Background: C.E.R.A., a continuous erythropoietin receptor activator, is in development to provide anemia correction and stable maintenance of hemoglobin (Hb) levels at extended administration intervals in patients with chronic kidney disease (CKD). This study examined its efficacy and safety when administered up to once monthly in patients who have CKD and are on dialysis and randomly convert directly from epoetin ␣ or  one to three times weekly.Design, setting, participants, and measurements: In this three-arm, comparator-controlled, open-label, randomized, parallelgroup, Phase III study, 572 dialysis patients (>18 yr) who were receiving stable subcutaneous epoetin one to three times weekly were randomly assigned (1:1:1) to continue epoetin or to receive subcutaneous C.E.R.A. once monthly or twice monthly for 52 wk. Conclusions: Subcutaneous C.E.R.A. once or twice monthly successfully maintained tight and stable Hb levels in patients who were on dialysis and randomly converted directly from epoetin one to three times weekly.
Kidneys from rats subjected to bilateral ureteral obstruction (BUO), unilateral ureteral obstruction (UUO) and UUO with subsequent release were analyzed for leukocyte infiltration. A time-dependent influx of leukocytes, predominantly macrophages and suppressor T lymphocytes, occurred in both the cortex and medulla following obstruction, and disappeared with release of the obstruction. Glomerular macrophages declined following obstruction but increased to levels above control following release. The influx of leukocytes following obstruction was paralleled by an increase in thromboxane B2 excretion by the kidney and coincided with a decrease in glomerular filtration rate (GFR). This would suggest that an influx of immune cells is a prominent feature of the acute renal response to ureteral obstruction. These cells may modulate some of the post-obstructive alterations in renal function via the production of vasoactive substances, such as thromboxane A2.
The prevalence of miscoding, misclassification and misdiagnosis of diabetes is high and there is substantial scope for further improvement in diagnosis and data quality. Algorithms which identify likely misdiagnosis, misclassification and miscoding could be used to flag cases for review.
Protein-overload proteinuria in rats induces tubular cell apoptosis. This effect is only partially balanced by proliferation and potentially provides a direct mechanism whereby heavy proteinuria can induce tubular atrophy and progressive renal failure.
Background. The majority of patients with chronic kidney disease (CKD) stages 3-5 are managed within primary care. We describe the effects, on patient outcomes, of the introduction of an algorithm-based, primary care disease management programme (DMP) for patients with CKD based on automated diagnosis using estimated glomerular filtration rate (eGFR) reporting. Results. Four hundred and eighty-three patients with CKD stage 4 or 5 were enrolled in the programme. There were significant improvements in the following parameters, expressed as median values (interquartile range) after 9 months in the programme, compared to baseline and percentage values patients achieving target at 9 months: total cholesterol 4.2 (3.45-5.0) mmol/l versus 4.6 (3.9-5.4) mmol/l (P < 0.01), 75.0% versus 64.5% (P < 0.001); LDL 2.2 (1.6-2.8) mmol/l versus 2.5 (1.9-3.2) mmol/l (P < 0.01), 81.9% versus 69.2% (P < 0.05); systolic blood pressure 130 (125-145) mmHg versus 139 (124-154) mmHg (P < 0.05), 56.2% versus 37.1% (P < 0.05) and diastolic blood pressure 71 (65-79) mmHg versus 76 (69-84) mmHg (P < 0.01), 68.4% versus 90.3% (P < 0.01).The median fall (interquartile range) in eGFR in the 9 months prior to joining the programme was 3.69 (1.49-7.46) ml/min/1.73 m 2 compared to 0.32 (−2.61-3.12) ml/min/1.73 m 2 in the 12 months after enrolment (P < 0.001). One hundred and twenty-two patients experienced a fall in eGFR of ≥5 ml/min/1.73 m 2 , median 9.90 (6.55-12.36) ml/min/1.73 m 2 in the 9 months prior to joining the programme, whilst in the 12 months after enrolment, their median fall in eGFR was −1.70 (−6.41-1.64) ml/min/1.73 m 2 (P < 0.001). In the remaining patients, the median fall in eGFR was 1.92 (0.41-3.23) ml/min/1.73 m 2 prior to joining the programme and 0.86 (−1.03-3.53) ml/min/1.73 m 2 in the 12 months after enrolment (P = 0.082). Conclusions. These data suggest that chronic disease management in this form is an effective method of identifying and managing patients with CKD within the UK. The improvement in cardiovascular risk factors and reduction in the rate of decline of renal function potentially have significant health benefits for the patients and should result in cost savings for the health economy.
The role of the albumin-carried fatty acids in the induction of tubulointerstitial injury was studied in protein-overload proteinuria. Rats were injected with fatty acid-carrying BSA [FA(+)BSA], fatty acid-depleted BSA [FA(-)BSA], or saline. Macrophage infiltration was measured by immunohistochemical staining, apoptotic cells were detected by in situ end labeling, and proliferating cells were identified by in situ hybridization for histone mRNA. Macrophage infiltration was significantly greater in the FA(+)BSA group than in the FA(-)BSA and saline groups. The infiltrate was largely restricted to the outer cortex. Apoptosis was greater in the FA(+)BSA group than in the FA(-)BSA and saline groups. Compared with the saline group, apoptosis was significantly increased in the FA(+)BSA group but not in the FA(-)BSA group. Cortical cells proliferated significantly more in the FA(+)BSA and FA(-)BSA groups than in the saline group. FA(+)BSA is therefore a more potent inducer of macrophage infiltration and cell death than FA(-)BSA. The fatty acids carried on albumin may be the chief instigators of tubulointerstitial injury in protein-overload proteinuria.
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