Agreement between cystatin-C and creatinine based eGFR estimates after a 12-month exercise intervention in patients with chronic kidney disease

Background

Estimation of GFR (eGFR) using formulae based on serum creatinine concentrations are commonly used to assess kidney function. Physical exercise can increase creatinine turnover and lean mass; therefore, this method may not be suitable for use in exercising individuals. Cystatin-C based eGFR formulae may be a more accurate measure of kidney function when examining the impact of exercise on kidney function. The aim of this study was to assess the agreement of four creatinine and cystatin-C based estimates of GFR before and after a 12-month exercise intervention.

Methods

One hundred forty-two participants with stage 3–4 chronic kidney disease (CKD) (eGFR 25–60?mL/min/1.73?m²) were included. Subjects were randomised to either a Control group (standard nephrological care [n?=?68]) or a Lifestyle Intervention group (12?months of primarily aerobic based exercise training [n?=?74]). Four eGFR formulae were compared at baseline and after 12?months: 1) MDRDcr, 2) CKD-EPIcr, 3) CKD-EPIcys and 4) CKD-EPIcr-cys.

Results

Control participants were aged 63.5[9.4] years, 60.3% were male, 42.2% had diabetes, and had an eGFR of 40.5?±?8.9?ml/min/1.73m². Lifestyle Intervention participants were aged 60.5[14.2] years, 59.5% were male, 43.8% had diabetes, and had an eGFR of 38.9?±?8.5?ml/min/1.73m². There were no significant baseline differences between the two groups. Lean mass (r?=?0.319, p?<?0.01) and grip strength (r?=?0.391, p?<?0.001) were associated with serum creatinine at baseline. However, there were no significant correlations between cystatin-C and the same measures. The Lifestyle Intervention resulted in significant improvements in exercise capacity (+?1.9?±?1.8 METs, p?<?0.001). There were no changes in lean mass in both Control and Lifestyle Intervention groups during the 12?months. CKD-EPIcys was considerably lower in both groups at both baseline and 12?months than CKD-EPIcr (Control?=???10.5?±?9.1 and???13.1?±?11.8, and Lifestyle Intervention?=???7.9?±?8.6 and???8.4?±?12.3?ml/min/1.73?m²), CKD-EPIcr-cys (Control?=???3.6?±?3.7 and???4.5?±?4.5, and Lifestyle Intervention?=???3.6?±?3.7 and???2.5?±?5.5?ml/min/1.73?m²) and MDRDcr (Control?=???9.3?±?8.4 and???12.0?±?10.7, Lifestyle Intervention?=???6.4?±?8.4 and???6.9?±?11.2?ml/min/1.73?m²).

Conclusions

In CKD patients participating in a primarily aerobic based exercise training, without improvements in lean mass, cystatin-C and creatinine based eGFR provided similar estimates of kidney function at both baseline and after 12?months of exercise training.

Trial registration

The trial was registered at www.anzctr.org.au (Registration Number ANZCTR12608000337370) on the 17/07/2008 (retrospectively registered).

     

Intussusception as a Cause of Bowel Obstruction in Adults from a Resource Limited Area,Cameroon

Background

Intussusception refers to the telescoping of a proximal segment of bowel into a distal segment. It is a rare cause of intestinal obstruction in adulthood.

Case Details

We report two cases of adult intussusception in a post-operative period following Caesarean Section (with no lead point) and Appendicectomy (due to colonic adenocarcinoma) respectively.

Conclusion

Though rare in adulthood, intussusception should be considered as a differential diagnosis to bowel obstruction in adults even in the post-operative period.     

Exercise training in chronic kidney disease patients

Chronic kidney disease (CKD) is a major public health problem that affects an estimated 1.7 million Australians. Patients with CKD commonly progress to end-stage kidney disease (ESKD) requiring dialysis and/or kidney transplantation. They are at high risk of cardiovascular disease and many die from this prior to reaching ESKD. Few therapies are available to slow CKD progression and reduce cardiovascular morbidity and mortality. The benefit of exercise training has been well demonstrated in a range of disease conditions including ESKD and was recently highlighted by a systematic review in haemodialysis patients and a recent Cochrane review of all stages of CKD. However, the effects of exercise training in patients with CKD have not been extensively investigated. Our systematic search of the literature found only ten clinical trials in this area. The aim of this review is to review these studies, and to discuss the findings, safety considerations and suggest future areas of research. Overall, the majority of the studies are small, non-randomized, non-controlled trials. They have found that exercise training can increase exercise capacity, improve muscle strength and function, decrease blood pressure, and improve inflammation and oxidative stress biomarkers. The effects of exercise training on kidney function, cardiovascular disease and quality of life are unknown. Studies are needed to answer these questions and develop evidence-based exercise training guidelines for individuals with CKD.     

Characteristics of white cell-reduced red cells stored in tri-(2- ethylhexyl)trimellitate plastic

BACKGROUND: Standard blood storage containers contain extractable plasticizers that accumulate in blood during storage and are an unintended transfusion product. However, extractable plasticizers have a protective effect on the red cell membrane and improve red cell storage variables. Prestorage white cell reduction also improves selected red cell storage variables. STUDY DESIGN AND METHODS: The study evaluated whether the beneficial effect of prestorage white cell reduction would offset the negative effect of the absence of extractable plasticizer in red cells stored in AS-3 for 42 days at 4 degrees C. Filtered red cells stored in polyvinylchloride containers with the nonextracting plasticizer, tri-(2-ethylhexyl)trimellitate (TEHTM), were compared to unfiltered red cells stored in polyvinylchloride containers with the extractable plasticizer di-(2- ethylhexyl)phthalate (DEHP). RESULTS: Poststorage supernatant potassium and red cell osmotic fragility were significantly higher in white cell- reduced TEHTM units than in unfiltered DEHP units. The mean 24-hour recovery of the filtered TEHTM red cells was significantly lower than that of the unfiltered DEHP red cells (69.1 +/− 7.4% vs. 77.1 +/− 5.1%, p < 0.05, n = 8). CONCLUSION: These data demonstrate that white cell reduction before 42-day storage in TEHTM containers with currently approved preservatives does not yield an acceptable red cell component.     

DNA ligation in relation to DNA strand breaks in phytohemagglutinin- stimulated blast cells from acute lymphoblastic and nonlymphoblastic leukemia

DNA ligase activity was determined in the WBCs from 306 cases of acute lymphoblastic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL). In T-ALL cells this activity was either low or absent. DNA analysis by nucleoid, alkaline elution, and alkaline sucrose centrifugation after cells were embedded in agarose inserts has shown more DNA breaks in T- ALL than in ANLL blasts. Phytohemagglutinin stimulation of T-ALL blasts resulted in the apparent joining of the DNA breaks. Apparent identical results can be obtained by the incubation of DNA with exogenous DNA ligase. The authors suggest that this enzyme is a crucially regulated step of replication and subsequent proliferation in this type of leukemia.     

Precision estimates of relative and absolute cerebral blood flow in Alzheimer’s disease and cognitively normal individuals

Alzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF). Although the gold standard for measuring CBF is [¹⁵O]H₂O PET, proxies of relative CBF, derived from the early distribution phase of amyloid and tau tracers, have gained attention. The present study assessed precision of [¹⁵O]H₂O derived relative and absolute CBF, and compared precision of these measures with that of (relative) CBF proxies. Dynamic [¹⁵O]H₂O, [¹⁸F]florbetapir and [¹⁸F]flortaucipir PET test-retest (TrT) datasets with eleven, nine and fourteen subjects, respectively, were included. Analyses were performed using an arterial input model and/or a simplified reference tissue model, depending on the data available. Relative CBF values (i.e. K₁/K₁′ and/or R₁) were obtained using cerebellar cortex as reference tissue and TrT repeatability (i.e. precision) was calculated and compared between tracers, parameters and clinical groups. Relative CBF had significantly better TrT repeatability than absolute CBF derived from [¹⁵O]H₂O (r = −0.53), while best TrT repeatability was observed for [¹⁸F]florbetapir and [¹⁸F]flortaucipir R₁ (r = −0.23, r = −0.33). Furthermore, only R₁ showed, better TrT repeatability for cognitively normal individuals. High precision of CBF proxies could be due to a compensatory effect of the extraction fraction, although changes in extraction fraction could also bias these proxies, but not the gold standard.     

Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24–71) (8/17), specificity of 85% (95% CI 42–99) (6/7), positive predictive value (PPV) of 89% (95% CI 51–99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17–67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6–51) (3/14), specificity of 100% (95% CI 56–100) (7/7), PPV of 100% (95% CI 31–100) (3/3), and NPV of 39% (95% CI 18–64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.