Proinflammatory cytokines predict the incidence of diabetic peripheral neuropathy over 5 years in Chinese type 2 diabetes patients: A prospective cohort study.

BACKGROUND: Inflammation has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN) as suggested in various cross-sectional studies. However, more convincing prospective studies in diabetes patients are scarce. Therefore, we aimed to evaluate whether proinflammatory cytokines could predict the incidence of DPN through a prospective study with a five-year follow-up. METHODS: We followed up 315 patients with diabetes who did not have DPN, recruited from five community health centers in Shanghai in 2014, for an average of 5.06 years. Based on the integrity of blood samples, 106 patients were selected to obtain the proinflammatory cytokines. Plasma markers of proinflammatory cytokines at baseline included interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1). Neuropathy was assessed by MSNI at baseline and during follow-up. FINDINGS: Among the 106 chosen patients, 63 developed DPN after 5.06±1.14 years of follow-up. The baseline plasma levels of TNF-α, IL-6, and ICAM-1 were higher in the neuropathic group (p<0.05). In multivariate models, increased plasma levels of TNF-α (hazard ratio, HR: 8.74 [95% confidence interval, CI: 1.05-72.68]; p <0.05) and ICAM-1 (HR 23.74 [95% CI:1.47-383.81]; p<0.05) were both associated with incident DPN, after adjusting for known DPN risk factors. INTERPRETATION: Increased plasma levels of proinflammatory factors, especially TNF-α and ICAM-1, predicted the incidence of DPN over 5 years in Chinese diabetes patients, but larger longitudinal studies are required for confirmation. FUNDING: National Natural Science Foundation of China, Shanghai Talent Development Fund Program, Shanghai Shenkang Hospital Developing Center Clinical Scientific and Technological Innovation Program, Shanghai Science and Technology Committee Program, Shanghai General Hospital Program of Chinese traditional and Western medicine combination and Shanghai Municipal Commission of Health and Family Planning Clinical Research Project.

Multicentric carpotarsal osteolysis syndrome (MCTO) with generalized high bone turnover and high serum RANKL: Response to denosumab.

MCTO is a rare disorder, caused by mutations in the MafB gene, a negative regulator of receptor activator of nuclear factor-кB ligand (RANKL). Manifestations include carpal and tarsal osteolysis and renal failure. Pathophysiology is poorly understood, and no effective treatment is available. In this case report we describe a patient with MCTO (MafB, mutation c.206C>T, p.Ser69Leu), diagnosed at the age of 5 years. At 7 years, skeletal survey showed diffuse osteopenia. BMD was mildly reduced, and bone turnover markers increased. He was treated with denosumab, a human monoclonal RANKL inhibitor for two years. Each injection was followed by a marked reduction in C-telopeptide (CTX). Following denosumab his BMD and bone symptoms improved and the osteolysis stabilized. At the age of 13 years, osteoporosis was diagnosed using high resolution peripheral quantitative computed tomography (HRpQCT) and serum RANKL was found to be markedly increased. This initial experience suggests that the associated osteoporosis may be ameliorated by denosumab, although further study will be needed to understand the appropriate dose, frequency, and the extent of efficacy. Monitoring of CTX and bone specific alkaline phosphatase will be especially useful in this regard. Further study in other MCTO patients is also needed to determine whether high bone turnover is specific to this mutation or more common than previously appreciated. We propose a model in which osteolysis in this condition is strongly associated with the systemic osteoporosis.

A higher ratio of refined grain to whole grain is associated with a greater likelihood of chronic kidney disease: a population-based study.

A growing number of studies suggest that diet and renal function are related. However, little is known about the link between both whole grain (WG) and refined grain (RG) consumption and kidney function parameters. Thus, we investigated the association of WG and RG with urinary albumin to creatinine ratio (ACR) and prevalent chronic kidney disease (CKD). Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were collected. Estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation. Survey design and sample weights were taken into consideration for statistical analyses. Finally, we included 16 325 participants from NHANES, 6·9 % of whom had prevalent CKD. In models adjusted for age, sex, race, fasting blood glucose, blood pressure, adiposity, hypertension and diabetes status, mean eGFR significantly increased across increasing quartiles of WG (Q1: 88·2 v. Q4: 95·4 ml/min per 1·73 m2, P<0·001), whereas it significantly decreased across increasing quartiles of RG (Q1: 97·2 v. Q4: 88·4 ml/min per 1·73 m2, P<0·001). Furthermore, serum uric acid levels and ACR significantly decreased across quartiles of WG (both P<0·001). In multivariable-adjusted logistic regression models, the likelihood of prevalent CKD was 21 % lower in the highest WG quartile compared with the lowest one. In conclusion, our results shed light on the beneficial impact of WG on kidney function and CKD, whereas RG is adversely associated with eGFR.

Successful Renal Outcome in Membranoproliferative Glomerulonephritis Following Treatment of the Underlying Subtle Clone: A Case Report.

Membranoproliferative glomerulonephritis (MPGN) secondary to a monoclonal gammopathy is a rare glomerular disease and is defined as a monoclonal gammopathy of renal significance. The disease is characterized by glomerular monotypic immunoglobulin deposits and specific changes on light microscopy and electron microscopy. Immunochemistry is required to establish monoclonality, and electron microscopy helps to characterize the deposits ultrastructurally. Investigation for the underlying monoclonal protein should be done. We report a case of MPGN secondary to monoclonal gammopathy of renal significance that responded to treatment of the underlying clone with chemotherapy, resulting in improvement in renal function. Patients with MPGN and immunoglobulin deposition should be evaluated for a monoclonal protein to guide the management strategy.