Clinical characterization of Dobrava hantavirus infections in Germany

There is increasing evidence that Dobrava (DOBV) but not Hantaan (HTNV) hantavirus is a hemorrhagic fever with renal syndrome (HFRS) causing agent in Central Europe. However, only single clinical cases of HFRS due to acute DOBV infection have been described so far. We report on three male patients from a non-endemic hantavirus focus in Northern Germany who suffered from mild to moderate HFRS strongly resembling nephropathia epidemica. Serotyping by detection of hantavirus species-specific neutralizing antibodies revealed acute infections by the HTNV-related hantavirus DOBV in all three cases. Since DOBV infections in the Balkans frequently present as severe HFRS, our cases suggest that Central-European DOBV infections have a different, less severe clinical outcome. These differences in DOBV virulence towards humans might be due to the existence of different genetic lineages of DOBV.     

Mesangiocapillary glomerulonephritis caused by Puumala hantavirus infection.

Nephropathia epidemica induced by Puumala hantavirus typically causes acute reversible renal function impairment. A typical renal biopsy finding is acute tubulointerstitial nephritis with slight glomerular mesangial changes. We describe here 5 patients who developed the nephrotic syndrome during the convalescent phase of an otherwise typical acute febrile nephropathia epidemica. Renal biopsy of all patients disclosed type I mesangiocapillary glomerulonephritis (MCGN). A clinical remission of the nephrotic syndrome was observed in 4 patients during the follow-up period, and 1 entered into chronic renal failure. Three patients had microscopic hematuria and proteinuria and 2 elevated blood pressure at the latest assessment visit. No patient had clinical or laboratory findings compatible with chronic bacterial, parasitic or viral infections (hepatitis B or C), malignancies, or other disorders known to be associated with MCGN. In conclusion, Puumala hantavirus has to be added to the list of potential agents associated with type I MCGN. Further studies are necessary to establish the incidence of MCGN caused by various hantavirus infections.     

Chronic renal failure after Puumala virus infection

Chronic renal failure has never been described after Puumala hantavirus infection, which usually causes acute renal failure with spontaneous full recovery. We report a 15-year-old boy who presented with Puumala hantavirus infection and initial severe acute renal failure. His renal function gradually improved, but more than 2 years after the acute episode it was still moderately impaired, with a creatinine clearance of about 60 ml/min per 1.73 m² Received: 25 June1998 / Revised: 19 February 1999 / Accepted: 19 February 1999     

Haemorrhagic fever with renal syndrome: an emerging disease

Summary: Worldwide about 150 000 people are hospitalized with haemorrhagic fever with renal syndrome (HRFS; 3–15% fatality) each year. the aetiologic agents of hantavirus infections are Hantaan, Belgrade, Seoul, Puumala and Sin Nombre virus of the genus Hantavirus, family Bunyaviridae. A severe form of HFRS caused by Hantaan and Belgrade virus occurs in Asian and Balcan countries. A new clinical form with 70% fatality, Hantavirus pulmonary syndrome, caused by novel hantaviruses occurs in Americas. A moderate form caused by Seoul virus occurs in Asia and in Europe and a mild form caused by Puumala virus occurs in Europe. Recently, Puumala virus infections in man and field mice were found in Siberia, in Korea and in Japan. the reservoirs of hantaviruses are rodents and other small mammals including bats and birds and mode of transmission is aerosol. Serologic and PCR studies of 72 hantaviruses isolated from patients and from animals throughout the world indicated that there are eight or more serotypes. Many hantavirus patients have been misdiagnosed as influenza, interstitial nephritis, leptospirosis, scrub typhus, dengue, hepatitis and pneumonia. Recently, we developed simple serologic differential diagnostic kits (HDPA test) for Hantaan, Seoul and Puumala virus infections. an inactivated Hantaan virus vaccine against HFRS is available. In the 1990s, it is highly possible to identify new hantavirus illness in parts of the world where the disease is not known because of the availability of diagnostic tools.     

Hantavirus nephropathy

Pathogenic rodent-borne hantaviruses cause in humans generalized infections that involve the peripheral vascular bed and severely affect their permeability. We describe a 30-yr-old male patient with clinical symptoms characterizing five conventional phases of hemorrhagic fever with renal syndrome after an uncommonly severe hantavirus infection with the Puumala strain. Renal biopsy in this situation typically demonstrates acute hemorrhagic interstitial nephritis, particularly pronounced in the outer medulla. Hantaviruses are not cytopathic for most cells, and their interactions with endothelial cells that activate immune mechanisms play a key role in the pathogenesis of vascular dysfunction characterizing this disease.     

肾移植患者术后重症肺部感染的诊治经验（附46例报告）

目的总结肾移植患者术后重症肺部感染的诊断和救治经验。方法回顾分析2008年1月至2010年12月期间诊治的46例肾移植术后并发重症肺部感染患者的临床资料。结果 38例肾移植术后重症肺部感染患者的发病时间为术后2～6个月,8例发生于术后6个月以上。46例的主要临床表现特点为不同程度的发热、咳嗽、胸闷、气促,其中并发急性呼吸窘迫综合征20例。胸部计算机断层摄影术检查结果均有明显间质性肺炎典型表现。检出病原体36例（78%）,未检出10例。细菌性肺炎7例,真菌性肺炎6例,混合感染23例,其中仅有3例为巨细胞病毒感染。治疗采用综合治疗方案,包括经验性降阶梯治疗方案治疗,停用或调整免疫抑制剂用量和组合方案,部分病例采用连续肾脏替代治疗,并予支持治疗、改善通气、纠正低氧血症、免疫替代治疗。46例患者中38例（83%）治愈,8例（17%）死亡。结论肾移植术后重症肺部感染多发生在术后6个月内,病原体呈多样性。及早确诊、积极采用综合治疗方案,包括给予经验性降阶梯治疗措施,及时调整免疫抑制方案,纠正低蛋白血症,加强全身支持治疗,适时应用呼吸机支持和改善通气,纠正低氧血症等是救治成功的关键。     

米卡芬净治疗肾移植术后肺部真菌感染的临床观察

目的评价米卡芬净治疗肾移植术后肺部真菌感染的疗效及安全性。方法 24例肾移植术后真菌感染患者给予米卡芬净治疗,取米卡芬净100mg用生理盐水230ml稀释后每日1次静脉滴注,重症患者用量加大至150mg/d,连用10～14d,临床症状基本得到控制后剂量减为50mg/d,连用时间为5～7d。同时调整免疫抑制剂方案等,观察其疗效及不良反应。结果 24例患者中痊愈10例,显效8例,进步2例,无效4例,有效率为75%。治疗过程中仅有2例出现轻微的肝功能异常,2例出现低钾血症,不良反应发生率为17%,未观察到严重的不良反应。22例患者治疗前后肾功能维持稳定,另2例肾移植术后移植物功能延迟恢复期间发生肺部真菌感染的患者,治疗期间肾功能有所改善。结论米卡芬净治疗肾移植术后肺部真菌感染疗效肯定,不良反应少。     

肾移植术后肺部感染致ARDS的治疗

目的：总结。肾移植术后重度肺部感染致急性呼吸窘迫综合征（ARDS）的治疗经验。方法：回顾性分析2000年7月-2009年1月期间24例肾移植术后重症肺部感染致ARDS患耆的临床资料：肺部感染致ARDS多在肾移植术后1～12个月发生。尤以术后2～6个月多见．且大剂量激素冲击多为诱因。24例患者均采用综合治疗方案,并按照抗排斥反应药物治疗方案分为三个阶段进行治疗。结果：24例患者中。9例死亡,2例放弃治疗．死亡率为37．5％;其中两个或两个以上器官障碍者死亡8例,最多见于上消化道出血和肾功能衰竭。1例最长呼吸机辅助呼吸达33灭．最终痊愈出院。本组患者肺部感染多为混合性感染,多以巨细胞病毒、真菌、耐药菌群和条件致病菌感染为主。结论：移植肾功能的保护或替代是治愈的决定因素;合理、及时调整抗生素是治愈的关键;肠内营养支持是治愈的基础;早期有利的呼吸功能支持是主要手段。     

Continuous peritoneal dialysis in acute renal failure from severe falciparum malaria

Severe falciparum malaria complicated by acute renal failure resulted in very high mortality. Ten patients with acute renal failure from falciparum malaria (infected rbc up to 80%) were continuously dialysed using Tenckhoff peritoneal catheter. Five were oliguric and BUN was maintained between 60 to 80 mg/dl (21.4 to 28.6 mmol/l) by hourly 1 to 1.5 liter dialysate exchange during the acute phase. The peritoneal urea clearance (mean +/- SD) was 12.1 +/- 1.2 ml/min with urea nitrogen removal of 13.4 +/- 2.3 g/day. In nonoliguric cases dialysis was also needed for additional removal of waste products since the remaining renal function could not cope with the hypercatabolic state. Peritoneal glucose absorption (135 to 565 g/day) gave considerable caloric supply without volume load and also contributed to the prevention of hypoglycemia. Varying degree of acute respiratory failure developed in all patients with 5 cases (2 oliguric and 3 nonoliguric) progressing to pulmonary edema. Swan-Ganz catheterization and hemodynamic study suggested the role of increased capillary permeability and volume overload from endogenous water formation in the development of pulmonary complication. Continuous removal of fluid and waste products minimized these problems and may prevent the progression of respiratory failure. One patient died of severe sepsis and the other nine survived. This study showed the beneficial contribution of continuous peritoneal dialysis in the management of acute renal failure from severe falciparum malaria.     

肾移植术后早期死亡原因分析

目的:分析肾移植术后早期(6个月内)死亡原因,总结经验,提高和改善移植效果。方法:回顾性分析2000年1月~2005年2月施行433例尸体肾移植患者的临床资料,对其中19例术后早期死亡原因及相关因素进行探讨。结果:术后早期死亡病因包括感染7例,占36.8%;急性心力衰竭4例,占21.1%;肾破裂致失血性休克3例,占15.8%;弥漫性血管内凝血2例,占10.5%;暴发性肝功能衰竭1例、急性心肌梗死1例、肺动脉栓塞1例,各占5.3%。除暴发性肝功能衰竭患者于术后118天死亡外,其余均在术后1个月内死亡。结论:感染是肾移植术后早期死亡最常见的原因,与术后免疫抑制过度、营养不良及术后并发症等有关,其中以肺部和泌尿系感染最重要;心血管疾病是引起移植术后早期死亡的另一重要因素,尤其是高龄和糖尿病患者;肾移植早期死亡与肾功能延迟恢复(包括急性排斥反应和急性肾小管坏死)有密切关系,积极合理的治疗对预防肾移植术后早期死亡具有重要意义。     

Treatment of renal vein thrombosis associated with nephrotic syndrome

Renal vein thrombosis is a rare entity in which true incidence is unknown. The disease occurs most frequently in patients with nephrotic syndrome, but it also can occur in the presence of other hypercoagulable state. Two cases of renal vein thrombosis with nephrotic syndrome which were treated by thrombectomy are reported here. One patient was successfully treated by renal vein and inferior vena cava thrombectomy before developing severe pulmonary embolism. The other was treated by renal vein thrombectomy by which fatal shock was able to be prevented. In those cases, immediate operation was indicated, primarily to prevent additional, possibly fatal, pulmonary embolism and also to improve perfusion of the kidney. In the hope of salvaging the kidney, thrombectomy may be the treatment of choice for acute renal vein thrombosis, complication of pulmonary embolism and inferior vena cava thrombosis, right renal vein thrombosis without collateral flow and acute renal vein thrombosis with shock.     

Polymerase chain reaction detection of Puumala virus RNA in formaldehyde-fixed biopsy material

BACKGROUND: Infections with hantaviruses, mainly Clethrionomys-derived Puumala viruses, are known causes of acute renal failure [hemorrhagic fever with renal syndrome (HFRS)] in western Europe. Laboratory diagnosis is primarily based on serology. At the time of clinical symptoms, viral RNA can hardly be detected in the blood or urine, indicating that polymerase chain reaction (PCR) is of little diagnostic value for these infections. Biopsy material is usually formaldehyde-fixed and, thus, regarded as poor quality for PCR applications. The aim of this study was to establish a technique to retrieve such material for laboratory diagnostic. METHODS: Formaldehyde-fixed, paraffin-embedded kidney biopsies of 14 patients with renal failure either clinically suspected for HFRS (7 cases) or caused by unknown (2 cases) or known other causes (drugs, sarcoidosis; 5 cases) were histologically investigated. An established S segment-specific PCR assay was applied to RNA isolated from the biopsies, and amplification products were verified by direct sequence determination. RESULTS: Investigations revealed a typical histopathological appearance for hantavirus infections in all seven suspected HFRS cases and one case of unknown cause. With five of the suspected HFRS cases, hantavirus-specific RNA was detected. Sequence comparison revealed a close relationship to corresponding nucleoproteins of known Puumala viruses. CONCLUSION: The established technique provides a simple and powerful tool that expands the diagnostic possibilities, especially for otherwise unidentified or retrospective cases. It further allows insight into the molecular epidemiology of HFRS-causing agents.     

肾移植术后并发重症肺部感染的原因与处理

目的:探讨肾移植术后并发重症肺部感染的原因与处理措施。方法:回顾性分析29例肾移植术后并发重症肺部感染患者的临床资料。结果:29例重症肺部感染患者中17例(58.6%)救治成功,12例(41.4%)因合并急性呼吸窘迫综合征抢救无效死亡。结论:重症肺部感染是肾移植受者术后近期死亡的主要原因之一;果断减少或停用免疫抑制剂,早期联合用药抗感染治疗,尽可能早期明确病原学诊断,积极纠正低氧血症和低蛋白血症等,是成功救治的关键。     

Clinical experience in renal transplantation

In Shiga Prefecture, 378 chronic renal failure patients were registered at the end of 1981. In 1982, the Kidney Transplantation Group, composed of the department of Urology and the 1st division of Surgery, was organized in our hospital and 10 living related renal transplantations and 8 cadaver renal transplantations were performed between July 1982 and October 1984. As immunosuppressants, azathioprine, mizoribine, cyclosporine, prednisolone, methylprednisolone and ALG were used. Azathioprine was used mainly for living transplantation and cyclosporine mainly for cadaver transplantation. ALG was used only for the initial 3 living transplantations. Mizoribine was sometimes used in combination with azathioprine to reduce the dose of azathioprine and reduce its severe side effects. Seven episodes of acute rejection were experienced and all episodes were remitted by methylprednisolone pulse therapy. There were 20 major post-transplant complications in 13 recipients and among them 2 pulmonary infections were fetal (1 from aspergillus infection and 1 from cytomegalovirus infection). The 10 living related kidney transplantation recipients are all well and none have undergone hemodialysis. Three of the 8 cadaver renal transplantation are well without hemodialysis. One patient could not obtain diuresis. In addition to our experience of renal transplantation, the preoperative scheduled blood transfusion with combination of azathioprine administration, was briefly discussed.     

A case report of infective endocarditis with acute pulmonary edema and renal dysfunction treated by emergent mitral valve replacement and postoperative extracorporeal ultrafiltration

A 40-year-old woman with staphylococcus aureus endocarditis of the mitral valve associated with acute pulmonary edema and renal dysfunction is presented. The patient was admitted to Hiroshima University Hospital with infective endocarditis. On the 14th day after admission, she suffered from severe cardiac failure and oligouria, then she was transferred ICU. Chest X-ray film showed pulmonary congestion and echocardiogram revealed 4th grade of mitral valve regurgitation. Emergent mitral valve replacement was performed and rupture of anterior mitral chorda was found as the cause of acute pulmonary edema. Postoperative care was difficult because of advanced renal failure and cardiac failure not responded to diuretics. Extracorporeal ultrafiltration method was effectively used on the 1st and the 2nd postoperative days and 3000 ml of water was filtered without hemodynamic change. Symptoms of renal and cardiac failure recovered promptly after ultrafiltration. Emergent operative and postoperative use of ultrafiltration method is effective in some cases of infective endocarditis complicated with cardiac and renal failure.     

Morbidity and mortality due to cerebral edema complicating the treatment of severe leptospiral infection

Although neurological signs and symptoms are well described in leptospiral infections, cerebral edema has not been reported previously. We have encountered two patients with severe leptospiral infection, associated with multisystem involvement, who developed cerebral edema. Both patients were in acute oligoanuric renal failure, one being treated by acetate hemodialysis and the other by hemofiltration. Grand mal seizures developed in both patients, followed by respiratory, then cardiac arrest, as a consequence of dialytic therapy. Only one patient could be resuscitated and he was left with a hemiparesis. Cerebral edema may develop in patients with severe leptospiral infections consequent to treatments used in the management of renal failure.     

The changing epidemiology of acute renal failure

Different definitions of acute renal failure (ARF) abound. The existence of multiple definitions makes it difficult to determine the true epidemiological characteristics of this condition. Despite this difficulty, it has been possible to detect notable variations in the epidemiology of ARF during the past few decades. The absolute incidence of ARF has increased, while associated mortality rate has remained relatively static. Several factors have contributed to this altered epidemiology. Here, we discuss the relative contribution of these factors, which include site of disease onset (developed or developing countries, community or hospital or intensive care unit), patient age, infections (HIV, malaria, leptospirosis and hantavirus), concomitant illnesses (cardiopulmonary failure, hemato-oncological disease), and interventions (hematopoietic progenitor cell and solid organ transplantation).     

Aztreonam can safely be used in combination with cyclosporin without aggravating nephrotoxicity

Abstract. The administration of antibiotics to renal transplant patients using cyclosporin can be difficult because of the risk of severe nephrotoxicity. An investigation was therefore carried out to determine whether aztreonam, a synthetic monocyclic β-lac-tam antibiotic, can safely be combined with cyclosporin. In this retrospective study 68 renal transplant patients who received preoperative antibiotic prophylaxis consisting of aztreonam, ampicillin, and lincomycin were compared with 68 patients who received ceftazidime instead of aztreonam. Both groups were treated with cyclosporin and prednisolone and followed for 3 months. After transplantation 28. 7% of the patients suffered from an acute renal failure and 1. 5% had a wound infection. There were no significant differences between the two groups in acute renal failure, wound infections, other infections, incidence of rejections, duration of admission, or graft survival. We therefore conclude that aztreonam can safely be administered together with cyclosporin. We also conclude that the combination of aztreonam, ampicillin, and lincomycin is a good preoperative antibiotic prophylaxis in renal transplant patients.     

Prediction of mortality in patients with bacteremia: the importance of pre-existing renal insufficiency

Pre-existing renal insufficiency serves as a common risk factor in the development of acute renal failure. Acute renal failure is a common finding in patients with bacteremia and is associated with poor prognosis. A total of 2722 consecutive patients 18 years old or older, fulfilling strike criteria of bacteremia or fungemia were prospectively evaluated to establish the prognostic importance of pre-existing renal insufficiency in bacteremic patients. They were classified according to serum creatinine levels upon admission into three groups. 915 patients had normal creatinine levels (< or = 1.0 mg/dL), 1528 had mild to moderate renal failure (creatinine 1.1-3 mg/dL) and 279 patients had severe renal failure upon admission (creatinine > 3.0 mg/dL). Mild to severe renal failure upon admission was associated with old age, male gender, diabetes mellitus, ischemic heat disease, hypertension and congestive heart failure. The serum albumin in patients with severe renal failure was significantly low, with a mean of 2-9 mg/dL. Urinary tract infections were more prevalent in patients with mild to severe renal failure, while intravenous line infections, bacterial endocarditis and soft and skin tissue infections were more common in patients with normal renal function. In the 279 patients with severe renal failure the mortality rate was significantly higher (50%) compared to patents with mild to moderate renal failure and patients with normal renal function (21% and 26% respectively, p = 0.0001). Multiple regression analysis revealed that pre-existing serum creatinine > 3 mg/dL was significantly associated with death attributable to bacteremia (OR = 1.7, 95% CI 1.0-2.7). In conclusion, adult bacteremic patients with pre-existing serum creatinine above 3 mg/dL upon admission are at increased risk of mortality due to bacteremia than patients with normal or mild to moderate renal failure.     

23例儿童肾移植临床分析

目的：探讨儿童肾移植的临床特点，提高肾移植效果。方法：对23例3～17岁的儿童肾移植资料进行回顾性分析。结果：术后随访5d至72个月，平均26．1个月，死亡1例，人、肾1年存活率分别为93．3％和86．6％。术后7例发生急性排斥反应，6例治疗后逆转，1例因并发移植肾静脉栓塞，切除移植肾；2例发生慢性排斥反应，1例移植肾功能丧失，恢复血液透析，另一例仍在随访治疗中；其它并发症有肺部感染4例，心力衰竭2例，肾静脉阻塞2例，肝功能损害2例，急性肾小管坏死1例。结论：儿童肾移植具有一定的特殊性，其血管较细、急性排斥反应发生率较高以及药物代谢快等都是应妥善处理的问题。