Naushad A. Junglee

Renal recovery with eculizumab in atypical hemolytic uremic syndrome following prolonged dialysis.

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) which encompasses hemolytic anemia, thrombocytopenia, and organ impairment. Around 10% of cases are atypical HUS (aHUS), a rare disease with poor outcomes caused by uncontrolled activation of the alternative complement pathway. This case describes a young woman with clinical manifestations compatible with TMA during childhood and adolescence who was formally diagnosed with aHUS at the age of 21. She was managed with intensive plasma exchange and hemodialysis, which failed to improve her severe acute kidney injury and other hematological manifestations of aHUS. This was further compounded by several episodes of flash pulmonary edema and the posterior reversible encephalopathy syndrome (PRES). Treatment with the monoclonal anti-C5 inhibitor, eculizumab, improved all hematological parameters with almost full renal recovery following 3.5 months of dialysis. So far, long-term use of eculizumab (> 11 months) continues to be effective and without complication. Our case illustrates the difficulty but importance of early consideration of aHUS in patients presenting with TMA. More importantly, we highlight that near-normal renal recovery may be attained with eculizumab in adults even after a long dependence on dialysis - an observation that has not been reported in the literature so far.

Exercising in a hot environment with muscle damage: Effects on acute kidney injury biomarkers and kidney function

Unaccustomed strenuous physical exertion in hot environments can result in heat stroke and acute kidney injury (AKI). Both exercise-induced muscle damage and AKI are associated with the release of interleukin-6, but whether muscle damage causes AKI in the heat is unknown. We hypothesized that muscle-damaging exercise, before exercise in the heat, would increase kidney stress. Ten healthy euhydrated men underwent a randomized, crossover trial involving both a 60-min downhill muscle-damaging run (exercise-induced muscle damage; EIMD), and an exercise intensity-matched non-muscle-damaging flat run (CON), in random order separated by 2 wk. Both treatments were followed by heat stress elicited by a 40-min run at 33°C. Urine and blood were sampled at baseline, after treatment, and after subjects ran in the heat. By design, EIMD induced higher plasma creatine kinase and interleukin-6 than CON. EIMD elevated kidney injury biomarkers (e.g., urinary neutrophil gelatinase-associated lipocalin (NGAL) after a run in the heat: EIMD-CON, mean difference [95% CI]: 12 [5, 19] ng/ml) and reduced kidney function (e.g., plasma creatinine after a run in the heat: EIMD-CON, mean difference [95% CI]: 0.2 [0.1, 0.3] mg/dl), where CI is the confidence interval. Plasma interleukin-6 was positively correlated with plasma NGAL (r = 0.9, P = 0.001). Moreover, following EIMD, 5 of 10 participants met AKIN criteria for AKI. Thus for the first time we demonstrate that muscle-damaging exercise before running in the heat results in a greater inflammatory state and kidney stress compared with non-muscle-damaging exercise. Muscle damage should therefore be considered a risk factor for AKI when performing exercise in hot environments.

Muscle-Damaging Exercise Increases Heat Strain during Subsequent Exercise Heat Stress

PURPOSE It remains unclear whether exercise-induced muscle damage (EIMD) increases heat strain during subsequent exercise heat stress, which in turn may increase the risk of exertional heat illness. We examined heat strain during exercise heat stress 30 min after EIMD to coincide with increases in circulating pyrogens (e.g., interleukin-6 [IL-6]) and 24 h after EIMD to coincide with the delayed muscle inflammatory response when a higher rate of metabolic energy expenditure (M˙) and thus decreased economy might also increase heat strain. METHODS Thirteen non-heat-acclimated males (mean ± SD, age = 20 ± 2 yr) performed exercise heat stress tests (running for 40 min at 65% V˙O2max in 33°C, 50% humidity) 30 min (HS1) and 24 h (HS2) after treatment, involving running for 60 min at 65% V˙O2max on either -10% gradient (EIMD) or +1% gradient (CON) in a crossover design. Rectal (Tre) and skin (Tsk) temperature, local sweating rate, and M˙ were measured throughout HS tests. RESULTS Compared with CON, EIMD evoked higher circulating IL-6 pre-HS1 (P < 0.01) and greater plasma creatine kinase and muscle soreness pre-HS2 (P < 0.01). The ΔTre was greater after EIMD than CON during HS1 (0.35°C, 95% confidence interval = 0.11°C-0.58°C, P < 0.01) and HS2 (0.17°C, 95% confidence interval = 0.07°C-0.28°C, P < 0.01). M˙ was higher on EIMD throughout HS1 and HS2 (P < 0.001). Thermoeffector responses (Tsk, sweating rate) were not altered by EIMD. Thermal sensation and RPE were higher on EIMD after 25 min during HS1 (P < 0.05). The final Tre during HS1 correlated with the pre-HS1 circulating IL-6 concentration (r = 0.67). CONCLUSIONS Heat strain was increased during endurance exercise in the heat conducted 30 min after and, to a much lesser extent, 24 h after muscle-damaging exercise. These data indicate that EIMD is a likely risk factor for exertional heat illness particularly during exercise heat stress when behavioral thermoregulation cues are ignored.

When pure is not so pure: Chloramine-related hemolytic anemia in home hemodialysis patients

Worldwide, chloramines are used as the preferred disinfectant for city water supplies. Although they have distinct advantages compared with chlorine and are deemed harmless to the general population, hemodialysis (HD) patients are at risk from chloramine‐induced hemolytic anemia. In recent years, this has been highlighted in regional dialysis units but not as frequently in the home HD group. We report on 2 home HD patients who succumbed to severe oxidative hemolysis due to high mains water chloramine concentrations. Both patients were extensively investigated for other cause of anemia before a definitive diagnosis was reached. Delays in diagnosing this uncommon condition can be costly in terms of significant morbidity and excessive usage of recombinant erythropoietin and blood transfusion. Prevention primarily involves enforcing strict water quality control and establishing regular communication with water supply boards and home HD patients. Double (inline) carbon filters should be installed in patients homes as an effective means for removing high incoming chloramine concentrations.

Does Proteinuria-Inducing Physical Activity Increase Biomarkers of Acute Kidney Injury?

Aim: We sought to determine if an acute kidney injury biomarker, neutrophil gelatinaseassociated lipocalin (NGAL), would be up-regulated by high-intensity proteinuria-inducing exercise. Methods: A prospective cohort design was utilised. 100 healthy, active adults (mean age 24 ± 4 (SD) years) were screened for post-exercise proteinuria (PeP); 10 PeP positive and 10 PeP negative participants then completed a high-intensity exercise protocol involving an 800 meter sprint. Plasma and urinary NGAL, urinary creatinine, urinary albumin and urine volume were obtained at the following time points: pre-run, immediately post-, 25 minutes, one hour and two hours post-run. Results: Following high-intensity exercise, 64% of participants had urinary NGAL concentrations above the normal range, particularly at 25 minutes post (P = 0.002). However, there was no difference in NGAL response between PeP positive and negative groups and plasma NGAL was decreased, not elevated, following exercise (P = 0.002). In some individuals normalizing urinary NGAL for urinary creatinine attenuated elevations. Urinary NGAL was also negatively correlated with urine volume (r = -0.701, P = 0.005). Conclusion: Proteinuria susceptibility did not influence an acute injury biomarker response to exercise. Nevertheless, urinary NGAL was elevated by exercise, possibly due to increased production by the proximal tubule, increased plasma clearance (given the decrease in plasma NGAL) and/or a concentrating effect of exercise-induced oliguria. Until correct normalisation of urinary biomarkers is determined, NGAL should be interpreted cautiously in exercise and acute kidney injury-induced oliguria. The inter-individual NGAL response to exercise also warrants further investigation.

Duodenal varices successfully treated with cyanoacrylate injection therapy

Duodenal varices are a rare complication of portal hypertension secondary to liver cirrhosis. Compared to oesophageal varices, they bleed less often but are also more difficult to diagnose and treat. There is no established treatment for bleeding duodenal varices and different treatment strategies have been employed with variable results. The authors present a case of 52-year-old male who was admitted with melaena. Upper gastrointestinal endoscopy was performed which identified bleeding varices in the second part of duodenum. The varices were injected with cyanoacrylate and the outcome was favourable. Subsequent endoscopies showed complete resolution of the varices. The authors conclude that cyanoacrylate injection is an effective first-line treatment for bleeding duodenal varices.

A Holistic Approach to Vascular Access in Hemodialysis

Vascular access for haemodialysis (HD) and other forms of renal replacement therapy where access to blood is required (such as haemofiltration) is a broad area that encompasses a vari‐ ety of specialties including nephrology, intensive care, interventional radiology and surgery. Within the acute setting, vascular access via catheter placement can be performed in an emergency. However, longer-term access in the form of an arteriovenous fistula (AVF) or graft requires considerable pre-procedural planning and often involves multidisciplinary in‐ put throughout the patient’s “dialysis lifetime”. In this chapter, we aim to discuss the com‐ mon types of access and provide a holistic approach from a UK perspective, whilst also focussing on some practical aspects that have been noted from our personal experience and evidence-base.

Arteriovenous fistula complication following MRI

Health professionals should be aware of medical procedures that cause vascular access complications. This case describes a haemodialysis patient who experienced pain, swelling and bruising over a radiocephalic fistula following MRI. Exactly the same signs and symptoms were evident following a second scan performed 3 months later. Plausible explanations include a radio frequency-induced electrical current being formed at the arteriovenous fistula, or varying gradients of the MRI sequence stimulating peripheral nerves, leading to a site of increased tissue stimulation. Of note, a juxta-anastomotic venous stenosis was confirmed by fistulogram 4 days after the second scan, although whether this access failure was due to the MRI scan per se could not be ascertained. Nevertheless, these previously undocumented observations suggest that careful patient and fistula monitoring is required when completing MRI scans in those with an arteriovenous fistula.

Synchronous primary oesophageal malignant melanoma and sigmoid adenocarcinoma

The authors present a case of a gentleman in his 70s who was referred to the gastroenterology outpatient clinic with dysphagia. An oesophagogastroduodenoscopy was performed which showed a polypoidal black coloured mass in the oesophagus. Endoscopic biopsies confirmed malignant melanoma. Further staging investigations were organised to assess suitability for surgery which revealed a mass in the sigmoid colon. Subsequent colonoscopy and biopsy confirmed adenocarcinoma. As this was an unusual case to associate these two malignancies at the same time, there was no ideal or recognised management plan available. Different treatment options were considered and a consensus was developed regarding best surgical approach but due to the lapse in time a repeat staging CT scan was organised which unfortunately now demonstrated lymph node metastasis. Patient was managed conservatively from this point onwards and he died 12 months later.