Left ventricular mass regression, all-cause and cardiovascular mortality in chronic kidney disease: a meta-analysis

Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.

Prediction of chronic kidney disease after orthotopic liver transplantation: development and validation of a nomogram model

Background We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT). Methods The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed. Results The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; p = 0.018), female sex (HR 2.867, 95% CI 1.709-4.810; p < 0.001), preoperative hypertension (HR 1.670, 95% CI 0.962-2.898; p = 0.068), preoperative eGFR (HR 0.996, 95% CI 0.991-1.001; p = 0.143), uric acid at 3 months (HR 1.002, 95% CI 1.001-1.004; p = 0.028), haemoglobin at 3 months (HR 0.970, 95% CI 0.956-0.983; p < 0.001), and average concentration of cyclosporine A at 3 months (HR 1.002, 95% CI 1.001-1.003; p < 0.001). According to these parameters, a nomogram model for predicting CKD after OLT was constructed and validated. The C-indices were 0.75 and 0.80 in the training and validation sets. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function. Conclusions With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT.

Ranking patients on the kidney transplant waiting list based on fuzzy inference system

Background Kidney transplantation is the best treatment for people with End-Stage Renal Disease (ESRD). Kidney allocation is the most important challenge in kidney transplantation process. In this study, a Fuzzy Inference System (FIS) was developed to rank the patients based on kidney allocation factors. The main objective was to develop an expert system, which would mimic the expert intuitive thinking and decision-making process in the face of the complexity of kidney allocation. Methods In the first stage, kidney allocation factors were identified. Next, Intuitionistic Fuzzy Analytic Hierarchy Process (IF-AHP) has been used to weigh them. The purpose of this stage is to develop a point scoring system for kidney allocation. Fuzzy if-then rules were extracted from the United Network for Organ Sharing (UNOS) dataset by constructing the decision tree, in the second stage. Then, a Multi-Input Single-Output (MISO) Mamdani fuzzy inference system was developed for ranking the patients on the waiting list. Results To evaluate the performance of the developed Fuzzy Inference System for Kidney Allocation (FISKA), it was compared with a point scoring system and a filtering system as two common approaches for kidney allocation. The results indicated that FISKA is more acceptable to the experts than the mentioned common methods. Conclusion Given the scarcity of donated kidneys and the importance of optimal use of existing kidneys, FISKA can be very useful for improving kidney allocation systems. Countries that decide to change or improve the kidney allocation system can simply use the proposed model. Furthermore, this model is applicable to other organs, including lung, liver, and heart.

Vitamin D receptor gene polymorphism predicts left ventricular hypertrophy in maintenance hemodialysis

Background To verify that the single nucleotide polymorphisms (SNP) of vitamin D receptor (VDR) may lead to genetic susceptibility to left ventricular hypertrophy (LVH), the present study was designed to study four SNPs of VDR associated with LVH in maintenance hemodialysis (MHD) patients of Han nationality. Methods 120 MHD patients were recruited at Department of Nephrology, Zhongnan Hospital of Wuhan University to analyze the expression of genotype, allele and haplotype of Fok I, Bsm I, Apa I and Taq I in blood samples, and to explore their correlation with blood biochemical indexes and ventricular remodeling. Results The results showed that the risks of CVD included gender, dialysis time, heart rate, SBP, glycated hemoglobin, calcium, iPTH and CRP concentration. Moreover, LAD, LVDd, LVDs, IVST and LVMI in B allele of Bsm I increased significantly. Fok I, Apa I and Taq I polymorphisms have no significant difference between MHD with LVH and without LVH. Further study showed that VDR expression level decreased significantly in MHD patients with LVH, and the B allele was positively correlated with VDR Expression. Conclusion VDR Bsm I gene polymorphism may predict cardiovascular disease risk of MDH patients, and provided theoretical basis for early detection and prevention of cardiovascular complications.

Development of a europium nanoparticles lateral flow immunoassay for NGAL detection in urine and diagnosis of acute kidney injury

Background AKI is related to severe adverse outcomes and mortality with Coronavirus Disease 2019 (COVID-19) patients, that early diagnosed and intervened is imperative. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising biomarkers for detection of acute kidney injury (AKI), but current detection methods are inadequacy, so more rapid, convenient and accuracy methods are needed to detect NGAL for early diagnosis of AKI. Herein, we established a rapid, reliable and accuracy lateral flow immunoassay (LFIA) based on europium nanoparticles (EU-NPS) for the detection of NGAL in human urine specimens. Methods A double-antibody sandwich immunofluorescent assay using europium doped nanoparticles was employed and the NGAL monoclonal antibodies (MAbs) conjugate as labels were generated by optimizing electric fusion parameters. Eighty-three urine samples were used to evaluate the clinical application efficiency of this method. Results The quantitative detection range of NGAL in AKI was 1-3000 ng/mL, and the detection sensitization was 0.36 ng/mL. The coefficient of variation (CV) of intra-assay and inter-assay were 2.57-4.98 % and 4.11-7.83 %, respectively. Meanwhile, the correlation coefficient between europium nanoparticles-based lateral fluorescence immunoassays (EU-NPS-LFIA) and ARCHITECT analyzer was significant (R2 = 0.9829, n = 83, p < 0.01). Conclusions Thus, a faster and easier operation quantitative assay of NGAL for AKI has been established, which is very important and meaningful to diagnose the early AKI, suggesting that the assay can provide an early warning of final outcome of disease.

Mild renal insufficiency and attributable risk of adverse In-hospital outcomes in patients with Acute Coronary Syndrome from the improving care for Cardiovascular Disease in China (CCC) project

Background Renal insufficiency (RI) is a frequent comorbidity among patients with acute coronary syndrome (ACS). We aimed to evaluate the attributable risk associated with mild RI for the in-hospital outcomes in patients with ACS. Methods The Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 92,509 inpatients with a discharge diagnosis of ACS were included. The attributable risk was calculated to investigate the effect of mild RI (eGFR 60-89 ml / min · 1.73 m2) on major adverse cardiovascular events (MACEs) during hospitalization. Results The average age of these ACS patients was 63 years, and 73.9% were men. The proportion of patients with mild RI was 36.17%. After adjusting for other possible risk factors, mild RI was still an independent risk factor for MACEs in ACS patients. In the ACS patients, the attributable risk of eGFR 60-89ml/min·1.73m2 to MACEs was 7.78%, 4.69% of eGFR 45-59 ml/min·1.73m2, 4.46% of eGFR 30-44 ml/min·1.73m2, and 3.36% of eGFR<30 ml/min·1.73m2. Conclusion Compared with moderate to severe RI, mild RI has higher attributable risk to MACEs during hospitalization in Chinese ACS population.

Graft function and pregnancy outcomes after kidney transplantation

Background After kidney transplantation, pregnancy and graft function may have a reciprocal interaction. We evaluated the influence of graft function on the course of pregnancy and vice versa. Methods We performed a retrospective observational study of 92 pregnancies beyond the first trimester in 67 women after renal transplantation from 1972 to 2019. Pre-pregnancy eGFR was correlated with outcome parameters; graft function was evaluated by Kaplan Meier analysis. The course of graft function in 28 women who became pregnant after kidney transplantation with an eGFR of < 50 mL/min/1.73m2 was compared to a control group of 79 non-pregnant women after kidney transplantation during a comparable time period and with a matched basal graft function. Results Live births were 90.5% (fetal death n = 9). Maternal complications of pregnancy were preeclampsia 24% (graft loss 1, fetal death 3), graft rejection 5.4% (graft loss 1), hemolytic uremic syndrome 2% (graft loss 1, fetal death 1), maternal hemorrhage 2% (fetal death 1), urinary obstruction 10%, and cesarian section. (76%). Fetal complications were low gestational age (34.44 ± 5.02 weeks) and low birth weight (2322.26 ± 781.98 g). Mean pre-pregnancy eGFR was 59.39 ± 17.62 mL/min/1.73m2 (15% of cases < 40 mL/min/1.73m2). Pre-pregnancy eGFR correlated with gestation week at delivery (R = 0.393, p = 0.01) and with percent eGFR decline during pregnancy (R = 0.243, p = 0.04). Pregnancy-related eGFR decline was inversely correlated with the time from end of pregnancy to chronic graft failure or maternal death (R = -0.47, p = 0.001). Kaplan Meier curves comparing women with pre-pregnancy eGFR of ≥ 50 to < 50 mL/min showed a significantly longer post-pregnancy graft survival in the higher eGFR group (p = 0.04). Women after kidney transplantation who became pregnant with a low eGFR of > 25 to < 50 mL/min/1.73m2 had a marked decline of renal function compared to a matched non-pregnant control group (eGFR decline in percent of basal eGFR 19.34 ± 22.10%, n = 28, versus 2.61 ± 10.95%, n = 79, p < 0.0001). Conclusions After renal transplantation, pre-pregnancy graft function has a key role for pregnancy outcomes and graft function. In women with a low pre-pregnancy eGFR, pregnancy per se has a deleterious influence on graft function. Trial registration Since this was a retrospective observational case series and written consent of the patients was obtained for publication, according to our ethics’ board the analysis was exempt from IRB approval. Clinical Trial Registration was not done. The study protocol was approved by the Ethics Committee of Hannover Medical School, Chairman Prof. Dr. H. D. Troeger, Hannover, December 12, 2015 (IRB No. 2995–2015).

A rare case of renal infarction due to heroin and amphetamine abuse: case report

Background Renal infarctions as a result of recreational drug use are rare and are commonly associated with cocaine use. Although amphetamines have a similar mechanism of action as cocaine, there are few reports linking them to ischemic events, and only one to renal infarction. Similarly, few reports link heroin use with infarcts, but never in the kidney. Although uncommon, several mechanisms have been implicated in heroin and amphetamine-induced infarction, including vasculopathy, vasculitis and the activation of the coagulation cascade. Case Presentation 47-year-old female with a past medical history of non-intravenous heroin and amphetamine abuse, chronic obstructive pulmonary disease, hypertension, hyperlipidemia presented with right lower extremity swelling and rash, which was diagnosed as cellulitis and treated appropriately. Incidentally, the patient was found to have an acute kidney injury and further workup identified multiple renal infarcts in the right kidney. The patient had no past medical history of clotting disorders. Blood culture and urine cultures were sterile; autoimmune and hypercoagulable workup were negative. Urinalysis was unremarkable. Urine toxicology was only positive for opiates and amphetamines, which were thought to be the most likely cause of the renal infarct. Patient was lost to outpatient follow up due to noncompliance, but returned to the hospital for re-emergence of her cellulitis, during which no new infarcts were discovered, and the previous renal infarct had scarred over. Conclusion There are very few reports of heroin and amphetamine-induced infarctions. This case report describes a rare but important complication of heroin/amphetamine abuse that could be easily overlooked.

Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy

Background The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN). Methods This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-β were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs). Results The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-β in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren’t any significant differences in the levels of IL-6, TNF-α, and TGF-β when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1. Conclusions The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

Utilizing the MEST score for prognostic staging in IgA nephropathy

Background The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. Methods A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). Results The mean follow-up time was 16.5 years (range 0.2–28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. Conclusions Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.