Enhanced renal expression for the renin-angiotensin system (RAS) is detected in IgA nephropathy (IgAN). Previous data showed an altered glomerular expression of angiotensin II type 1 receptor (AT1R), suggesting a regulatory response to high intrarenal angiotensin II (Ang II) concentration in IgAN. In this study, the expression and regulation of Ang II receptors were examined in human proximal tubular epithelial cells (PTEC) in IgAN. Tubular expression of AT1R and Ang II type 2 receptor (AT2R) was increased in IgAN. In vitro culture experiment showed that the upregulation of Ang II receptors was not due to the direct effect of IgA but the indirect effect after IgA deposition on human mesangial cell. When PTEC were cultured with conditioned culture medium from human mesangial cells activated with IgA, Ang II production was upregulated, leading to inflammation and apoptosis via the AT1R and AT2R, respectively. Sequential expression of Ang II receptors determined the injury of PTEC induced by mediators in the conditioned medium. The initial interaction between Ang II and AT1R activated both protein kinase C and mitogen-activated protein kinase pathways, leading to inflammatory responses. This early AT1R-dependent event was followed by upregulation of AT2R expression and continued Ang II release. The interaction between Ang II and AT2R subsequently led to expression of cleaved poly[ADP-ribose] polymerase through downregulation of the mitogen-activated protein kinase pathway. The data suggest that appropriate control of Ang II receptor activities in PTEC may ameliorate tubulointerstitial injury in IgAN.
High depression and anxiety scores were prevalent in incident PD patients where PD-first policy is adopted and were associated with inferior QOL. There was no improvement after 1 year of PD. The impact of strategic interventions targeting patient groups at risk such as those with diabetes or of younger age warrants further investigation.
Objective We undertook to study the attitudes toward dialysis of patients approaching end-stage renal failure and to analyze those attitudes from a cultural perspective. Setting The study was performed in the pre-dialysis clinic of a tertiary referral renal center. Patients All patients of Chinese ethnic origin seen in the pre-dialysis clinic from 1995 to 2000 for assessment of dialysis therapy were included. Method We performed a retrospective analysis of patient records with regard to attitudes of the patients toward dialysis, reasons for those attitudes, and factors that could lead to a subsequent change in attitude. Results We assessed 462 patients over the 6-year period. Their mean age was 65.5 ± 13.3 years, and 43.9% of the patients had diabetes. Peritoneal dialysis (PD) was offered to 74% of the patients, and hemodialysis (HD) to 3.9%. Among the patients offered PD, only 44% accepted dialysis. After counselling, 54% of the patients who originally declined PD ultimately accepted it. The major reasons for refusing PD were the ideas of “having lived long enough” and “lack of family support.” Most other reasons could be overcome by counselling. Only a minority of patients demanded hemodialysis. Conclusions Declining an offer of dialysis was common. Counselling helped patients to accept PD. Certain cultural elements that hindered acceptance of dialysis were involved in the ideas of “having lived long enough” and “lack of family support.” Those cultural elements should be tackled more specifically during counselling.
Late acute rejection is uncommon in Chinese kidney transplant recipients but is associated with reduced allograft survival. Risk factors include acute rejection in the first post-transplant year and trough CsA level below 80 μg/L in patients on CsA-based maintenance immunosuppression. Minimization of immunosuppression in apparently stable kidney transplant recipients must be exercised with caution.
Aim
Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose‐strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher‐dose preparations in dialysis patients converting from Aranesp® to NESP®.
Methods
Adult dialysis patients on Aranesp® with stable haemoglobin of 9–12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months.
Results
Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient‐reported pain score and 38% reduction of drug cost.
Conclusion
Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.
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