Proteinuria selectivity index as a prognostic biomarker in lupus nephritis.

Lupus nephritis (LN) is characterized by a highly variable clinical course. It has been reported that histopathologic lesions are risk factors for the progression of LN. The aim of this study is to investigate the relationship among the co-deposition of C1q, clinicopathological features, and renal outcomes in patients with LN. The clinical and histological parameters were studied in patients with International Society of Nephrology/Renal Pathology Society Class III or IV LN, who underwent two kidney biopsies. The patients were divided into two groups based on the glomerular C1q deposits: C1q-positive and C1q-negative. The impact of C1q status and longterm renal outcome on the doubling of serum creatinine and the rate of remission in the two groups were further investigated. Fifty-three patients had pure proliferative nephritis and 37.7% of these had a co-deposition of C1q. Doubling of serum creatinine was observed in 25% of patients with C1q-positive and 24.2% of patients with C1q-negative deposits. There was no difference between the two groups in terms of achieving complete or partial remission. The renal survival in the two groups was similar (P = 0.75). Upon repeat biopsy, the persistence of C1q positivity was associated with a poor outcome (P = 0.007). C1q deposition in the glomerulus in the baseline biopsy was not associated with a poor renal outcome or severe pathologic features in patients with proliferative LN. However, the persistence of C1q positivity in repeat kidney biopsy is associated with a poor renal outcome.

Lupus nephritis (LN) is a rare disease but is the strongest predictor of poor outcome in patients with Systemic Lupus Erythematosis (SLE). It is associated with significant morbidity, with 10-20% of patients developing end stage renal failure. As there is a paucity of randomized clinical trial data in LN, and no consistent literature regarding baseline factors that predict renal outcome, we were prompted to analyse our centre's complete experience of managing LN. A retrospective analysis was undertaken of all patients presenting to our renal centre with biopsy proven LN from 1979-2003. Patients were divided into two categories, those with stable or deteriorating renal function over time. Baseline parameters were correlated with renal outcome. Complete clinical records were available for 45 (40 female) patients. Mean (SD) age of onset of SLE was 32 +/- 14 years, and mean age onset of LN was 36 +/- 13 years. Patients were followed up for an average of 74 +/- 56 months. Four patients (9%) had WHO Class II LN, 11 (24%) WHO Class III and there were 15 (33%) each in Class IV and V, respectively on renal biopsy. Five (11%) patients presented with acute renal failure and all had proliferative changes on biopsy. The chief arbiters of renal functional deterioration over follow up were longer time to development of LN (P = 0.04), a high platelet count and worse baseline renal function (both P = 0.05). There was a trend relating low haemoglobin or membranous histology to poor renal outcome, and Class IV histology to better outcome. The study has identified that longer time to development of LN, high platelet count and poorer renal function at baseline suggest a worse renal outcome in LN. The study was small but LN is a rare condition. A combination of factors is likely to influence renal outcome in LN and larger prospective trials are required to ascertain consistent baseline prognostic markers.

Background and objectivesDespite much research about lupus nephritis, none of the urinary biomarkers has been proven to be truly reflecting lupus nephritis activity, response to treatment, or prognosis. We aimed to study urinary biomarkers in lupus nephritis and test their relation to kidney damage.Patients and methodsForty patients with systemic lupus erythematosus (SLE) were divided into two graoups: (1) lupus nephritis group with biopsy-proven proliferative lupus nephritis (classes III and IV) and who did not receive immunosuppressive drugs within the preceding 3 months except for glucocorticoids and (2) lupus non-nephritis group with SLE patients without any renal manifestation. We assessed disease activity by the SLE disease activity index. uNGAL, uKim-1, uNGAL to urinary creatinine excretion (mg/dl), and uKim-1 to urinary creatinine excretion were measured in random spot urine samples at the time of renal biopsy and 6 months after the induction therapy.ResultsThe LN group before treatment showed higher levels of uNGAL and uKIM-1 (P-value < 0.001). ROC analysis showed that uNGAL at level of > 59 has a 95 % sensitivity, a 100 % specificity, and an AUC = 0.996 in the ability to diagnose LN. While the uKIM-1 ROC showed that at level of > 1.6, it has an 85 % sensitivity, an 80 % specificity, and an AUC = 0.919. uNGAL and uKIM levels were significantly lower after treatment (P-value < 0.001). No significant correlations were found between urinary markers before and after treatment with other clinical, inflammatory, and serological markers of lupus nephritis.ConclusionuNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio can be used as a predictor and a marker of disease activity for lupus nephritis.Key Points• Renal biopsy is the current standard for diagnosis of lupus nephritis and none of the urinary biomarkers has been fully concluded to have a diagnostic power to reflect the activity or the response to treatment.• However, based on the finding of the current study, uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio showed significant diagnostic performance and were powerful indices of renal involvement in systemic lupus patients and as markers of disease activity.

Accumulating evidence suggests that a relationship exists between serum uric acid (UA) and the progression of chronic kidney disease (CKD), but information regarding idiopathic membranous nephropathy (IMN) is limited. Patients with renal biopsy-confirmed diagnosis of IMN between 2009 and 2017 were identified. The demographic and clinical data recorded at the time of renal biopsy were considered the baseline values. The included cases were separated into three groups based on tertiles of the baseline serum UA level, and the relationship between serum UA and poor renal outcome was investigated by receiver operating characteristic (ROC) and time-event analyses. The primary endpoint was poor renal outcome, which was defined as a decrease in the estimated glomerular filtration rate to 50% of the baseline level or progression to end-stage renal disease during the follow-up. Of 989 cases, 572 eligible patients were included. During a median of 18months of follow-up, 45 (7.9%) patients progressed to the primary endpoint. Both baseline serum UA and time-averaged UA levels could be used for discrimination of renal outcomes, but the difference was not significant (p value = 0.6). Our Cox regression analysis further demonstrated that baseline serum UA was an independent predictor of poor renal outcome in IMN patients, and subgroup analysis revealed a gender difference in the predictive effect of serum UA. Our study demonstrated that baseline serum UA was an independent predictor of poor renal outcome in patients with IMN, and a gender difference in the predictive effect was observed in our cohort.

Involvement of the complement system in the pathogenesis of lupus nephritis (LN) is well accepted, but its exact role remains unclear. The aim of this study was to investigate the relationship of complement activation pathway to clinical and pathological characteristics and renal outcome in patients with LN. Patients with LN were divided into two groups: those in whom the complement system was mainly activated through the classical pathway (low serum C3 and C4 levels; CP group); and those in whom the complement system was solely activated through the alternative pathway (low serum C3 with normal C4 levels; AP group). Clinical and pathological data and renal outcomes were compared between the two groups. Atotal of 102 LN patients were enrolled in this study, 63patients (61.8%) in the CP group and 39patients (38.2%) in the AP group. LN patients in the CP group had significantly higher SLEDAI (p < 0.001), more anti-dsDNA (p = 0.001), higher renal activity index (p < 0.001), and more classIV LN (p = 0.008) than LN patients in the AP group. Mean length of follow-up was 50.6 ± 26.4months. Renal outcome in the form of progression of kidney disease was significantly poorer in the CP group in the AP group (p = 0.037). Our findings suggest that evaluation of the complement activation pattern may be useful for evaluating disease activity and predicting the prognosis of LN.

Lupus nephritis is a serious complication of systemic lupus erythematosus. Currently, therapy is guided by findings in the renal biopsy, following the International Society of Nephrology / Renal Pathology Society classification. Austin and Hill's histomorphological indexes are not routinely obtained. In this retrospective single-centre study, we aimed to analyze the importance and applicability of the different morphological indexes in predicting response to treatment and prognosis. Patients with kidney biopsy demonstrating lupus nephritis from the 2010 - 2016 period were included. We analyzed their demographic data, comorbidities, clinical presentation and laboratorial evaluation at the time of renal biopsy. We evaluated the following outcomes: clinical remission, renal function and proteinuria at end of follow-up. Histologic analysis was performed using the International Society of Nephrology / Renal Pathology Society classification and the morphological indexes described by Austin (Activity and Chronicity) and Hill. Univariate and multivariate statistical analysis was performed using STATA software. We analyzed 46 biopsy-proven lupus nephritis cases, with a median follow-up of 31.9 (13.2 - 45.6) months. Based on biopsy findings, 35 patients were started on immunosuppressive therapy. We observed that Class IV patients had, at presentation, lower estimated glomerular filtration rate (67.3 vs 94.6 mL/min; p = 0.02), higher proteinuria (4.26 vs 2.37 g/24 hours; p = 0.02) and a non-significantly higher C3 consumption (58.9 vs 77.4 mg/dL; p = 0.06). We did not observe correlations between International Society of Nephrology / Renal Pathology Society classification and the outcomes at the end of follow-up. In contrast, both the Hill biopsy index and Austin's Chronicity index were correlated with renal function and proteinuria at the end of follow-up. Austin's Activity index correlated with the immunological findings (C3, C4 and anti-dsDNA) at presentation. Because clinical activity poorly correlates with histologic activity, histological findings are fundamental when assessing patients with suspected lupus nephritis. The most recent International Society of Nephrology / Renal Pathology Society report supports the European League Against Rheumatism guidelines, encouraging the adoption of histomorphological indexes when evaluating lupus nephritis. Our data, showing a correlation between the renal outcomes and the indexes described by Austin and Hill, supports this view. The histomorphological indexes in lupus nephritis are easily obtainable, can predict renal outcomes and may help in the management of such patients.

Background: Both sodium glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1Ras) showed robust evidences for not only cardiovascular but also renal outcomes and the combination treatment of these drugs is increasing in clinical practice. We previously reported that the preceding drug did not influence the renal outcomes in patients with these combination treatments. We also reported the importance of post blood pressure (BP) management for the renal outcomes in SGLT2i-treated patients, however, it is poorly surveyed in patients with the combination treatment. Method: A retrospective study was conducted in 418 patients who were treated with both SGLT2i and GLP1Ra. The progression of the albuminuria stage, the eGFR decline of ≥30%, or both were defined as the renal composite outcome. The cut off value of post-treatment mean arterial pressure (post-MAP) were calculated using receiver ROC curve analysis. The patients were divided into two groups by the cut-off value and propensity score (PS) matching method was performed for comparisons between the two groups. Results: The calculated cutoff value of post-MAP was 87.3 mmHg and the patients were divided into two groups: 281 patients in post-MAP≥87.3 group and 137 patients in post-MAP&amp;lt;87.3 group. Of the 111 PS-matched patients in each group, the renal composite outcome after the combination treatment was observed in 38 patients (34.2%) in post-MAP≥87.3 group, which was significantly higher than in 18 patients (17.1%) in post-MAP&amp;lt;87.3 group (p=0.005). The progression of albuminuria stage was significantly more frequent in post-MAP≥87.3 group (23.4%) than post-MAP&amp;lt;87.3 group (8.1%) (p=0.004), however no significant difference was observed for the eGFR decline of ≥30%. Conclusion: Poor BP management after combination treatment of SGLT2i and GLP1Ra treatment worsened the renal composite outcomes, especially the progression of albuminuria stage. Disclosure K. Kobayashi: None. M. Toyoda: None. D. Kawanami: None. K. Tamura: None.

Background and Aims Progressive deterioration of proteinuria and glomerular filtration rate (GFR) is notified in 20-30% of patients with IgA nephropathy during 20-30 years follow-up period. Popular traditional approach for patients with rapid deterioration of renal function is the immunosuppressive treatment with steroid, which efficacy is still remained in debate. We searched the factors related to renal outcomes among patients presumed to need steroid treatment. Method Among 472 adult patients with IgA nephropathy diagnosed by renal biopsy during 2003-2017 in a tertiary hospital, we selected 86 patients with initiation of steroid treatment for more than 1 months and with dose of more than 1000 mg of prednisolone after renal biopsy. We excluded patients with steroid treatment started one month or more before renal biopsy. The renal outcome was defined as decrease of GFR more than 50% from GFR at renal biopsy, decrease of GFR to less than 15 ml/min/1.73 m2, or a status to need renal replacement therapy during follow-up period after renal biopsy. Results At admission for renal biopsy, estimated GFR by CKD-EPI 2009 equation was 68.5 ± 33.3 ml/min/1.73 m2 and urine protein to creatinine ratio (UPCR) was 2.81 ± 2.23 g/g creatinine (no missing data). The renin-angiotensin-aldosterone inhibitor was used in 80 patients (93.0 %) after renal biopsy. Steroid was started at 8.4 ± 23.1 months after renal biopsy. Majority of patients (63 patients) had been prescribed steroid medication within 2 months after renal biopsy. Total dose of steroid was 13.5 ± 13.1 g. The results of eGFR and UPCR before starting steroid medication were 63.7 ± 31.2 ml/min/1.73 m2 and 2.82 ± 2.01 g/g creatinine, respectively. During 63.6 ± 48.8 months of follow-up period after renal biopsy, there were 39 patients (45.3 %) developed the renal outcome. Factors related to development of the renal outcome searched by correlation coefficient were eGFR and UPCR at renal biopsy, medications of anti-diabetic agent, anti-hypertensive agent, immunosuppressive agent other than steroid, dose of steroid, or vitamin D3 agent after renal biopsy, pathologic findings of segmental sclerosis, interstitial inflammation, and tubular atrophy on light microscopic examination, deposition of C3 and IgA on immunofluorescent staining, and Oxford classification of T, period of starting steroid treatment after renal biopsy, and eGFR before starting steroid medication. With Cox's hazard proportional model, the independent factors to predict the renal outcome were eGFR before steroid treatment or eGFR at renal biopsy, immunosuppressive medication other than steroid, pathologic finding of C3 deposition, and period of starting steroid treatment. Hazard ratio to estimate the renal outcome (HR) was 1.025 (95% CI: 1.010-1.039, p = 0.001) for one-month delay of starting steroid medication after renal biopsy. The HR for the renal outcome in patients started steroid medication at 2 months after renal biopsy was 2.353 (95% CI: 1.140-4.856, P = 0.021) compared to patients started steroid within 2 months after renal biopsy. Conclusion For the patients supposed to have indications for steroid treatment at renal biopsy, early initiation of steroid treatment would indicate better renal outcome.

BackgroundDespite standard therapy (ST) for LN, only 20–40% of pts achieve Complete Renal Response (CRR) at 0.5–1 year and 20–25% relapse in 3–5 years. Achieving CRR is often more difficult...

The effects of volatile induction and maintenance of anesthesia and selective spinal anesthesia on QT interval, QT dispersion, and arrhythmia incidence

ObjectiveRenal injury is common in SLE. Immune complex deposition plays an important role in the development of lupus nephritis (LN), while little is known about glomerular IgG4 deposition in patients...

sBackground: Recent studies have identified the significance of proteinuria levels after initial induction therapies on the renal outcomes in patients with proliferative lupus nephritis, but the issue has not been evaluated in Japanese patients.Methods: Based on the ISN/RPS classification, only patients diagnosed with lupus nephritis class III or IV were included. The remission of proteinuria 12 months after diagnosis, as well as the clinicopathological features at diagnosis, on renal outcomes was examined retrospectively. Renal progression was defined as a 50% decrease in the estimated glomerular filtration rate or the development of end-stage renal disease.Results: This study included 82 Japanese patients with a median follow-up period of seven years. Although all patients received intensive induction therapy, 15 patients (18%) showed progression. Proteinuric remission 12 months after diagnosis predicted a good renal outcome by multivariate analysis. A receiver-operating characteristic analysis of 38 patients whose quantitative urinary protein excretion levels at 12 months were available for analysis showed that a cut-off value of 0.8 g/day predicted renal progression most effectively. Neither the renal function nor proteinuria level at diagnosis were associated with the renal outcomes.Conclusion: In Japanese patients with lupus nephritis class III or IV, proteinuria levels after 12 months under intensive therapy predicted renal outcomes more accurately than did factors identified at diagnosis.

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.

Renal dysfunction is common and associated with a poor prognosis in patients with heart failure. However, the association of cardiac structure and function with decline in kidney function in this population is unknown. We aimed to assess the association between individual measures of cardiac structure and function with changes in renal function and renal outcomes in patients with heart failure with preserved ejection fraction. Patients enrolled in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) echocardiographic substudy were included. The association between each echocardiographic parameter (expressed in standardized units) and changes over time in estimated glomerular filtration rate was calculated with repeated-measures mixed-effect models. Multivariable Cox proportional hazards models were used to identify individual cardiac parameters associated with the composite renal outcome (≥50% decline in estimated glomerular filtration rate relative to baseline, development of end-stage renal disease, or death attributable to renal causes), after adjusting for covariates. Among 1097 patients (mean age 74±8 years and 53% women), over a median follow-up of 2.9 years, 28 composite renal events (0.9 per 100 person-years) occurred. Higher left ventricular (LV) mass index and higher E/average e' ratio were associated with significantly more profound annual decline in estimated glomerular filtration rate (for both, -0.4 [95% CI, -0.7 to -0.1] mL/min/1.73 m2/y per 1 higher SD). Higher LV mass index, LV end-diastolic volume index, right ventricular end-diastolic area, and a lower right ventricular fractional area change were each associated with a significantly higher risk for the composite renal outcome. In the PARAGON-HF echocardiographic substudy, higher LV mass and filling pressures were independently associated with more profound kidney function decline, and higher LV mass and volume, as well as impaired right ventricular structure and function, were each associated with renal events. Assessing these parameters may help identify patients with heart failure with preserved ejection fraction at higher risk for adverse renal events and indicate potential therapeutic targets. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

The deposition of extracellular matrix is a major pathogenic mechanism leading to fibrosis and progressive decline in renal function in patients with lupus nephritis (LN). Currently, available clinicopathologic features cannot predict renal outcome consistently. To test that the expression of renal fibrogenic genes correlates with renal fibrosis at the time of biopsy and is predictive of renal outcomes. Renal gene expression levels of transforming growth factor β-1 (TGFB1), and collagen I (COL1) were studied by real-time multiplex quantitative polymerase chain reaction in a prospective cohort of patients with LN (n = 39). Extracellular matrix index (ECMI) and collagen I/III matrix index were measured from Picro-Sirius Red-stained slides under normal and polarized light, respectively. After follow-up (median, 43.9 months), renal failure (50% reduction in glomerular filtration rate [GFR] or dialysis) had developed in 13 subjects. The expression levels of renal fibrogenic genes were increased as compared to controls without LN. COL1 correlated with collagen I/III matrix index at baseline. Both high expression of TGFB1 or COL1 tended to predict renal failure by univariate analysis. By multivariate analysis, high ECMI and low GFR were predictive of renal failure. In patients with baseline GFR of 60 mL/min/1.73 m(2) or greater, high renal COL1 expression was an independent (hazard ratio = 4.4, P = .04) predictor of renal failure. High renal COL1 expression is a strong predictor of adverse renal outcome in patients with LN and preserved baseline GFR. These findings support larger prospective studies to confirm the benefits of COL1 in identifying patients at high risk of progression to renal disease.