Progranulin and Its Receptor Predict Kidney Function Decline in Patients With Type 2 Diabetes.

Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pathways. TNFR is a well-known predictor of glomerular filtration rate (GFR) decline in a variety of diseases. Therefore, we measured circulating PGRN in addition to TNFR using an enzyme-linked immunosorbent assay and explored whether it predicted renal prognosis in 201 Japanese patients with type 2 diabetes. During a median follow-up of 7.6 years, 21 participants reached primary renal endpoint, which involves a decline of at least 57% in eGFR from baseline, or the onset of end-stage renal disease. Univariate Cox regression analysis revealed that classical renal measures (GFR and albuminuria), two TNF-related biomarkers (PGRN and TNFR), and BMI were associated with this outcome. Multivariate analysis demonstrated that high levels of PGRN [HR 2.50 (95%CI 2.47-2.52)] or TNFR1 [HR 5.38 (95%CI 5.26-5.50)] were associated with this outcome after adjusting for relevant covariates. The high levels of PGRN as well as TNFR1 were associated with a risk of primary renal outcome in patients with type 2 diabetes after adjusting for established risk factors.

Immunotactoid Glomerulopathy with Nontuberculous Mycobacterial Infection: A Novel Association.

A 70-year-old woman underwent a renal biopsy due to nephrotic syndrome. She had suffered from nontuberculous mycobacterial infection (NTM) for 14 years. The patient was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type 3 and immunoglobulin (Ig)-associated MPGN based upon LM/erythromycin and IF findings, respectively. In high-magnification imaging, electron-dense deposits showed immunotactoid glomerulopathy (ITG). There was no evidence of hematological cancer, and the patient improved after receiving treatments for NTM. To the best of our knowledge, this patient is the first to show an association between ITG and NTM. Although ITG is generally considered as related to lymphoproliferative disease, it is suggested that ITG is driven by bacterial infection and is a potential outcome of Ig-associated MPGN.

Fractional excretion of tumor necrosis factor receptor 1 and 2 in patients with type 2 diabetes and normal renal function.

AIMS/INTRODUCTION: Increased concentrations of serum tumor necrosis factor (TNF) receptors (TNFRs; TNFR1 and TNFR2) are positively associated with the urinary albumin-to-creatinine ratio (ACR), and negatively associated with the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. However, the mechanism underlying this increase and the relationship between TNFRs in serum, and urine and kidney measures (ACR and eGFR) are unclear. MATERIALS AND METHODS: This was a cross-sectional study that included 499 patients with type 2 diabetes and eGFR ≥60 mL/min/1.73 m2 . The concentrations of TNFRs in serum and urine, and their respective fractional excretion, were measured. RESULTS: Serum and urinary TNFR levels were positively associated with the ACR, and negatively associated with the eGFR. The fractional excretion of TNFRs did not differ between patients with an eGFR ≥90 and those with an eGFR 60-89 mL/min/1.73 m2 , and also did not correlate with eGFR. After adjustment for relevant covariates, the serum TNFRs were associated with a lower eGFR (60-89 mL/min/1.73 m2 ) and an increased ACR (≥30 mg/gCr), but urinary TNFRs were associated with an increased ACR (≥30 mg/gCr) alone, in the multivariate logistic model. CONCLUSIONS: The pattern of fractional excretion TNFRs showed that an increase in serum TNFRs might result from their increased systemic production, including in the kidney, rather than being a simple reflection of GFR decline. Kidney measures appear to be strongly associated with serum TNFRs rather than urinary TNFRs in patients with type 2 diabetes and normal renal function.