The role of microRNAs (miRs), which are endogenous RNA oligonucleotides that regulate gene expression, in diabetic nephropathy is unknown. Here, we performed expression profiling of cultured proximal tubular cells (PTCs) under high-glucose and control conditions. We identified expression of 103 of 328 microRNAs but did not observe glucose-induced changes in expression. Next, we performed miR expression profiling in pooled RNA from formalin-fixed, paraffin-embedded tissue from renal biopsies. We studied three groups of patients with established diabetic nephropathy and detected 103 of 365 miRs. Two miRs differed by more than two-fold between progressors and nonprogressors, and 12 miRs differed between late presenters and other biopsies. We noted the greatest change in miR-192 expression, which was significantly lower in late presenters. Furthermore, in individual biopsies, low expression of miR-192 correlated with tubulointerstitial fibrosis and low estimated GFR. In vitro, treatment of PTCs with TGF-␤1 decreased miR-192 expression. Overexpression of miR-192 suppressed expression of the E-Box repressors ZEB1 and ZEB2, thereby opposing TGF-␤-mediated downregulation of E-cadherin. In summary, loss of miR-192 expression associates with increased fibrosis and decreased estimated GFR in diabetic nephropathy in vivo, perhaps by enhancing TGF-␤-mediated downregulation of E-cadherin in PTCs.

ObjectiveChronic kidney disease (CKD) affects nearly 9% of global populations and is strongly associated with older age. Neurocognitive disorders (NCDs), which include mild cognitive impairment and dementia, are rising as a result of ageing populations throughout the world. This investigation’s aim is to report the frequency of mild to major NCD in a clinical cohort of adults with mild to moderate CKD and diabetes.SettingGlan Clwyd District general Hospital, North Wales, UK.ParticipantsWe enrolled 178 patients with CKD and diabetes, aged 55 years and over with an estimated glomerular filtration rate <60 >15 mL/min/1.73 m2, attending a specialist renal and diabetic outpatient clinic.Outcome measuresFrequency of mild and major NCD and the association with the stage of CKD was assessed in all patients attending the specialist clinic. The diagnosis of NCD was based on patient and informant interview, case note review, neuropsychological assessment and application of Diagnostic and Statistical Manual of Mental Disorders version 5.ResultsThis investigation found 86/178 (48%) of the cohort with an NCD ranging from mild (n=49) to major symptoms (n=37). No association was found with NCD and the stage of CKD. Mild and major NCD was associated poorer outcomes in several cognitive domains, including, language, executive, memory, fluency and attention function (p<0.05).ConclusionsThis is the first UK investigation to report that cognitive changes occur in a significant number of older adults with CKD and diabetes. The unexpected finding was that prior to cognitive assessment, not any of the cohort had a pre-existing diagnosis of cognitive impairment, suggesting that the current prevalence and incidence rates of NCD in the general population are possibly significantly underestimated. Our findings also suggest that the cognitive function of patients with CKD should be screened and monitored routinely as part of their overall care management.