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- Bazzi, Claudio, et al.
(författare)
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Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness.
- 2014
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Ingår i: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment of idiopathic membranous nephropathy with nephrotic syndrome is still controversial. There is currently little known about the clinical use of renal biomarkers which may explain contradictory results obtained from clinical trials. In order to assess whether IgG-uria can predict the outcome in membranous nephropathy, we examined the value of baseline EF-IgG in predicting remission and progression of nephrotic syndrome. METHODS: In a prospective cohort of 84 (34 female) idiopathic membranous nephropathy patients with nephrotic syndrome we validated the ability of the clinically available urine biomarker, IgG, to predict the risk of kidney disease progression and the beneficial effect of immunosuppression with steroids and cyclophosphamide. The fractional excretion of IgG (FE-IgG) and α1-microglobulin (FE-α1m), urine albumin/creatinine ratio, and eGFR were measured at the time of kidney biopsy. Primary outcome was progression to end stage kidney failure or kidney function (eGFR) decline ≥ 50% of baseline. Patients were followed up for 7.2 ± 4.1 years (range 1-16.8). RESULTS: High FE-IgG (≥ 0.02) predicted an increased risk of kidney failure (Hazard Ratio, (HR) 8.2, 95%CI 1.0-66.3, p=0.048) and lower chance of remission (HR 0.18, 95%CI 0.09-0.38, p<0.001). The ten-year cumulative risk of kidney failure was 51.7% for patients with high FE-IgG compared to only 6.2% for patients with low FE-IgG. During the study, only 24% of patients with high FE-IgG entered remission compared to 90% of patients with low FE-IgG. Combined treatment with steroids and cyclophosphamide decreased the progression rate (-40%) and increased the remission rate (+36%) only in patients with high FE-IgG. CONCLUSION: In idiopathic membranous nephropathy patients with nephrotic syndrome, FE-IgG could be useful for predicting kidney disease progression, remission, and response to treatment.
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- Carlsson, Michael, et al.
(författare)
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Different fractions of human serum glycoproteins bind galectin-1 or galectin-8, and their ratio may provide a refined biomarker for pathophysiological conditions in cancer and inflammatory disease
- 2012
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Ingår i: Biochimica et Biophysica Acta - General Subjects. - : Elsevier. - 0304-4165 .- 1872-8006 .- 0006-3002. ; 1820:9, s. 1366-1372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Changes in glycosylation of serum proteins are common, and various glycoforms are being explored as biomarkers in cancer and inflammation. We recently showed that glycoforms detected by endogenous galectins not only provide potential biomarkers, but also have different functions when they encounter galectins in tissue cells. Now we have explored the use of a combination of two galectins with different specificities, to further increase biomarker sensitivity and specificity. less thanbrgreater than less thanbrgreater thanMethods: Sera from 14 women with metastatic breast cancer, 12 healthy controls, 14 patients with IgA-nephritis (IgAN), and 12 patients with other glomerulonephritis were fractionated by affinity chromatography on immobilized human galectin-1 or galectin-8N, and the protein amounts of the bound and unbound fractions for each galectin were determined. less thanbrgreater than less thanbrgreater thanResults: Each galectin bound largely different fractions of the serum glycoproteins, including different glycoforms of haptoglobin. In the cancer sera, the level of galectin-1 bound glycoproteins was higher and galectin-8N bound glycoproteins lower compared to the other patients groups, whereas in IgAN sera the level of galectin-8N bound glycoproteins were higher. less thanbrgreater than less thanbrgreater thanConclusion: The ratio of galectin-1 bound/galectin-8N bound glycoproteins showed high discriminatory power between cancer patients and healthy, with AUC of 0.98 in ROC analysis, and thus provides an interesting novel cancer biomarker candidate. less thanbrgreater than less thanbrgreater thanGeneral significance: The galectin-binding ability of a glycoprotein is not only a promising biomarker candidate but may also have a specific function when the glycoprotein encounters the galectin in tissue cells, and thus be related to the pathophysiological state of the patient. This article is part of a Special Issue entitled Glycoproteomics.
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- Carlsson, Michael, et al.
(författare)
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Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins
- 2012
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Ingår i: Journal of Clinical Immunology. - : Springer Verlag (Germany). - 0271-9142 .- 1573-2592. ; 32:2, s. 246-255
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Tidskriftsartikel (refereegranskat)abstract
- Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.
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- Habeb, Abdelhadi M, et al.
(författare)
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High incidence of childhood type 1 diabetes in Al-Madinah, North West Saudi Arabia (2004-2009).
- 2011
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X. ; 12, s. 676-681
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Tidskriftsartikel (refereegranskat)abstract
- Habeb AM, Al-Magamsi MSF, Halabi S, Eid IM, Shalaby S, Bakoush O. High incidence of childhood type 1 diabetes in Al-Madinah, North West Saudi Arabia (2004-2009). Background: There is a geographical variation in the incidence of childhood type 1 diabetes mellitus (T1DM) with a steady increase reported from some countries. However, data on the incidence of childhood T1DM in Kingdom of Saudi Arabia are limited. Objective: To identify the incidence rate (IR) and epidemiological trends of childhood T1DM in the largest city of northwest Saudi Arabia. Methods: All patients with newly diagnosed T1DM aged 0-12 yr living in the city between 2004 and 2009 were identified from different sources. The data were analyzed according to age, sex, and month of presentation. Results: In total, 419 patients (249 girls) were diagnosed between 2004 and 2009 inclusive. The mean age at diagnosis was 6.9 ± 3.5 yr. The mean annual age-standardized IR was 29.0 (95% confidence interval 26.0-32.0). The incidence was significantly higher in the 10-12-yr age group than in younger children (p < 0.001) and higher in girls than in boys (33.0 vs. 22.2 per 100 000; p < 0.001). There was no significant increase in the annual incidence during the 6-yr period (p = 0.68) and more cases were diagnosed during autumn and winter months (p = 0.002). Conclusions: Al-Madinah city has the highest reported incidence of childhood T1DM in the Middle East and North Africa region. Further studies to identify the reasons for this high incidence are needed.
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- Stevens, Lesley A., et al.
(författare)
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Development and validation of GFR-estimating equations using diabetes, transplant and weight
- 2010
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 25:2, s. 449-457
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Tidskriftsartikel (refereegranskat)abstract
- Methods. Linear regression was used to relate log-measured GFR (mGFR) to sex, race, diabetes, transplant, weight, various transformations of creatinine and age with and without interactions. Equations were developed in a pooled database of 10 studies [2/3 (N = 5504) for development and 1/3 (N = 2750) for internal validation], and final model selection occurred in 16 additional studies [external validation (N = 3896)]. Results. The mean mGFR was 68, 67 and 68 ml/min/ 1.73 m(2) in the development, internal validation and external validation datasets, respectively. In external validation, an equation that included a linear age term and spline terms in creatinine to account for a reduction in the magnitude of the slope at low serum creatinine values exhibited the best performance (bias = 2.5, RMSE = 0.250) among models using the four basic predictor variables. Addition of terms for diabetes and transplant did not improve performance. Equations with weight showed a small improvement in the subgroup with BMI < 20 kg/m(2). Conclusions. The CKD-EPI equation, based on creatinine, age, sex and race, has been validated and is more accurate than the MDRD study equation. The addition of weight, diabetes and transplant does not significantly improve equation performance.
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- Tofik, Rafid, et al.
(författare)
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Increased urinary IgM excretion in patients with chest pain due to coronary artery disease
- 2013
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Tofik, Rafid, et al.
(författare)
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The value of IgG-uria in predicting renal failure in idiopathic glomerular diseases. A long-term follow-up study.
- 2011
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71, s. 123-128
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background. Proteinuria is the hallmark of glomerular disease and non-selective proteinuria is often associated with progression to renal failure. The predictive value of urine IgG excretion was studied comprehensively in patients with nephrotic syndrome. In the present follow-up study, we examine the predictive value of IgG-uria in patients with idiopathic glomerular diseases with a wide range of proteinuia. Methods. A total of 189 (113 males and 76 females) patients with idiopathic glomerulonephritis and serum creatinine of less than 150 μmol/L diagnosed between 1993 and 2004 were followed up to their last visit in 2009. Measurement of urine excretion of albumin, IgG, and protein HC were performed in the early morning of spot urine samples collected at the time of the diagnostic renal biopsy. Patients were stratified according to urine protein concentrations and the progression rate to end-stage renal disease (ESRD) calculated using Kaplan-Meier survival analysis. ESRD was defined as the start of renal replacement therapy. Results. During the study follow-up time of 1429 person-years; 26 (13.8%) patients reached ESRD. The overall mean kidney survival time of studied patients with serum creatinine less than 150 were 13.4 years. The incidence rate of ESRD was ∼18 per 1000 person-years. Stratified analysis identified urinary excretion of IgG, but not albuminuria, as predictor of ESRD. The progression rate to ESRD was 36 per 1000 person-years in patients with urine IgG concentration exceeding 5 mg/mmol urine creatinine, compared to a progression rate of 6/1000 person-years for patients with lower levels of urine IgG. Conclusion. The findings of the study suggest that at early stages, the level of IgG-uria is useful to be used in risk stratification of patients with proteinuric glomerular diseases.
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