No detection of tick-borne encephalitis virus RNA in blood, urine or saliva of hospitalised immunocompetent tick-borne encephalitis patients.

Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by vaccination or cross-reactivity to previous flavivirus infections may result in false positive TBEV serology. Detection of TBEV RNA may be an alternative diagnostic approach to detect viral presence and circumvent the diagnostic difficulties present when using serology. Viral RNA in blood is commonly detectable only in the first viremic phase usually lasting up to two weeks, and not in the second neurologic phase, when the patients contact the health care system and undergo diagnostic work-up. TBEV RNA has previously been detected in urine in a few retrospective TBE cases in the neurologic phase, and furthermore RNA of other flaviviruses has been detected in patient saliva. In this study, blood, saliva and urine were collected from 31 hospitalised immunocompetent patients with pleocytosis and symptoms of aseptic meningitis and/or encephalitis, suspected to have TBE. We wanted to pursue if molecular testing of TBEV RNA in these patient materials may be useful in the diagnostics. Eleven of the 31 study patients were diagnosed with TBE based on ELISA detection of TBEV specific IgG and IgM antibodies. None of the study patients had TBEV RNA detectable in any of the collected patient material.

Patterns of urinary albumin and IgM associate with markers of vascular ageing in young to middle-aged individuals in the Malmö offspring study.

BACKGROUND: Increased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality. The objective of this study was to investigate the association between urinary IgM, albuminuria, and vascular parameters reflecting arterial structure and function. METHODS: Subjects of the present study were from the Malmö Offspring study (MOS) cohort, and included 1531 offspring (children and grand-children) to first-generation subjects that participated in the Malmö Diet Cancer-Cardiovascular Arm study cohort. At baseline, technical measurements of arterial stiffness (carotid-femoral pulse wave velocity; c-f PWV), carotid arterial morphology, 24-h ambulatory blood pressure recordings, ankle-brachial-index (ABI), and evaluation of endothelial function (reactive hyperemia index, RHI) were performed. Urinary (U) IgM, U-albumin, and U-creatinine were measured. Multivariate adjusted logistic regression was used to test whether U-IgM excretion and increasing urinary albumin excretion were related to vascular parameters. RESULTS: Detectable U-IgM was independently associated with higher systolic blood pressure, odds ratio (OR) 1.021, 95% confidence interval (CI, 1.003-1.039), p = 0.025 and lower ABI; ABI dx: OR 0.026, 95% CI (0.002-0.381), p = 0.008, ABI sin: OR 0.040, 95% CI (0.003-0.496), p = 0.012. Low-grade albuminuria was independently associated with systolic and diastolic blood pressure, aortic blood pressure, the c-f PWV and the number of carotid intima plaques (p < 0.05). CONCLUSIONS: In young to middle-aged, mostly healthy individuals, increased U-IgM excretion and low-grade albuminuria are associated with adverse vascular parameters. Increased U-IgM excretion may reflect subclinical peripheral atherosclerosis, whereas increased U-albumin excretion is associated with a wide range of cardiovascular abnormalities. This may reflect different pathophysiological mechanisms.

Urological detection of specific antibodies against Neospora caninum infection in mice: A prospect for novel diagnostic approach of Neospora.

The intracellular protozoan parasite Neospora caninum is incriminated to induce drastic economic losses in both livestock and pet animal industries. Neosporosis is primarily characterized by abortion in cattle and paralytic symptoms in dogs. Because there are no effective treatments or vaccines, diagnosis is critical for Neospora control. Thus, diversification of laboratory tests and specimens used for diagnosis of N. caninum is an essential scientific endeavor to judge and select the most appropriate diagnostic tool. Herein, we provide the first evidence for the utility of urine samples for demonstration of specific antibodies against N. caninum employing an experimentally infected murine model. Specific antibodies to recombinant N. caninum dense granule 7, surface antigen 1, and lysate antigen were assayed using different antibodies-based ELISAs. Urine based IgG ELISA efficiently discriminated between infected mice (acute or chronic infection), and those of non-infected mice. This effect was also noticed for IgG1 and IgG2a suggesting the utility of urine for assessment of T-helper 2- and T-helper 1-mediated immunities, respectively. In addition, reactivity of specific antibody in urine was also confirmed against parasites when indirect fluorescent antibody test was employed. Usefulness of urine as an additional clinical sample for Neospora diagnosis was confirmed via comparison with the relevant control non-infected and infected mouse sera as reference samples. Because of minimum invasiveness and ease of urine collection, this approach might offer new diagnostic opportunities for N. caninum either for the field or research purposes. However, further studies are required to extrapolate this preliminary study and results in the animal species of interest particularly in dogs.

Clinical characteristics and outcomes of oligosecretory and non-secretory multiple myeloma.

Secretion of monoclonal immunoglobulins (MIg) detected in the serum and/or urine is one of the typical features of multiple myeloma (MM). However, some patients secrete MIg in quantities below "measurable" (termed oligosecretory MM) and others have no detectable MIgs by standard serum and urine immunofixation (termed non-secretory MM). In a cohort of 852 consecutive patients with active myeloma, we identified 100 (11.7%) patients with oligo/non-secretory MM, including 20 (2.3%) with non-secretory MM. Compared to patients with secretory MM, these were younger, less anemic, and had less often renal dysfunction and less extensive bone marrow infiltration. Presence and extent of bone disease were similar, however, hypercalcemia was less common and more often is ISS (International Staging System)-1 and, in those with available FISH (Fluoresense In Situ Hybridization) , high-risk cytogenetics were less common. FLCs (Free Light Chains) were available in 17 patients with non-secretory MM: only 3 had normal FLC ratio; the others had abnormal ratio and 9/14 had involved FLC ≥ 100 mg/L. The 4-year OS for patients with oligo/non-secretory disease was 64% vs 58% for secretory MM. In multivariate analysis, oligo/non-secretory disease was not an independent prognostic factor per se. Thus, 12% of MM patients present with oligo/non-secretory disease at diagnosis and have different biologic characteristics but similar outcome to other MM patients.

Absence of Evidence of Zika Virus Infection in Cord Blood and Urine from Newborns with Congenital Abnormalities, Indonesia.

Zika virus (ZIKV) has recently been confirmed as endemic in Indonesia, but no congenital anomalies (CA) related to ZIKV infection have been reported. We performed molecular and serological testing for ZIKV and other flaviviruses on cord serum and urine samples collected in October 2016 to April 2017 during a prospective, cross-sectional study of neonates in Jakarta, Indonesia. Of a total of 429 neonates, 53 had CA, including 14 with microcephaly. These 53, and 113 neonate controls without evidence of CA, were tested by ZIKV-specific real-time reverse transcription polymerase chain reaction (RT-PCR), pan-flavivirus RT-PCR, anti-ZIKV and anti-DENV IgM ELISA, and plaque reduction neutralization test. There was no evidence of ZIKV infection among neonates in either the CA or non-CA cohorts, except in three cases with low titers of anti-ZIKV neutralizing antibodies. Further routine evaluation throughout Indonesia of pregnant women and their newborns for exposure to ZIKV should be a high priority for determining risk.

The detection of anti-dengue virus IgM in urine in participants enrolled in an acute febrile illness study in Puerto Rico.

BACKGROUND: Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study. METHODS: Between May 2012-March 2013, 1538 study participants with fever for ≤7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (≤5 days post-illness onset [DPO]) and late (6-14 DPO) in the clinical course was associated with dengue severity. RESULTS: Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course. CONCLUSION: While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue.

Epidemiological and immunochemical parameters of monoclonal plasma cell dyscrasias of 2121 cases in Algeria.

BACKGROUND: Plasma cell dyscrasias (PCD) are a heterogeneous group of diseases characterized by the expansion of monoclonal bone marrow plasma cells that produce a monoclonal immunoglobulin (M-component). PURPOSE: This is a retrospective study that describes the epidemiological, immunochemical features and etiology of monoclonal gammopathies diagnosed between 1998 and 2016 in the Teaching Hospital Beni-Messous of Algiers. PATIENTS AND METHODS: 2121 cases of monoclonal gammopathies (MG) were collected during this period. Serum/urine protein electrophoresis, serum/urine immunofixation and serum free light chain measurements were used to demonstrate M protein. RESULTS: The middle age of the patients at the time of the diagnosis were 62.96 ± 13.19 years with extremes ranging from 07 to 99 years. The study included 1013 (47, 76 %) men and 1108 (52, 23 %) women with a sex ratio 0,91. Isotypes repartition was: IgG (60.91 %), IgA (17.91 %), light chain (10.46 %), IgM (6.6 %), IgD (1.03 %) and IgE (0.09 %) of cases. The most frequent diagnosis was: Multiple Myeloma (55.20 %), followed by monoclonal gammopathy of undetermined significance (34.13 %). CONCLUSION: In our study, two particularities were noted. There is no male predominance in Algerian PCD patients. Moreover, we observed a higher frequency of light chain multiple myeloma and lower frequency of IgM isotype compared to western studies.

Urinary IgM excretion: a reliable marker for adverse pregnancy outcomes in women with chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) pregnancies are at high risk of developing adverse outcomes. In non-pregnant subjects with CKD, higher urinary IgM levels are associated with poor renal survival and higher rates of cardiovascular deaths. In this study, we assessed whether urinary IgM levels are associated with an increased risk of adverse pregnancy outcomes (APO) in CKD pregnancies. METHODS: We performed a nested case-control study within a cohort of CKD patients with singleton pregnancies attended at a tertiary care hospital. The study included 90 CKD patients who eventually developed one or more APO and 77 CKD patients who did not. Urinary IgM excretion was determined from the 24-h urine samples at enrollment by an ultrasensitive enzyme immunoassay. RESULTS: The risk for combined APO and for preeclampsia (PE) was higher among women with urinary IgM and proteinuria levels values in the highest quartile or with CKD stages 4-5 (odds ratios, OR ≥ 2.9), compared with the lowest quartile or with CKD stage 1. Urinary IgM levels were more closely associated with the risk of either combined or specific APO (PE, preterm birth, and for having a small-for-gestational-age infant; OR ≥ 5.9) than either the degree of total proteinuria or CKD stages. Among patients with CKD stage 1, the risk of combined APO, PE, and preterm birth was higher in women with urinary IgM levels values in the highest quartile (OR ≥ 4.8), compared with the three lower quartiles, independently of proteinuria. CONCLUSION: In CKD pregnancies, at the time of initial evaluation, proteinuria and CKD stage are associated with increased risk of combined APO. However, urinary IgM concentrations appear to be better predictors of an adverse outcome and may be useful for risk stratification in CKD pregnancies.

AIM associated with the IgM pentamer: attackers on stand-by at aircraft carrier.

Circulating immunoglobulin M (IgM) exists in a pentameric form, possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens; thus, it is involved in both beneficial and detrimental immune responses, including protection from infection and the progression of autoimmunity. On the other hand, IgM also behaves as a carrier of the apoptosis inhibitor of macrophage (AIM) protein, storing a large amount of the inactivated form of AIM in the blood through this association. Under different disease conditions, AIM can dissociate from IgM locally or systemically to exert its function, inducing the removal of various biological debris such as excess fat, bacteria, cancer cells or dead cell debris. Most typically, upon induction of acute kidney injury (AKI), IgM-free AIM is filtered by the glomerulus in the kidney, which stimulates the clearance of intraluminal dead cells debris at the obstructed proximal tubules, thereby facilitating the repair of kidney injury. Interestingly, cats exhibit a deficiency in AIM release from IgM, which may increase their susceptibility to renal failure. Conversely, association with AIM inhibits IgM binding to the Fcα/µ receptor on follicular dendritic cells at the splenic germinal center, thereby protecting the IgM immune complex from Fcα/µ receptor-mediated internalization, which supports IgM-dependent antigen presentation to B cells and stimulates high-affinity IgG antibody production. The regulation of AIM-IgM binding, resulting from the discovery of reciprocal actions between AIM and IgM, could lead to the development of novel therapies against different diseases.

Evaluation of the performances of six commercial kits designed for dengue NS1 and anti-dengue IgM, IgG and IgA detection in urine and saliva clinical specimens.

BACKGROUND: Rapid diagnostic tests (RDTs) have been commercialized in order to help physicians in dengue diagnosis. Until recently, only blood samples were used for those tests but it has been shown in several studies that urine and saliva can also be employed for dengue diagnosis. RDTs for the detection of NS1 antigen and anti-dengue IgG, IgM and IgA in urine and saliva specimens have thus been developed by Standard Diagnostics. The aim of this study was to evaluate the performances these new commercial assays. METHODS: Two panels of clinical specimens were used: one for the evaluation of the NS1-detection devices and the second for the evaluation of the antibody-detection kits. Each panel consisted of urine and saliva specimens collected sequentially from 86 patients with a confirmed dengue infection. A total of 291 saliva and 440 urine samples were included in the NS1-evaluation panel and 530 saliva and 528 urine specimens constituted the antibody-evaluation panel. All samples were tested in parallel by in-house ELISAs and by the commercial RDTs. RESULTS: The RDTs demonstrated an overall sensitivity of 15.5 %/27.9 %/10.7 % for NS1/IgG/IgA detection in urine samples and 20.4 %/ 34.8 %/11 %/6.2 % for NS1/IgG/IgM/IgA detection in saliva samples. Compared to the in-house NS1 ELISA, the results obtained with the NS1 RDT demonstrated a good correlation with urine samples (kappa coefficient: 0.88) but not with saliva specimens (kappa coefficient: 0.28). RDTs designed for antibody detection in saliva and urine were extremely specific (100 %), but less sensitive than the in-house ELISAs (i.e., reduction of the overall sensitivity by 12.2 % for the RDT designed for IgG detection in urine and by 23.7 % for the RDT detecting anti-DENV IgM in saliva). IgM were not detected in urine, either by RDT or ELISA. CONCLUSIONS: Although the RDTs evaluated here offer an apparently attractive approach for dengue diagnosis, this study suggests that these new commercial kits would require further improvement to increase the sensitivity.

Plasma pro-inflammatory cytokines, IgM-uria and cardiovascular events in patients with chest pain: A comparative study.

BACKGROUND: Risk stratification of patients presenting with acute chest pain is crucial for immediate and long-term management. Traditional predictors are suboptimal; therefore inflammatory biomarkers are studied for clinical assessment of patients at risk. Recently, we reported the association of IgM-uria with worse cardiovascular outcome in patients with acute chest pain. In this study, in the same cohort of patients with chest pain, we compared the value of IgM-uria to pro-inflammatory cytokines in predicting the occurrence of subsequent cardiovascular events. METHODS: A total of 178 consecutive patients presenting with acute chest pain to the emergency department at the University Hospital of Lund, were recruited. Twenty-seven of 57 patients with acute coronary syndrome (ACS), and 18 of 118 patients with non-specific chest pain at baseline developed a subsequent major cardiovascular event during the 18 months follow-up. Urinary proteins (IgM-uria and Microalbuminuria) and plasma inflammatory markers (IL-6, Il-8, IL-10, IFN-γ and TNF-α) were measured at time of admission. RESULTS: Using the receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.71 (95%CI 0.61-0.81) for IgM-uria, 0.61 (95%CI 0.51-0.71) for IL-6, 0.63 (95%CI 0.53-0.72) for IL-8, 0.65 (95%CI 0.56-0.74) for IL-10, and 0.64 (95% CI 0.54-0.74) for TNF-α. In multivariate Cox-regression analysis adjusted for age, microalbuminuria, IgM-uria, IL-10, TNF-α, troponin T, hsCRP and ACS at baseline; IgM-uria was the only biomarker that remained an independent predictor of outcome (HR = 4.2, 95%CI 2.2-7.8, p < 0.001). CONCLUSION: In patients with chest pain with or without acute coronary syndrome, IgM-uria could better predict the occurrence of cardiovascular events than plasma pro-inflammatory cytokines.

Feasible quantitative detection of cytomegalovirus from urine sediment in stem cell transplant patients.

BACKGROUND: Urine is an important source for the detection of infections caused by CMV in stem cell transplant patients. Currently, there is no agreement about the type of urine specimen. In order to investigate which is the better specimen type for quantitative detection of CMV, we compared the results from urine supernatant and sediment from the same patients. METHODS: Seventy urine specimens were collected from patients with hematological disorders or solid tumors. After performing shell vial culture, residual urine specimens were centrifuged. Then, 10 mL of each urine supernatant and sediment were taken and immediately frozen at -70 degrees C. Afterwards, archived urine specimens were thawed at room temperature and CMV-quantitative PCR was performed on both the supernatant and sediment fraction of urine. The results from each patient were reviewed for CMV antigenemia, blood shell vial culture, CMV-IgM or IgG, and clinical symptoms. RESULTS: CMV-qPCR results for the urine sediment fraction revealed a significant difference (p = 0.012) between the active CMV infection group and the latent CMV infection group. In addition, receiver operating characteristic curves for active CMV infection revealed that CMV-qPCR using urine sediment produced more accurate results than urine supernatant. CONCLUSIONS: These findings suggest that the sediment fraction of urine is a more suitable specimen in CMV-qPCR testing.

Evaluation of 98 immunocompetent children with cytomegalovirus infection: importance of neurodevelopmental follow-up.

UNLABELLED: This study aims to analyze and evaluate the clinic and demographic features of immunocompetent children that have been diagnosed with cytomegalovirus (CMV) infection. The data of children diagnosed with CMV infection between January 2005 and December 2010 and their follow-ups for 2 years were retrospectively evaluated. Ninety-eight patients were included, and the median age at admission was 5.6 months (5 days-36 months). 54.1% was male. The diagnosis of CMV infection was performed by measurement of serum anti-CMV specific Ig M and IgG titers and PCR method in blood and/or urine. In 3.06% of the patients, congenital infection was detected, whereas possible congenital infection was observed in 36.7% of the patients. Furthermore, 44 patients (44.8%) were detected to have perinatal infection while postnatal infection was spotted in 15.3% of the patients. The common presenting manifestations were prolonged jaundice, diarrhea, vomiting, abdominal distension, skin eruption, and seizure. And the most common physical examination findings were hepatosplenomegaly, microcephaly, jaundice, and petechia. The mainstream laboratory results were elevated transaminases (50%), anemia (30.6%), leukocytosis (27.5%), and thrombocytopenia (18.3%). There were intracranial calcification in 5.1% and eye findings in 5.1%. On follow-up of patients, complete improvement (59.1%), neuromotor developmental delay (11.2%), epilepsy (10.2%), hearing loss (3.06 %), hemolytic anemia (2.04%), and growth retardation (1.02%) were detected. CONCLUSION: CMV infection is a significant disease both in congenital and perinatal period. It must be considered that diagnosed patients need to be monitored for a long time with special attention to their neurodevelopmental follow-ups.

Increased urinary IgM excretion in patients with chest pain due to coronary artery disease.

BACKGROUND: Micro-albuminuria is a recognized predictor of cardiovascular morbidity and mortality in patients with coronary artery disease. We have previously reported, in diabetic and non-diabetic patients, that an increased urinary excretion of IgM is associated with higher cardiovascular mortality. The purpose of this study was to investigate the pattern of urinary IgM excretion in patients with acute coronary syndrome (ACS) and its correlation to cardiovascular outcome. METHODS: Urine albumin, and IgM to creatinine concentration ratios were determined in 178 consecutive patients presenting with chest pain to the Department of Emergency Medicine (ED) at the University Hospital of Lund. Fifty eight (23 female) patients had ACS, 55 (19 female) patients had stable angina (SA), and 65 (35 female) patients were diagnosed as non-specific chest pain (NS). RESULTS: Urine albumin and IgM excretions were significantly higher in patients with ACS (p = 0.001, and p = 0.029, respectively) compared to patients with NS-chest pain. During the 2 years follow-up time, 40 (19 female) patients suffered a new major cardiovascular event (ACS, acute heart failure, stroke) and 5 (4 male/1 female) patients died of cardiovascular cause. A high degree of albuminuria and IgM-uria significantly predicted cardiovascular mortality and morbidity (HR = 2.89, 95% CI: 1.48 - 5.66, p = 0.002). Microalbuminuric patients (≥3 mg/mmol) with high IgM-uria (≥0.005 mg/mmol) had a 3-fold higher risk for cardiovascular new events compared to patients with low IgM-uria (RR = 3.3, 95% CI: 1.1 - 9.9, p = 0.001). CONCLUSION: In patients with chest pain, an increased urine IgM excretion, is associated with coronary artery disease and long-term cardiovascular complications. Measuring urine IgM concentration could have a clinical value in risk stratification of patients with ACS.

Anti-Toxoplasma gondii antibody detection in serum and urine samples by enzyme-linked immunosorbent assay in HIV-infected patients.

BACKGROUND: Toxoplasmosis is a common parasitic infection of man, and reactivation of latent disease in HIV-infected patients can cause fatal encephalitis. Diagnosis depends on demonstration of parasite-specific antibodies in serum. In HIV-infected patients, IgM is often undetectable, whereas IgG remains detectable in the majority. Urine sample is very easily available and has not been evaluated for immunodiagnosis of toxoplasmosis. AIM: The study was an effort to find whether urine sample can be used in place of serum for immunodiagnosis of toxoplasmosis. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) was carried out in serum and urine samples collected from 100 HIV-infected patients to detect anti-toxoplasma IgG and IgM antibodies and whether positivity correlated with the CD4 T-cell counts of patients. RESULTS: In this study, we observed that there was no significant difference in positivity of anti-toxoplasma IgM and IgG between serum and urine samples of HIV-infected patients by ELISA. There was a negative correlation between CD4 count and seropositivity. CONCLUSION: Urine sample can be satisfactorily used in place of serum for immunodiagnosis of toxoplasmosis.

Urine high and low molecular weight proteins one-year post-kidney transplant: relationship to histology and graft survival.

Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM were measured in banked urine samples from 221 individuals 1 year after renal transplantation (age 52 ± 13 years, 55% male, 93% Caucasian and 82% living donor). Levels of all proteins measured were higher than in normal nontransplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with interstitial fibrosis and tubular atrophy plus inflammation (ci>0, cg = 0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15%,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.

Low- and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: a prospective study.

BACKGROUND: Selective urinary biomarkers have been considered superior to total proteinuria in predicting response to treatment and outcome in patients with membranous nephropathy (MN). METHODS: We prospectively tested whether urinary (U) excretion of retinol-binding protein (RBP), α1-microglobulin (α1M), albumin, immunoglobulin IgG and IgM and/or anti-phospholipase 2 receptor (PLA(2)R) levels could predict response to rituximab (RTX) therapy better than standard measures in MN. We also correlated changes in antibodies to PLA(2)R with these urinary biomarkers. RESULTS: Twenty patients with MN and proteinuria (P) >5 g/24 h received RTX (375 mg/m(2) × 4) and at 12 months, 1 patient was in complete remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR) and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in 1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at baseline (mg/24 h) was a significant predictor of change in proteinuria at 12 months (Δ urinary protein) (P = 0.04). In addition, fractional excretion (FE) of IgG, urinary alpha 1 microglobulin (Uα1M) (mg/24 h) and URBP (µg/24 h) were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P = 0.10, 0.27, 0.22 and 0.20, respectively). However, when results were analyzed in relation to proteinuria at 24 months, none of the U markers that predicted response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20). Decline in anti-PLA(2)R levels was associated with and often preceded urinary biomarker response but positivity at baseline was not a predictor of proteinuria response. CONCLUSIONS: The results suggest that in patients with MN, quantification of low-, medium- and high-molecular-weight urinary proteins may be associated with rate of response to RTX, but do not correlate with longer term outcomes.

Urine IgM-excretion as a prognostic marker for progression of type 2 diabetic nephropathy.

UNLABELLED: Although the clinical manifestations of type 2 diabetic nephropathy and decline in kidney function are similar to those in type 1, the clinical course and the renal structural changes are more heterogeneous in type 2 diabetic patients. Previous studies have shown that an increased urine IgM excretion in patients with type 1 diabetic nephropathy was associated with poor outcome. In the present follow-up study we examine the prognostic value of baseline urine IgM excretion in patients with type 2 diabetes mellitus. METHODS: A cohort of 106 (74 male and 32 female) patients with type 2 diabetes regularly attending our diabetes out-patient clinic at Skane University Hospital in Lund. They were recruited prospectively under the period between 1992 and 2004. Patients were followed-up until January 2009. The end point was cardiovascular (CV) death or end-stage renal disease (ESRD). The median follow-up time was 5 years (0.5-13 years). Participants were divided according to degree of albuminuria and IgM-uria. RESULTS: During follow-up time, 28 (19 male and 9 female) patients died of CV events and 41 (26 male and 15 female) developed ESRD. The risk of CV mortality was 2.4 fold, and the risk of renal failure 4.9 fold higher in patients with increased urine IgM excretion compared to patients with low urine IgM excretion. Stratified analysis showed that an increased urine IgM excretion was an independent predictor of renal and cardiovascular death irrespective of the degree of albuminuria (HR=3.6, 95% CI: 2.1-6.0, P<0.001). In conclusion, type 2 diabetic nephropathy patients with high urine IgM excretion rates carry an increased risk of renal and cardiovascular death.