Impaired K+ regulation contributes to exercise limitation in end-stage renal failure

Background

Patients with end-stage renal failure (ESRF) exhibit grossly impaired maximal exercise performance. This study investigated whether K+ regulation during exercise is impaired in ESRF and whether this is related to reduced exercise performance.

Methods

Nine stable hemodialysis patients and eight controls (CON) performed incremental cycling exercise to volitional fatigue, with measurement of peak oxygen consumption (VdotO2 peak). Arterial blood was sampled during and following exercise and analyzed for plasma [K+] (PK).

Results

The VdotO2 peak was approximately 44% less in ESRF than in CON (P < 0.001), whereas peak exercise PK was greater (7.23 plusminus 0.38 vs. 6.23 plusminus 0.14 mmol dot L-1, respectively, P < 0.001). In ESRF, the rate of rise in PK during exercise was twofold greater (0.43 plusminus 0.05 vs. 0.23 plusminus 0.03 mmol dot L-1dotmin-1, P < 0.005) and the ratio of rise in PK relative to work performed was 3.7-fold higher (90.1 plusminus 13.5 vs. 24.7 plusminus 3.3 nmol dot L-1dot J-1, P < 0.001). A strong inverse relationship was found between VdotO2 peak and the DeltaPKdot work-1 ratio (r = -0.80, N = 17, P < 0.001).

Conclusions

Patients with ESRF exhibit grossly impaired extrarenal K+ regulation during exercise, demonstrated by an excessive rise in PK relative to work performed. We further show that K+ regulation during exercise was correlated with aerobic exercise performance. These results suggest that disturbed K+ regulation in ESRF contributes to early muscle fatigue during exercise, thus causing reduced exercise performance.

Immune reconstitution sarcoidosis presenting with hypercalcaemia and renal failure in HIV infection

An HIV-positive white man developed hypercalcaemia and renal failure 15 months after starting highly active antiretroviral therapy. Investigations showed systemic sarcoidosis affecting parotids, skin and kidneys. This presentation was thought to be a manifestation of immune reconstitution inflammatory syndrome, and the patient was successfully treated with corticosteroid therapy.

Renal and gastrointestinal amyloidosis in an HIV-infected injection drug user

A 30-year-old HIV-infected intravenous drug user presented with sepsis, acute renal failure, oedema, proteinuria and iron deficiency anaemia. After extensive investigation, a diagnosis of reactive systemic AA (amyloid, serum amyloid A protein) amyloidosis was made on the basis of renal, gastric and duodenal biopsies.

Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial)

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes γ-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

A pilot randomized controlled crossover study comparing regional heparinization to regional citrate anticoagulation for continuous venovenous hemofiltration

OBJECTIVE: To evaluate the efficacy and safety of a regional heparinization and a regional citrate method of anticoagulation in CVVH.
DESIGN: Randomized controlled cross-over study.
SUBJECTS: Ten critically ill patients with acute renal failure.
SETTING: ICU of tertiary hospital.
INTERVENTION: CVVH was performed with pre-filter fluid replacement at 2000 ml/h and a blood flow rate of 150 ml/min. Regional heparinization was by the administration of heparin pre-filter at 1500 IU/h and protamine post-filter at 15 mg/h. Regional citrate anticoagulation was by means of a citrate-based replacement fluid (14 mmol/L) administered pre-dilution.
RESULTS: We studied nine males and one female. The mean age and APACHE II score were 70.5 and 17 respectively. Median circuit life was 13 hours (IQR 9.28) for the regional heparinization method compared to 17 hours (IQR 12,19.5) for the regional citrate method (p=0.77). There were no episodes of bleeding in either group.
CONCLUSION: Regional heparinization and regional citrate anticoagulation achieve similar circuit life in critically ill patients receiving CVVH.

Renal transplantation in patients with primary immunoglobulin A nephropathy

Background. Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial.
Methods. We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984–2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed.
Results. Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 ± 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 ± 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001).
Conclusions. Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.

A prospective observational study of prevalence and outcomes of patients with Gold Standard Framework criteria in a tertiary regional Australian Hospital

OBJECTIVES: Report the use of an objective tool, UK Gold Standards Framework (GSF) criteria, to describe the prevalence, recognition and outcomes of patients with palliative care needs in an Australian acute health setting. The rationale for this is to enable hospital doctors to identify patients who should have a patient-centred discussion about goals of care in hospital.

DESIGN: Prospective, observational, cohort study.

PARTICIPANTS: Adult in-patients during two separate 24 h periods.

MAIN OUTCOME MEASURES: Prevalence of in-patients with GSF criteria, documentation of treatment limitations, hospital and 1 year survival, admission and discharge destination and multivariate regression analysis of factors associated with the presence of hospital treatment limitations and 1 year survival.

RESULTS: Of 626 in-patients reviewed, 171 (27.3%) had at least one GSF criterion, with documentation of a treatment limitation discussion in 60 (30.5%) of those patients who had GSF criteria. Hospital mortality was 9.9%, 1 year mortality 50.3% and 3-year mortality 70.2% in patients with GSF criteria. One-year mortality was highest in patients with GSF cancer (73%), renal failure (67%) and heart failure (60%) criteria. Multivariate analysis revealed age, hospital length of stay and presence of the GSF chronic obstructive pulmonary disease criteria were independently associated with the likelihood of an in-hospital treatment limitation. Non-survivors at 3 years were more likely to have a GSF cancer (25% vs 6%, p=0.004), neurological (10% vs 3%, p=0.04), or frailty (45% vs 3%, p=0.04) criteria. After multivariate logistic regression GSF cancer criteria, renal failure criteria and the presence of two or more GSF clinical criteria were independently associated with increased risk of death at 3 years. Patients returning home to live reduced from 69% (preadmission) to 27% after discharge.

CONCLUSIONS: The use of an objective clinical tool identifies a high prevalence of patients with palliative care needs in the acute tertiary Australian hospital setting, with a high 1 year mortality and poor return to independence in this population. The low rate of documentation of discussions about treatment limitations in this population suggests palliative care needs are not recognised and discussed in the majority of patients.

TRIAL REGISTRATION NUMBER: 11/121.

The case | Allograft dysfunction in a patient with sickle cell disease

The article focuses on the study concerning the diagnosis of acute renal allograft in patient with sickle cell disease. The 33 year old underwent several surgeries with immediate graft function. The percutaneous renal biopsy of the patient shows focal cortical necrosis and acute tubular damage coherent with ischemia. It concludes that the allograft sickling is the primary cause of the acute renal dysfunction in patients with sickle cell disease.

Risk factors, microbiological findings and outcomes of necrotizing fasciitis in New Zealand: a retrospective chart review

Background
The incidence and mortality from necrotizing fasciitis (NF) are increasing in New Zealand (NZ). Triggered by a media report that traditional Samoan tattooing was causing NF, we conducted a chart review to investigate the role of this and other predisposing and precipitating factors and to document NF microbiology, complications and interventions in NZ.

Methods
We conducted a retrospective review of 299 hospital charts of patients discharged with NF diagnosis codes in eight hospitals in NZ between 2000 and 2006. We documented and compared by ethnicity the prevalence of predisposing and precipitating conditions, bacteria isolated, complications and interventions used.

Results
Out of 299 charts, 247 fulfilled the case definition. NF was most common in elderly males. Diabetes was the most frequent co-morbid condition, followed by obesity. Nearly a quarter of patients were taking non-steroidal anti-inflammatory drugs (NSAID). Traditional Samoan tattooing was an uncommon cause. Streptococcus pyogenes and Staphylococcus aureus were the two commonly isolated bacteria. Methicillin-resistant Staphylococcus aureus was implicated in a relatively small number of cases. Shock, renal failure, coagulation abnormality and multi-organ dysfunction were common complications. More than 90% of patients underwent surgical debridement, 56% were admitted to an intensive care unit (ICU) and slightly less than half of all patients had blood product transfusion. One in six NF cases had amputations and 23.5% died.

Conclusion
This chart review found that the highest proportion of NF cases was elderly males with co-morbidities, particularly diabetes and obesity. Tattooing was an uncommon precipitating event. The role of NSAID needs further exploration. NF is a serious disease with severe complications, high case fatality and considerable use of health care resources.

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

Background:
Acute kidney injury (AKI) is a major complication for infants following an asphyxic insult at birth. We aimed to determine if kidney structure and function were affected in an animal model of birth asphyxia and if maternal dietary creatine supplementation could provide an energy reserve to the fetal kidney, maintaining cellular respiration during asphyxia and preventing AKI.

Methods:
Pregnant spiny mice were maintained on normal chow or chow supplemented with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty-four hours after insult, kidneys were collected for histological or molecular analysis. Urine and plasma were also collected for biochemical analysis.

Results:
AKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a twofold increase (P < 0.02) in expression of Ngal (early marker of kidney injury), and decreased expression of the podocyte differentiation marker nephrin. Maternal creatine supplementation prevented the glomerular and tubular abnormalities observed in the kidney at 24 h and the increased expression of Ngal.

Conclusion:
Maternal creatine supplementation may prove useful in ameliorating kidney injury associated with birth asphyxia.

Cross-cultural adaption of the Health Educaiton Impact Questionnaire: experimental study showed expert committee, not back-translation, added value

Objectives
To assess the contribution of back-translation and expert committee to the content and psychometric properties of a translated multidimensional questionnaire.

Study Design and Setting
Recommendations for questionnaire translation include back-translation and expert committee, but their contribution to measurement properties is unknown. Four English to French translations of the Health Education Impact Questionnaire were generated with and without committee or back-translation. Face validity, acceptability, and structural properties were compared after random assignment to people with rheumatoid arthritis (N = 1,168), chronic renal failure (N = 2,368), and diabetes (N = 538). For face validity, 15 bilingual people compared translations quality with the original. Psychometric properties were examined using confirmatory factor analysis (metric and scalar invariance) and item response theory.

Results
Qualitatively, there were five types of translation errors: style, intensity, frequency/time frame, breadth, and meaning. Bilingual assessors ranked best the translations with committee (P = 0.0026). All translations had good structural properties (root mean square error of approximation <0.05; comparative fit index [CFI], ≥0.899; and Tucker–Lewis index, ≥0.889). Full measurement invariance was observed between translations (ΔCFI ≤ 0.01) with metric invariance between translations and original (lowest ΔCFI = 0.022 between fully constrained models and models with free intercepts). Item characteristic curve analyses revealed no significant differences.

Conclusion
This is the first experimental evidence that back-translation has moderate impact, whereas expert committee helps to ensure accurate content.

Cardiovascular alterations and management

This chapter reviews the support of cardiovascular function in the face of
many compromises to the system. It focuses on two of the most prevalent and fatal diseases affecting the heart: coronary heart disease and heart failure. These diseases are also a common comorbidity in elderly patients admitted to critical care units. The first section on coronary heart disease reviews the pathophysiological concepts of myocardial ischaemia and associated complications, with detailed consideration of the clinical implications, assessment and associated management. Heart failure is discussed in terms of the body’s compensatory mechanisms and the clinical sequelae and associated clinical features of heart failure. Nursing and medical management is outlined including the management of acute exacerbations of heart failure. Finally, other cardiovascular disorders commonly managed in critical care units are reviewed, ranging from other forms of heart failure to hypertensive emergencies and aortic aneurysms. The case study presented at the end of the chapter highlights the key aspects of the management of coronary heart disease and heart failure in patients admitted to critical care units.

Analysis of fetal heart rate asymmetry before and after 35 weeks of gestation

In this study, we have investigated the evidence of fetal heart rate asymmetry and how the fetal heart rate asymmetry changes before and after 35 weeks of gestation. Noninvasive fetal electrocardiogram (fECG) signals from 45 pregnant women at the gestational age from16 to 41 weeks with normal single pregnancies were analysed. A nonlinear parameter called heart rate asymmetry (HRA) index that measures time asymmetry of RR interval time-series signal was used to understand the changes of HRA in early and late fetus groups. Results indicate that fetal HRA measured by Porta's Index (PI) consistently increases after 35 weeks gestation compared to foetus before 32 weeks of gestation. It might be due to significant changes of sympatho-vagal balance towards delivery with more sympathetic surge. On the other hand, Guzik's Index (GI) showed a mixed effect i.e., increases at lower lags and decreases at higher lags. Finally, fHRA could potentially help identify normal and the pathological autonomic nervous system development.

Cross-platform urine metabolomics of experimental hyperglycemia in type 2 diabetes

Hyperglycemia causes diabetic nephropathy, a condition for which there are no specific diagnostic markers thatpredict progression to renal failure. Here we describe a multiplatform metabolomic analysis of urine from individualswith type 2 diabetes, collected before and immediately following experimental hyperglycemia. We used targetednuclear magnetic resonance spectroscopy (NMR), liquid chromatography - mass spectrometry (LC-MS) and gaschromatography - MS (GC-MS) to identify markers of hyperglycemia. Following optimization of data normalisation andstatistical analysis, we identified a reproducible NMR and LC-MS based urine signature of hyperglycemia. Significantincreases of alanine, alloisoleucine, isoleucine, leucine, N-isovaleroylglycine, valine, choline, lactate and taurine anddecreases of arginine, gamma-aminobutyric acid, hippurate, suberate and N-acetylglutamate were observed. GC-MSanalysis identified a number of metabolites differentially present in post-glucose versus baseline urine, but these could not be identified using current metabolite libraries. This analysis is an important first step towards identifying biomarkers of early-stage diabetic nephropathy.