Cardiac Remodelling in Patients Undergoing in-Centre Nocturnal Haemodialysis: Results from the MIDNIGHT Study, a Non-Randomized Controlled Trial.

Evidence suggests extended-hours haemodialysis (HD) may improve cardiovascular, medical and quality-of-life outcomes. In-centre nocturnal haemodialysis (INHD) is an established but underutilized method of providing extended-hours treatment. This 6-month, non-randomized controlled trial (ISRCTN16672784) recruited 13 INHD patients and 12 control patients on conventional HD. The effects of treatment on left ventricular (LV) structure, function and myocardial fibrosis were assessed using cardiac magnetic resonance imaging and native T1 mapping. Quality-of-life and clinical measures were also collected. INHD led to significant reductions in LV mass (-14.75 vs. +6.54 g; p = 0.02), global T1 (-30.62 vs. 0.4 ms; p = 0.05) and non-septal native T1 values (-30.93 vs. 8.96 ms; p = 0.02) over time. There were also significant improvements in serum phosphate (-0.39 vs. +0.02 mmol/L; p = 0.03) and reductions in ultrafiltration rates (-2.32 vs. +0.70 mL/h/kg p = 0.05) between INHD and controls. Six-months of INHD was associated with favourable LV remodelling and reduced myocardial fibrosis compared to patients on conventional haemodialysis.

Sometimes when you hear hoof beats, it could be a zebra: consider the diagnosis of Fabry disease.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of the enzyme α-galactosidase A. Fabry disease is present in 4-5% of men with unexplained left ventricular hypertrophy or cryptogenic stroke. As enzyme replacement therapy is now more widely available, it is important to recognise the signs and symptoms of the disease and establish the diagnosis so that early treatment can be started before irreversible organ damage occurs. CASE PRESENTATION: A previously fit and well 32-year-old Caucasian male presented with multisystem dysfunction including renal impairment. Although he had no suggestive symptoms, a diagnosis of Fabry disease was first established on a native renal biopsy. This was confirmed by enzymatic testing and subsequent genetic analysis that revealed a potentially new pathogenic variant. CONCLUSIONS: This case highlights the importance both of Fabry disease as a differential diagnosis in patients with renal impairment in the context of multi-system disease and also of adequate tissue sampling for electron microscopy when performing native renal biopsies.

Evaluating the clinical experience of a regional in-center nocturnal hemodialysis program: The patient and staff perspective.

INTRODUCTION: End-stage kidney disease causes significant morbidity, mortality, and reduced quality of life. Despite improvements in conventional hemodialysis, these problems persist. In-center nocturnal hemodialysis (INHD) has been shown to be beneficial in observational studies. This report outlines a 4-year renal network experience of INHD from the patient and frontline staff perspective. METHODS: Staff and patients' experiences of INHD were evaluated through two work streams. Work stream one: 12 patients who chose to stop INHD and 24 patients who chose to continue with INHD completed an anonymous survey. Work stream two: one-to-one interviews with 20 patients receiving INHD and seven staff working INHD shifts were conducted. Clinical incident reporting for conventional hemodialysis and INHD from April 2014 to December 2018 was reviewed. FINDINGS: Work stream one: Five themes were identified; facilities, time, health and well-being, sleep, and transport. A patient "starter pack" was developed and improvements to the dialysis unit were completed. Work stream two: Patient interviews demonstrated starter packs to aid sleep were well received; sleep itself was not a single reason to discontinue INHD. Staff indicated that their greatest concern was staffing levels; although staff-to-patient ratio remains unchanged, total numbers on INHD shifts were fewer, causing concern around less colleague availability for support during an emergency. SAFETY: 363 clinical incidents were reported across all dialysis shifts; for conventional hemodialysis, a larger proportion were due to medical interventions, infection control, and transport; for INHD, most incidents centered around communication with patients and relatives, delays in patient transfer, and issues with medical equipment or facilities. DISCUSSION: Patients continue with INHD due to increased social time and perceived health benefits. Patient starter packs and adjustments to the dialysis unit may enhance sleep. This experience has optimized the design of the NightLife study; a randomized controlled trial evaluated the effect of INHD on quality of life.

Nutrition in CAPD: serum bicarbonate and the ubiquitin-proteasome system in muscle.

BACKGROUND: Metabolic acidosis in chronic renal failure (CRF) induces loss of lean body mass while elimination of acidosis during a one year trial improved anthropometric indices in continuous ambulatory peritoneal dialysis (CAPD) patients. In rats with CRF, the mechanisms causing loss of lean body mass have been linked to acidosis-induced destruction of the essential, branched-chain amino acids (BCAA) and activation of the ubiquitin-proteasome system that degrades muscle protein; the latter response includes increased transcription of the ubiquitin gene. METHOD: Our aim was to determine if increasing the serum bicarbonate (HCO3) concentration of CAPD patients would improve their nutritional status, increase plasma BCAA levels, and reduce ubiquitin mRNA in their muscle as an index of suppressed activity of the ubiquitin-proteasome system. Eight, stable, long-term CAPD patients underwent vastus lateralis muscle biopsy before being randomized to continue 35 mmol/L lactate dialysate or convert to a 40 mmol/L lactate dialysate. After four weeks, measurements were repeated. RESULTS: Serum HCO3 increased in all patients and final values did not differ statistically between the two groups so results for all patients were combined. Weight and body mass index increased significantly as did plasma BCAA. Muscle levels of ubiquitin mRNA decreased significantly; serum tumor necrosis factor-alpha (TNF-alpha) also decreased. CONCLUSION: Our results indicate that even a small correction of serum HCO3 improves nutritional status, and provide evidence for down-regulation of BCAA degradation and muscle proteolysis via the ubiquitin-proteasome system. Whether acidosis and inflammatory cytokines (such as, TNF-alpha) interact to impair nutrition is unknown.

Glucocorticoid antagonist RU38486 fails to block acid-induced muscle wasting in vivo or in vitro.

BACKGROUND: Increased protein degradation during metabolic acidosis contributes to muscle wasting in uraemia. Adrenalectomy experiments in severely acidotic rats (arterial pH approximately 7.15) have shown that this is prevented in the absence of glucocorticoid. It should therefore be possible to block such muscle wasting with glucocorticoid receptor antagonist 11beta-(4-dimethylaminophenyl)-17beta-hydroxy,-17a-(prop-1-ynyl)-estra-4,9-dien-3-one (RU38486). METHODS: The effect of oral RU38486 (50 mg/kg body weight/day) was studied in vivo by administration to rats receiving dietary HCl supplements which yielded moderate acidosis (plasma HCO(3)(-) 19.7 +/- 1.2 mmol/l), comparable with that observed in uraemia. The effect of the glucocorticoid dexamethasone (DEX) (up to 500 nmol/l) and RU38486 (up to 5 micro mol/l) was also studied in vitro in acidified cultures of L6-G8C5 rat skeletal muscle cells. RESULTS: In vivo 15 days of moderate acidosis slowed weight gain and induced muscle wasting (6% weight loss in gastrocnemius with a commensurate decline in muscle protein) but, at this level of acidosis, muscle protein degradation showed no detectable increase. Wasting was not inhibited by RU38486 in spite of blockade of 80% of the glucocorticoid receptors in gastrocnemius. Unexpectedly, weight gain was significantly slower in acidotic rats receiving RU38486 than in acidotic rats receiving vehicle. In vitro acid spontaneously stimulated protein degradation, but even under strongly acidic conditions (pH 7.1) this was only weakly and transiently stimulated by 5 nmol/l DEX and transiently blunted by 5 micro mol/l RU38486. In contrast, as little as 1 nmol/l insulin-like growth factor I (IGF-I) almost abolished the effect of acid and this was partly restored by 5 nmol/l DEX. CONCLUSIONS: IGF-I is a potent determinant of acid-induced protein degradation in vitro and is antagonized by glucocorticoid. If glucocorticoid acts in this indirect way in vivo this may explain why, in moderate metabolic acidosis with intact adrenal glands, the action of RU38486 via glucocorticoid is too weak to be of therapeutic value.