Unaccustomed eccentric contractions impair plasma K+ regulation in the absence of changes in muscle Na+,K+-ATPase content.

The Na+,K+-ATPase (NKA) plays a fundamental role in the regulation of skeletal muscle membrane Na+ and K+ gradients, excitability and fatigue during repeated intense contractions. Many studies have investigated the effects of acute concentric exercise on K+ regulation and skeletal muscle NKA, but almost nothing is known about the effects of repeated eccentric contractions. We therefore investigated the effects of unaccustomed maximal eccentric knee extensor contractions on K+ regulation during exercise, peak knee extensor muscle torque, and vastus lateralis muscle NKA content and 3-O-MFPase activity. Torque measurements, muscle biopsies, and venous blood samples were taken before, during and up to 7 days following the contractions in six healthy adults. Eccentric contractions reduced peak isometric muscle torque immediately post-exercise by 26±11% and serum creatine kinase concentration peaked 24 h post-exercise at 339±90 IU/L. During eccentric contractions, plasma [K+] rose during Set 1 and remained elevated at ∼4.9 mM during sets 4-10; this was despite a decline in work output by Set 4, which fell by 18.9% at set 10. The rise in plasma [K+] x work(-1) ratio was elevated over Set 2 from Set 4- Set 10. Eccentric contractions had no effect on muscle NKA content or maximal in-vitro 3-O-MFPase activity immediately post- or up to 7 d post-exercise. The sustained elevation in plasma [K+] despite a decrease in work performed by the knee extensor muscles suggests an impairment in K+ regulation during maximal eccentric contractions, possibly due to increased plasma membrane permeability or to excitation-contraction uncoupling.

Exercise intervention in New Zealand Polynesian peoples with type 2 diabetes: Cultural considerations and clinical trial recommendations.

The Maori and Pacific Islands peoples of New Zealand suffer a greater burden of type 2 diabetes mellitus (T2DM) and associated comorbidities than their European counterparts. Empirical evidence supports the clinical application of aerobic and resistance training for effective diabetes management and potential remission, but few studies have investigated the effectiveness of these interventions in specific ethnic cohorts. We recently conducted the first trial to investigate the effect of prescribed exercise training in Polynesian people with T2DM. This article presents the cultural considerations undertaken to successfully implement the study. The research procedures were accepted and approved by cultural liaisons and potential participants. The approved methodology involved a trial evaluating and comparing the effects of two, 16-week exercise regimens (i.e. aerobic training and resistance training) on glycosylated haemoglobin (HbA1c), related diabetes markers (i.e. insulin resistance, blood lipids, relevant cytokines and anthropometric and hemodynamic indices) and health-related quality of life. Future exercise-related research or implementation strategies in this cohort should focus on cultural awareness and techniques to enhance participation and compliance. Our approach to cultural consultation could be considered by researchers undertaking trials in this and other ethnic populations suffering an extreme burden of T2DM, including indigenous Australians and Americans.

Mortality in dialysis patients may not be associated with ESA dose: a 2-year prospective observational study.

BACKGROUND: Anaemia of chronic kidney disease increases the risk of death and adverse events, but can be managed using erythropoiesis stimulating agents (ESAs). However, recent evidence suggests that targeting a higher haemoglobin concentration ([Hb]) increases mortality risk, and both higher [Hb] targets and ESA doses have been implicated. Nonetheless, a causative role has not been demonstrated, and this potential relationship requires further appraisal in such a complex patient group. METHODS: The relationship between the haematopoietic response to ESAs and patient survival in 302 stable, prevalent dialysis patients was explored in a prospective, single-centre study. Clinical and laboratory parameters influencing mortality and ESA resistance were analysed. Patients were stratified into 5 groups, according to their [Hb] and ESA dosage, and were followed for 2 years. RESULTS: Little difference in co-morbidities between groups was identified. 73 patients died and 36 were transplanted. Initial analysis suggested a direct relationship between mortality and ESA dosage. However, Cox proportional hazards multivariate analysis demonstrated mortality risk was associated only with age (adjusted HR per year: 1.061, 95% CI 1.031-1.092), dialysis duration (adjusted HR: 1.010, 95% CI 1.004-1.016), peripheral vascular disease (adjusted HR: 1.967, 95% CI 1.083-3.576) and CRP (adjusted HR: 1.024, 95% CI 1.011-1.039). Mortality was increased in patients poorly responsive to ESAs (55.5%). CONCLUSION: ESA dose does not appear to contribute substantially to mortality risk in dialysis patients. Instead, age and co-morbidities appear to be the critical determinants. A poor response to ESAs is a marker of overall poor health status.

Impaired exercise performance and muscle Na(+),K(+)-pump activity in renal transplantation and haemodialysis patients.

BACKGROUND: We examined whether abnormal skeletal muscle Na(+),K(+)-pumps underlie impaired exercise performance in haemodialysis patients (HDP) and whether these are improved in renal transplant recipients (RTx). METHODS: Peak oxygen consumption ( O(2peak)) and plasma [K(+)] were measured during incremental exercise in 9RTx, 10 HDP and 10 healthy controls (CON). Quadriceps peak torque (PT), fatigability (decline in strength during thirty contractions), thigh muscle cross-sectional area (TMCSA) and vastus lateralis Na(+),K(+)-pump maximal activity, content and isoform (α(1)-α(3), ß(1)-ß(3)) abundance were measured. RESULTS: O(2peak) was 32 and 35% lower in RTx and HDP than CON, respectively (P < 0.05). PT was less in RTx and HDP than CON (P < 0.05) but did not differ when expressed relative to TMCSA. Fatigability was ∼1.6-fold higher in RTx (24 ± 11%) and HDP (25 ± 4%) than CON (15 ± 5%, P < 0.05). Na(+),K(+)-pump activity was 28 and 31% lower in RTx and HDP, respectively than CON (P < 0.02), whereas content and isoform abundance did not differ. Pooled (n = 28) O(2peak) correlated with Na(+),K(+)-pump activity (r = 0.45, P = 0.02). CONCLUSIONS: O(2peak) and muscle Na(+),K(+)-pump activity were depressed and muscle fatigability increased in HDP, with no difference observed in RTx. These findings are consistent with the possibility that impaired exercise performance in HDP and RTx may be partially due to depressed muscle Na(+),K(+)-pump activity and relative TMCSA.

Effects of endurance training on extrarenal potassium regulation and exercise performance in patients on haemodialysis.

BACKGROUND: Haemodialysis patients (HDP) with anaemia display impaired plasma K(+) regulation during exercise and poor exercise performance. Epoetin treatment and exercise training improve exercise performance in HDP, but whether this is associated with improved K(+) regulation is unknown. METHODS: Six HDP with near-normal [Hb] were tested for aerobic power ( ) and plasma [K(+)] during incremental exercise; quadriceps muscle strength (peak torque, PT) from 0 to 360 degrees s(-1) and fatiguability (decline in strength during thirty contractions). Tests were conducted at baseline, after 6 weeks of normal activity (pre-train) and following 6 weeks cycle training (post-train). Six healthy untrained controls (CON) matched for age, sex, mass and height were tested at baseline. RESULTS: In HDP at baseline, and PT from 0 to 360 degrees s(-1) were respectively reduced by 37% and 27-42%, compared to CON (P < 0.05). Plasma [K(+)], the rise in [K(+)] (Delta[K(+)]) and the Delta[K(+)] relative to total work done (Delta[K(+)] work(-1) ratio) during incremental exercise were all higher in HDP at baseline compared to CON (P < 0.05). Exercise training increased time to fatigue by 12% (P < 0.05) but did not improve K(+) regulation or . An inverse correlation was found between the Delta[K(+)] work(-1) ratio and for pooled CON and HDP data. CONCLUSIONS: In HDP treated with epoetin, poor exercise performance was related to impaired extrarenal K(+) regulation, whilst training improved exercise performance but not K(+) regulation. Thus, although impaired extrarenal K(+) regulation may contribute to poor exercise performance in HDP, exercise performance can still improve with training despite unchanged K(+) regulation.

Exercise performance falls over time in patients with chronic kidney disease despite maintenance of hemoglobin concentration.

Physical function is limited in patients with kidney disease, although previous studies have been confounded by anemia. What is not clear is how physical performance changes over time as renal function deteriorates. A cohort of 12 patients (10 male, two female; mean +/- SD age 49 +/- 11 yr) who had stages 3 to 4 chronic kidney disease without previous anemia were examined, and nine were followed for a 2-yr period. Assessments were made of peak oxygen consumption (VO2peak) by cycle ergometry, leg extension strength, and fatigue on an isokinetic dynamometer and thigh muscle cross-sectional area (TMCSA) by computed tomography. At baseline, creatinine clearance was 31 +/- 13 ml/min and hemoglobin concentration ([Hb]) was 129 +/- 9 g/L. VO2peak was low (1.88 L/min, 82% of predicted), and maximal isometric voluntary contraction was 188 +/- 42 Nm, with a TMCSA of 144 +/- 27 cm2. VO2peak correlated with creatinine clearance corrected for body surface area (r = 0.613, P = 0.034) but not to [Hb]. VO2peak adjusted for patient weight correlated with leg fatigue (r = -0.693, P = 0.012). For those with follow-up tests, there were falls in renal function by 28% (P = 0.007) and VO2peak by 9% (P = 0.03), whereas [Hb] did not change. Leg strength fell across a range of isokinetic speeds (P = 0.04), whereas no change in TMCSA was observed. In conclusion, exercise performance as measured by aerobic (VO2peak) and leg strength tests were reduced in patients with stages 3 to 4 chronic kidney disease. As renal function declined over time, there was a corresponding decline in exercise performance even when [Hb] was maintained.

Haemoglobin response to subcutaneous versus intravenous epoetin alfa administration in iron-replete haemodialysis patients.

BACKGROUND: Numerous prior studies have reported that a substantially higher dose of epoetin is required to maintain haemoglobin (Hb) concentration when patients are switched from a subcutaneous (s.c.) to intravenous (i.v.) route of administration. Many of the reported trials, however, involved patients who did not have adequate serum iron levels. It was hypothesized that patients with adequate iron stores who are switched from one route of administration to the other without a change in dose will experience substantially less change in their Hb concentration. METHODS: Haemodialysis patients who were iron replete (ferritin 300-800 microg/L, transferrin saturation (TSAT) 25-50%) participated in a prospective, randomized cross-over trial receiving epoetin for 3 months either by s.c. or i.v. injection followed by a further 3 months of epoetin via the other route. The principal aim was to determine changes in Hb concentration without altering the weekly epoetin dose. The secondary aim was to assess whether the frequency of dosing (once, twice or thrice weekly) influenced the Hb concentration response. RESULTS: Eighty-one patients (mean age 62 years, 60% male) entered the study and 15 withdrew prior to study completion. Forty-three patients began s.c. epoetin alfa administration (group A) and 38 on i.v. (group B). Median ferritin and TSAT at entry for groups A and B were 409 and 394 microg/L (NS) and 31 and 32% (NS), respectively, which remained within the target range during the study. Median epoetin doses for groups A and B were similar (90 vs 93 IU/kg per week, NS). After 3 months, the mean Hb concentration rose for group A (SC; 118.7-121.9 g/L (P = 0.03)) but it fell for group B (i.v.; 119.1-116.0 g/L (P = 0.019)). Following the change in route of administration, the Hb concentration for group A (i.v.) fell by 5.1% over 3 months (121.9-115.4, P < 0.001) and rose by 2.8% for group B (s.c.) over 3 months (116.0-119.7, P = 0.001). Similar significant changes in the Hb concentration were seen at different dosing frequencies. CONCLUSION: Subcutaneous administration of epoetin produces a significant, although slight clinical change in Hb concentration compared with i.v. administration in stable, iron replete, haemodialysis patients. A similar effect appears to prevail regardless of the frequency of injections given.

Acute renal failure associated with Legionella pneumonia and acute cholecystitis.

BACKGROUND AND AIMS: Acute cholecystitis in critically ill patients has a high morbidity and mortality. We observed a number of patients presenting with Legionella pneumonia and acute renal failure who subsequently developed acute cholecystitis. There has previously been no reported association between Legionella pneumonia, renal failure and cholecystitis, prompting this examination of the cases and review of the available literature. METHODS: The Western Hospital patient record discharge codes (DRG) from 1993 to 2001 were searched retrospectively for all cases of Legionella pneumonia or acute renal failure requiring dialysis (ARF) at presentation or during their period of hospitalization. Acute cholecystitis was then included as a cross-search and results analysed. RESULTS: Twenty-six cases of isolated Legionella pneumonia and 112 of ARF were identified with a further 10 having both conditions simultaneously. Of these 10 cases, three were identified as also having acute cholecystitis. The combination of Legionella pneumonia and ARF was associated with an increased risk of acute cholecystitis (P = 0.002) whereas neither condition in isolation demonstrated this association. CONCLUSIONS: Patients with Legionella pneumonia can become critically ill with multiple complications including acute renal failure requiring dialysis. In this setting, they may have an increased risk of developing acute cholecystitis, which clinically can be difficult to ascertain. Diagnosis requires a high index of suspicion and vigilance.