Dietary protein restriction as a treatment for slowing chronic kidney disease progression: The case against

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Risk stratification of patients with chronic kidney disease: Results of screening strategies incorporating clinical risk scoring and dobutamine stress echocardiography

Background Cardiac disease is the principal cause of death in patients with chronic kidney disease (CKD). Ischemia at dobutamine stress echocardiography (DSE) is associated with adverse events in these patients. We sought the efficacy of combining clinical risk evaluation with DSE. Methods We allocated 244 patients with CKD (mean age 54 years, 140 men, 169 dialysis-dependent at baseline) into low- and high-risk groups based on two disease-specific scores and the Framingham risk model. All underwent DSE and were further stratified according to DSE results. Patients were followed over 20 +/- 14 months for events (death, myocardial infarction, acute coronary syndrome). Results There were 49 deaths and 32 cardiac events. Using the different clinical scores, allocation of high risk varied from 34% to 79% of patients, and 39% to 50% of high-risk patients had an abnormal DSE. In the high-risk groups, depending on the clinical score chosen, 25% to 44% with an abnormal DSE had a cardiac event, compared with 8% to 22% with a.normal DSE. Cardiac events occurred in 2.0%, 3.1 %, and 9.7% of the low-risk patients, using the two disease-specific and Framingham scores, respectively, and DSE results did not add to risk evaluation in this subgroup. Independent DSE predictors of cardiac events were a lower resting diastolic blood pressure, angina during the test, and the combination of ischemia with resting left ventricular dysfunction. Conclusion In CKD patients, high-risk findings by DSE can predict outcome. A stepwise strategy of combining clinical risk scores with DSE for CAD screening in CKD reduces the number of tests required and identifies a high-risk subgroup among whom DSE results more effectively stratify high and low risk.

Protein kinase C activation and its role in kidney disease

Protein kinase C (PKC) comprises a superfamily of isoenzymes, many of which are activated by cofactors such as diacylglycerol and phosphatidylserine. In order to be capable of activation, PKC must first undergo a series of phosphorylations. In turn, activated PKC phosphorylates a wide variety of intracellular target proteins and has multiple functions in signal transduced cellular regulation. A role for PKC activation had been noted in several renal diseases, but two that have had most investigation are diabetic nephropathy and kidney cancer. In diabetic nephropathy, an elevation in diacylglycerol and/or other cofactor stimulants leads to an increase in activity of certain PKC isoforms, changes that are linked to the development of dysfunctional vasculature. The ability of isoform-specific PKC inhibitors to antagonize diabetes-induced vascular disease is a new avenue for treatment of this disorder. In the development and progressive invasiveness of kidney cancer, increased activity of several specific isoforms of PKC has been noted. It is thought that this may promote the kidney cancer's inherent resistance to apoptosis, in natural regression or after treatments, or it may promote the invasiveness of renal cancers via cellular differentiation pathways. In general, however, a more complete understanding of the functions of individual PKC isoforms in the kidney, and development or recognition of specific inhibitors or promoters of their activation, will be necessary to apply this knowledge for treatment of cellular dysregulation in renal disease.

Analysis of line x environment interactions for yield in navy beans. 2. Pattern analysis of lines and environment within years

Seven years of multi-environment yield trials of navy bean (Phaseolus vulgaris L.) grown in Queensland were examined. As is common with plant breeding evaluation trials, test entries and locations varied between years. Grain yield data were analysed for each year using cluster and ordination analyses (pattern analyses). These methods facilitate descriptions of genotype performance across environments and the discrimination among genotypes provided by the environments. The observed trends for genotypic yield performance across environments were partly consistent with agronomic and disease reactions at specific environments and also partly explainable by breeding and selection history. In some cases, similarities in discrimination among environments were related to geographic proximity, in others management practices, and in others similarities occurred between geographically widely separated environments which differed in management practices. One location was identified as having atypical line discrimination. The analysis indicated that the number of test locations was below requirements for adequate representation of line x environment interaction. The pattern analyses methods used were an effective aid in describing the patterns in data for each year and illustrated the variations in adaptive patterns from year to year. The study has implications for assessing the number and location of test sites for plant breeding multi-environment trials, and for the understanding of genetic traits contributing to line x environment interactions.

Polycystic kidney disease in Bull Terriers: an autosomal dominant inherited disorder

The prevalence, mode of inheritance and urinalysis findings in Bull Terriers with polycystic kidney disease were assessed by screening 150 clinically normal dogs. The disorder was diagnosed in 39 dogs on the basis of renal ultrasound results and family history of the disease. In equivocal cases confirmation required gross and histopathological renal examination. Necropsy was performed on nine affected dogs and the kidneys from another five affected animals were also examined. Renal cysts were usually bilateral, occurred in cortex and medulla and varied from less than 1 mm to over 2.5 cm in diameter. Cysts were lined by epithelial cells of nephron origin. Abnormal urine sediment and proteinuria were common in affected dogs. The disease appears to be inherited in a highly penetrant autosomal dominant manner.

Optimum inclusion of field peas, faba beans, chick peas and sweet lupins in poultry diets. II. Broiler experiments

1. Three experiments were undertaken to determine the optimum inclusion rates of held peas, faba beans, chick peas and sweet lupins in broiler starter and finisher diets in amounts up to 360 g/kg. 2. In experiment A chickens in cages grown to 21 d on diets with field peas and faba beans gave better growth rate and feed efficiency than those with sweet lupins and chick peas. Growth rate and Food conversion ratio (FCR) improved with increasing amounts of faba beans in the diet while for chick peas growth rate and FCR declined. Digesta viscosity and excreta stickiness scores were much higher on diets with sweet lupins. Steam pelleting improved growth rate and FCR on all diets. 3. In experiment B birds were in cages and grown from 21 to 42 d. There were no differences between grain legumes (when combined for all inclusions) for growth rate, food intake or FCR. Viscosity was again much higher on the sweet lupin-based diets while the pancreas was significantly enlarged on the diets with chick peas, as observed previously in chickens grown to 21 d. Steam pelleting of diets gave a consistent and positive response for weight gain and FCR. 4. Experiment C was carried out in pens each holding 60 birds under semi-commercial conditions and grown to 4 2 d on starter and finisher diets with the same grain legumes as used previously but each at 2 rates of inclusion similar to those in commercial practice. Field peas at 200 to 300 g/kg and chick peas at 150 to 220 g/kg gave inferior growth to faba beans (150 to 180 g/kg) and sweet lupins (120 g/kg). 5. The results of these experiments allowed tentative recommendations to be made to industry for inclusion rates of these cultivars of the 4 grain legumes. These were: field peas 300 g/kg; faba beans 200 g/kg, chick peas 100 g/kg and sweet lupins