Clinical course of hantavirus-induced nephropathia epidemica in children compared to adults in Germany-analysis of 317 patients.

BACKGROUND: Hantavirus infections are endemic worldwide, and its incidence in Europe has been steadily increasing. In Western Europe, hantavirus infections are typically caused by Puumala hantavirus and cause nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. Up to now, there is only little data about the course of acute NE in children, but it has been suggested that hantavirus infections take a lighter course in children when compared to adults. We performed a retrospective analysis of adults and children diagnosed with acute NE in two counties in South-Western Germany to investigate if there are differences in the course of the disease. METHODS: We reviewed the medical records of 295 adults and 22 children with acute NE regarding clinical presentation, laboratory findings, complications and outcome. RESULTS: Acute kidney injury (AKI) and thrombocytopenia occurred at similar frequencies and severity in both groups. Sudden onset of fever and back/loin pain were two of the three most common symptoms in both adults and children. However, adults presented more frequently with arthralgia and visual disturbances, whereas abdominal pain and nausea/vomiting could be detected more often in children. No significant differences were found in the incidence of complications (haemodialysis, long-term outcome of kidney function, length of hospital stay). CONCLUSIONS: The clinical course of acute NE was similar in adults and children with high frequency of AKI as well as thrombocytopenia, but with full recovery of all patients.

Advanced myocardial tissue characterisation by a multi-component CMR protocol in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of suffering from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) mapping techniques might be appropriate tools to complement late gadolinium enhancement (LGE) for the assessment of myocardial involvement. This study aimed to perform advanced myocardial tissue characterisation in RA patients by a multicomponent CMR protocol. METHODS: 22 RA patients were prospectively enrolled and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers served as controls. RESULTS: Mean LV-EF was 66%; prevalence of LGE was 18%. RA patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49 ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2 mapping showed the highest prevalence of values beyond the 95% percentile of controls. CONCLUSION: RA patients demonstrated higher T1, ECV and T2 values compared to controls, with most significant differences for T2. Since these results seem to be independent of the presence of LGE, advanced myocardial tissue characterisation including CMR mapping techniques in addition to LGE-CMR might be useful in the evaluation of myocardial involvement in RA patients. KEY POINTS: • RA patients had higher T1, ECV and T2 values compared to controls. • Most significant differences were observed for T2. • Our results seem to be independent of the presence of LGE. • Mapping might be useful in the evaluation of myocardial involvement in RA.

Alteration of membrane complement regulators is associated with transporter status in patients on peritoneal dialysis.

INTRODUCTION: A growing body of evidence from animal models and cell culture studies indicate an important role of a local regulatory complement system (CS) in peritoneal injury during peritoneal dialysis (PD). We investigated the expression of the local regulatory CS (reflected by CD46,CD55,CD59) in the peritoneal tissue of patients with different membrane function characteristics. PATIENTS AND METHODS: Biopsies from the parietal peritoneum were taken from 24 patients on PD, 22 uremic patients prior to PD. PD patients were grouped according to the dialysate-to-plasma ratio of creatinine (D/P Cre) and ratio of dialysate glucose at 4 hours versus dialysate glucose at time zero (D/D0 glucose) into low or low-average peritoneal transport status (L/LA) and high-average or high-transport status (HA/H) groups. CD46, CD55, and CD59 RNA expression were analyzed by real-time polymerase chain reaction (RT-PCR). Further localization of membrane complement regulators (CRegs) and semiquantitatively analysis was done by immunohistochemistry (IHC). RESULTS: CD46 and CD59 expression were similar in all groups. CD55 expression was significantly decreased in the HA/H group compared to the L/LA group and to uremic controls (p < 0.05 and p = 0.05, respectively). No statistically significant differences in CD46, CD55, and CD55 expression were detected when considering the history of peritonitis. There was no statistically significant correlation between PD duration and the expressions of CD46, CD55, and CD59. IHC revealed strong CD46, CD55, and CD59 expression in mesothelial cells. CD55 and CD59 were additionally detected in the vasculature. Using IHC, CD46 was lower in PD patients compared to uremic controls (p>0.05), but there was no difference between the L/LA compared to the H/HA group. Moreover IHC confirmed decreased expression of CD55 in the HA/H group compared to the L/LA group and uremic controls (p<0.0001 and p = 0.0001, respectively). CONCLUSION: CD55 expression is decreased in patients with fast transporter membrane function, whereas peritonitis and PD duration do not appear to alter CReg expression.

Gender-Specific Differences in Peritoneal Dialysis.

BACKGROUND/AIMS: Gender-specific differences between patients on renal replacement therapy have so far rarely been investigated. In the present study we aimed to describe gender-specific differences in a large cohort of peritoneal dialysis (PD) patients. METHODS: Clinical information for all patients who started PD at our center has been collected since the start of the PD-program in 1979. We used Cox regression to examine associations between technique failure and gender. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 745 patients (315 women and 430 men with a median age of 57 years; IQR 43-67) started PD between 1979 and 2015 in our center. Women were significantly younger at PD start 54 (40-65) years vs. 58 (47-68) years, p<0.001. Within the last almost 15 years, more man than women started PD, but technical survival rates were significantly better in female compared to men (HR=0.662, CI 95% (0.496-0.885) P=0.005). Cardiovascular events were the main cause of death over the study period in both sexes, but decreased over time. Additionally, death due to PD-associated peritonitis decreased significantly over the three decades in both sexes. CONCLUSIONS: Our data suggest that technical survival rates were significantly better in female compared to men over three decades and death due to cardiovascular events and PD-associated peritonitis decreased significantly over the three decades in both sexes.

CD147 expression in peritoneal injury.

BACKGROUND: Peritoneal injury is an important cause of technical failure of long-term peritoneal dialysis (PD). Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term PD with potentially life threatening consequences. CD147 is a glycoprotein with diverse functions including modulation of extracellular matrix via induction of matrix metalloproteinases, cell adhesion, and regulation of immune reactions. We hypothesized that CD 147 plays a role in the peritoneal cavity. METHODS: In this retrospective study, we localized CD147 by immunohistochemistry in peritoneal biopsies from uremic patients not on PD (n = 8), on PD without signs of EPS (n = 7), and in biopsies in patients with the diagnosis of EPS (n = 7). Double immunofluorescence was used to co-localize α-smooth-muscle actin (α-SMA) and CD147 in selected biopsies from each group. Expression was scored semi-quantitatively. RESULTS: In biopsies from uremic controls, CD147 was prominently expressed in mesothelial cells, focally between fat cells and by some perivascular cells. In patients on PD, a similar distribution was present (although mesothelium was rarely conserved), with some focal accentuation. In EPS, layers of fibroblastic cells were positive for CD147. EPS biopsies demonstrated a significantly higher score in a blinded evaluation, compared to uremic patients. Cells expressing CD147 were α-SMA positive myofibroblasts as demonstrated by double immunofluorescence. Mean CD147 scores did not differ between patients with different transporter status. CONCLUSIONS: This is the first study demonstrating CD147 on a major part of fibroblastic cells in EPS. Future studies need to address the role of these cells in this severe complication of long-term PD.

T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

BACKGROUND: Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. METHODS: Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. RESULTS: Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p < 0.001), lower post-contrast T1 (488 vs. 524 ms, p = 0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p < 0.001), and higher T2 (53 vs. 49 ms, p < 0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. CONCLUSION: AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

Comprehensive Cardiovascular Magnetic Resonance Assessment in Patients With Sarcoidosis and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Cardiac sarcoidosis (CS) may manifest as arrhythmia or even sudden cardiac death. Because patients with CS often present with nonspecific symptoms, normal electrocardiography, and preserved left ventricular ejection fraction, a reliable diagnostic tool for the work-up of CS is needed. Late gadolinium enhancement-cardiovascular magnetic resonance has proven diagnostic value in CS but has some limitations that may be overcome by adding newer cardiovascular magnetic resonance mapping techniques. The aim of our study was to evaluate a comprehensive cardiovascular magnetic resonance protocol, including late gadolinium enhancement and mapping sequences in sarcoid patients with no symptoms or unspecific symptoms and preserved left ventricular ejection fraction. METHODS AND RESULTS: Sixty-one sarcoid patients were prospectively enrolled and underwent comprehensive cardiovascular magnetic resonance imaging. Twenty-six healthy volunteers served as control group. Mean left ventricular ejection fraction was 65%; late gadolinium enhancement was only present in sarcoid patients (n=15). Sarcoid patients had a higher median native T1 (994 versus 960 ms; P<0.001), lower post contrast T1 (491 versus 526 ms; P=0.001), expanded extracellular volume (28 versus 25%; P=0.001), and higher T2 values (52 versus 49 ms; P<0.001) compared with controls. Among patients with values higher than the 95% percentile of healthy controls, most significant differences were observed for native T1 and T2 values. Most of these patients were late gadolinium enhancement negative. CONCLUSIONS: Patients with sarcoidosis demonstrate higher T1, extracellular volume, and T2 values compared with healthy controls, with most significant differences for native T1 and T2. While promising, the clinical significance of the newer mapping techniques with respect to early diagnosis and therapy of CS will have to be determined in future studies.

Evaluation of myocardial involvement in patients with connective tissue disorders: a multi-parametric cardiovascular magnetic resonance study.

BACKGROUND: Severe arrhythmias or heart failure may be surrogates of myocardial involvement in patients with connective tissue disorders (CTD). However, most patients present with unspecific symptoms, normal ECG, and preserved left ventricular ejection fraction (LV-EF). Therefore, timely diagnosis by an accurate technique is crucial. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has proven value for the detection of focal processes, but due to the often diffuse character of fibrosis/inflammation in CTD patients, CMR mapping techniques might be of incremental value for the assessment of myocardial involvement. Purpose of this study was to evaluate a multi-parametric CMR protocol as a screening tool for myocardial involvement in CTD patients. METHODS: Forty CTD patients were prospectively enrolled and underwent CMR, twenty healthy volunteers served as control group. RESULTS: Mean LV-EF was 62 %; LGE prevalence was low (18 %). CTD patients had higher native T1 (1008 vs. 962 ms, p = 0.001), lower post contrast T1 (494 vs. 526 ms, p = 0.008), expanded extracellular volume (ECV) (28 vs. 25 %, p = 0.001), and higher T2 values (53 vs. 49 ms, p < 0.001) compared to controls. Among patients with values higher than the 95 % percentile of healthy controls, native T1 and T2 values seem to be the most promising discriminators. CONCLUSION: CTD patients showed higher T1, ECV, and T2 values compared to controls, with most significant differences for native T1 and T2, which seem to be independent of the presence of LGE. Our data suggest that CMR mapping techniques are of incremental value in the detection of myocardial involvement in CTD patients.

Cardiac involvement in patients with rheumatic disorders: Data of the RHEU-M(A)R study.

BACKGROUND: The diagnosis of cardiac involvement in rheumatic disorders is challenging due to its varying clinical presentation. Since clinical consequences range from immediate treatment changes to adverse long-term outcome, individual risk stratification is of great clinical interest. Primary aim was to evaluate the prevalence of cardiac involvement in patients with different rheumatic disorders using late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-CMR). In addition, we sought to investigate if different rheumatic disorders would demonstrate different LGE patterns. METHODS: Two-hundred-ninety-seven patients with rheumatic disorders were included and underwent LGE-CMR for work-up of cardiac involvement, which was defined by the presence of LGE in the myocardium. Patients were divided into five subgroups: 1) ANCA-associated vasculitis, 2) non-ANCA-associated vasculitis, 3) connective tissue disorders, 4) arthritis, and 5) sarcoidosis. RESULTS: Mean ejection fraction in the overall population was 65%, with a mean age of 55yrs. Prevalence of cardiac involvement in the five subgroups were as follows: 54% in the ANCA-associated vasculitis group, 22% in the non-ANCA-associated vasculitis group, 14% in the group with connective tissue disorders, 21% in the arthritis group, and 24% in sarcoid patients. Each of the five subgroups demonstrated a distinct pattern of LGE. CONCLUSION: There is a wide range in the prevalence of cardiac involvement in different rheumatic disorders (54%-14%). Different groups of rheumatic disorders demonstrate different patterns of LGE. CONDENSED ABSTRACT: Primary aim of the study was to evaluate the presence of cardiac involvement in patients with different rheumatic disorders using LGE-CMR. In addition, we sought to investigate if different rheumatic disorders would reveal different LGE patterns. In our 297 patients, the highest prevalence of cardiac involvement was found in patients with ANCA-associated vasculitis (54%), whereas the lowest prevalence was demonstrated in patients with connective tissue disorders (14%). Furthermore, different groups of rheumatic disorders demonstrate distinct patterns of LGE.

The number of patients with severe encapsulating peritoneal sclerosis is decreasing in a large referral center in Germany.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is the most severe complication associated with long-term peritoneal dialysis (PD). Previous studies noticed a sharp decline in new patients with severe EPS. We investigated the number of severe EPS patients in our large referral center over almost 20 years. METHODS: All late-stage EPS patients who underwent major surgery due to extensive symptoms caused by bowel obstruction (vomiting, abdominal pain, and weight loss) between March 1997 and end of December 2015 in our hospital were included in the present study. An index was calculated between the number of patients with severe EPS and the implanted PD catheters in our center. RESULTS: Between 1979 and 2015, a total of 745 PD catheters were implanted in our center, with a steady increase in the numbers between 2003 and 2015. First patient with severe EPS was treated in 1998, then a rise in the number of patients with EPS was present in 2005. The number of patients with EPS peaked in the period of 2010-2012 (15 patients within 3 years). Afterward, both the absolute numbers and the index between the number of patients with severe EPS and the implanted catheters demonstrated a prominent reduction in the next 3-year period from 2013 to 2015. CONCLUSION: Our data support the hypothesis that there seems to be a decrease of late-stage EPS incidence over the last years, but data about milder or asymptomatic patients are lacking. This should be kept in mind while giving the patients information about different renal replacement therapies at start of dialysis.

Smoking Is a Risk Factor for Severe Acute Kidney Injury in Hantavirus-Induced Nephropathia Epidemica.

BACKGROUND/AIMS: Hantaviruses are zoonotic pathogens causing emerging diseases worldwide. Patients typically present with fever, acute kidney injury (AKI) and thrombocytopenia. Puumala virus (PUUV) that causes nephropathia epidemica (NE) is common in Germany. Recently, a study from Finland revealed an association between nicotine consumption and the severity of AKI in NE. Differences between individuals in Finland and Germany might modulate the effect; therefore, the aim of our study was to prove that smoking is a risk factor for a severe course of NE in Germany. METHODS: A cross-sectional prospective survey of 485 patients with hantavirus infections was performed. Clinical and laboratory data during the acute course of the disease were obtained from medical reports and files, while follow-up (including smoking status) data were collected prospectively. RESULTS: Smoking information was available for 298 out of 485 patients (61%). Male was the predominant gender (67%), median age at the time of diagnosis was 50 (interquartile range, IQR 41-60) years and 34% of patients were current smokers during the phase of acute NE. Patients in the smoking group were significantly younger than in the non-smoking group (p < 0.0001). Peak serum creatinine levels were significantly higher in the smoking group than in the non-smoking patients (median 301 (IQR 186-469 µmol/l) vs. median 240 (IQR 137-469 µmol/l), p < 0.05). In addition, severe AKI (stages 2 and 3 using KDIGO criteria) was more common in current smokers (80%) than in the non-smokers (68%, p < 0.05). CONCLUSION: Current smoking is a risk factor for severity of AKI in patients with acute PUUV infection in Germany. Therefore, information about smoking habits needs to be an integral part of the documentation in patients with suspected acute PUUV infection, and increased monitoring of kidney function should be done in NE patients who are current smokers.

Electrocardiographic abnormalities and relative bradycardia in patients with hantavirus-induced nephropathia epidemica.

BACKGROUND: Nephropathia epidemica (NE), caused by Puumala virus (PUUV), is characterized by acute kidney injury (AKI) and thrombocytopenia. Cardiac involvement with electrocardiographic (ECG) abnormalities has been previously reported in NE; however, its prognostic value is unknown. Relative bradycardia is an important clinical sign in various infectious diseases, and previous smaller studies have described pulse-temperature deficit in patients with PUUV infection. METHODS: We performed a cross-sectional survey of 471 adult patients with serologically confirmed NE. Data were collected retrospectively from medical records and prospectively at follow-up visits. Patients for whom ECGs were recorded during the acute phase of disease were enrolled retrospectively (n=263). Three patients were excluded because of documented pre-existing ECG abnormalities prior to NE. All patients with ECG abnormalities during the acute phase underwent follow-up. RESULTS: A total of 46 patients had ECG abnormalities at the time of admission to hospital (18%). T-wave inversion was the most frequent ECG abnormality (n=31 patients), followed by ST segment changes (nine patients with elevation and six with depression). No major adverse cardiac events occurred during follow-up (median 37months; range 34-63months). Of note, ECG abnormalities reverted to normal in the majority of the patients during follow-up. During the acute phase of NE, 149 of 186 patients had relative bradycardia, without implications for disease course. CONCLUSIONS: Transient ECG abnormalities were detected in 18% of patients during acute NE but were not associated with negative cardiovascular outcome. Relative bradycardia was identified in 80% of the patients with acute NE.

Puumala Hantavirus-Induced Hemorrhagic Fever with Renal Syndrome Must Be Considered across the Borders of Nephrology to Avoid Unnecessary Diagnostic Procedures.

BACKGROUND: Nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome, is caused by Puumala virus and is characterized by acute kidney injury and thrombocytopenia. METHODS: A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. RESULTS: Of the 456 investigated patients, 335 had received inpatient treatment. At time of admission to hospital, 72% of the patients had still an AKI and thrombocytopenia was present in 64% of the patients. The 335 patients were treated in 29 different hospitals and 6 of which had nephrology departments. 10 out of 335 patients received treatment in university hospitals and 63% of patients admitted themselves to hospital. Initially, the patients were admitted to 12 different clinical departments (29% of the patients were referred to a nephrology department) and during the course of the disease, 8% of the patients were transferred to another department in the same hospital and 3% were transferred to a nephrology department at another hospital. Regarding diagnostic procedures, in 28% of the inpatients computed tomography to exclude pulmonary embolism or due to severe gastrointestinal symptoms, lumbar puncture to exclude meningitis, magnetic resonance tomography of the brain owing to suspected stroke because of visual disorders, gastroscopy, or colonoscopy due to gastrointestinal symptoms was performed at time of admission to hospital. CONCLUSIONS: NE must be considered by physicians across the borders of nephrology to avoid unnecessary diagnostic procedures especially in areas where NE is endemic.

Diagnostic impact of percutaneous renal biopsy.

BACKGROUND: Ultrasound-guided percutaneous renal biopsy (PRB) is an important diagnostic tool for nephrologists. Athough widely used and without question of pivotal importance for the diagnosis of renal diseases, little systematic data regarding standardized indications, outcomes, or consequences for this procedure are available. The aim of this study was to compare the clinically suspected diagnosis with the morphological results and the potential impact of PRB on the treatment of the patient. METHODS: 205 patients who underwent PRB of the native kidney within a 4-year period were included in this retrospective analysis. The biopsy results (BR), discharge diagnosis (DD), and the suspected diagnoses (SD) of the attending nephrologists prior to biopsy were documented. RESULTS: Mean age of the patients was 58 (range 44 - 77) years. The majority of patients (61%) received PRB during an acute disease phase, whereas 39% had elective PRB. Percutaneous biopsy of the native kidney led to a discharge diagnosis in 92% of the patients, with low complication rates (with 3 out of 205 patients had major bleeding complications). In ~ 2/3, the nephrologists were correct with the suspected diagnosis prior to the biopsy. In ~ 74% of the biopsies, a disease was identified that was potentially responsive to treatment modification. CONCLUSIONS: In summary, PRB was found to be a safe procedure that confirmed the suspected clinical diagnosis in two thirds of patients. As one third of the histopathological analyses demonstrated a non-suspected disease, the biopsies were of major importance for the correct treatment of the patients.

Microbiological Surveillance of Peritoneal Dialysis Associated Peritonitis: Antimicrobial Susceptibility Profiles of a Referral Center in GERMANY over 32 Years.

OBJECTIVES: Peritonitis is one of the most important causes of treatment failure in peritoneal dialysis (PD) patients. This study describes changes in characteristics of causative organisms in PD-related peritonitis and antimicrobial susceptibility. METHODS: In this single center study we analyzed retrospective 487 susceptibility profiles of the peritoneal fluid cultures of 351 adult patients with peritonitis from 1979 to 2014 (divided into three time periods, P1-P3). RESULTS: Staphylococcus aureus decreased from P1 compared to P2 and P3 (P<0.05 and P<0.01, respectively). Methicillin-resistant S. aureus (MRSA) occurred only in P3. Methicillin-resistant Staphylococcus epidermidis (MRSE) increased in P3 over P1 and P2 (P <0.0001, respectively). In P2 and P3, vancomycin resistant enterococci were detected. The percentage of gram-negative organisms remained unchanged. Third generation cephalosporin resistant gram-negative rods (3GCR-GN) were found exclusively in P3. Cefazolin-susceptible gram-positive organisms decreased over the three decades (93% in P1, 75% in P2 and 58% in P3, P<0.01, P<0.05 and P<0.0001, respectively). Vancomycin susceptibility decreased and gentamicin susceptibility in gram-negatives was 94% in P1, 82% in P2 and 90% in P3. Ceftazidim susceptibility was 84% in P2 and 93% in P3. CONCLUSIONS: Peritonitis caused by MSSA decreased, but peritonitis caused by MRSE increased. MRSA peritonitis is still rare. Peritonitis caused by 3GCR-GN is increasing. An initial antibiotic treatment protocol should be adopted for PD patients to provide continuous surveillance.

Evaluation of lipase levels in patients with nephropathia epidemica--no evidence for acute pancreatitis.

BACKGROUND: The most common causative agent for hemorrhagic fever with renal syndrome in Germany is Puumala virus (PUUV) and a high percentage of patients with PUUV infection have gastrointestinal (GI) symptoms. The aim of the present study was to determine the prevalence of increased lipase levels and acute pancreatitis during nephropathia epidemica (NE) in 166 patients from Germany. METHODS: Clinical and laboratory data during the acute phase of the disease were obtained from medical reports and files from 456 patients during acute hantavirus infection. Patients in whom serum lipase levels were determined during acute course of the disease were included in the study. RESULTS: Lipase levels at the time of diagnosis were determined in 166 of the 456 NE patients (36%). Of the 166 patients, 25 (15%) had elevated lipase levels at the time of admission to hospital or first contact with general practitioner/nephrologist. In total 7 patients had a threefold increased serum lipase above the normal range. Abdominal pain was not more often present in the group of patients with elevated serum lipase compared to the lipase-negative group (9/25 vs 58/141). Abdominal ultrasound and CT scans revealed no signs of pancreatitis in any of the patients. Patients with elevated serum lipase had higher serum creatinine peak levels (p = 0.03) during the course of the disease. CONCLUSIONS: Elevated lipase levels were common in our patient cohort and might reflect a more severe form of NE. NE does not lead to acute pancreatitis.

Activation of nuclear factor of activated T cells 5 in the peritoneal membrane of uremic patients.

Peritoneal inflammation and fibrosis are responses to the uremic milieu and exposure to hyperosmolar dialysis fluids in patients on peritoneal dialysis. Cells respond to high osmolarity via the transcription factor nuclear factor of activated T cells (NFAT5). In the present study, the response of human peritoneal fibroblasts to glucose was analyzed in vitro. Expression levels of NFAT5 and chemokine (C-C motif) ligand (CCL2) mRNA were quantified in peritoneal biopsies of five nonuremic control patients, five uremic patients before PD (pPD), and eight patients on PD (oPD) using real-time PCR. Biopsies from 5 control patients, 25 pPD patients, and 25 oPD patients were investigated using immunohistochemistry to detect the expression of NFAT5, CCL2, NF-κB p50, NF-κB p65, and CD68. High glucose concentrations led to an early, dose-dependent induction of NFAT5 mRNA in human peritoneal fibroblasts. CCL2 mRNA expression was upregulated by high concentrations of glucose after 6 h, but, most notably, a concentration-dependent induction of CCL2 was present after 96 h. In human peritoneal biopsies, NFAT5 mRNA levels were increased in uremic patients compared with nonuremic control patients. No significant difference was found between the pPD group and oPD group. CCL2 mRNA expression was higher in the oPD group. Immunohistochemistry analysis was consistent with the results of mRNA analysis. CD68-positive cells were significantly increased in the oPD group. In conclusion, uremia results in NFAT5 induction, which might promote early changes of the peritoneum. Upregulation of NFAT5 in PD patients is associated with NFκB induction, potentially resulting in the recruitment of macrophages.

Determination of procalcitonin levels in patients with nephropathia epidemica - a useful tool or an unnecessary diagnostic procedure?

BACKGROUND/AIMS: Puumala virus causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome that occurs in Central and Northern Europe. Several studies have sought to identify risk factors for severe NE. However, elevated procalcitonin (PCT) levels have not previously been investigated as a predictive marker for a severe course of NE. METHODS: A cross-sectional prospective survey of 456 adults with serologically confirmed NE was performed. RESULTS: PCT levels at the time of diagnosis were available for 43 out of 456 patients, and in 24 of these patients (56%) PCT levels were elevated ("PCT positive"). C-reactive protein (CRP) levels at admission to hospital and peak CRP levels during the acute course of the disease were higher in the PCT-positive compared with the PCT-negative group (p<0.05). Severe acute kidney injury (AKI) (RIFLE I and F) was present in similar numbers of PCT-positive and -negative patients (p=0.7), but antibiotics were more frequently used in the PCT-positive than the PCT-negative group (p<0.05). Within the PCT-positive group, PCT levels were similar among those receiving and not receiving antibiotics (p=0.13), and neither the duration of hospital stay nor CRP peak levels were lower in those treated with antibiotics (p=0.12 and p=0.13, respectively). CONCLUSIONS: Elevated PCT levels are common in patients with acute NE. There was no association between PCT levels and severity of disease, including AKI or thrombocytopenia. It is important to distinguish Puumala virus infection from other causes of AKI with thrombocytopenia. However, PCT might not be useful in differentiating hantavirus infection from bacterial infection.

Drug-induced acid-base disorders.

The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal anti-inflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g., anesthetics, sedatives) or hyperventilation (e.g., salicylates, epinephrine, nicotine).

Clinical course and long-term outcome of hantavirus-associated nephropathia epidemica, Germany.

Human infection with Puumala virus (PUUV), the most common hantavirus in Central Europe, causes nephropathia epidemica (NE), a disease characterized by acute kidney injury and thrombocytopenia. To determine the clinical phenotype of hantavirus-infected patients and their long-term outcome and humoral immunity to PUUV, we conducted a cross-sectional prospective survey of 456 patients in Germany with clinically and serologically confirmed hantavirus-associated NE during 2001-2012. Prominent clinical findings during acute NE were fever and back/limb pain, and 88% of the patients had acute kidney injury. At follow-up (7-35 mo), all patients had detectable hantavirus-specific IgG; 8.5% had persistent IgM; 25% had hematuria; 23% had hypertension (new diagnosis for 67%); and 7% had proteinuria. NE-associated hypertension and proteinuria do not appear to have long-term consequences, but NE-associated hematuria may. All patients in this study had hantavirus-specific IgG up to years after the infection.