Terapia de reemplazo renal continua. Presentación de un caso / Continuous renal replacement therapy. Case report

RESUMEN La insuficiencia renal aguda es definida como la pérdida de función del riñón ocasionada por diversas causas, entre ellas infección e ingesta de fármacos. Esta entidad tiene alta morbilidad y mortalidad en las unidades de cuidados críticos. El tratamiento de la misma va desde la propia protección renal hasta la sustitución artificial de las funciones del riñón lesionado. En la actualidad la terapia de reemplazo renal continua se ha utilizado como soporte renal, y ofrece mayor estabilidad clínica a los pacientes más inestables. En esta revisión se comentan conceptos, indicaciones y los más recientes estudios que validan el uso de esta terapéutica, así como el método de programación que se utilizó en un paciente con diagnóstico de una leptospirosis icterohemorrágica (síndrome de Weil), que estuvo en shock séptico con disfunción multiorgánica, donde se empleó esta terapia con resultados satisfactorios (AU).

ABSTRACT Acute kidney failure is defined as the loss of kidney function caused by various causes, including infection and drug intake. This entity has high morbidity and mortality in critical care units. Treatment ranges from renal protection to artificial replacement of the functions of the injured kidney. Currently, continuous renal replacement therapy has been used as renal support, and offers greater clinical stability to the most unstable patients. In this review, authors discuss concepts, indications and the most recent studies that validate the use of this therapeutic, as well as the programming method that was used in a patient with diagnosis of icteric-hemorrhagic leptospirosis (Weil syndrome), who was in septic shock with multiorgan dysfunction, where this therapy was used with satisfactory results (AU).

Detecção de Espécies Reativas de Oxigênio no sangue periférico de pacientes com leptospirose grave / Detection of Reactive Oxygen Species in peripheral blood patients with severe leptospirosis

Leptospirose é uma zoonose que pode levar a graves complicações, como a síndrome de Weil e a síndrome pulmonar hemorrágica, porém os mecanismos patogênicos que levam ao desenvolvimento das formas graves da doença ainda são desconhecidos. Após a penetração no indivíduo, as leptospiras invadem a corrente sanguínea e se disseminam para os órgãos. Dessa forma, a leptospirose apresenta características semelhantes as da sepse, doença que tem o estresse oxidativo como um dos principais responsáveis pelo seu agravamento. Entretanto, pouco se sabe sobre o envolvimento do estresse oxidativo na leptospirose. O presente estudo teve como objetivo avaliar se a produção de espécies reativas de oxigênio (ROS) e os níveis do antioxidante glutationa (GSH) estão relacionados com as manifestações clínicas mais graves de pacientes hospitalizados com leptospirose. A produção de ROS e os níveis de GSH foram avaliados nas amostras de sangue de doze pacientes e nove indivíduos saudáveis através dos ensaios de quimioluminescência e de absorbância, respectivamente. Nós observamos que os níveis de ROS estavam aumentados (p=0.0012) e os de GSH diminuídos (p=0.0002) nos pacientes quando comparados com os indivíduos saudáveis. Dentre os pacientes, a diminuição de GSH estava correlacionada com a trombocitopenia (r=0.63) e com elevados níveis de creatinina (r= -0.64), enquanto que a produção de ROS estava fortemente correlacionada com os níveis elevados de potássio sérico (r=0.8). A compreensão da importância biológica de ROS e do GSH na leptospirose faz-se necessária, pois uma investigação mais detalhada pode levar ao desenvolvimento de terapias adjuvantes focadas no estresse oxidativo.

Leptospirosis is a zoonotic disease that causes severe manifestations such as Weil’s disease and pulmonary hemorrhage syndrome, however the underlying mechanisms that lead to the development of severe forms are not clear. Leptospires penetrate through skin, reach the bloodstream and disseminate to the organs. Thus, leptospirosis and sepsis have similar characteristics. Although there is vast literature demonstrating that oxidative stress play an important role in the severity of sepsis, none is known about it in leptospirosis. The aim of this study was to evaluate whether reactive oxygen species (ROS) production and antioxidant reduced glutathione (GSH) levels are related to complications in patients hospitalized with leptospirosis. ROS production and GSH levels were measured in blood samples of twelve patients and nine healthy controls using chemiluminescence and absorbance assays. We found that ROS production was higher (p=0.0012) and GSH levels were lower (p=0.0002) in leptospirosis patients compared with healthy individuals. Among patients, GSH depletion was correlated with thrombocytopenia (r=0.63) and elevated serum creatinine (r= -0.64), while a strong positive correlation was observed between ROS production and elevated serum potassium (r=0.8). Additional investigation of the biological significance of ROS production and GSH levels is warranted as they may guide the development of novel adjuvant therapies for leptospirosis targeting oxidative stress.

Increased Immunogenicity to LipL32 of Leptospira interrogans when Expressed as a Fusion Protein with the Cholera Toxin B Subunit

Leptospirosis is one of the most widespread zoonosis in the world. The development of a recombinant leptospira vaccine remains a challenge. In this study, we cloned the Leptospira interrogans open reading frame (ORF) coding the external membrane protein LipL32, an immunodominant antigen found in all pathogenic leptospira, downstream of the highly immunogenic cholera toxin B subunit (CTB) ORF. Expression and assembly of the CTB-LipL32 fusion protein into oligomeric structures of pentameric size were observed in soluble fractions by Western blot analysis. The CTB-LipL32 protein demonstrated strong affinity for monosialotetrahexosylgaglioside (GM1-ganglioside) in an enzyme-linked immunosorbent assay (ELISA), suggesting that the antigenic sites for binding and proper folding of the pentameric CTB structure were conserved. Furthermore, antisera against LipL32 also recognized the CTB-LipL32 fusion protein, suggesting that LipL32 also conserved its antigenic sites, a fact confirmed by an ELISA assay showing soluble CTB-LipL32 recognition by sera from convalescent patients. In addition, soluble CTB-LipL32 generated higher specific titers in mice immunized without external adjuvant than co-administration of CTB with LipL32. The data presented here provide support for CTB-LipL32 as a promising antigen for use in the control and study of leptospirosis.

Renal involvement in leptospirosis: new insights into pathophysiology and treatment: [review]

Acute renal failure (ARF) is one of the most common complications of leptospirosis although the causal mechanisms are still unclear. Diverse mechanisms are implicated in leptospiral nephropathy and new data supports the role of peculiar ion transport defects. Besides antibiotic therapy, ARF management in leptospirosis requires dialytic therapy which is most efficient when started early. Dialysis is the standard supportive therapy even though recent evidence suggests clinical benefit from alternative treatments such as plasmapheresis and hemofiltration. Renal recovery is achieved soon after clinical improvement. The comprehension of the primary mechanisms of renal dysfunction will be helpful in the development of additional therapeutic tools for improving supportive therapy for leptospiral nephropathy. This review discusses new insights into mechanisms implicated in leptospiral ARF and recent advances in treatment.

Pneumonia por leptospirose / Leptospiral pneumonia

A leptospirose é uma doença infecciosa caracterizada pelo envolvimento de múltiplos sistemas. O acometimento pulmonar é comum, geralmente leve e freqüentemente negligenciado. Quando os sintomas respiratórios são a principal manifestação da doença, existe grande possibilidade de confusão diagnóstica. Os autores apresentam um caso de pneumonia grave por leptospirose, com o objetivo de chamar a atenção para esta possibilidade etiológica no diagnóstico diferencial das pneumonias comunitárias, especialmente quando há um perfil epidemiológico suspeito

Evaluation of penicillin therapy in patients with leptospirosis and acute renal failure

The effectiveness of specific antibiotic treatment in severe leptospirosis is still under debate. As part of a prospective study designed to evaluate renal function recovery after leptospirosis acute renal failure (ARF) (ARF was defined as Pcr > or = 1.5 mg/dL), the clinical evolutions of 16 treated patients (T) were compared to those of 18 untreated patients (nT). Treatment or non-treatment was the option of each patient's attending infectologist. The penicillin treatment was always with 6 million IU/day for 8 days. No difference was found between the two groups in terms of age, gender, number of days from onset of symptoms to hospital admission, or results of laboratory tests performed upon admission and during hospitalization, but proteinuria was higher in the treated group. There were no significant difference in the other parameters employed to evaluate patients' clinical evolution as: length of hospital stay, days of fever, days to normalization of renal function, days to total bilirubins normalized or reached 1/3 of maximum value and days to normalization of platelet counts. Dialytic treatment indication and mortality were similar between group T and nT. In conclusion, penicillin therapy did not provide better clinical outcome in patients with leptospirosis and ARF

Leptospirosis hemorrágica pulmonar / Hemorrhagic pulmonary leptospirosis

La leptospirosis es una enfermedad infecciosa característica de países orientales húmedos. La incidencia en países occidentales es relativamente infrecuente. La enfermedad suele manifestarse de dos formas clínicas principales: la hepato-renal y la pulmonar, generalmente con cierto grado de solapamiento entre ambas.Presentamos un paciente con una presentación severa de leptospirosis hemorrágica pulmonar que en el curso de la enfermedad, presentó un cuadro de embolismo multisistémico (bazo, riñón y sistema nervioso central -SNC-). (AU)

Leptospirosis: revisión de 5 casos / Leptospirosis: review of five cases

Se han revisado retrospectivamente 5 casos de leptospirosis entre 1978 y 1996. Los 5 casos eran varones con una edad media de 34,2 años. Los factores epidemiológicos se encontraron en los 5 pacientes. Todos los pacientes tenían la triada clínica clásica de fiebre, mialgias e ictericia. Observamos afectación hepatorrenal en 4 de los 5 pacientes (80%), fenómenos hemorrágicos en 4 pacientes (80%), en 4 pacientes observamos alteraciones del ritmo cardíaco (80%); no se diagnosticó afectación del sistema nervioso central en ninguno de los casos. Un paciente presentó shock séptico con insuficiencia respiratoria a aguda y síndrome de distrés respiratorio del adulto. Los serogrupos de Leptospira que se identificaron fueron icterohemorrágica en 3 casos y en los 2 restantes no se pudo definir. La recuperación con tratamiento antibiótico fue completa en todos los casos. En este artículo se discuten los aspectos epidemiológicos, clínicos, analíticos y terapéuticos (AU)

Aspectos clínicos, serológicos y evolutivos en leptospirosis / Clinical, serologics and evolutives aspects in leptospirosis

Se estudió 32 pacientes en Leptospirosis en el Hospital Nacional Guillermo Almenara Irigoyen - IPSS, entre 1955 y 1990. Las características clínicas correspondieron a enfermedad infecciosa sistémica con especial compromiso renal, hepático y hemorrágico. Las reacciones serológicas positivas fueron más frecuentes para los serovares copenhageni, monymusk, canicola y el serogrupo icterohaemorrhagiae. El seguimiento de los pacientes mostró: en el 81.25 por ciento buena respuesta al tratamiento; el 18.75 por ciento falleció.

Urinary diagnostic indices in the management of leptospirosis: selection of patients for dialysis therapy

Cases of leptospirosis admitted to the Queen Elizabeth Hospital (QEH), Barbados, were assessed for the presence of "pre-renal azotaemia" (NON-ARF) as opposed to "acute renal failure" (ARF). Distiction between the two diagnoses was made on the basis of clinical course. Peritoneal dialysis was inappropriately utilised in 26 percent of patients receiving such therapy. This study evaluates diagnostic tests for pre-renal azotaemia, and acute renal failure in leptospirosis, and indicates guidelines for the management of azotaemia in such patients. U/P urea and osmolar ratios show high sensitivity and specificity in diagnosing pre-renal azotaemia. While "early" dialysis is essential for patients with acute leptospiral renal failure, in those with plasma creatinines less than 600 umol/litre on entry and indices indicating NON-ARF, decisions regarding dialysis can safely be delayed for 48-72 hours while the effect of rehydration is assessed (AU)

Urinary diagnostic indices in the management of leptospirosis: selection of patients for dialysis therapy

Cases of leptospirosis admitted to the Queen Elizabeth Hospital (QEH), Barbado, were assessed for the presence of "pre-renal azotaemia" (NON-ARF) as opposed to "acute renal failure" (ARF). Distinction between the two diagnoses was made on the basis of clinical course. Peritoneal dialysis was inappropriately utilised in 26% of patients receiving such therapy. This study evaluates diagnóstic tests for pre-renal azotaemia, and acute renal failure in leptospsirosis, and indicates guidelines for the management of azotaemia in such patientes. U/P urea and osmolar ratios show high sensitivity in diagnosing pre-renal azotaemia. While "early" dialysis is essential for patients with acute leptospiral renal failure, in those with plasma creatinines less than 600 micronmol/litre on entry and indices indicating NON-ARF, decisions regarding dialysis con safely be delayed for 48-72 hours while the effect of rehydration is assessed

Renal failure indices in the management of leptospirosis selection of patients for dialysis therapy - abstract

Renal failure indices were analysed for applicability in the maangement of patients with azotaemia due to leptospirosis. Urine/plasma (U/P) urea, U/P creatinine and U/P osmolar ratios, urinary sodium concentration, renal failure index and fractional excretion of sodium were measured on days 1, 2 and 3 after admission. Only cases with plasma creatinine > 200 micromol/l and those treated by dialysis were analysed. Patients were designated "pre-renal azotaemia" (NON-ARF) or"acute renal failure" (ARF) on the basis of the clinical course and by comparison of renal failure indices with values conventionally used to distinguish pre-renal from intrinsic renal failure. U/P urea ratio > 8 and U/P creatinine ratio 20 discriminated well between patients with NON-ARF and those with ARF. Of 12 patients satisfying both these criteria for pre-renal azotaemia, 7 also had U/P osmolar ratios > 1.2. As might be predicted by the "indices"' all responded to rehydration with a decline in plasma creatinine concentration. Among 14 patients with ARF, ten out of 11 had a U/P urea ratio <7 while only 7 of 11 had a U/P creatinine < 20. However, all nine patients assessed had a U/P osmolar ratio <1.2. The renal failure index and the fractional excretion of sodium were both >1 in 8 out of 10 patients. A U/P urea ratio < 7 and U/P osmolar ratio <1.2 were therefore the most consistent discriminators in the presence of acute renal failure. Our results suggest that renal failure indices can predict resolution of azotaemia with rehydration, identify patients with acute intrinsic renal failure and prevent inappropriate dialysis in those whose azotaemia is due to dehydration (AU)

Pulsoterapia com metilprednisolona e evoluçäo na nefropatia da leptospirose humana / Pulse therapy with met by e predinosolone and evaluation of the pathology of renal disease in human leptospirosis

Com o objetivo de avaliar a eficácia da pulsoterapia com metilpredinisolona em pacientes com insuficiência renal aguda causada por leptospirose, foram estudados 20 pacientes divididos em dois gurpos de 10 (Grupo I, Experimental; Grupo II, Controle). Foram incluídos no estudo apenas pacientes com diagnóstico clínico e laboratorial de leptospirose e com insuficiência renal aguda comprovada através de dosagens de uréia e creatinina. Os dois grupos foram comparáveis em relaçäo à idade, tempo de doença ao internamento, forma de apresentaçäo clínica e níveis de uréia, creatinina, transminases, bilirrubinas e demais dosagens realizadas ao internamento. Os 20 pacientes tiveram o diagnostico confirmado através de reaçöes de soroaglutinaçäo, todos tinham insuficiência renal com diurese. A evoluçäo se mostrou semelhante nos dois grupos. Noventa por cento dos pacientes evoluiu para a cura em tempo médio semelhante nos dois grupos, independente do uso da droga. Houve um óbito em cada grupo e a incidência de complicaçöes foi similar. Näo houve efeitos colaterais danosos que pudessem se atribuídos à droga. A única alteraçäo estatisticamente significante foi o achado de fosfatase alcalina aumentada no grupo tratado. A pulsoterapia com metilprednisolona näo pareceu influenciar de modo significante a evoluçäo dos 10 pacientes tratados. Estes resultados näo excluem a possibilidade de a droga ser eficaz em pacientes oligúricos. Isto poderá ser objeto de investigaçäo futura