Effects of Prolonged Administration of Tenofovir Disoproxil Fumarate-Containing Antiviral Regimen on Renal Function in Low-Risk of Kidney Injury HIV Patients.

This study intended to investigate the impact of long-term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)-infected patients with low-risk of kidney injury. The observational study involving 100 HIV-infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine ß2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood ß2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood ß2 microglobulin was statistically significant at month 6 and months 12-30 (P < .05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine ß2 microglobulin fluctuated from 0.5 (0.3-1.1) to 0.8 (0.5-1.35) mg/L at months 18-30, which was higher than 0.41 (0.18-1.1) mg/L at month 0 (P < .05). The abnormal concentration proportion of urine ß2 microglobulin fluctuated from 72.7% to 81.3% at months 18-30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood ß2 microglobulin, urine ß2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = -0.008, r3 = -0.165, P > .05). Long-term TDF antiviral regimen in low-risk of kidney injury HIV-infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine ß2 microglobulin levels may be helpful in screening for renal dysfunction.

Correlation between glycated hemoglobin A1c, urinary microalbumin, urinary creatinine, ß2 microglobulin, retinol binding protein and diabetic retinopathy.

BACKGROUND: Retinopathy is the most common microvascular disease of type 2 diabetes, and seriously threatens the life, health and quality of life of patients. It is worth noting that the development of diabetic retinopathy (DR) can be hidden, with few symptoms. Therefore, the preliminary screening of diabetic patients should identify DR as soon as possible, delay disease progression, and play a vital role in its diagnosis and treatment. AIM: To investigate the correlation between glycated hemoglobin A1c (HbA1c), urinary microalbumin (U-mALB), urinary creatinine (U-CR), mALB/U-CR ratio, ß2 microglobulin (ß2MG), retinol binding protein (RBP) and DR. METHODS: A total of 180 patients with type 2 diabetes mellitus attending the Second People's Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists. Based on whether they had combined retinopathy and its degree, 68 patients with diabetes mellitus without retinopathy (NDR) were assigned to the NDR group, 54 patients with non-proliferative DR (NPDR) to the NPDR group, and 58 patients with proliferative DR to the PDR group. General data, and HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR results were collected from the patients and compared among the groups. Pearson's correlation method was used to analyze the correlation between HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR indices, and multiple linear regression was applied to identify the risk factors for DR. Receiver operator characteristic (ROC) curves were also drawn. RESULTS: The differences in age, gender, systolic and diastolic blood pressure between the groups were not statistically significantly (P > 0.05), but the difference in disease duration was statistically significant (P < 0.05). The differences in fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglyceride between the groups were not statistically significant (P > 0.05). HbA1c in the PDR group was higher than that in the NPDR and NDR groups (P < 0.05). The levels of mALB, ß2MG, RBP, mALB/U-CR and U-CR in the PDR group were higher than those in the NPDR and NDR groups (P < 0.05). Multiple linear regression analysis showed that disease duration, HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR were risk factors for the development of DR. The ROC curve showed that the area under the curve (AUC) for the combination of indices (HbA1c + mALB + mALB/U-CR + U-CR + ß2MG + RBP) was 0.958, with a sensitivity of 94.83% and specificity of 96.72%, which was higher than the AUC for single index prediction (P < 0.05). CONCLUSION: HbA1c, mALB, mALB/U-CR, U-CR, ß2MG and RBP can reflect the development of DR and are risk factors affecting PDR, and the combination of these six indices has predictive value for PDR.

A Spontaneous Bilateral Quadriceps Tendon Rupture in a Patient Undergoing Long-Term Hemodialysis.

Spontaneous quadriceps tendon rupture is very rare. Its occurrence is usually linked to an underlying disease that weakens the tendons causing them to rupture. Here, we report the case of a 44-year-old patient undergoing long-term hemodialysis who had spontaneous bilateral quadriceps tendon rupture. We present the clinical presentation and the management of this injury.

Changes in erythropoiesis-stimulating agent responsiveness after transfer to combined therapy with peritoneal dialysis and hemodialysis for patients on peritoneal dialysis: A prospective multicenter study in Japan.

INTRODUCTION: Inadequate dialysis and fluid overload are corrected after starting combined therapy with peritoneal dialysis (PD) and hemodialysis (HD). However, the effects on anemia management has not been elucidated. METHODS: We conducted a prospective, multicenter, observational cohort study of 40 PD patients (age, 60 ± 10 years; male, 88%; median PD duration, 28 months) starting combined therapy and investigated changes in several clinical parameters, including erythropoiesis-stimulating agent (ESA) resistance index (ERI). RESULTS: ERI decreased significantly during 6 months after switching to combined therapy (from 11.8 [IQR 8.0-20.4] units/week/kg/(g/dL) to 7.8 [IQR 3.9-18.6] units/week/kg/(g/dL), p = 0.047). Body weight, urinary volume, serum creatinine and the dialysate-to-plasma creatinine ratio (D/P Cr) decreased, whereas hemoglobin and serum albumin increased. In subgroup analysis, the changes in ERI were not affected by cause for starting combined therapy, PD holiday and D/P Cr. CONCLUSION: Although detailed mechanism was unclear, ESA responsiveness improved after switching from PD alone to combined therapy.

Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact.

To promote the potential of arachidonic acid (ARA) for cancer prevention and management, experiments were implemented to disclose the mechanisms of its tumoricidal action. Hepatocellular, lung, and breast carcinoma and normal hepatocytes cell lines were exposed to 0 or 50 µM ARA for 30 min and then assessed for proliferative capacity, surface membrane-associated sphingomyelin (SM) content, neutral sphingomyelinase (nSMase) activity, beta 2 microglobulin (ß2 m) expression, and ceramide (Cer) levels. Reactive oxygen species (ROS) content and caspase 3/7 activity were evaluated. Exposure to ARA for 30 min led to impairment of the tumor cells' proliferative capacity and revealed that the different cell lines display remarkably similar surface membrane SM content but diverse responses to ARA treatment. Arachidonic acid tumoricidal impact was shown to be associated with nSMase activation, exposure of cell surface membrane ß2 m to antibody binding, and hydrolysis of SM to Cer, which accumulated on the cell surface and in the cytosol. The ARA and Cer-mediated inhibition of tumor cell viability appeared to be independent of ROS generation or caspase 3/7 activation. The data were compared and contrasted to findings reported in the literature on ARA tumoricidal mechanisms.

Estimated glomerular filtration rate based on creatinine, cystatin C, ß-trace protein and ß2 microglobulin in patients undergoing nontraumatic lower extremity amputation.

AIMS: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, ß-trace protein (BTP) and ß2 microglobulin (B2M) among patients undergoing major amputation. METHODS: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. RESULTS: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (-0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. CONCLUSION: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

ß2-Microglobulin exacerbates neuroinflammation, brain damage, and cognitive impairment after stroke in rats.

ß2-Microglobulin (ß2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer's disease. Although upregulation of ß2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of ß2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that ß2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit ß2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased ß2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by ß2M silencing. These findings suggest that ß2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

Monocyte or white blood cell counts and ß2 microglobulin predict the durable efficacy of daratumumab with lenalidomide.

Background: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. Objectives: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. Design: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. Methods: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. Results: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower ß2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. Conclusion: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/µl; 1 point for <200/µl) or WBC counts (0 points for ⩾3500/µl; 1 point for <3500/µl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.

Correlation Analysis of Early Renal Injury in Elderly Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Objective: To investigate the correlation between serum cystatin C (Cys-C) and beta-2 (ß2) microglobulin (ß2-MG) levels and renal injury in elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with a view to detecting renal injury in its early stages. Methods: A total of 106 patients with AECOPD were enrolled and divided into three groups according to their oxygen partial pressure (PO2) levels: severe hypoxia group, moderate hypoxia group, and mild hypoxia group. Another 60 healthy subjects were selected as the control group. General clinical data were collected from all the study subjects, along with measurements of arterial blood gas, Cys-C, ß2-MG, serum creatinine (Scr), urea nitrogen (BUN), partial pressure of carbon dioxide (PCO2), and high-sensitivity C-reactive protein (hs-CRP). Results: The levels of hs-CRP, Cys-C, ß2-MG, Scr, and BUN were highest in the severe hypoxia group, followed by the moderate hypoxia group, then the mild hypoxia group, and lowest in the control group. The differences between the groups were statistically significant for these indicators (P < 0.05). Apart from in the cases of Scr and BUN, there were no statistically significant differences between the mild group and the control group (P > 0.05). The levels of Cys-C and ß2-MG were positively correlated with the levels of hs-CRP, PCO2, Scr, and BUN and negatively correlated with PO2 levels. hs-CRP and PO2 were high-risk factors influencing Cys-C levels, and ß2-MG was a risk factor influencing Cys-C levels. The level of PO2 was a high-risk factor influencing ß2-MG levels, and PCO2 and Cys-C were risk factors influencing ß2-MG levels. Conclusion: Renal injury was found to be present in patients with AECOPD and worsened with increasing degrees of hypoxia. Hypoxia and inflammation might be risk factors for renal injury in patients with AECOPD, Cys-C and ß2-MG could be sensitive indicators for the early detection of renal injury.

Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: identification of a HAM-like phenotype in a proportion of asymptomatic carriers.

Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (> 1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), ß2-microglobulin (ß2M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Retrospective analysis of cross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), ß2M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and ß2M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this 'HAM-like' profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.

Clinical feasibility of transfer to combined therapy with peritoneal dialysis and hemodialysis for patients on peritoneal dialysis: A prospective multicenter study in Japan.

INTRODUCTION: Although combined therapy with peritoneal dialysis (PD) and hemodialysis (HD) is widespread in Japan, its clinical utility has been reported only in retrospective or before-and-after test lacking a control group. METHODS: We conducted a prospective, multicenter, observational cohort study of 176 incident PD patients and compared patient survival and changes in clinical parameters between patients on different dialysis modalities. RESULTS: During a median follow-up of 41 months, 47 patients transferred to combined therapy and 35 patients transferred directly to HD. Patients transferred to combined therapy had a significantly better survival than those transferred directly to HD. However, we could not establish this difference in a multivariate analysis because only six patients died among these groups. The decreases in urea nitrogen and serum creatinine were more prominent among patients directly transferred to HD. CONCLUSION: This is the first report revealing clinical feasibility of transfer to combined therapy for PD patients.

A high triglyceride glucose index is associated with early renal impairment in the hypertensive patients.

Objective: Serum ß2-microglobulin (ß2-MG) and serum cystatin C (CysC) are sensitive and reliable indicators of early renal impairment. Triglyceride glucose index (TyG) is an emerging vital indicator of insulin resistance and is associated with increased risk of hypertension. We aimed to analyze the relationship between TyG and early renal impairment in hypertensive patients. Methods: A retrospective analysis was performed on 881 hypertensive patients treated in Qinghai Provincial People, s Hospital from March 2018 to March 2021, their clinical data and corresponding laboratory index values were recorded, and the TyG index was calculated. According to the TyG index, the patients were divided into a low TyG (L-TyG) group (TyG ≤ 8.50, n=306), medium TyG (M-TyG) group (8.51≤TyG ≤ 8.94, n=281), and high TyG (H-TyG) group (TyG>8.95, n=294) in sequence by using tertiles. Then, according to serum ß2-MG and CysC levels, they were divided into a normal renal function group (ß2-MG ≤ 2.4 mg/L, n=700 and CysC ≤ 1.25mg/L, n=721) and a renal function injury group (ß2-MG>2.4 mg/L, n=181, and CysC>1.25 mg/L, n=160). Multivariate linear regression analysis was used to analyze the influencing factors of serum ß2-microglobulin and cystatin C. Multivariate Logistic regression was used to analyze the relationship between the TyG index and early renal impairment in hypertensive patients. The receiver operating characteristic curve (ROC) was used to determine the value of the TyG index in predicting early renal impairment in patients with hypertension. Result: As the TyG index level increased, serum ß2-MG and CysC levels also gradually increased. Multivariate linear regression analysis showed that TyG index was the influencing factor of serum ß2-MG (B=0.060, P=0.007) and serum CysC (B=0.096, P<0.001). For every 1 standard deviation increase in the TyG index, the serum ß2-MG and CysC increased by 0.06mg/L and 0.096mg/L, respectively. When compared to the normal group, the TyG level (8.91 ± 0.65 vs 8.64 ± 0.60, P<0.001) was higher in the renal impairment group with ß2-MG>2.4 mg/L. The results of multivariate logistic regression analysis revealed that for every 1 standard deviation increase in the TyG index, the risk of early renal impairment in hypertensive patients increased 1.53 times (OR=1.53, 95%CI 1.006-2.303).The ROC curves showed that the TyG index was not superior to TG in predicting early renal impairment in hypertensive patients. the AUC values were 0.623 and 0.617, respectively. Then, when CysC>1.25 mg/L was used as the renal damage group, the level of TyG was still higher than that in the normal group (8.94 ± 0.67 and 8.64 ± 0.60, P<0.001). Multivariate Logistic regression analysis showed that for every 1 standard deviation increase in the TyG index, the risk of early renal impairment in hypertensive patients increased 2.82 times (OR=2.82, 95%CI 1.863-4.262). The ROC curves showed that the TyG index was not superior to TG in predicting early renal impairment in hypertensive patients. the AUC values were 0.629 and 0.626, respectively. Conclusion: TyG index is an influential factor in serum ß2-MG and CysC levels. The elevated TyG index levels are closely associated with the occurrence and development of early renal impairment in hypertensive patients, but it should be used cautiously in the prediction of early renal impairment.

Dialysis-related carpal tunnel syndrome in the past 40 years.

PURPOSE AND METHOD: Patients on hemodialysis develop carpal tunnel syndrome (CTS) due to an accumulation of dialysis-related ß2 microglobulin (ß2m) amyloid (DRA). In Japan, dialysis technology has progressed remarkably in the past 40 years and has increased the time until patients require surgery for CTS. However, unclear is whether the time from the start of hemodialysis to the first surgery for CTS is associated with ß2m clearance by the different hemodialysis techniques. Therefore, we retrospectively evaluated ß2m clearance, serum ß2m levels, and the change in the length of this period in patients across 4 periods according to the year that first surgery for CTS was performed: period 1, 1982-1989; period 2, 1990-1999; period 3, 2000-2009; and period 4, 2010-2019. RESULT: A total of 222 patients who met the selection criteria were included. Mean ß2m clearance was -1.8 ± 16.7% in period 1, and improved to 65.4 ± 8.6% in period 3. Accordingly, the serum ß2m value after hemodialysis decreased significantly. The time from the start of hemodialysis to the first surgery for CTS was 12.4 ± 2.9 years in period 1 but increased to 21.8 ± 6.3 years in period 3. In multivariable linear regression analysis, the significant factors contributing to ß2m clearance were periods 2, 3, and 4. In particular, the relation between removal of ß2m and the extension of the dialysis vintage in period 1 and 2 was remarkable compared with periods 3 and 4. CONCLUSION: Our findings indicate that improvement of ß2m clearance via advances in dialysis technology might result in a significant extension in the time between starting HD and the first surgery for CTS.

Global Proteotoxicity Caused by Human ß2 Microglobulin Variants Impairs the Unfolded Protein Response in C. elegans.

Aggregation of ß2 microglobulin (ß2m) into amyloid fibrils is associated with systemic amyloidosis, caused by the deposition of amyloid fibrils containing the wild-type protein and its truncated variant, ΔN6 ß2m, in haemo-dialysed patients. A second form of familial systemic amyloidosis caused by the ß2m variant, D76N, results in amyloid deposits in the viscera, without renal dysfunction. Although the folding and misfolding mechanisms of ß2 microglobulin have been widely studied in vitro and in vivo, we lack a comparable understanding of the molecular mechanisms underlying toxicity in a cellular and organismal environment. Here, we established transgenic C. elegans lines expressing wild-type (WT) human ß2m, or the two highly amyloidogenic naturally occurring variants, D76N ß2m and ΔN6 ß2m, in the C. elegans bodywall muscle. Nematodes expressing the D76N ß2m and ΔN6 ß2m variants exhibit increased age-dependent and cell nonautonomous proteotoxicity associated with reduced motility, delayed development and shortened lifespan. Both ß2m variants cause widespread endogenous protein aggregation contributing to the increased toxicity in aged animals. We show that expression of ß2m reduces the capacity of C. elegans to cope with heat and endoplasmic reticulum (ER) stress, correlating with a deficiency to upregulate BiP/hsp-4 transcripts in response to ER stress in young adult animals. Interestingly, protein secretion in all ß2m variants is reduced, despite the presence of the natural signal sequence, suggesting a possible link between organismal ß2m toxicity and a disrupted ER secretory metabolism.

Serum beta-2 microglobulin analysis in patients with oral squamous cell carcinoma.

AIM: This study aims to compare the level of serum beta-2 microglobulin (ß2-M) in normal healthy individuals and patient with squamous cell carcinoma (SCC). METHODOLOGY: This study has been conducted in patients attending the Department of Oral and Maxillofacial Surgery, Yenepoya Dental College, Deralakatte, Mangalore. Sample comprises of 25 cases of clinically and histologically diagnosed oral cancer and 25 normal healthy individuals as control group. The serum was analyzed for ß2-M by enzyme-linked immunosorbent assay. RESULTS: It was observed that there was a significant increase in serum ß2-M levels in oral SCC patients as compared to controls. Circulating levels in serum ß2-M were also elevated significantly among different clinical stages with progressive rise from stage I to stage IV of the disease. CONCLUSION: The evaluation of these markers would be useful in assessing malignant change, increasing accuracy of clinical diagnosis and also in assessing the spread and invasiveness of the cancer of the oral cavity.

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses via the inhibition of renal oxidative stress and mitochondrial dysfunction. Moreover, the fusion protein could also improve diabetic kidney disease by increasing insulin sensitivity. Collectively, our findings indicate that the bifunctional VEGF-B antibody and IL-22 fusion protein could improve the progression of DN, which highlighted a novel therapeutic approach to DN.

Long-term clinical characteristics and renal prognosis of children with tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, especially in children. Owing to the short-term observational period and the small number of patients analyzed in previous reports, the long-term clinical and laboratory characteristics and renal prognosis of children with TINU syndrome remain unclear. METHODS: In this retrospective observational study, we enrolled 29 children with TINU syndrome from February 1990 to February 2019. RESULTS: During the median follow-up duration of 38 months, the kidney function, urinary ß2 microglobulin-creatinine ratio (U-ß2MG/Cr), and uveitis in the patients had significantly improved at 24, 6, and 36 months after diagnosis. Higher U-ß2MG/Cr was associated with longer duration of kidney function normalization. Half of the patients required uveitis treatment for 5 years after the diagnosis. CONCLUSIONS: Patients with severe low-molecular weight proteinuria at diagnosis needed a longer duration to achieve improvements in kidney function. Uveitis has a much longer treatment period than tubulointerstitial nephritis. This study demonstrates the good prognosis of children with TINU syndrome in terms of their long-term clinical and laboratory characteristics.

Mass spectrometry of urinary ß2 microglobulin oligomer in patients with proteinuria.

Urinary ß2 microglobulin (ß2-m) is a marker of renal tubule dysfunction; however, ß2-m might become degraded under acidic conditions. To confirm the degradation and consequent deactivation of ß2-m under acidic conditions, we used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) to detect the levels and forms of ß2-m in the urine samples of patients with high proteinuria (n = 21) and healthy subjects (n = 6). ß2-m was purified in crude form using immunoprecipitation. A signal of 11.74 kDa, corresponding to the molecular weight of ß2-m, was detected in all samples. In addition, several high-molecular-weight proteins were detected in a patient as integrals of the intensity at 11.74 kDa. These results indicate that posttranslational modifications of ß2-m might be involved in the pathological process of proteinuria. Therefore, MS can be used for monitoring proteinuria and predicting the risk of progression.

An atypical presentation of multiple myeloma in a young patient with pathological fracture.

We report a case of a 34-year-old male with a history of pulmonary tuberculosis and pathological fracture of shaft of long bone presented with symptoms of lower respiratory tract infection. The patient did not have any typical symptoms of multiple myeloma or hypercalcemia on presentation. Throughout his hospitalization, his serum globulin level was very high along with mild normocytic normochromic anemia and mild renal function derangement without apparent cause. Acute phase markers of inflammation, for example, erythrocyte sedimentation rate (ESR) were not elevated in this patient and there was no lytic lesion in bone radiographs. He was eventually diagnosed as a case of stage 3 multiple myeloma by immuno-fixation electrophoresis and bone marrow study. Multiple myeloma represents a pathology of diverse distribution and has varied unusual presenting symptoms. We consider it an underdiagnosed disease often missed especially in young because it is not considered by clinicians.

The urinary ß2 microglobulin-creatinine ratio is inversely associated with lumbar spine bone mineral density in the elderly Chinese males.

Renal tubule cells play a pivotal role in maintaining bone homeostasis. Hence, renal tubular function may be associated with bone mineral density. Our study found that urinary ß2 microglobulin-creatinine ratio (UBCR) levels correlated negatively with lumbar spine bone mineral density (BMD) and T and Z values, and may be a marker for osteoporosis in Chinese elderly male adults. PURPOSE: To study the association of UBCR levels with BMD and the predictive value of UBCR for osteoporosis in elderly Chinese male adults. METHODS: A cross-sectional study of 149 (65 to 85 years, 69.7 ± 4.6) Chinese male adults who underwent health checkups in Huadong Hospital in Shanghai China was conducted. BMD was measured by dual-energy X-ray absorptiometry. The clinical variables and BMD of the participants in the low UBCR group (B1, UBCR < 300 µg/g) and the high UBCR group (B2, UBCR ≥ 300 µg/g) were compared. Associations between UBCR with clinical variables and BMD were analyzed by Pearson's correlation coefficient and multiple regression analysis. BMD and T and Z values were compared between the B1 and B2 groups. The odds ratios (ORs) for dose-dependent increases in osteoporosis between B1 and B2 were analyzed by binary logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was used to analyze the capacity of UBCR to predict osteoporosis. RESULTS: UBCR was significantly higher in the osteoporosis group. After adjusting for multiple confounders, UBCR levels correlated negatively with BMD and T and Z values of the lumbar spine. Lumbar spine BMD and T and Z values were significantly lower in the B2 UBCR group than in the B1 UBCR group. Compared with the B1 participants, the ORs for "osteoporosis" were 12.401 times higher in B2 participants (P = 0.005) by binary logistic regression analysis after adjusting for potential confounders. The UBCR index (cutoff = 362.48 µg/g) had a sensitivity of 78.6% and a specificity of 68.7% for identifying osteoporosis, with an area under the ROC curve of 0.760. CONCLUSIONS: These results suggest that UBCR levels correlate negatively with lumbar spine BMD and T and Z values and may serve as a marker for osteoporosis in Chinese elderly male adults.