Lessons of the month 3: Duodenal perforation after polystyrene sulfonate.

Ion-exchange resins, sodium or calcium polystyrene sulfonate, are commonly used medications for management of hyperkalaemia. However, the drug can be associated with serious bowel injury. We report a case of a renal transplant recipient who developed duodenal ulcer perforation secondary to the use of calcium polystyrene sulfonate. Characteristic eosinophilic non-polarisable rhomboid shaped crystals were evident in the affected area of ulceration on histologic examination in addition to features of cytomegalovirus inclusions. We also hypothesised that gastroparesis secondary to autonomic dysfunction could have led to prolonged luminal contact time with polystyrene, further predisposing to bowel injury.

Chronic kidney disease epidemic: How do we deal with it?

Chronic kidney disease (CKD) is a leading cause of mortality and morbidity around the world. The prevalence of CKD increases steadily over the past decade in parallel to the rapid expansion of diabetic population. Apart from increased mortality, CKD also has significant impact on quality of life and the economy. The approach to deal with the global CKD epidemic is multifaceted. Early detection by screening high-risk individuals such as those with hypertension and diabetes is important and cost-effective. However, low CKD awareness in many countries may impose barriers to early intervention. Hence raising CKD awareness among public and policy makers should be encouraged. In addition, the use of peritoneal dialysis, a less costly and home-based dialysis modality compared with in-center haemodialysis, should be promoted to maximize access to dialysis with limited resources. Finally, ongoing research and clinical trials through international collaborations could provide further insight into the pathophysiology of CKD progression, and establish the foundation for development of specific therapeutic agents to retard progression to end stage renal failure.

Clinical and patient-reported outcomes of Chinese patients undergoing haemodialysis in hospital or in the community: A 1-year longitudinal study.

AIM: Little is known about the effect of haemodialysis (HD) setting on outcomes of patients with end stage renal disease (ESRD). The study aimed at comparing clinical outcomes and patient-reported outcomes (PRO) of patients on community-based (CBHD) and hospital-based haemodialysis (HBHD). METHODS: A prospective cohort of Chinese ESRD patients receiving HBHD (n = 89) or CBHD (n = 117) in Hong Kong were followed up for 12 months. Subjects were assessed on clinical outcomes of dialysis adequacy (Kt/V) and blood haemoglobin and PRO of health-related quality of life (SF-12v2), general health condition (Global Rating Scale (GRS)) and confidence to cope with their illness (Patient Enablement Instrument (PEI)). Differences between groups were analyzed by independent t-tests for the SF-12v2, GRS and PEI scores. χ(2) tests were used to analyze the difference in proportion of patients reaching the targets of Kt/V and blood haemoglobin and with GRS > 0 and PEI > 0. Multiple linear and logistic regressions were performed to assess the adjusted difference-in-difference estimation. RESULTS: The mean PEI and GRS scores of CBHD patients at 12 months were significantly higher than those of HBHD patients. CBHD patients had significantly greater improvement in self-efficacy and were more likely to be enabled after 12 months than the HBHD patients. CONCLUSION: The study showed similar clinical outcomes and PRO between CBHD and HBHD but CBHD was more effective than HBHD in promoting patient enablement over a 12-month period. The results suggest added value for patients receiving CBHD and support the transfer of HD care from the hospital to the community.

MicroRNAs in IgA nephropathy.

IgA nephropathy is globally the most common primary glomerulonephritis, but the pathogenesis of this condition is still only partially understood. MicroRNAs (miRNAs) are short, noncoding RNA molecules that regulate gene expression. Genome-wide analysis of renal miRNA expression has identified a number of novel miRNAs related to immunological and pathological changes. Specifically, overexpression of miR-148b might explain the aberrant glycosylation of IgA1, which has a central pathogenetic role in the early phase of IgA nephropathy. By contrast, miR-29c is an antifibrotic miRNA that is probably important in the late stages of disease progression. In addition, urinary levels of several miRNAs are significantly changed in patients with IgA nephropathy compared with healthy individuals; some alterations seem to be disease-specific, whereas others are apparently damage-related. As miRNAs in urinary sediment are relatively stable and easily quantified, they have the potential to be used as biomarkers for the diagnosis and monitoring of disease. However, to date, limited data are available on the role of miRNAs in the pathogenesis of IgA nephropathy and their potential application as biomarkers. Consequently, further studies are urgently needed to address this shortfall. Here, we review the available literature on miRNAs in relation to IgA nephropathy.

Intrarenal expression of microRNAs in patients with IgA nephropathy.

MicroRNAs (miRNAs) are noncoding, single-stranded RNA molecules that have important roles in a number of physiological and pathological processes. Previous studies have proved that miRNAs targeting ZEB1 and ZEB2 may repress epithelial-to-mesenchymal transition. In this work, we studied the intrarenal expression of miR-200 family, miR-205 and miR-192 in patients with immunoglobulin A (IgA) nephropathy. We studied 43 patients with biopsy-proven IgA nephropathy (IgA group). The intrarenal expression of miRNAs was quantified and compared with that of 15 patients with noninflammatory glomerulosclerosis (GS group) and 20 patients with nephrectomy for kidney cancer as controls (CTL group). The level of intrarenal miR-200c was downregulated, whereas the levels of intrarenal miR-141, miR-205 and miR-192 were upregulated in IgA but not GS group. Proteinuria significantly correlated with the intrarenal expression of miR-200c (r=-0.324, P=0.011) and glomerular filtration rate (GFR) significantly correlated with the intrarenal expression of miR-205 (r=-0.280, P=0.030). The degree of tubulointerstitial scarring correlated with miR-205 expression (r=0.389, P=0.021), whereas glomerulosclerosis correlated with miR-192 expression (r=-0.311, P=0.045). The rate of GFR decline significantly correlated with the intrarenal expression of miR-192 (r=0.373, P=0.015). The intrarenal expression of E-cadherin significantly correlated with the intrarenal expression of miR-200c (r=0.392, P=0.002). The results show that intrarenal expression of miR-200c, miR-141, miR-205 and miR-192 was diversely regulated and correlated with disease severity and progression in patients with IgA nephropathy. These miRNA species may be important in the pathogenesis and progression of IgA nephropathy.

Urinary FOXP3 mRNA in patients with lupus nephritis--relation with disease activity and treatment response.

OBJECTIVE: Regulatory T lymphocytes (Tregs) probably play an important role in the pathogenesis of SLE. METHODS: We quantified messenger RNA (mRNA) expression of FOXP3, a critical regulator for the development and function of Tregs, in the urinary sediment of 25 subjects with active lupus nephritis (LN), 17 with inactive lupus and 7 healthy subjects. RESULTS: We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (24.5 +/- 45.8 vs 0.8 +/- 1.0 vs 0.6 +/- 0.8 copy; P < 0.001). In the active group, urinary FOXP3 mRNA expression level was higher in patients with proliferative LN than non-proliferative nephritis (34.6 +/- 56.3 vs 2.7 +/- 2.1 copy; P = 0.019). Urinary FOXP3 mRNA level significantly correlated with SLEDAI (r = 0.668; P < 0.001) and proteinuria (r = 0.414; P = 0.006). In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (r = 0.541; P = 0.009) and marginally with intra-renal FOXP3 mRNA level (r = 0.360; P = 0.08). Urinary FOXP3 mRNA in patients with no response to therapy was higher than those with partial response or complete response (57.6 +/- 69.8 vs 2.4 +/- 1.9 copies; P = 0.02). CONCLUSION: We concluded that urinary FOXP3 mRNA is markedly up-regulated in patients with active LN, and the level of expression is closely correlated with the clinical and histological disease activity. A high urinary FOXP3 mRNA in LN predicts a poor therapeutic response. Measurement of FOXP3 mRNA in urine sediment may be a non-invasive biomarker for assessing the severity and risk stratification in LN.