LN) affects nearly 60% of patients with systemic lupus erythematosus and up to 30% of them will progress to end-stage renal disease (ESRD), despite receiving aggressive immunosuppressive therapy. The prognostic value of ISN/RPS classification is controversial. Therefore, we aimed to identify clinical and pathological predictors of outcome in LN patients independent of this classification. Material and methods Thirty-seven patients with LN who underwent percutaneous kidney biopsy between 1997 and 2016 were included in this study. Twenty clinical and twenty histological variables were tested for their association with a composite end-point of doubling of serum creatinine, ESRD and death. Univariate and multivariate Cox proportional hazard regression analysis were performed to identify independent predictors of outcome. Results During a median follow-up period of 48 months (IQR: 17.5-120 months), 21.6% of patients reached the composite end-point. The overall survival rate of our cohort was 89% at one year, 86% at five years, 74% at 10 years and 64% at 20 years. Patients with Class IV LN showed the worst prognosis with 44% survival at 10 years, while those who additionally showed crescents and global sclerosis on kidney biopsy had an even lower survival of 21% and 0% at 10 years, respectively. After multivariate adjustment, we identified estimated glomerular filtration rate at baseline (HR, 0.91 per ml/min /1.73 m2; 95% CI, 0.84 to 0.99), 24-hour proteinuria at baseline (HR, 2.04 per g/d; 95% CI, 1.19 to 3.5), crescents (HR, 1.068 per %; 95% CI, 1.003 to 1.091), global sclerosis (HR, 1.036 per %; 95% CI, 0.984 to 1.091), presence of adhesions (HR, 9.2; 95% CI, 1.38 to 61.2) and tubulitis (HR, 13.1; 95% CI; 1.3 to 131) as independent predictors of outcome in our cohort of LN. Conclusions Our study identified glomerular (crescents, global sclerosis, adhesions) and tubulointerstitial (tubulitis) lesions, in addition to clinical variables (renal function, 24-hour proteinuria), as important predictors of renal outcome, independent of the ISN/RPS classification. We suggest that the ISN/RPS classification could be improved by a quantitative assessment of glomeruli with active and chronic lesions and by a greater emphasis given to tubulointerstitial lesions.

Combined utilization of untimed single urine of MCP-1 and TWEAK as a potential indicator for proteinuria in lupus nephritis: A case-control study.

The aim of this study was to determine whether combined utilization of untimed single urine monocyte chemoattractant protein 1 (uMCP-1) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (uTWEAK) could serve as a screening test for proteinuria in patients with lupus nephritis (LN).A case-control study that contained 39 biopsy-proven LN patients, 20 non-LN systemic lupus erythematosus (SLE) patients, and 10 healthy controls (HCs) were carried out. Correlations between uMCP-1, uTWEAK, and traditional clinical markers were analyzed by Spearman correlation test. Diagnostic values of uMCP-1, uTWEAK, and urine albumin/creatinine ratio (uACR) in the assessment of proteinuria were investigated by receiver operating characteristic (ROC) curves.Biopsy-proven LN patients showed higher levels of uMCP-1 and uTWEAK than non-LN patients. uMCP-1 and uTWEAK were elevated in renal active patients (rSLEDAI ≥4). Both uMCP-1 and uTWEAK showed significant correlation with patients' rSLEDAI, 24-hour urine proteinuria (24hr UP), and anti-double-stranded DNA (anti-dsDNA) antibodies. No correlations of these 2 biomarkers between cystatin C (Cys-C), creatinine (Cr), and blood urea nitrogen (BUN) were observed. An algorithm combining the moderate sensitivity of uMCP-1 and high specificity of uTWEAK displayed great specificity and sensitivity for proteinuria screening.Both uMCP-1 and uTWEAK were positively correlated with the impairments of LN, and the combined utility of untimed single uMCP-1 and uTWEAK might be used as potential predictors for proteinuria in LN.

Study on the affection of TLR of aralia in renal tissue of diabetic mice

Objective To investigate the protective effect of aralia total saponins on renal injury induced by streptozotocin (STZ) in type 2 diabetic mice, meanwhile to explore its protective mechanism. Methods Fifty male Kunming mice were randomly divided into the normal group, the model group and the aralia total saponins low, middle and high does groups. All the rats were given high fat diet 8 weeks and then received STZ 45 mg/kg to built type 2 diabetic mice model, except the noraml group. After the models establishment, the aralia total saponins low, middle and high does groups were given the aralia total saponins 30, 60, 120 mg/kg treatment, andthe normal group and the model group were given the equal normal saline, once each day. After 4th and 8th week administration, the urinary protein levels of 24 h in each group were detected. After the last treatment, all the mice were sacrificed to detected the changes of blood glucose, insulin and inflammatory related factors. Immunohistochemistry, Western blotting and real-time quantitative PCR were used to observe the expression of TLR2 and TLR2 in the kidney tissue. Results Compared with the model group, the low, middle and high does groups in 24-hour proteinuria, blood glucose, insulin resistance index decreased (P<0.05), the insulin increased(P<0.05). The serum TNF-α (16.66 ± 0.20 ng/L, 14.49 ± 0.27 ng/L, 13.52 ± 0.22 ng/L vs. 20.33 ± 0.56 ng/L), IL-1β (0.46 ± 0.04 ng/L, 0.44 ± 0.04 ng/L, 0.37 ± 0.04 ng/L vs. 0.55 ± 0.05 ng/L), NF-κB (28.71 ± 6.14 ng/L, 26.26 ± 5.48 ng/L, 25.69 ± 5.61 ng/L vs. 36.55 ± 8.90 ng/L) significantly decreased (P<0.05). The kidney TLR2 mRNA (1.92 ± 0.18, 1.46 ± 0.23, 1.28 ± 0.21 vs. 2.69 ± 0.22), TLR4 mRNA(2.20 ± 0.19, 2.08 ± 0.27, 1.57 ± 0.22 vs. 2.78 ± 0.23), TLR2 porteins (0.82 ± 0.11, 0.52 ± 0.06, 0.44 ± 0.07 vs. 0.77 ± 0.13), TLR4 proteins (0.52 ± 0.04, 0.42 ± 0.09, 0.26 ± 0.06 vs. 0.86 ± 0.12) significantly decreased (P<0.05). Conclusions The aralia total saponins can significantly reduce the blood glucose, insulin resistance index and 24-hour urinary protein in type 2 diabetic nephropathy of mice, increase the insulin, and analyzing its mechanism may be total saponins can inhibit the expression of TLR2 and TLR4 protein in the kidney, and further reduce the inflammatory response. Key words: Diabetic nephropathies; Aralia chinensis; Toll-like receptor 2; Toll-like receptor 4; Inflammation; Mice

Single-Center Long-Term Follow-Up of Kidney Donors in Argentina (Hospital Italiano de Buenos Aires)

IntroductionLiving kidney donor (LKD) transplantation is increasing due to organ shortage. Clinical studies have shown that the risk of developing end-stage renal disease (ESRD) in donors is similar to that in the general population. Our goal was to evaluate postdonation renal outcomes assessed by glomerular filtration rate (GFR), proteinuria, and blood pressure. MethodsA total of 210 LKD transplants were performed at Hospital Italiano de Buenos Aires between 2000 and 2014. Postdonation outcomes were analyzed in 109 donors. GFR was assessed by 24-hour creatinine clearance (as 24-hour ClCr) and estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Additionally, we correlated the predonation renal functional reserve (RFR) with postdonation GFR. Donor results were compared to the expected GFR (adjusted to age and single kidney). Other renal outcome indicators measured were albuminuria and blood pressure, and they were compared (predonation and postdonation) using univariate analysis. ResultsA total of 109 patients were followed up for 47 ± 34 months (range, 12–168): 70% were female, age at donation was 48.58 years (range, 25–70), and predonation serum creatinine was 0.85 ± 0.17 mg/dL. Postnephrectomy GFR (24-hour ClCr) was significantly lower compared to predonation GFR (105.38 ± 21.78 mL/min/1.73 m2 vs 90.14 ± 17.78 mL/min/1.73 m2). However, postdonation GFR was not significantly different compared to the expected GFR. No differences were found for blood pressure or albuminuria. Age >50 and an RFR (<20%) was associated with a lower GFR. ConclusionsIn this population of LKD, renal outcome (24-hour CrCl, albuminuria, and blood pressure) was within the expected outcome for healthy individuals after uninephrectomy.

24-Hour Proteinuria Weakly Correlated with Estimated Glomerular Filtration Rate in Lupus Nephritis Patients

Background: Lupus Nephritis (LN) is still the most frequent complication in Systemic Lupus Erythematous (SLE) patients which causing the major and significance morbidity and mortality. Proteinuria and Glomerular Filtration Rate (GFR) serves as objective and routine examinations to assessrenal function. 24-hour proteinuria still regarded as gold standard to quantify amount protein in urine. Estimated GFR (eGFR) is preferably used due its convenient. On the hand, estimated GFR (eGFR) is preferably used due its convenient. However, both of them should be measured in order to determine renal progression and prognosis. Only few studies have been conducted to find out the correlation between 24-hour proteinuria and eGFR in lupus nephritis patients as both of them serve as potential marker in progression of renal involvement. Thisstudy addressed to find out correlation between 24-hour proteinuria and eGFR in lupus nephritis patients.Method: Analytic-correlation study with cross-sectional approach at Dr. Hasan Sadikin Hospital, Bandung was done. Secondary data was used and paralleled with previous study entitled “Correlation of Random Urine Protein Creatinine (P-C) Ratio with 24-Hour Protein Urinein Lupus Nephritis Patients” carried out from October to December 2014.Correlation coefficient was analyzed by Spearmans’ correlation test.Results: Forty five samples were obtained based on inclusion criteria. Spearmans’ correlation test revealed non significant and very weak correlation between 24-hour proteinuria and eGFR (r=-0.095) with p&gt;0.05.Conclusion: The 24-hour proteinuria and eGFR are weakly correlated. Despite the weak correlation, these examinationsshould be considered as important markers to monitor prognosis of renal involvement in lupus nephritis patients Keywords: Estimated glomerular filtration rate (eGFR),Lupus Nephritis (LN), Proteinuria, Systemic Lupus Erythematosus (SLE).

Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal.

Nailfold capillaroscopy is an easy, non-invasive technique to assess microvascular involvement in rheumatic diseases. Multiple studies describe capillaroscopic changes in systemic lupus erythematosus (SLE), including a wide range of non-specific findings. On behalf of the European League Against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases, a systematic review was done to obtain all original research studies (in English) in which SLE patients had capillaroscopy. Forty such studies are identified. This article firstly provides a résumé of the results of these studies according to capillaroscopic parameters (density, dimensions, morphology, haemorrhages), semi-quantitative assessment and qualitative assessment of capillaroscopy in SLE patients. Secondly, the correlations between capillaroscopic parameters in SLE patients and clinical and laboratory parameters (including auto-immune parameters) are outlined. The following capillaroscopic parameters are found to be significantly more prevalent in SLE patients compared to healthy controls: tortuous capillaries, abnormal morphology and haemorrhages. Hairpin-shaped capillaries are significantly less prevalent than in healthy persons. The semi-quantitatively determined nailfold capillaroscopic score (NFC score) in SLE patients is also higher than in healthy controls. Several correlations between clinical and laboratory parameters and capillaroscopic parameters are identified in the review. Disease activity is correlated with NFC score in seven studies, with abnormal morphology (i.e. "meandering") in one study and with haemorrhages in one study. Frequent attacks of Raynaud's phenomenon (RP) and gangrene are significantly correlated with dilated capillaries. In two studies a possible correlation between anti-SSA antibodies and lower density of capillaries is withheld. About other immune parameters conflicting results are found. In one study a significant negative correlation is found between 24-hour proteinuria and abnormal morphology (i.e. "meandering"). For the first time, an overview of the nailfold capillaroscopic changes that have been described in SLE and their correlations with clinical and laboratory findings is given. Further large-scale research on the identification of capillaroscopic changes in SLE and their correlations with standardised clinical and laboratory parameters, is ongoing at the EULAR study group on microcirculation in rheumatic diseases.