Acute kidney injury associated with rhabdomyolysis in a patient with COVID-19 / Lesão renal aguda associada à rabdomiólise em um paciente com COVID-19

Abstract Rhabdomyolysis is defined as the breakdown of skeletal muscle leading to the release of muscle contents into the extracellular fluid. Patients with rhabdomyolysis can be asymptomatic or have myalgia symptoms, weakness, myoglobinuria with dark urine, significant electrolyte imbalance, and acute kidney injury. Here we describe a case on acute kidney injury associated to rhabdomyolysis in a patient with COVID-19.

Resumo A rabdomiólise é definida como a lise da musculatura esquelética levando à liberação do conteúdo muscular para o fluido extracelular. Pacientes com rabdomiólise podem ser assintomáticos ou apresentar sintomas de mialgia, fraqueza, mioglobinúria com urina escura, desequilíbrio eletrolítico significativo e lesão renal aguda. Aqui descrevemos um caso de lesão renal aguda associada à rabdomiólise em um paciente com COVID-19.

Cell-in-cell phenomenon in urinary sediment: a case report.

The internalization of apoptotic cells by non-phagocytic cells has been observed in different tissues and could be an important mechanism for the elimination of dying cells. Here, we describe a probable event of phagocytosis of apoptotic cells mediated by urothelial cells in urinary sediment. A 90-years-old male patient was admitted unconscious to the hospital, visible signs included: pale skin and dry mucous membranes, presumptively diagnosed as dehydration. Blood test revealed anaemia (haemoglobin 130 g/L) and hyperglycaemia (glucose 7.8 mmol/L), urinalysis showed a picture of urinary tract infection (leukocyturia and bacteriuria). The microscopic analysis of urinary sediment revealed the presence of urothelial cells and leukocytes internalized in urothelial cells. Anti-CD68 (membrane marker of macrophages) was tested by immunocytochemistry and a negative result was observed. Based on the findings phagocytosis of apoptotic cells mediated by urothelial cells was identified. This phenomenon can be observed in urinary sediment and should not be confused with a neoplastic process since it is a physiological event of cell elimination.

Acute kidney injury associated with rhabdomyolysis in a patient with COVID-19.

Rhabdomyolysis is defined as the breakdown of skeletal muscle leading to the release of muscle contents into the extracellular fluid. Patients with rhabdomyolysis can be asymptomatic or have myalgia symptoms, weakness, myoglobinuria with dark urine, significant electrolyte imbalance, and acute kidney injury. Here we describe a case on acute kidney injury associated to rhabdomyolysis in a patient with COVID-19.

Neutrophils phagocytosing fungal hyphae in urinary sediment / Neutrófilos fagocitando hifas no sedimento urinário

Abstract The Phagocytosis of fungal structures by neutrophils is a well-documented function of these immune cells. However, neutrophil phagocytosis of hyphal structures in the urine sediment is not usually observed during routine sample evaluation. This is a case of hyphal phagocytosis by neutrophils in the urine of a kidney allograft recipient patient.

Resumo A fagocitose de estruturas fúngicas por neutrófilos é uma função bem documentada destas células imunes. No entanto, a fagocitose de hifas por neutrófilos no sedimento urinário não é normalmente observada durante avaliação de rotina de amostras. Este é um caso de fagocitose de hifas por neutrófilos na urina de um paciente receptor de aloenxerto renal.

Neutrophils phagocytosing fungal hyphae in urinary sediment.

The Phagocytosis of fungal structures by neutrophils is a well-documented function of these immune cells. However, neutrophil phagocytosis of hyphal structures in the urine sediment is not usually observed during routine sample evaluation. This is a case of hyphal phagocytosis by neutrophils in the urine of a kidney allograft recipient patient.

Koilocytes due to HPV in the urine sediment / Coilócitos por HPV no sedimento urinário

ABSTRACT Koilocytes are the hallmark of human papillomavirus (HPV) infection and can be observed during routine cytology tests stained by Papanicolaou. However, the test is not part of the routine urinalysis report. Here we describe a case on HPV subtype 6 infection diagnosed after finding koilocytes in fresh and unstained urine sediment of a kidney allograft recipient male patient.

RESUMO Os coilócitos são um sinal característico da infecção por papilomavírus humano (HPV) e podem ser observados durante testes citológicos de rotina, corados pelo exame de Papanicolau. Contudo, o exame não faz parte do laudo de rotina da urinálise. O presente artigo descreve um caso de infecção por HPV subtipo 6, diagnosticada após a identificação de coilócitos em sedimento urinário fresco não corado de um paciente do sexo masculino receptor de aloenxerto renal.

Urine Sediment Findings and the Immune Response to Pathologies in Fungal Urinary Tract Infections Caused by Candida spp.

Fungi are pathogenic agents that can also cause disseminated infections involving the kidneys. Besides Candida, other agents like Cryptococcus spp. can cause urinary tract infection (UTI), as well as other non-yeast fungi, especially among immunocompromised patients. The detection and identification of fungi in urine samples (by microscopy and culture) plays an essential role in the diagnosis of fungal UTI. However, variable cutoff definitions and unreliable culture techniques may skew analysis of the incidence and outcome of candiduria. The sediment analysis plays a key role in the identification of fungal UTI because both yeasts and pseudohyphae are easily identified and can be used as a clinical sign of fungal UTI but should not be overinterpreted. Indeed, urine markers of the immune response (leukocytes), urine barriers of tissue protection (epithelial cells), and urine markers of kidney disease (urinary casts) can be found in urine samples. This work explores the manifestations associated with the fungal UTI from the urinalysis perspective, namely the urinary findings and clinical picture of patients with fungal UTI caused by Candida spp., aspects associated with the immune response, and the future perspectives of urinalysis in the diagnosis of this clinical condition.

Koilocytes due to HPV in the urine sediment.

Koilocytes are the hallmark of human papillomavirus (HPV) infection and can be observed during routine cytology tests stained by Papanicolaou. However, the test is not part of the routine urinalysis report. Here we describe a case on HPV subtype 6 infection diagnosed after finding koilocytes in fresh and unstained urine sediment of a kidney allograft recipient male patient.

Escherichia coli spheroplasts in a Croatian patient misclassified by two urine sediment analysers as erythrocytes: case report.

INTRODUCTION: It has already been reported that subinhibitory concentrations of ß-lactam antibiotics can cause abnormal changes of bacterial forms, such as spheroplasts. Herein we report a case of Croatian male patient with Escherichia coli spheroplasts present in urine after treatment with tazobactam, on the tenth day of hospitalization. The aim of this report is to emphasize the inability of imaging based automated urine analysers to recognize some relatively uncommon forms of bacterial presentation in urine sediment. MATERIALS AND METHODS: During routine urine analysis, unusual particles were observed in patient urine. Urine sediment was examined by two urine analysers: Atellica 1500 (Siemens, Germany) and Iris iQ200 (Beckman Coulter, USA). Additionally, urine was sent for culture testing to Microbiology department. RESULTS: Both urine analysers didn't indicate presence of bacteria in urine sediment. Unusual particles observed on the tenth day were classified as erythrocytes by both instruments. Dipstick test showed blood trace and microscopic analysis revealed bacteria in urine. Urine culture was positive for Escherichia coli. Careful examination of urine sediment has confirmed that shapes present in urine were abnormal bacterial forms called spheroplasts. CONCLUSIONS: Imaging based automated urine analysers are not able to recognize bacterial spheroplasts in urine sediment misclassifying it as erythrocytes. Microscopic examination remains the gold standard for urines with blood trace or negative blood, in which erythrocytes are reported by urine analyser in urine sediment. Failure to identify and follow up such cases may lead to inaccurate treatment decisions and puts patient safety at risk.

Strongyloides stercoralis larvae or egg: Which came first?

Strongyloides stercoralis (SS) hyperinfection is a well-documented condition. However, SS eggs in stool samples are not commonly observed during routine analysis. Here, we report a case on SS hyperinfection where both larvae and eggs were observed in the stool sample of an immunossupressed liver allograft transplanted patient.

Quantitative detection of BK virus in kidney transplant recipients: a prospective validation study.

INTRODUCTION: BK virus (BKV) infection in renal transplant patients may cause kidney allograft dysfunction and graft loss. Accurate determination of BKV viral load is critical to prevent BKV-associated nephropathy (BKVAN) but the cut-off that best predicts BKVAN remains controversial. OBJECTIVE: To evaluate the performance of a commercial and an in-house qPCR test for quantitative detection of BK virus in kidney transplant recipients. METHODS: This was a prospective study with kidney transplant recipients from two large university hospitals in Brazil. Patients were screened for BKV infection every 3 months in the first year post-transplant with a commercial and an in-house real time polymerase chain reaction (qPCR) test. BKVAN was confirmed based on histopathology. The area under the curve for plasma qPCR was determined from receiver operating characteristic analysis. RESULTS: A total of 200 patients were enrolled. Fifty-eight percent were male, 19.5% had diabetes mellitus, and 82% had the kidney transplanted from a deceased donor. BKV viremia was detected in 32.5% and BKVAN was diagnosed in 8 patients (4%). BKVAN was associated with viremia of 4.1 log copies/mL, using a commercial kit. The cut-off for the in-house assay was 6.1 log copies/mL. The linearity between the commercial kit and the in-house assay was R2=0.83. CONCLUSION: Our study shows that marked variability occurs in BKV viral load when different qPCR methodologies are used. The in-house qPCR assay proved clinically useful, a cheaper option in comparison to commercial qPCR kits. There is an urgent need to make BKV standards available to the international community.

Blue-green discoloration of urine and false nephrotic range proteinuria at dipstick urinalysis.

A 32 year-old woman presented to the emergency department with symptoms of urinary tract infection. Over the past 2 days, she reported the use of a medication whose active compounds were methenamine (120 mg) + methylthioninium chloride (20 mg). A collected urine sample had a strong blue-green discoloration. Uroculture was negative and dipstick urinalysis revealed the following results: SG 1.015, pH  7, Albumin 3+, Bilirubin 2+ and Haemoglobin 2+. Urine microscopic analysis revealed 5-6 squamous epithelial cells/high power field (HPF), 5-6 leukocytes/HPF and 7-8 erythrocytes/HPF. No bacteria, cellular casts, or renal tubular epithelial cells were present in the urine sample. The most remarkable feature of the urine sediment was that some cells (squamous epithelial cells, macrophages, leukocytes and erythrocytes) were strongly stained in blue. The albuminuria measured by dipstick shows 3+ (300 mg/dL), but in turbidimetric method the urine protein concentration was 18 mg/dL, showing an important interference of methylene blue on the dipstick albumin area.

Quantitative detection of BK virus in kidney transplant recipients: a prospective validation study / Detecção quantitativa de vírus BK em receptores de transplante renal: um estudo prospectivo de validação

Abstract Introduction: BK virus (BKV) infection in renal transplant patients may cause kidney allograft dysfunction and graft loss. Accurate determination of BKV viral load is critical to prevent BKV-associated nephropathy (BKVAN) but the cut-off that best predicts BKVAN remains controversial. Objective: To evaluate the performance of a commercial and an in-house qPCR test for quantitative detection of BK virus in kidney transplant recipients. Methods: This was a prospective study with kidney transplant recipients from two large university hospitals in Brazil. Patients were screened for BKV infection every 3 months in the first year post-transplant with a commercial and an in-house real time polymerase chain reaction (qPCR) test. BKVAN was confirmed based on histopathology. The area under the curve for plasma qPCR was determined from receiver operating characteristic analysis. Results: A total of 200 patients were enrolled. Fifty-eight percent were male, 19.5% had diabetes mellitus, and 82% had the kidney transplanted from a deceased donor. BKV viremia was detected in 32.5% and BKVAN was diagnosed in 8 patients (4%). BKVAN was associated with viremia of 4.1 log copies/mL, using a commercial kit. The cut-off for the in-house assay was 6.1 log copies/mL. The linearity between the commercial kit and the in-house assay was R2=0.83. Conclusion: Our study shows that marked variability occurs in BKV viral load when different qPCR methodologies are used. The in-house qPCR assay proved clinically useful, a cheaper option in comparison to commercial qPCR kits. There is an urgent need to make BKV standards available to the international community.

Resumo Introdução: A infecção pelo vírus BK (BKV) em pacientes de transplante renal pode levar a disfunção do aloenxerto renal e perda do enxerto. A determinação precisa da carga viral do BKV é fundamental para prevenir a nefropatia associada ao BKV (BKVAN), mas o ponto de corte de melhor valor preditivo para BKVAN ainda é foco de debates. Objetivo: Avaliar o desempenho de um teste de qPCR comercial e outro desenvolvido internamente para detecção quantitativa de vírus BK em receptores de transplante renal. Métodos: O presente estudo prospectivo incluiu receptores de transplante renal de dois grandes hospitais universitários no Brasil. Os pacientes foram testados para infecção por BKV a cada três meses no primeiro ano pós-transplante com um teste comercial de reação em cadeia de polimerase quantitativa em tempo real (qPCR) e outro desenvolvido internamente. A presença de BKVAN foi confirmada com base na histopatologia. A área sob a curva para o qPCR plasmático foi determinada a partir da análise da característica de operação do receptor. Resultados: Um total de 200 pacientes foram incluídos. Cinquenta e oito por cento eram do sexo masculino, 19,5% tinham diabetes mellitus e 82% tiveram seus rins transplantados de doadores falecidos. Viremia de BKV foi detectada em 32,5% dos pacientes e oito (4%) foram diagnosticados com BKVAN. BKVAN foi associada a viremia de 4,1 log cópias/mL usando o kit comercial. O corte para o ensaio interno foi de 6,1 log cópias/mL. A linearidade entre o kit comercial e o ensaio interno foi R2 = 0,83. Conclusão: Nosso estudo demonstrou uma acentuada variabilidade na carga viral de BKV quando diferentes metodologias de qPCR foram utilizadas. O ensaio interno de qPCR mostrou-se clinicamente útil, além de ser uma opção menos onerosa em relação aos kits comerciais de qPCR. Há uma necessidade urgente de se definir padrões de BKV para a comunidade internacional.

Klebsiella pneumoniae ESBL forming spheroplasts in the fresh and unstained urine sediment. / Klebsiella pneumoniae ESBL formando esferoplastos em sedimento urinário a fresco sem coloração.

A 60 year-old man was submitted to kidney transplantation in 2013 due to chronic renal insufficiency caused by hypertension. He had recurrent episodes of urinary tract infection and came to the hospital due to a 4 day-long fever, abdominal pain, burning urination and nausea. Routine urinalysis revealed a picture of infection (> 50 leucocytes/high power field associated to massive bacteriuria). The urine sediment revealed elongated like elements with an enlarged part in the middle of the structure body.

Klebsiella pneumoniae ESBL formando esferoplastos em sedimento urinário a fresco sem coloração / Klebsiella pneumoniae ESBL forming spheroplasts in the fresh and unstained urine sediment

Resumo Um homem de 60 anos de idade foi submetido a transplante renal em 2013 devido à insuficiência renal crônica causada por hipertensão. Ele teve episódios recorrentes de infecção do trato urinário e veio para o hospital devido a 4 dias de febre, dor abdominal, ardência para urinar e náusea. Análise do sedimento urinário revelou um quadro de infecção (> 50 leucócitos/campo de grande aumento associado à bacteriúria maciça). O sedimento urinário revelou elementos alongados com um alargamento na parte central do corpo da estrutura.

Abstract A 60 year-old man was submitted to kidney transplantation in 2013 due to chronic renal insufficiency caused by hypertension. He had recurrent episodes of urinary tract infection and came to the hospital due to a 4 day-long fever, abdominal pain, burning urination and nausea. Routine urinalysis revealed a picture of infection (> 50 leucocytes/high power field associated to massive bacteriuria). The urine sediment revealed elongated like elements with an enlarged part in the middle of the structure body.

Lipoprotein glomerulopathy: a case report of a rare disease in a Brazilian child.

Lipoprotein glomerulopathy (LPG) is a rare autosomal recessive glomerulopathy associated with the deposition of lipoprotein thrombi in the capillary lumina due to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase in serum apoliprotein E (apoE) are characteristic clinical data. The compromised patients can present nephrotic syndrome, hematuria, and progressive renal failure. Herein, the authors present the first described case of LPG in a Brazilian male patient, 11 years, who presented with a steroid-resistant nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly enlarged glomerulus, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and veins showed normal histologic aspect. Genotypic study for the apoE gene showed the presence of the alleles E3 and E4. The diagnosis of LPG was then performed. The patient received lipid-lowering treatment. After 2 years of follow-up, renal function is gradually decreasing, with persisting heavy proteinuria, despite a marked decrease in serum cholesterol and triglycerides levels.

Lipoprotein glomerulopathy: a case report of a rare disease in a brazilian child / Glomerulopatia por lipoproteinas: relato de caso de uma doenca rara em crianca brasileira

Lipoprotein glomerulopathy (LPG) is a rare autosomal recessive glomerulopathy associated with the deposition of lipoprotein thrombi in the capillary lumina due to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase in serum apoliprotein E (apoE) are characteristic clinical data. The compromised patients can present nephrotic syndrome, hematuria, and progressive renal failure. Herein, the authors present the first described case of LPG in a Brazilian male patient, 11 years, who presented with a steroid-resistant nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly enlarged glomerulus, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and veins showed normal histologic aspect. Genotypic study for the apoE gene showed the presence of the alleles E3 and E4. The diagnosis of LPG was then performed. The patient received lipid-lowering treatment. After 2 years of follow-up, renal function is gradually decreasing, with persisting heavy proteinuria, despite a marked decrease in serum cholesterol and triglycerides levels.

A Glomerulopatia por Lipoproteínas (GLP) é uma glomerulopatia autossômica recessiva rara associada à deposição de trombos de lipoproteína nos lúmens capilares devido a mutações do gene de ApoE. Perfil anormal das lipoproteínas do plasma e aumento acentuado no soro de apolipoproteína E (apoE) são dados clínicos característicos. Os pacientes acometidos podem apresentar síndrome nefrótica, hematúria e insuficiência renal progressiva. Aqui, os autores apresentam o primeiro caso descrito de GLP em um paciente brasileiro do sexo masculino, 11 anos, que se apresentou com uma síndrome nefrótica corticoide resistente. A função renal era normal. A biópsia renal mostrou glomérulos marcadamente aumentados, com capilares dilatados e lúmens ocupados por trombos de lipoproteínas fracamente eosinofílicos. Interstício, túbulos, artérias e veias mostraram aspecto histológico normal. O estudo genotípico para o gene apoE mostrou a presença dos alelos E3 e E4. O diagnóstico de GLP foi então realizado. A paciente recebeu tratamento hipolipemiante. Depois de 2 anos de seguimento, a função renal está diminuindo gradualmente, com a persistência de marcada proteinúria, apesar de uma diminuição acentuada dos níveis séricos de colesterol e triglicerídios.