Anti-Neuron-Derived Neurotrophic Factor Antibodies in Secondary Membranous Nephropathy Caused by Syphilis: A Case Report.

We present the case of a 61-year-old man who developed nephrotic syndrome as a result of syphilis-associated secondary membranous nephropathy (MN). The patient showed nephrotic syndrome remission following antibiotic treatment for syphilis alone. Pathologically, the target antigen of immune complexes accumulated on glomerular basement membranes (GBM) in secondary MN caused by syphilis has been reported to be neuron-derived neurotrophic factor (NDNF). His renal histopathology was consistent with secondary MN caused by syphilis, with a full-house pattern on immunofluorescence microscopy, in addition to NDNF deposits that colocalized with IgG deposits granularly on the GBM. However, to date, there is no serological evidence for the involvement of NDNF in the GBM. In the present study, we found that anti-NDNF autoantibodies in the acute-phase serum disappeared in the convalescent-phase serum of a patient who recovered from syphilis and nephrotic syndrome after antibiotic therapy alone. This result supports the hypothesis that treatment of syphilis with antibiotics suppresses NDNF's antigenicity. In summary, we found new serological evidence emphasizing that NDNF is an etiological antigen in secondary MN caused by syphilis.

Comparative Impact of Isolated Ultrafiltration and Hemodialysis on Fluid Distribution: A Bioimpedance Study.

INTRODUCTION: Isolated ultrafiltration (IUF) is an alternative treatment for diuretic-resistant patients with fluid retention. Although hemodialysis (HD) predominantly decreases extracellular water (ECW), the impact of IUF on fluid distribution compared with HD remains unclear. METHODS: We compared the effect of HD (n = 22) and IUF (n = 10) sessions on the body fluid status using a bioimpedance analysis device (InBody S10). RESULTS: The total ultrafiltration volume was similar between HD and IUF (HD 2.5 ± 0.3 vs. ICF 2.1 ± 0.3 L/session, p = 0.196). The reduction rate of ECW was significantly higher than that of intracellular water (ICW) after HD (ECW -7.9% ± 0.8% vs. ICW -3.0% ± 0.9%, p < 0.001) and IUF (ECW -5.8% ± 0.9% vs. ICW -3.6% ± 0.8%, p = 0.048). However, the change in the ratio of ECW to total body water in HD was significantly larger than that in IUF (HD -3.2% ± 0.3% vs. ICF -1.1% ± 0.4%, p < 0.001). The reduction rates in serum tonicity (effective osmolality) were higher after HD than after IUF (HD -1.8% ± 0.5% vs. IUF -0.6% ± 0.2%, p = 0.052). Among the components of effective osmolality, the reduction rates of serum K+ and glucose levels after HD were significantly higher than those after IUF (serum K+: HD -30.5% ± 1.6% vs. IUF -0.5% ± 3.8%, p < 0.001; serum glucose: HD -15.4% ± 5.0% vs. IUF 0.7% ± 4.8%, p = 0.026), while the serum Na+ level was slightly and similarly reduced (HD -0.8% ± 0.4% vs. IUF -0.8% ± 0.4%, p = 0.500). The reduction in the osmolal gap value (measured osmolality-calculated osmolarity) was significantly greater after HD sessions than after IUF sessions (HD -12.4 ± 1.4 vs. IUF 2.0 ± 1.0 mOsm/kg, p = 0.001). CONCLUSION: The extracellular fluid reduction effect of HD is stronger than that of IUF. The different changes in effective osmolality and osmolal gap after HD and IUF sessions may be related to the different effects of HD and IUF on fluid distribution.

A case of vastus lateralis muscle metastasis of tongue carcinoma.

Distant metastasis is the most important prognostic factor for head and neck cancer. This report presents the case of a 50-year-old man with distant metastasis of tongue carcinoma to the vastus lateralis muscle which presented to Nihon University Itabashi Hospital, Tokyo, Japan. Tumourectomy was performed with a diagnosis of tongue carcinoma (cT2N0M0, Stage II). Seven months later, radical neck dissection was performed for lymph node metastasis to a left supraclavicular lymph node. In addition, metastasis was then detected outside the neck dissection region. Tumourectomy and radiotherapy (50 Gy) were, therefore, added to the treatment regimen. However, left-sided vastus lateralis muscle metastasis was then observed. To the best of our knowledge, this is the first report of distant metastasis of oral squamous cell carcinoma to the vastus lateralis muscle.

The psychological effects of COVID-19 on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship.

The aim of the present study was to investigate the psychological effects of the COVID-19 outbreak and associated factors on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship. This cross-sectional, survey-based study collected demographic data, mental health measurements, and stress-related questionnaires from workers in 2 hospitals in Yokohama, Japan, from March 23, 2020, to April 6, 2020. The prevalence rates of general psychological distress and event-related distress were assessed using the 12-item General Health Questionnaire (GHQ-12) and the 22-item Impact of Event Scale-Revised (IES-R), respectively. Exploratory factor analysis was conducted on the 26-item stress-related questionnaires. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes for workers both at high- and low-risk for infection of COVID-19. A questionnaire was distributed to 4133 hospital workers, and 2697 (65.3%) valid questionnaires were used for analyses. Overall, 536 (20.0%) were high-risk workers, 944 (35.0%) of all hospital workers showed general distress, and 189 (7.0%) demonstrated event-related distress. Multivariable logistic regression analyses revealed that 'Feeling of being isolated and discriminated' was associated with both the general and event-related distress for both the high- and low-risk workers. In this survey, not only high-risk workers but also low-risk workers in the hospitals admitting COVID-19 patients reported experiencing psychological distress at the beginning of the outbreak.

Nineteen-year prognosis in Japanese patients with biopsy-proven nonalcoholic fatty liver disease: Lean versus overweight patients.

BACKGROUND: Many studies have investigated the prognosis of nonalcoholic fatty liver disease (NAFLD); however, most studies had a relatively short follow-up. To elucidate the long-term outcome of NAFLD, we conducted a retrospective cohort study of patients with biopsy-proven NAFLD. METHODS: We re-evaluated 6080 patients who underwent liver biopsy from 1975 to 2012 and identified NAFLD patients without other etiologies. With follow-up these patients, we evaluated the outcome-associated factors. RESULTS: A total of 223 patients were enrolled, 167 (74.9%) was non-alcoholic steatohepatitis (NASH). The median follow-up was 19.5 (0.5-41.0) years and 4248.3 person-years. The risk of type 2 diabetes mellitus (T2DM) and hypertension was 11.7 (95% confidence interval [CI] 8.70-15.6) and 7.99 (95% CI 6.09-10.5) times higher, respectively, in NAFLD patients than in the general population. Twenty-three patients died, 22 of whom had NASH. Major causes of death were extrahepatic malignancy and cardiovascular disease (21.7%) followed by liver-related mortality (13.0%). All-cause mortality was significantly higher in NASH patients than in nonalcoholic fatty liver patients (P = 0.041). In multivariate analysis, older age (hazard ratio [HR] 1.09 [95% CI 1.05-1.14], P<0.001) and T2DM (HR 2.87 [95% CI 1.12-7.04], P = 0.021) were significantly associated with all-cause mortality. The factors significantly associated with liver-related events were older age, T2DM, milder hepatic steatosis, and advanced liver fibrosis. Body mass index wasn't associated with either mortality or liver-related events. CONCLUSIONS: T2DM was highly prevalent in NAFLD patients and was significantly associated with both all-cause mortality and liver-related events. The lean patients' prognosis wasn't necessarily better than that of overweight patients.

Clinical outcomes in donors and recipients of kidney transplantations involving medically complex living donors - a retrospective study.

We retrospectively compared the post-transplantation graft survival and the donor's estimated glomerular filtration rates (eGFRs) following living donor kidney transplantations (LDKTs) involving medically complex living donors (MCLDs) (the elderly and patients with obesity, hypertension, diabetes mellitus, or reduced renal function) and standard living donors (SLDs). The clinical data on patients who underwent LDKTs at our institution from 2006-2019, including 192 SLDs and 99 MCLDs, were evaluated. Regarding recipients, the log-rank test and multivariable Cox proportional hazards analyses showed a higher incidence of overall and death-censored graft loss in the recipients who received kidneys from MCLDs (Hazard ratio = 2.16 and 3.25, P = 0.015 and 0.004, respectively), after adjusting for recipient-related variables including age, sex, duration of dialysis, ABO compatibility, and donor-specific antibody positivity. Regarding donors, a linear mixed model showed significantly lower postdonation eGFRs (-2.25 ml/min/1.73 m2 , P = 0.048) at baseline in MCLDs than SLDs, but comparable change (difference = 0.01 ml/min/1.73 m2 /year, P = 0.97). In conclusion, although kidneys from MCLDs are associated with impaired graft survival, the donation did not adversely affect the MCLDs' renal health in at least the short-term. LDKTs involving carefully selected MCLDs would be an acceptable alternative for recipients with no SLDs.

Mito-mice∆ and mitochondrial DNA mutator mice as models of human osteoporosis caused not by aging but by hyperparathyroidism.

Mitochondrial DNA (mtDNA) mutator mice showing accelerated accumulation of mtDNA with somatic mutations are potentially useful models of human aging, whereas mito-miceΔ showing accelerated accumulation of mtDNA with a deletion mutation (ΔmtDNA) are potentially useful models of mitochondrial diseases but not human aging, even though both models express an age-associated decrease in mitochondrial respiration. Because osteoporosis is the only premature aging phenotype observed in mtDNA mutator mice with the C57BL/6J nuclear genetic background, our previous study precisely examined its expression spectra and reported that both mtDNA mutator mice and mito-miceΔ, but not aged mice, developed decreased cortical bone thickness. Moreover, decreased cortical bone thickness is usually not seen in aged humans but is commonly seen in the patients with hyperparathyroidism caused by oversecretion of parathyroid hormone (PTH). In the present study, we showed higher concentrations of blood PTH in mtDNA mutator mice and mito-miceΔ than in aged mice. We also found that both models developed decreased mitochondrial respiration in the duodenum or renal tubules, which would lead to hypocalcemia, oversecretion of PTH, and ultimately osteoporosis. Thus, mtDNA mutator mice and mito-miceΔ may be useful models of human osteoporosis caused not by aging but by hyperparathyroidism.

Selection of peripheral intravenous catheters with 24-gauge side-holes versus those with 22-gauge end-hole for MDCT: A prospective randomized study.

PURPOSE: To compare the 24-gauge side-holes catheter and conventional 22-gauge end-hole catheter in terms of safety, injection pressure, and contrast enhancement on multi-detector computed tomography (MDCT). MATERIALS & METHODS: In a randomized single-center study, 180 patients were randomized to either the 24-gauge side-holes catheter or the 22-gauge end-hole catheter groups. The primary endpoint was safety during intravenous administration of contrast material for MDCT, using a non-inferiority analysis (lower limit 95% CI greater than -10% non-inferiority margin for the group difference). The secondary endpoints were injection pressure and contrast enhancement. RESULTS: A total of 174 patients were analyzed for safety during intravenous contrast material administration for MDCT. The overall extravasation rate was 1.1% (2/174 patients); 1 (1.2%) minor episode occurred in the 24-gauge side-holes catheter group and 1 (1.1%) in the 22-gauge end-hole catheter group (difference: 0.1%, 95% CI: -3.17% to 3.28%, non-inferiority P=1). The mean maximum pressure was higher with the 24-gauge side-holes catheter than with the 22-gauge end-hole catheter (8.16±0.95kg/cm2 vs. 4.79±0.63kg/cm2, P<0.001). The mean contrast enhancement of the abdominal aorta, celiac artery, superior mesenteric artery, and pancreatic parenchyma in the two groups were not significantly different. CONCLUSION: In conclusion, our study showed that the 24-gauge side-holes catheter is safe and suitable for delivering iodine with a concentration of 300mg/mL at a flow-rate of 3mL/s, and it may contribute to the care of some patients, such as patients who have fragile and small veins. (Trial registration: UMIN000023727).

Subtraction CT angiography for the diagnosis of iliac arterial steno-occlusive disease.

PURPOSE: Accurate evaluation of stenosis in severely calcified arteries is a major challenge in conventional CT angiography (CTA) for peripheral arterial disease (PAD). The aim of this study was to evaluate the efficacy of subtraction CTA compared with conventional CTA and conventional angiography. MATERIALS AND METHODS: 175 arterial segments of 31 consecutive patients with PAD who underwent CTA and subsequent digital subtraction angiography (DSA) were evaluated. The percentage stenosis of diseased arteries was measured in iliac arteries with caliper methods on conventional CTA and subtraction CTA, and the concordance of each CTA method with DSA in the identification of >50 % stenosis was evaluated. Interpretation of CTA was always based only on maximum intensity projection (MIP). RESULTS: 174 (99 %) segments were interpretable on subtraction CTA and showed a good correlation with DSA (R (2) = 0.844), although 55 (31 %) segments were not evaluable on conventional CTA due to severe calcification. On subtraction CTA, the segmental accuracy, sensitivity, and specificity were 90.5, 78.9, and 80.0 %, respectively. CONCLUSION: Subtraction CTA is an accurate diagnostic tool for the evaluation of PAD. It may be easier to interpret stenosis in the presence of calcifications using subtraction CTA rather than with the conventional CTA approach. Also, subtraction CTA using only MIP presented a similar accuracy to DSA.

CT-Guided Percutaneous Radiologic Gastrostomy for Patients with Head and Neck Cancer: A Retrospective Evaluation in 177 Patients.

PURPOSE: The purpose of this study was to assess the technical success rate and adverse events (AEs) associated with computed tomography (CT)-guided percutaneous gastrostomy for patients with head and neck cancer (HNC). MATERIALS AND METHODS: This retrospective study included patients with HNC who had undergone CT-guided percutaneous gastrostomy between February 2007 and December 2013. Information regarding the patients' backgrounds, CT-guided percutaneous gastrostomy techniques, technical success rate, and AEs were obtained from the medical records. In all patients, the stomach was punctured under CT fluoroscopy with a Funada gastropexy device. RESULTS: During the study period, 177 patients underwent CT-guided percutaneous gastrostomy. The most common tumor location was the oral cavity, followed by the pharynx and maxilla. The indication for CT-guided percutaneous gastrostomy were tumor obstruction in 78 patients, postoperative dysphagia in 55 patients, radiation edema in 43 patients, and cerebral infarction in 1 patient. The technical success rate was 97.7 %. The overall mean procedure time was 25.3 min. Major AEs occurred in seven patients (4.0 %), including bleeding (n = 4), colonic injury (n = 1), gastric tear (n = 1), and aspiration pneumonia (n = 1). Minor AEs occurred in 15 patients (8.5 %), which included peristomal leakage (n = 6), irritation (n = 4), inadvertent removal (n = 2), peristomal hemorrhage (n = 1), peristomal infection (n = 1), and wound granulation (n = 1). The mean follow-up period was 111 days (range 1-1106 days). CONCLUSION: Our study suggests that CT-guided gastrostomy may be suitable in patients with HNC.

[Failure to Remove Long-Term Indwelling Central Venous Catheters in Two Patients].

The use ofa central venous(CV)port system has become common for the treatment of patients with tumors. We report on the failure to remove CV catheters in 2 patients. The first patient was a 50 years woman with acute myeloid leukemia. She underwent CV port implantation via the left brachial approach 11 years previously. The second patient was an 80 years man with a lower gingival carcinoma. He underwent CV port implantation via the left brachial approach 6 years previously. CV catheter removal was attempted in both patients, but was unsuccessful because of strong adhesion to the vessel wall. Based on our experience, if catheter removal is impossible, its retention is more suitable.

Efficient cleavage of DNA oligonucleotides by a non-FokI-type zinc finger nuclease containing one His4-type finger domain derived from the first finger domain of Sp1.

In this study, we sought to improve the hydrolytic activity of a His4-type single finger domain (f2), which was previously derived from the second finger domain (f2') of the Sp1 zinc finger protein (Sp1wt), which has 3 tandem finger domains (f1', f2', and f3'). To this end, 2 His4-type single finger domains were generated by mutating 2 Cys residues participating in Zn(II) coordination with the His residues in the first (f1') and third finger (f3') domains of Sp1wt. Circular dichroism spectroscopy results showed that the first and second His4-type zinc finger domains (f1 and f2) adopted folded ßßα structures in the presence of Zn(II), but that the third His4-type zinc finger domain (f3) did not. Non-FokI-type zinc finger nucleases containing 3 or 4 finger domains were also prepared by combining a His4-type zinc finger domain with the Sp1wt scaffold. We studied their DNA-binding abilities and hydrolytic activities against DNA oligonucleotides by performing gel-mobility-shift assays. The results showed that f1 had higher hydrolytic activity for a DNA oligonucleotide with a GC box (5'-GGG GCG GGG-3'), compared with that of f2, although both His4-type single finger domains had similar DNA-binding affinities. The difference in the hydrolytic activity between f1 and f2 was ascribed not only to the zinc coordinate structure, but also to its folding structure and the stability of finger domain.

Transmitochondrial mito-miceΔ and mtDNA mutator mice, but not aged mice, share the same spectrum of musculoskeletal disorders.

The spectra of phenotypes associated with aging and mitochondrial diseases sometimes appear to overlap with each other. We used aged mice and a mouse model of mitochondrial diseases (transmitochondrial mito-miceΔ with deleted mtDNA) to study whether premature aging phenotypes observed in mtDNA mutator mice are associated with aging or mitochondrial diseases. Here, we provide convincing evidence that all the mice examined had musculoskeletal disorders of osteoporosis and muscle atrophy, which correspond to phenotypes prevalently observed in the elderly. However, precise investigation of musculoskeletal disorders revealed that the spectra of osteoporosis and muscle atrophy phenotypes in mtDNA mutator mice were very close to those in mito-miceΔ, but different from those of aged mice. Therefore, mtDNA mutator mice and mito-miceΔ, but not aged mice, share the spectra of musculoskeletal disorders.

[Subcutaneous implantation type central venous port management in patients with malignant tumors effect of different antiseptic agents on central venous port-related infection].

Subcutaneous implantation type central venous ports(CV ports)are used in chemotherapy. Here, we prospectively examined the frequency of CV port-related infections when the disinfectant was changed from 10% povidone iodine to 1% chlorhexidine ethanol or 70% ethanol. The subjects were patients with malignant tumors, who had newly been implanted with CV ports. We examined CV port-related infections at 1 week after CV port implantation and every 2 weeks thereafter, following sterilization upon insertion of a Huber needle to the CV port. CV port evulsion due to CV port-related infection was noted in 3 patients(4.8%)in whom 15%chlorhexidine ethanol was used(n=62)and in 2 patients(3.3%)in whom 70% ethanol was used(n=60). Infection rates per 1,000 days of CV port use were 1.48% and 1.01%, respectively. Thus, the outcomes of sterilization using 1% chlorhexidine ethanol and 70% ethanol did not differ significantly from those on using 10% povidone iodine for sterilization, based on preliminary results at our institution(3 of 59 patients[5.1%]had port evulsion due to CV port-related infection and the infection rate per 1,000 days of CV port use was 1.47%, Akahane et al, 2012). Chlorhexidine ethanol and ethanol are very convenient to use because they dry quickly and do not need discoloration. Accordingly, chlorhexidine ethanol and ethanol might be useful in CV port management.

Estrogen receptor ligands ameliorate fatty liver through a nonclassical estrogen receptor/Liver X receptor pathway in mice.

UNLABELLED: Liver X receptor (LXR) activation stimulates triglyceride (TG) accumulation in the liver. Several lines of evidence indicate that estradiol-17ß (E2) reduces TG levels in the liver; however, the molecular mechanism underlying the E2 effect remains unclear. Here, we show that administration of E2 attenuated sterol regulatory element-binding protein (SREBP)-1 expression and TG accumulation induced by LXR activation in mouse liver. In estrogen receptor alpha (ERα) knockout (KO) and liver-specific ERα KO mice, E2 did not affect SREBP-1 expression or TG levels. Molecular analysis revealed that ERα is recruited to the SREBP-1c promoter through direct binding to LXR and inhibits coactivator recruitment to LXR in an E2-dependent manner. Our findings demonstrate the existence of a novel liver-dependent mechanism controlling TG accumulation through the nonclassical ER/LXR pathway. To confirm that a nonclassical ER/LXR pathway regulates ERα-dependent inhibition of LXR activation, we screened ERα ligands that were able to repress LXR activation without enhancing ERα transcriptional activity, and, as a result, we identified the phytoestrogen, phloretin. In mice, phloretin showed no estrogenic activity; however, it did reduce SREBP-1 expression and TG levels in liver of mice fed a high-fat diet to an extent similar to that of E2. CONCLUSION: We propose that ER ligands reduce TG levels in the liver by inhibiting LXR activation through a nonclassical pathway. Our results also indicate that the effects of ER on TG accumulation can be distinguished from its estrogenic effects by a specific ER ligand.

Usefulness of dynamic volume scanning with 320-row CT in detecting recanalization of pulmonary arteriovenous fistula after coil embolization.

Pulmonary arteriovenous fistula is a congenital and rarely acquired anomalous direct communications between pulmonary arteries and veins. Transcatheter embolization using metallic coil or detachable balloon is one of the common treatment procedure. However, recanalization after the embolization is one of the concern and its differentiation from the retrograde filling via pulmonary vein is difficult except using invasive angiography. We report a case with recanalized pulmonary arteriovenous fistula non-invasively detected by dynamic CT angiography with 320-rows multi detector CT. A 45-year-old women who had underwent coil embolization for pulmonary arteriovenous fistula was examined with dynamic CT angiography and antegrade contrast enhancement of the fistula was noted. The recanalization through the embolized artery was confirmed by digital subtraction angiography, and the second coil embolization was performed. The follow-up dynamic CT angiography at three months after the second procedure found the retrograde enhancement of aneurysmal sac and no antegrade shunt. The dynamic CT angiography was useful for the detect the recanalization of pulmonary arteriovenous fistula. Delayed pulmonary artery recanalization was reported to be observed in 5- 10% of cases as a complication after the successful occlusion of segmental pulmonary artery. Lack of change in aneurysmal diameter of pulmonary arteriovenous fistula demonstrated by CT was reported as the result of persistent aneurysmal perfusion or aneurysmal thrombosis. However, the retrograde filling of aneurysmal sac via pulmonary vein or remnant collateral pathway to the pulmonary arteriovenous fistula were also considered. Therefore, before the invasive procedure, we performed dynamic CT angiography to detect the flow direction and pathway to the pulmonary arteriovenous fistula. Using dynamic CT angiography, we could obtain hemodynamic information through the aneurysmal sac of pulmonary arteriovenous fistula and decide to proceed to the invasive embolotherapy. Prospective perfusion CT scan could be an alternative to invasive angiography in the initial follow-up after the embolotherapy or in the cases with the recanalization of pulmonary arteriovenous fistula.

Central venous port-related infection in patients with malignant tumors: an observational study.

PURPOSE: We evaluated the characteristics of central venous port (CVP)-related infection with microbiological assessments in patients with malignant tumors. MATERIALS AND METHODS: In a prospective setting, patients with CVP for the treatment of malignant tumors were enrolled in this study. The incidence of CVP-related infection during three months was determined. Microbiological surveillance from skin swab was performed before and after CVP placement. RESULTS: Fifty-nine patients were enrolled in this study, and 60 CVPs were implanted. Thirty-six (61%) patients had head and neck malignancies. Access route was subclavian vein in 43 (71.7%) CVPs and forearm vein in 17 (28.3%). CVP-related infection was observed in three (5.1%) patients: port-pocket infection in one and probable CVP-related infection in two patients, respectively. No definitive CVP-related bloodstream infection was observed. Before the placement of CVP, colonization at the insertion site was observed in ten subclavian CVP patients, while no colonization was observed in the forearm CVP patients. At 1 and 4 weeks, detection rates of colonization were also higher in subclavian CVP patients. No definitive relationship was demonstrated between skin colonization and clinical development of CVP-related infection. CONCLUSION: The rate of CVP-related infection in this prospective evaluation in patients with malignant tumors was comparable to previous studies. Colonization of the skin was more prominent in the subclavian site than in the forearm site. Although skin colonization was not proven to be a risk factor of infection, these results may draw attention to the adequate maintenance of CVP. ( TRIAL REGISTRATION: UMIN000003664).

Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis.

OBJECTIVE: To investigate the relationship of urinary biomarkers and established measures of renal function to histologic findings in lupus nephritis (LN), and to test whether certain combinations of the above-mentioned laboratory measures are diagnostic for specific histologic features of LN. METHODS: Urine samples from 76 patients were collected within 2 months of kidney biopsy and assayed for the urinary biomarkers lipocalin-like prostaglandin D synthase (L-PGDS), α(1) -acid glycoprotein (AAG), transferrin (TF), ceruloplasmin (CP), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1). Using nonparametric analyses, levels of urinary biomarkers and established markers of renal function were compared with histologic features seen in LN, i.e., mesangial expansion, capillary proliferation, crescent formation, necrosis, wire loops, fibrosis, tubular atrophy, and epimembranous deposits. The area under the receiver operating characteristic curve (AUC) was calculated to predict LN activity, chronicity, or membranous LN. RESULTS: There was a differential increase in levels of urinary biomarkers that formed a pattern reflective of specific histologic features seen in active LN. The combination of MCP-1, AAG, and CP levels plus protein:creatinine ratio was excellent in predicting LN activity (AUC 0.85). NGAL together with creatinine clearance plus MCP-1 was an excellent diagnostic test for LN chronicity (AUC 0.83), and the combination of MCP-1, AAG, TF, and creatinine clearance plus C4 was a good diagnostic test for membranous LN (AUC 0.75). CONCLUSION: Specific urinary biomarkers are associated with specific tissue changes observed in conjunction with LN activity and chronicity. Especially in combination with select established markers of renal function, urinary biomarkers are well-suited for use in noninvasive measurement of LN activity, LN chronicity, and the presence of membranous LN.