Primary antiphospholipid syndrome in the elderly: Four strokes and mechanical thrombectomies until the diagnosis - A case report.

Antiphospholipid syndrome (APS) is known as a rare etiology of embolic ischemic stroke. In individuals below 50 years, up to 20% of strokes are associated with APS, whereas in patients >50 years, it is considered a very seldom cause of stroke. We describe the course of a 66-year-old white woman, who experienced four embolic strokes with large vessel occlusion over a period of 2 years, which were repeatedly and successfully treated by mechanical thrombectomy. Initially attributed to atrial fibrillation and treated with direct oral anticoagulants, the patient was finally diagnosed with primary APS due to isolated anti-beta 2-glycoprotein antibodies and successfully treated after several stroke recurrences. After initiation of Vitamin K antagonist therapy, no further strokes occurred. For recurrent embolic stroke despite oral anticoagulation, late-onset APS might be considered a rare etiology also in the elderly.

Outcome of kidney transplantations from ≥65-year-old deceased donors with acute kidney injury.

Kidney transplantation (KT) from donors with acute kidney injury (AKI) has been associated with delayed graft function (DGF) but similar graft survival compared with KT from donors without AKI. Kidneys from ≥65-year-old donors with comorbidities are more susceptible to cold ischemia time (CIT) and DGF and it is unknown whether such elderly kidneys with AKI can also be transplanted with satisfactory outcomes. All KTs from ≥65-year-old donors performed at our center from 1999 to 2019 (n = 233) were retrospectively analyzed and short- as well as long-term outcomes were compared for KTs from donors with (n = 64) and without AKI (n = 169). There were no significant differences regarding the frequency of DGF as well as the estimated glomerular filtration rate (eGFR) 1 and 3 years post-transplant between the no-AKI and the AKI group (DGF: no-AKI 30.2% vs. AKI 40.6%, P = .17; eGFR at 1-year: 31.9 ml/min/1.73 m2 vs. 35.5 ml/min/1.73 m2 , P = .32; at 3-years: 33.8 ml/min/1.73 m2 vs. 40.9 ml/min/1.73 m2 , P = .18; respectively). Death-censored graft survival and patient survival were also not significantly different. Multivariable Cox regression analysis did not identify AKI as a significant risk factor for graft loss or death. Following careful donor and recipient selection, kidneys from ≥65-year-old AKI donors may potentially be transplanted with satisfactory outcomes.

Impact of the explanting surgeon's impression of donor arteriosclerosis on outcome of kidney transplantations from donors aged ≥65 years.

PURPOSE: Careful donor selection is important for kidney transplantations (KT) from suboptimal donors aged ≥65 years. Several tools such as histopathological assessment of preimplant biopsies have been shown to predict allograft survival and can be applied for selection. Whether the explanting surgeon's appraisal is associated with outcomes of KTs from suboptimal donors is unknown. METHODS: We compared outcomes of KTs from ≥65-year-old deceased donors performed at our centre between 1999 and 2018 for which grading of macroscopic 'donor arteriosclerosis' (n=104) and 'organ quality' (n=208) as judged by the explanting surgeon and documented on the Eurotransplant kidney organ report was available. RESULTS: No association was observed between degree of macroscopic donor arteriosclerosis and death-censored graft survival in univariable or multivariable regression analyses. Compared to KTs from donors with no/mild arteriosclerosis, KTs from donors with moderate/severe arteriosclerosis were associated with a significantly impaired allograft function 3 months, 1 year and 3 years after transplantation (e.g. at 3 years: 176.8 µmol/l vs 137.0 µmol/l, P=0.003). Following multivariable regression analysis, these differences remained significant at 3 months and 3 years after KT. No association was observed between degree of macroscopic arteriosclerosis and mortality or primary non-function as well as no consistent association with delayed graft function and histological arteriosclerosis. Assessment of 'organ quality' was not associated with outcomes. CONCLUSION: Our data suggest that the explanting surgeon's assessment of donor arteriosclerosis is associated with allograft function. Larger studies and better standardization of kidney inspection after explantation are required to further explore the impact of surgeon's appraisal in KT.

Impact of cardiopulmonary resuscitation on outcome of kidney transplantations from braindead donors aged ≥65 years.

INTRODUCTION: Patients with a history of cardiopulmonary resuscitation (CPR) and subsequent brain death are frequently evaluated for organ donation. Whether kidneys from ≥65-year-old braindead donors with a history of CPR can be transplanted with satisfactory outcomes is unknown. MATERIAL & METHODS: All kidney transplants (KTs) from ≥65-year-old donors performed at our center from 1999 to 2018 (n = 185) were retrospectively analyzed and outcome was compared for KTs from donors with and without a history of CPR (n = 27 and n = 158, respectively). RESULTS: No significant differences in the incidence of delayed graft function (DGF) as well as 1- and 3-year graft function were observed between the CPR and the no-CPR group (DGF: 26.0% vs. 31.0%, p = .76; 1-year serum creatinine: 150.4 µmol/L vs. 177.0 µmol/L, p = .11; 3-year serum creatinine: 150.4 µmol/L vs. 168.2 µmol/L, p = .52, respectively). Death-censored graft survival was comparable after 1 and 5 years (CPR group: 81.5% and 76.7% vs. no-CPR group: 86.6% and 75.7%, p = .70). Likewise, patient survival was not significantly different. Multivariable Cox regression analysis also did not identify CPR as a significant risk factor for graft loss or death. CONCLUSION: Our study suggests that, following stringent donor selection, the outcome of KTs from ≥65-year-old braindead donors with and without a history of CPR is comparable.

Kidneys From Elderly Deceased Donors-Is 70 the New 60?

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the "Collaborative Transplant Study" were analyzed using Kaplan-Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997-2006 and 2007-2016 with the donor age categories 18-49, 50-59, 60-69, and ≥70 years were considered. From 1997-2006 to 2007-2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997-2006 and 2007-2016, the 5-year graft survival improved in all donor age categories. During 2007-2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997-2006. This was true both for younger recipients (18-64 years) and older recipients (≥65 years). Among the younger recipients, 45-64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007-2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997-2006. Our analysis indicates that within only one further decade (1997-2006 vs. 2007-2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade.

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.

Severe acute kidney injury due to violent sadomasochistic play.

Bondage and discipline, dominance and submission, sadism and masochism (BDSM) refers to a variety of primarily erotic practices. Although safety is crucial for most BDSM practitioners, there are violent forms that may cause serious injury. We present the case of 61-year-old man with no history of chronic kidney disease who developed severe acute anuric kidney injury following violent BDSM play. He had been strapped tightly onto a wooden spanking bench and then received approximately 1000 vigorous hits onto his bare buttocks and thighs. Subsequently, he developed haematuria and became anuric. Laboratory testing revealed strongly elevated serum creatinine levels. Kidney biopsy was unremarkable except mild tubulointerstitial damage. Urinary production increased spontaneously again after 4 days, and serum creatinine normalised over the course of 4 weeks. We believe that a combination of intermittent abdominal compartment syndrome and blunt kidney trauma may have been responsible for this severe acute kidney injury.

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.

Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI during Hospitalization among Patients Presenting to the Emergency Department.

BACKGROUND AND OBJECTIVES: Emergency departments (EDs) have a growing role in hospital admissions, but few studies address AKI biomarkers in the ED. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients admitted to the internal medicine service were enrolled during initial workup in the ED at Robert-Bosch-Hospital, Stuttgart, Germany. Daily serum creatinine (sCr) and urine output (UO) were recorded for AKI classification by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cystatin C, kidney injury molecule-1, liver-type fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were measured in blood and urine, and IL-18, insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and [TIMP-2]⋅[IGFBP7] were measured in urine collected at enrollment, after 6 hours, and the following morning. Association between these biomarkers and the end point of moderate-severe AKI (KDIGO stage 2-3) occurring within 12 hours of each sample collection was examined using generalized estimating equation logistic regression. Performance for prediction of the AKI end point using two previously validated [TIMP-2]-[IGFBP7] cutoffs was also tested. RESULTS: Of 400 enrolled patients, 298 had sufficient sCr and UO data for classification by KDIGO AKI criteria: AKI stage 2 developed in 37 patients and AKI stage 3 in nine patients. All urinary biomarkers, sCr, and plasma cystatin C had statistically significant (P<0.05) odds ratios (ORs) for the AKI end point. In a multivariable model of the urine biomarkers and sCr, only [TIMP-2]⋅[IGFBP7] and sCr had statistically significant ORs. Compared with [TIMP-2]⋅[IGFBP7]<0.3 (ng/ml)(2)/1000, values between 0.3 and 2.0 (ng/ml)(2)/1000 indicated 2.5 (95% confidence interval [95% CI], 1.1 to 5.2) times the odds for the AKI end point and values >2.0 (ng/ml)(2)/1000 indicated 11.0 (95% CI, 4.4 to 26.9) times the odds. Addition of [TIMP-2]⋅[IGFBP7] to a clinical model significantly improved area under the receiver-operating characteristic curve from 0.67 (95% CI, 0.61 to 0.78) to 0.77 (95% CI, 0.72 to 0.86) (P<0.001); however, including both markers in the model was not significantly different from including either marker alone. CONCLUSIONS: Urinary [TIMP-2]⋅[IGFBP7] with pre-established cutoffs provides valuable information about risk for imminent AKI in the ED that is complementary to sCr and clinical risk factors.

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.