Werner Keenswijk

Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome, a preliminary study

AbstractDiarrhea-associated hemolytic uremic syndrome (D+HUS) is a common thrombotic microangiopathy during childhood and early identification of parameters predicting poor outcome could enable timely intervention. This study aims to establish the accuracy of BUN-to-serum creatinine ratio at admission, in addition to other parameters in predicting the clinical course and outcome. Records were searched for children between 1 January 2008 and 1 January 2015 admitted with D+HUS. A complicated course was defined as developing one or more of the following: neurological dysfunction, pancreatitis, cardiac or pulmonary involvement, hemodynamic instability, and hematologic complications while poor outcome was defined by death or development of chronic kidney disease. Thirty-four children were included from which 11 with a complicated disease course/poor outcome. Risk of a complicated course/poor outcome was strongly associated with oliguria (p = 0.000006) and hypertension (p = 0.00003) at presentation. In addition, higher serum creatinine (p = 0.000006) and sLDH (p = 0.02) with lower BUN-to-serum creatinine ratio (p = 0.000007) were significantly associated with development of complications. A BUN-to-sCreatinine ratio ≤40 at admission was a sensitive and highly specific predictor of a complicated disease course/poor outcome. Conclusion: A BUN-to-serum Creatinine ratio can accurately identify children with D+HUS at risk for a complicated course and poor outcome.What is Known:• Oliguria is a predictor of poor long-term outcome in D+HUSWhat is New:• BUN-to-serum Creatinine ratio at admission is an entirely novel and accurate predictor of poor outcome and complicated clinical outcome in D+HUS• Early detection of the high risk group in D+HUS enabling early treatment and adequate monitoring

Is eculizumab efficacious in Shigatoxin-associated hemolytic uremic syndrome? A narrative review of current evidence

Severe complications due to Shigatoxin-associated hemolytic uremic syndrome (STEC-HUS) currently present a serious challenge since no specific treatment for this condition is available. Eculizumab, a terminal complement inhibitor, has been used especially in STEC-HUS patients with severe neurological involvement, but the efficacy remains undetermined. In order to determine its efficacy, we searched the databases Pubmed, Web of Science, Embase, and LiLACS for reports describing outcomes of eculizumab administration in STEC-HUS. We retrieved 11 reports ranging from case reports to cohort studies with the largest study population emanating from the 2011 German outbreak. Outcomes were variable and difficult to interpret in light of the absence of high-quality studies but seemed to point towards potential efficacy of eculizumab if administered early in the course.Conclusion: The efficacy of eculizumab in STEC-HUS could not be established nor disproven based on current data, and there is a desperate need for randomized controlled trials.What is known?• Eculizumab has been used in complicated cases of Shigatoxin-associated hemolytic uremic syndrome but the efficacy remains unknown?What is new?• Eculizumab might be efficacious if given early in selected cases of Shigatoxin-associated hemolytic uremic syndrome; however, randomized trials are needed to assess this.

Atypical Hemolytic Uremic Syndrome in Low Resource Settings: Which Options Do We Have?

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A devastating case of diarrhea-associated hemolytic uremic syndrome associated with extensive cerebral infarction; why we need to do better

Abstract A 4-year-old girl with diarrhea-associated hemolytic uremic syndrome (D+HUS) was transferred to the PICU of our center due to deteriorating renal function and neurological involvement. On admission, a comatous child was seen with hypoventilation and she was placed on mechanical ventilation. Hemodialysis was commenced but plasma exchange was discontinued due to repeated hypersensitivity reactions. A trial of eculizumab was given in light of the worsening of her neurologic condition with development of a pyramidal syndrome and deepening of the coma. Hematological and renal improvement were noted but severe neurologic involvement persisted. MRI revealed extensive bilateral zones of corticocerebral infarction and neurological damage proved to be irreversible. Diarrhea-associated hemolytic uremic syndrome is a common cause of Acute Kidney Injury associated with severe short- and long-term complications. Neurologic involvement is frequent but often reversible. Currently, no effective treatment strategies are available and a paucity of data exists concerning the efficacy of potential treatment options such as early plasma exchange, eculizumab, and high dose corticosteroids. A concerted effort is needed to early identify patients at risk for poor outcome with trials aimed at evaluating the efficacy of potential treatment options for this subgroup.

An atypical case of a 2-year-old boy with acute kidney injury: a race against time. Questions

We report the case of a 2-year-old Caucasian Belgian boy who was transferred to the pediatric intensive care unit of our hospital with persistent fever and acute kidney injury. At the time of his initial visit to the general practitioner he presented with high fever, respiratory symptoms (coughing, rhinitis), vomiting, abdominal pain and cervical lymphadenopathy; he was prescribed oral amoxicillin and ibuprofen for a suspected upper respiratory tract infection. However, 3 days later he had to be admitted to the local hospital due to persistent fever. Bacterial sepsis was suspected, and his antibiotic treatment was switched to intravenous amoxicillin–clavulanate, but without improvement. He had no history of any major illnesses or kidney disease and had no previous history of medication use. His condition worsened, and high spiking fever (temperatures ≥104 °F) persisted, but repeated cultures (blood, urine) remained negative. Elevated serum creatinine and blood urea nitrogen (BUN) levels were also noted, and he developed metabolic acidosis for which sodium bicarbonate was given. These symptoms led to a suspicion of a tubulointerstitial nephritis secondary to sepsis. He was transferred to our hospital on the fifth day of illness because of increasing serum creatinine and BUN levels with a potential need for dialysis. At presentation, the child had an ill-looking appearance and was tachycardic, with a normal blood pressure, normal oxygen saturation and a capillary refill of ≤2 s. Bilateral conjunctivitis, periorbital edema, a hyperemic pharynx, dry cracked lips with blood crusts and cervical lymphadenopathy were also noted. Several petechiae were clearly visible on his shoulders and axillary areas, but no exanthema was present. Mild respiratory distress with wheezing on lung auscultation was noted in addition to a tender abdomen with normal peristalsis.

An infant presenting with failure to thrive and hyperkalaemia owing to transient pseudohypoaldosteronism: case report

Abstract A 3-month-old boy presented with failure to thrive and a history of a prenatally detected unilateral hydroureteronephrosis which was confirmed after birth. His growth and developmental milestones had been normal during the first 2 months but in the third month his appetite was poor with reduced intake but no vomiting. At presentation, his temperature was normal, there was mild dehydration and there was weight loss (his weight had decreased by 270 g in the past month). Haemoglobin was 11.9 g/dL, total white cell count 20.2 × 109/L (7–15) [neutrophils 30% (39–75) and lymphocytes 61% (16–47)], platelets 702 × 109/L (150–450), BUN12.1 mmol/L (2.1–16.1), serum creatinine 35.4 μmol/L (15.0–37.1), sodium 126 mmol/L (135–144), potassium 6.8 mmol/L (3.6–4.8), chloride 88 mmol/L (98–106) and bicarbonate 14 mmol/L (19–24). Intravenous rehydration with sodium chloride 0.9% solution was commenced and he was transferred to the paediatric intensive care unit. A salt-wasting syndrome was suspected and a differential diagnosis included adrenal insufficiency, pseudohypoaldosteronism and congenital adrenal hyperplasia (owing to 21-hydroxylase deficiency). Urinalysis confirmed a urinary tract infection. Serum aldosterone was 3608 ng/dL (3.7–43.2), plasma renin activity > 38.9 pmol/L (<0.85), random cortisol 459 nmol/L (74–289), adrenocorticotropic hormone (ACTH) 6.01 pmol/L (1.32–6.60) and 17-hydroxyprogesterone 4.01 nmol/L (<3.2). Treatment of the urinary tract infection was followed by normalisation of serum electrolytes and other biochemical abnormalities, return of appetite and normal growth, which confirmed the diagnosis of transient pseudohypoaldosteronsim (TPHA). TPHA is discussed and insight provided to enable early recognition and adequate treatment of this rare clinical entity.

Epidemiology and outcome of acute kidney injury in children, a single center study

Background: Information on the epidemiology of Acute Kidney Injury (AKI) in children is scarce. We performed a single center retrospective cohort study to analyze the incidence of AKI, the male/female ratio, the underlying etiology, and age at presentation. We also aimed to assess outcome measured by mortality, duration of PICU stay, and development of Chronic Kidney Disease (CKD). Methods: Records were searched for children presenting with or developing AKI between 1st January 2008 and 1st January 2015. AKI was classified according to the pediatric Rifle criteria while the cause of AKI was defined as the major underlying disease. Results: Of the 28,295 children admitted, 167 episodes of AKI were identified, equaling 5.9 cases per 1000 children. Patients classified as Failure at presentation according to pRifle criteria where significantly more likely to need dialysis (27/50, 54%) compared to those presenting with Injury (12/57, 21.1%) or Risk (6/60, 10 %). Diarrhea-associated Hemolytic Uremic Syndrome (D+HUS) was the most frequent cause (20.3 %) peaking during the summer months, followed by cardiac surgery (13.7%), medication-related nephrotoxicity (13.2%), and acute Glomerulonephritis (12%). The median age of children admitted with AKI was 6.1 years (range 0.1–17) and 50.8% of cases were male. Twenty five (15%) children died while 27 (16.1%) developed CKD. Conclusions: Pediatric AKI poses a significant problem and strategies aimed at prevention, early detection, treatment, and adequate follow-up are needed. D+HUS is the most common underlying cause and effective surveillance of Enterohemorrhagic E. coli infections in association with additional measures is highly recommended.

Is Plasma exchange efficacious in Shigatoxin-associated hemolytic uremic syndrome? A narrative review of current evidence: Plasma exchange and STEC-HUS

Shiga toxin‐associated hemolytic uremic syndrome (STEC‐HUS) is associated with significant mortality and morbidity. Case fatalities are often associated with severe neurological involvement in children and advanced age in adults but specific treatment is currently unavailable. Plasma exchange (PE) could theoretically enable removal of Shiga toxins, pro‐inflammatory cytokines, and prothrombotic factors and has been used in deteriorating patients with STEC‐HUS but the efficacy remains uncertain. In order to assess efficacy of PE in STEC‐HUS, a literature review was performed. PubMed, Web of Science, Embase, and LiLACS were searched for reports describing the outcomes of patients with STEC‐HUS treated with PE and 16 reports were included. Reports ranged from case reports to cohort studies and one case–control study with the largest study population coming from the 2011 German STEC‐HUS outbreak. Outcomes were variable but seemed to point towards lower case fatality rates in the elderly and improved outcomes in children with STEC‐HUS, treated with PE early in the course. However studies were mostly of low quality with risk of observation bias and confounding. Currently no definitive answers concerning the efficacy of PE in STEC‐HUS can be given, highlighting the need for well performed randomized controlled trials.

A case of Graves' disease associated with membranoproliferative glomerulonephritis and leukocytoclastic vasculitis.

Abstract Background The association of hyperthyroidism with renal disease is very rare and the importance of timely clinical recognition cannot be overemphasized. Case presentation An 11-year-old girl presented with gastrointestinal symptoms while hypertension, edema and abdominal pain were noticed on clinical examination. Laboratory investigation revealed: hemoglobin 9.4 (11.5–15.5) g/dL, total white cell count 16 (4.5–12)×109/L, platelets 247 (150–450)×109/L, C-reactive protein (CRP) 31.8 (<5) mg/L, blood urea nitrogen (BUN) 126 (13–43) mg/dL, creatinine 0.98 (0.53–0.79) mg/dL, albumin 25 (35–52) g/dL, complement factor C3 0.7 (0.9–1.8) g/L, complement factor C4 0.1 (0.1–0.4) g/L, tri-iodothyronine 6.5 (2.5–5.2) pg/mL, free thyroxine 2.4 (1–1.7) ng/dL, thyroid stimulating hormone (TSH) <0.02 (0.5–4.3) mU/L. Urinalysis showed nephrotic range proteinuria. Renal function deteriorated necessitating hemodialysis (HD). A renal biopsy revealed an immune complex-mediated membranoproliferative glomerulonephritis (MPGN). Elevated thyroid hormones and suppressed TSH levels with elevated thyroperoxidase antibodies and thyroid stimulating immunoglobulins confirmed the diagnosis of Graves’ disease. Corticosteroids were commenced and eventually thiamazole was added with gradual improvement of renal function, cessation of HD and discharge from the hospital. Conclusions Graves’ disease complicated by MPGN is extremely rare, but can cause life-threatening complications.

A child presenting with severe hypertension and circulatory failure, a diagnostic conundrum: Questions

A 4-year-old Caucasian girl was referred to the pediatric intensive care unit (PICU) with persistent nonbillious vomiting (>20 times) during the prior 24 h and decreased responsiveness. She had no history of any major illness. The vomiting started the day before and was not accompanied by diarrhea, fever, or respiratory symptoms. Hours before admission, she had become less responsive while vomiting persisted, prompting her parents to seek professional medical help. There were no other siblings, and her father had been diagnosed with essential hypertension a couple of years previously. They had not visited countries outside of Western Europe in recent years. The child had received no recent vaccinations ormedication and was vaccinated according to national guidelines. Growth and developmental milestones were normal. At clinical examination, a lethargic and very ill-looking girl with poor peripheral circulation (cool and pale-gray extremities) was seen. She was tachycardic (220 beats/min), with a blood pressure (BP) of 150/80 mmHg and saturation of 92%. Saturation remained low even with oxygen supplementation (15 L/min). No rash, petechia, or purpura were noticed, and nuchal rigidity was absent. At auscultation, bilateral crepitations were recorded. No abnormal cardiac murmurs were noticed, and the rest of the clinical examination showed no abnormalities. She weighed 21 kg and was 110-cm tall.