Trabecular bone score in patients with chronic kidney disease.

Patients with chronic kidney disease have high risk of osteoporotic fractures. Lower trabecular bone score (TBS) was associated with poorer kidney function and higher fracture risk when kidney function was normal. Addition of TBS to The Fracture Risk Assessment Tool with bone mineral density did not improve fracture risk prediction. INTRODUCTION: We sought to determine whether trabecular bone score (TBS) either independently or adjusted for The Fracture Risk Assessment Tool (FRAX) could predict risk of major osteoporotic fractures (MOFs) in a large population-based sample of patients with all stages of chronic kidney disease (CKD). METHODS: We used population-based administrative databases to identify patients above age 20 years who had dual-energy X-ray absorptiometry (DXA) scan and serum creatinine measured within 1 year, during the years 2005 to 2010. Patients were excluded if they were on dialysis or had a functioning renal transplant. We stratified patients by estimated glomerular filtration rate (eGFR). We collected femoral neck bone mineral density (BMD), lumbar spine TBS, incident major osteoporotic fractures (MOF) and hip fractures, and other clinical characteristics. RESULTS: Among 8289 patients, there were 6224 (75.1%) with eGFR ≥ 60 mL/min/1.73 m2, 1624 (19.6%) with eGFR 30-60 mL/min/1.73 m2, and 441 (5.3%) with eGFR < 30 mL/min/1.73 m2. There were 593 patients (7.2%) with MOFs and 163 (2.0%) with hip fractures. Lower TBS score was associated with increased risk of MOF and hip fractures across all eGFR strata in unadjusted Cox proportional hazards models but after adjusting for FRAX with BMD, lower TBS was only statistically significant for MOF prediction for eGFR ≥ 60 mL/min/1.73 m2. CONCLUSION: Lower TBS scores were associated with lower eGFR and increased fracture risk in patients with eGFR ≥ 60 mL/min/1.73 m2. However, the addition of TBS to the FRAX score with BMD did not significantly improve fracture risk prediction in patients with CKD.

Sodium thiosulfate-based treatment in calcific uremic arteriolopathy: a consecutive case series.

BACKGROUND: Calcific uremic arteriolopathy (CUA) is a rare complication in end stage renal disease with high mortality. Numerous case reports and one case series of 3 patients report the benefit of sodium thiosulfate (STS) for treatment of CUA. The purpose of this evaluation was to examine the response to a STS-based treatment approach in patients with CUA with 1 year follow up. METHODS: A retrospective case series of 6 consecutive patients from Manitoba, Canada who met predefined diagnostic criteria for CUA and received STS between 2006 and 2008 were included. STS responders were defined as improvement in at least one of the following three parameters: pain severity, wound size and diagnostic imaging/radiography. Mortality, STS dose, duration, adverse events and cost were also collected. RESULTS: Four patients were classified as responders. The 2 responders who survived at 1 year of follow-up demonstrated an improvement in all 3 parameters examined including an improvement in their follow-up diagnostic imaging results within the first 4 - 6 weeks of STS treatment. At 1 year of follow-up, 3 patients died. CONCLUSION: Using an STS-based multifaceted treatment approach for CUA, 4 patients responded but 3 of 6 patients died within 1 year. Further larger prospective studies are needed to delineate STS responders from non-responders.

Differential cytokine genotype frequencies among Canadian Aboriginal and Caucasian populations.

Genetic diversity related to the human immune response is a key factor in individual and population survival throughout human history. Population diversity in disease susceptibility and resistance have been identified and linked to differences in cytokine mRNA and protein expression levels. Polymorphisms in the regulatory regions of cytokine genes can influence gene transcription levels and they have been associated with susceptibility to, and/or severity of, autoimmune disorders such as rheumatoid arthritis, meningococcus and sepsis. It is reported here that in two study populations, Canadian Aboriginal individuals have a higher frequency of cytokine single-nucleotide polymorphisms favouring a low production of TNFalpha, IFNgamma and IL-10 and high production of IL-6 as compared to a Caucasian population. We postulate that the evolution of this unique cytokine genotype profile may be linked to the Aboriginal adaptation to selection pressures related to an environment in which helminthic, parasitic and fungal infections predominated.

The urine protein to creatinine ratio (P/C) as a predictor of 24-hour urine protein excretion in renal transplant patients.

BACKGROUND: The purpose of this study was to examine the utility of the random urine protein to creatinine ratio (P/C) in evaluation and longitudinal management of proteinuria in adult renal transplant recipients with or without overt nephropathy in an outpatient clinic. METHODS: A total of 289 adult renal transplant recipients provided 24-hr urine collections for total protein and creatinine, followed by a random urine for protein and creatinine. For longitudinal analysis, 192 of these patients provided two 24-hr urine collections with concomitant random urine specimens separated on average by 6.8 months. As well, 134 patients provided a total of 851 multiple-paired spot and 24-hr urine samples (range 2 to 12) over a 2-year period. RESULTS: The log random urine P/C ratio correlated significantly to the log 24 UP (r=0.749, P<0.0001) with or without nephrotic range proteinuria. High sensitivity (74.4-90%) and specificity values (93-98%) were found for estimating proteinuria from 0.5 to 2 g/day. However, the precision of estimation decreased as the level of urinary protein excretion increased to >3 g/day. The positive predictive value decreased as proteinuria became >3 g/day, perhaps because of the low prevalence of patients with high level proteinuria in our sample. The direction of change in P/C ratio longitudinally was accompanied by a similar direction of change in 24 UP, which was highly significant (r=0.7555, P<0.0001). CONCLUSION: We conclude that the urine P/C ratio is a useful and convenient screening and longitudinal test for proteinuria.

Factors governing cardiovascular risk in the patient with a failing renal transplant.

Cardiomyopathy and IHD are important morbid complications among renal transplant recipients. Age, diabetes, and sex remain important markers of risk. Smoking, hyperlipidemia, and hypertension appear to be the major reversible risk factors for IHD. Anemia and hypertension predict CHF. Definitive evidence on optimal intervention is lacking. Similarities in the renal transplant recipients to CRI patients with respect to cardiomyopathy and to the general population with respect to IHD suggest that extrapolation from those groups is reasonable in the interim.

Long-term changes in left ventricular hypertrophy after renal transplantation.

BACKGROUND: Concentric and eccentric left ventricular hypertrophy are common progressive disorders in dialysis patients and are associated with cardiac failure and death. Although partial regression of these abnormalities is known to occur during the first post-transplant year, their long-term evolution is unknown. METHODS: A total of 143 of 433 dialysis patients participating in a long-term prospective cohort study received renal transplants. Laboratory parameters were assessed monthly. Echocardiography was performed annually. Left ventricular mass index (LVMI) and cavity volume index were calculated according to standard formulae. Multiple linear regression was used to model change in LVMI as a function of baseline clinical and laboratory variables. RESULTS: LVMI fell from 161 g/m2 at 1 year to 146 g/m2 (P=0.009) g/m2 after 2 years. No further regression was seen in years 3 and 4. Left ventricular volume index showed similar trends, with a decline from year 1 to year 2 (P=0.05) followed by stabilization in years 3 and 4. Older age, long duration of hypertension, need for more than one antihypertensive, high pulse pressure in normal-size hearts, and low pulse pressure in dilated hearts were significantly associated with failure of regression of LVMI between the first and second years (MLR, P<0.000001, r2=0.57). CONCLUSIONS: Regression of left ventricular hypertrophy continues beyond the first year after renal transplantation, reaching a nadir at 2 years and persisting into the third and fourth posttransplant years. Failure to regress was associated with older age, hypertension, high pulse pressure in normal-size hearts and low pulse pressure in dilated hearts.

Chronic treatment with propranolol induces antioxidant changes and protects against ischemia-reperfusion injury.

The goal of this study was to examine whether chronic administration of propranolol offers protection against ischemia-reperfusion injury and whether it induces any change in the myocardial endogenous antioxidant enzyme activities and their gene expression. Rats were treated with propranolol (10 mg/kg/day, i.p.) for either 6 or 18 days. Forty-eight h after the last propranolol injection, isolated hearts were subjected to 60 min of global ischemia and 40 min of reperfusion. Resting tension in the control and treated groups after ischemia was 385+/-30 and 150+/-15%; and upon reperfusion was 140+/-11 and 49+/-6%, respectively, as compared to the pre-ischemic values. Recovery of the contractile function in globally ischemic hearts upon reperfusion was about 35% in the treated group as compared to about 16% in the control group at 10 and 20 min. A positive response to catecholamine was observed in hearts from propranolol group (C, 3.41+/-0.36; epi, 6.03+/-0.47 g/g) and was comparable to control hearts (C, 3.55+/-0.31; epi, 6.48+/-0.42 g/g). Myocardial antioxidants, catalase and glutathione peroxidase enzyme activities, in the treated group, prior to ischemia-reperfusion were increased by 67+/-9 and 45+/-11%, respectively, over those in controls. Superoxide dismutase activity did not show any change. The mRNA expression for the three antioxidant enzymes did not change in the hearts of the treated group as compared to control. Lipid peroxidation, both before and after the ischemia-reperfusion episode, was significantly reduced in the propranolol-treated hearts compared to the control group. Hearts studied at the end of reperfusion showed no difference in enzyme activities between treated and control groups. These data show that propranolol treatment of the animals protects against ischemia-reperfusion injury in isolated hearts in the absence of beta-blockade. Increased endogenous antioxidant enzyme activities due to propranolol treatment may have a role in this protection.

Ventilatory response to hypoxia in unanesthetized newborn kittens.

We studied the ventilatory response to hypoxia in 11 unanesthetized newborn kittens (n = 54) between 2 and 36 days of age by use of a flow-through system. During quiet sleep, with a decrease in inspired O2 fraction from 21 to 10%, minute ventilation increased from 0.828 +/- 0.029 to 1.166 +/- 0.047 l.min-1.kg-1 (P less than 0.001) and then decreased to 0.929 +/- 0.043 by 10 min of hypoxia. The late decrease in ventilation during hypoxia was related to a decrease in tidal volume (P less than 0.001). Respiratory frequency increased from 47 +/- 1 to 56 +/- 2 breaths/min, and integrated diaphragmatic activity increased from 14.9 +/- 0.9 to 20.2 +/- 1.4 arbitrary units; both remained elevated during hypoxia (P less than 0.001). Younger kittens (less than 10 days) had a greater decrease in ventilation than older kittens. These results suggest that the late decrease in ventilation during hypoxia in the newborn kitten is not central but is due to a peripheral mechanism located in the lungs or respiratory pump and affecting tidal volume primarily. We speculate that either pulmonary bronchoconstriction or mechanical uncoupling of diaphragm and chest wall may be involved.