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

Tofik, Rafid; Torffvit, Ole; Rippe, Bengt; Bakoush, Omran

doi:10.1016/j.diabres.2011.10.008

Cited by 17 publications

(13 citation statements)

References 33 publications

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“…A high predictive value of outcome of HMW protein excretion has been observed in other types of GN; IgG in glomerulonephritis [23, 24], idiopathic membranous nephropathy [25–27], crescentic [28] and noncrescentic IgA nephropathy [29, 30] with different cutoffs for each type of GN; IgM (MW: 900 kDa) in ANCA-associated renal vasculitis [31] and type 2 diabetic nephropathy [32]. …”

Section: Discussionmentioning

confidence: 99%

“…methylprednisolone pulses (1 g/day on alternate days) followed by oral prednisone (1 mg/kg/day with tapering) and 12 patients (32%) started treatment with oral prednisone (1 mg/kg/day with tapering). The duration of oral treatment with prednisone in all 38 patients was 9.3 ± 5.5 months [4–32]. Steroid responsiveness (complete or partial remission) was assessed at the end of the fourth month of steroid treatment; 13 patients (34%) were steroid responsive; 25 patients (66%) were unresponsive; in 28 patients (20 steroid unresponsive and 8 steroid responsive but relapsing) treatment with cyclophosphamide (CYP) was associated with steroids: in 10 patients with i.v.…”

Section: Methodsmentioning

confidence: 99%

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Urinary IgG andα2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome

Bazzi¹,

Rizza

Casellato

et al. 2013

BioMed Research International

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Objective. To assess whether high-molecular-weight proteins excretion predicts outcome and therapy-responsiveness in patients with FSGS and nephrotic syndrome. Research Design and Methods. Thirty-eight patients measured at biopsy fractional excretion of IgG (FEIgG) and urinary α2-macroglobulin/creatinine ratio (α2m/C). Low and high risk groups were defined by cutoffs assessed by ROC analysis. In all patients first-line therapy was with steroids alone or in combination with cyclophosphamide. Results. α2m/C and FEIgG were correlated with segmental sclerosis (r = 0.546; r = 0.522). Twenty-three patients (61%) entered Remission and 9 (24%) progressed to ESRD. Comparing low and high risk groups, by univariate analysis remission was predicted by FEIgG (77% versus 25%, P = 0.016) and α2m/C (81% versus 17%, P = 0.007) and ESRD at best by FEIgG (0% versus 75%, P < 0.0001) and α2m/C (4% versus 67%, P < 0.0001). By multivariate analysis FEIgG was the only independent predictor of remission and α2m/C the most powerful predictor of ESRD. Low and high risk groups of FEIgG and α2m/C in combination had very high predictive value of sustained remission and ESRD in response to therapy. Conclusions. FEIgG and α2m/C are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide; their predictive value, if validated in prospective studies, may be useful in clinical practice suggesting first-line alternative treatments in high risk patients.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Urinary IgG andα2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome

Bazzi¹,

Rizza

Casellato

et al. 2013

BioMed Research International

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“…As in other types of glomerular diseases, the primary main lesion in IMN is alteration of the glomerular filtration barrier (GFB) function with increased excretion of albumin (molecular radius, r =36 Å) and high molecular weight proteins such as IgG (r = 55 Å) and IgM (r = 120 Å) [13,14]. Thus, increased urine IgG concentrations in nephrotic patients could reflect activity and severity of the glomerulonephritis [13,15,16].…”

Section: Introductionmentioning

confidence: 99%

Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness

Bazzi¹,

Rizza

Casellato

et al. 2014

BMC Nephrol

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BackgroundTreatment 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.MethodsIn 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).ResultsHigh 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.ConclusionIn 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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“…MA could reflect widespread endothelial dysfunction due to atherosclerotic disease [9], with relative lack of endothelial nitric oxide (NO) production and increased levels of oxidative stress [10]. Long-term follow up studies on proteinuric patients have revealed that IgM-uria may be associated with a higher risk for cardiovascular (CV) mortality [11-13]. For instance, type 2 diabetic patients with MA and IgM-uria had a 3-fold higher risk for CV mortality than patients with merely MA.…”

Section: Introductionmentioning

confidence: 99%

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

Tofik

Ekelund

Torffvit

et al. 2013

BMC Cardiovasc Disord

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BackgroundMicro-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.MethodsUrine 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).ResultsUrine 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).ConclusionIn 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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Urine IgM-excretion as a prognostic marker for progression of type 2 diabetic nephropathy

Cited by 17 publications

References 33 publications

Urinary IgG andα2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome

Urinary IgG andα2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome

Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness

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

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