Risk Factors for Acute Kidney Injury and Death in Patients Infected With the Yellow Fever Virus During the 2018 Outbreak in São Paulo, Brazil.

Introduction: There have been few studies investigating acute kidney injury (AKI) in patients with yellow fever (YF). The objective of this study was to identify the risk factors for AKI and death in such patients. Methods: We evaluated 95 consecutive critically ill adult patients with the sylvatic form of YF, as confirmed by reverse-transcriptase polymerase chain reaction, in Brazil. The outcome measures were AKI (as defined by Kidney Disease: Improving Global Outcomes [KDIGO] criteria) and in-hospital death. Results: Of the 95 patients, 73 (76.8%) had AKI and 59 (62.1%) died from it. A total of 70 patients (73.7%) required dialysis because of AKI. After adjusting for age, sex, and the Simplified Acute Physiology Score 3 (SAPS 3), we found that elevated fractional excretion of sodium and requiring dialysis were independent risk factors for in-hospital mortality and that proteinuria correlated with AKI-associated mortality. Conclusion: Our findings indicate that, in patients with sylvatic YF, AKI is common and is associated with significant mortality. The data presented here could prove useful for improving understanding of the pathogenesis of AKI in YF and informing decisions regarding the care of the affected patients.

Continuous renal replacement therapy in COVID-19-associated AKI: adding heparin to citrate to extend filter life-a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. METHODS: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV - AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. RESULTS: Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV - AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25-0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV - AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18-0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99-4.68). CONCLUSIONS: In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Cov-hep study: heparin in standard anticoagulation based on citrate for continuous veno-venous hemodialysis in patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. TRIAL DESIGN: Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. PARTICIPANTS: Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. DATA COLLECTION: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient's age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts (<100.000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. EXCLUSION CRITERIA: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. INTERVENTION AND COMPARATOR: Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. MAIN OUTCOMES: The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. RANDOMIZATION: RedCap→ randomization - 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. BLINDING (MASKING): No blinding - Open label format NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Total number of patients 90 (45 per group) TRIAL STATUS: Trial version 2.0 - ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 TRIAL REGISTRATION: Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Atypical presentation of acute post-infectious glomerulonephritis in patients with sickle cell disease: report of two cases.

BACKGROUND: Sickle cell disease (SCD) is a highly prevalent genetic disease worldwide. In the natural evolution of SCD, glomerular lesions can develop, presenting histopathological patterns of segmental or focal membranoproliferative glomerulosclerosis, with or without thrombotic microangiopathy. We report two cases of acute post-infectious glomerulonephritis (APIGN), with atypical presentations, in patients with SCD. CASE PRESENTATION: Case 1: An 18-year-old female with SCD presented with a 21-day history of progressive oedema, accompanied by dyspnoea, productive cough, fever, and chest pain. Blood tests showed the following: haemoglobin 6.1 g/dl; leucocytes 18,820 cells/mm3; and creatinine 0.49 mg/dl. A urine sample evidenced leucocyturia and haematuria. The 24-h proteinuria was 8.99 g, serum albumin level was 1.2 g/dl, low serum C3 levels and high levels of anti-streptolysin O. Renal biopsy was consistent with APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving to reversal of the renal alterations. Case 2: A 12-year-old male with SCD presented with a 20-day history of a non-productive cough and progressive oedema, together with hypertension. The serum creatinine concentration was 0.48 mg/dl. A urine sample evidenced leukocyturia and haematuria. The 24-h proteinuria was 12.5 g, and the serum albumin level was 2.6 g/dl. The levels of C3 and C4 were normal. Renal biopsy revealed APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving reversal of the renal alterations. CONCLUSIONS: The presentation of the two cases reported here are not typical of SCD-related kidney injury. Analysis of the renal biopsy specimens elucidated the diagnosis, affecting the prognosis, because that of APIGN is highly favourable, unlike that of nephrotic syndrome associated with SCD glomerulopathy.

Chronic Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis (SIAD) in an Adult Woman with Corpus Callosum Agenesis (CCA).

BACKGROUND Corpus callosum agenesis (CCA) is one of the most common congenital brain abnormalities, and is associated with neurodevelopmental and neuropsychiatric disorders. In CCA, defects in osmoregulation have been reported. This report presents a rare case of chronic hyponatremia associated with the syndrome of inappropriate antidiuresis (SIAD) in a woman with CCA. CASE REPORT A 41-year-old woman presented to the renal unit with symptomatic hyponatremia. In her past medical history, she had a four-year history of systemic arterial hypertension and Sjögren's syndrome, and a three-year history of systemic lupus erythematosus (SLE), which was treated with cyclophosphamide. She had CCA but with irregular neurological follow-up. During the previous eight years, her plasma sodium levels ranged from between 118-134 mEq/L. On this hospital admission, she had plasma hypo-osmolality, measured in milli-osmoles per kilogram of H2O (mOsm/kg H2O), of 251 mOsm/Kg H2O, and a urinary hyper-osmolality of 545 mOsm/Kg H2O, and increased level of plasma antidiuretic hormone (ADH) (1.8 pg/ml). Bone densitometry was consistent with osteoporosis. The patient remained asymptomatic during her hospital stay. Chronic hyponatremia associated with the SIAD was diagnosed. Water restriction and increased protein intake resulted in a partial improvement in the serum sodium level (128-134 mEq/L). The patient was discharged from the hospital with outpatient follow-up. CONCLUSIONS A rare case of chronic hyponatremia due to the SIAD associated with CCA is reported that demonstrates the importance of correct diagnosis, management, and clinical follow-up of the SIAD, including bone densitometry.

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

PURPOSE: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fiber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. METHODS: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS) served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantified by means of quantitative image analysis. RESULTS: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may influence the functional outcome. The event should be considered during the neurosurgery strategies.

OBJETIVO: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS), um tipo de glia periférica, também reagem com a lesão do nervo, podendo interferir com o reparo e cicatrização, crescimento de fibras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ciático poder alterar o padrão da ativação astrocitária nos cornos anterior e posterior da medula espinal do rato. MÉTODOS: Suspensão de CS cultivadas ou extrato homogeneizado de medula espinal lesada de rato foram inoculados num reservatório feito a partir de dois esmagamentos aplicados no nervo ciático do rato distantes 0,5mm entre si. Injeção local de salina tamponada serviu como controle. Os ratos foram mortos uma semana após e os astrócitos da medula espinal marcados por método imunohistoquímico e quantificados por análise de imagem. RESULTADOS: No corno anterior da medula, ipsilateral à lesão, ativação astrocitária leve foi vista após as injeções de tampão ou CS, entretanto, ativação celular intensa foi observada nesta região com a inoculação neural do extrato homogeneizado de tecido medular lesado. Adicionalmente, as inoculações de CS e de extrato homogeneizado de tecido medular promoveram forte reação astrocitária no corno dorsal da medula espinal, bilateralmente. CONCLUSÕES: Os astrócitos da medula espinal reagem em função do processo de reparo do nervo lesado, o que pode influenciar o resultado funcional esperado, algo que deve ser considerado durante o planejamento da estratégia neurocirúrgica.

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair.

PURPOSE: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fiber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. METHODS: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS) served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantified by means of quantitative image analysis. RESULTS: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. CONCLUSION: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may influence the functional outcome. The event should be considered during the neurosurgery strategies.