Infectious Complications in Peritoneal Dialysis: The Spectrum of Causative Organisms and Recommended Treatment Options

Peritoneal dialysis (PD) has become a real alternative to hemodialysis (HD) in recent decades, with comparable survival rates, lower costs, and improved patient quality of life. Nevertheless, PD‐related infections, including peritonitis, exit‐site infections (ESI), and tunnel infections, are important complications, resulting in significant morbidity and a 3.5–10.0% risk of death. Patients with peritonitis usually present with cloudy PD‐fluid and abdominal pain; however, PD‐associated peritonitis should always be included in differential diagnosis of PD patients with abdominal pain. The most common causative organisms for PD‐associated peritonitis are gram‐positive bacteria; however, gram‐negative species are clinically important, due to the antibiotic resistance. The selection of empiric antibiotics depends on the center‐specific distribution of microorganisms and antimicrobial susceptibility profiles. Typically, a first‐generation cephalosporin is used in combination with broad gram‐negative coverage (e.g., aminoglycoside, ceftazidime, or cefepime). High levels of methicillin‐resistant Staphylococcus epidermidis or Enterococcus spp. strains require the use of vancomycin in many centers. Furthermore, for patients without clinical improvement after 5 days, or with fungal peritonitis, catheter removal is indicated

Acute kidney injury and tools for risk-stratification in 456 patients with hantavirus-induced nephropathia epidemica

BACKGROUND Puumala virus (PUUV) is the most common species of hantavirus in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute kidney injury (AKI) and thrombocytopenia. The major goals of this study were to provide a clear clinical phenotyping of AKI in patients with NE and to develop an easy prediction rule to identify patients, who are at lower risk to develop severe AKI. METHODS A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. Data were collected from medical records and prospectively at follow-up visit. Severe AKI was defined by standard criteria according to the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) classification. Fuller statistical models were developed and validated to estimate the probability for severe AKI. RESULTS During acute NE, 88% of the patients had AKI according to the RILFE criteria during acute NE. A risk index score for severe AKI was derived by using three independent risk factors in patients with normal kidney function at time of diagnosis: thrombocytopenia [two points; odds ratios (OR): 3.77; 95% confidence intervals (CI): 1.82, 8.03], elevated C-reactive protein levels (one point; OR: 3.02; 95% CI: 1.42, 6.58) and proteinuria (one point; OR: 3.92; 95% CI: 1.33, 13.35). On the basis of a point score of one or two, the probability of severe AKI was 0.18 and 0.28 with an area under the curve of 0.71. CONCLUSION This clinical prediction rule provides a novel and diagnostically accurate strategy for the potential prevention and improved management of kidney complications in patients with NE and, ultimately, for a possible decrease in unnecessary hospitalization in a high number of patient

Histological and clinical findings in patients with post-transplantation and classical encapsulating peritoneal sclerosis: A European multicenter study

Background: Encapsulating peritoneal sclerosis (EPS) commonly presents after peritoneal dialysis has been stopped, either post-transplantation (PT-EPS) or after switching to hemodialysis (classical EPS, cEPS). The aim of the present study was to investigate whether PT-EPS and cEPS differ in morphology and clinical course. Methods: In this European multicenter study we included fifty-six EPS patients, retrospectively paired-matched for peritoneal dialysis (PD) duration. Twenty-eight patients developed EPS after renal transplantation, whereas the other twenty-eight patients were classical EPS patients. Demographic data, PD details, and course of disease were documented. Peritoneal biopsies of all patients were investigated using histological criteria. Results: Eighteen patients from the Netherlands and thirty-eight patients from Germany were included. Time on PD was 78(64-95) in the PT-EPS and 72(50-89) months in the cEPS group (p>0.05). There were no significant differences between the morphological findings of cEPS and PT-EPS. Podoplanin positive cells were a prominent feature in both groups, but with a similar distribution of the podoplanin patterns. Time between cessation of PD to the clinical diagnosis of EPS was significantly shorter in the PT-EPS group as compared to cEPS (4(2-9) months versus 23(7-24) months, p<0.001). Peritonitis rate was significantly higher in cEPS. Conclusions: In peritoneal biopsies PT-EPS and cEPS are not distinguishable by histomorphology and immunohistochemistry, which argues against different entities. The critical phase for PT-EPS is during the first year after transplantation and therefore earlier after PD cessation then in cEPS

Identification of new antigen-/antibody systems in patients with autoimmune hepatitis

Hintergrund: Autoantikörper spielen bei der Diagnostik und Klassifikation der autoimmunen Hepatitis (AIH) eine wichtige Rolle. Darüber hinaus wird über eine eventuelle Bedeutung von Autoantikörpern bei der Pathogenese der Erkrankung spekuliert. Bei der AIH Typ III kommen Autoantikörper gegen Leber-/Pankreas (LP)- bzw. ein lösliches Leber-Antigen (SLA) vor. Diese Autoantikörper sind krankheitsspezifisch und reagieren im Westernblot unter Verwendung eines 100 000g Überstandes aus Rattenleber mit einem 52 kDa Protein, das mittlerweile als UGA-Suppressor Transfer RNA (tRNA) assoziiertes Protein (tRNP(Ser)Sec) identifiziert wurde. Seren von Patienten mit AIH Typ III erkennen jedoch weitere Proteine, u.a. eine 48 kDa Determinante, die bisher nicht identifiziert werden konnten und auch mit Seren von Patienten beobachtet wurden, bei denen klinisch/histologisch die typische Konstellation einer AIH vorlag, die bisher bekannten relevanten Autoantikörper aber fehlten. Ziel der vorliegenden Arbeit war daher, diese Reaktionsmuster besser zu definieren und hinsichtlich ihrer Spezifität für eine AIH zu überprüfen. Methoden und Ergebnisse: Seren von 11 Patienten mit anti-LP/SLA positiver AIH III sowie von 27 Patienten mit klinisch/histologisch hochgradigem Verdacht auf AIH (n=27) und 58 Patienten mit AIH Typ I wurden im Westernblot gegen den 100 000g Überstand aus Rattenleber getestet. Als Kontrollgruppen dienten Seren von 6 Patienten mit primär-biliärer Zirrhose sowie von 35 Blutspendern. In Seren der AIH III-Patienten wurden neben Antikörpern gegen die LP/SLA-assoziierte 52kDa Determinante weitere Antikörper gegen 66, 60, 48 und 35 kDa-Proteine beobachtet. Weitere Aufreinigung über Sucrosedichtegradientenzentrifugation ergab eine Anreicherung der 66, 48 und 35 kDa Proteine in einer 1.14-Gradientenfraktion, die für weitere Untersuchungen eingesetzt wurde. 45% der Seren der AIH Typ III- Patienten und 81 % der Seren der Patienten mit v.a. AIH reagierten mit der 66 kDa Bande. Zusätzlich kamen bei diesen Patienten gehäuft Reaktionen im Bereich 48kDa (45% bzw. 37%) und 35 kDa (55% bzw. 37%) vor. Patienten mit AIH Typ I hatten Antikörper gegen das 66 kDa Protein in 9% und gegen das 35 kDa Protein in 3% der Fälle. Gesunde Kontrollen waren negativ; von den sechs PBC-Patienten hatten zwei (33%) Antikörper gegen die 66 und/oder die 48 bzw., 35 kDa-Determinante, und bei diesen Patienten bestand klinisch der Hinweis auf ein Überlappungssyndrom mit einer AIH. Um die Antigene besser zu charakterisieren, wurden die entsprechenden Proteinbanden aus den SDS-Gelen ausgeschnitten und einer massenspektrometrischen Analyse unterworfen. Ferner wurde das 66 kDa-Protein über Immunpräzipitation isoliert und ebenfalls der massenspektrometrischen Analyse zugeführt. Diese Untersuchungen führten aber bisher zu keinen aussagekräftigen Ergebnissen. Schlussfolgerung: Die in dieser Arbeit vorgelegten Ergebnisse zeigen, dass bei Patienten mit AIH Typ III weitere Antikörper vorkommen, die mit Proteinen bei 66, 48 und 35 kDa reagieren. Da dieselben Antikörper auch bei Patienten zu beobachten waren, bei denen der hochgradige Verdacht auf eine AIH bestand, jedoch alle bisher bekannten Autoantikörper negativ waren, könnte es sich um ‚neue’ Markerantikörper handeln, die die Definition einer weiteren Subgruppe von Patienten mit AIH erlauben und damit helfen, die serologische Diagnose der AIH zu verbessern. Die Identifizierung dieser Proteine auf molekularer Ebene steht jedoch noch aus.Background: Autoantibodies play in the diagnosis and classification of autoimmune hepatitis (AIH) an important role. In addition to that, there is speculation about a possible role of autoantibodies in the pathogenesis of the disease. In AIH type III autoantibodies against Liver-/pancreas (LP) - or a soluble liver antigen (SLA) occur. These autoantibodies are disease specific and react in Western blot using a 100 000g supernatant from rat liver with a 52 kDa protein, which is identified as a UGA-suppressor transfer RNA (tRNA)-associated protein (tRNP (Ser) Sec). Sera from patients with AIH type III however identify other proteins including a 48 kDa determinant in western blot. This determinant could not be identified yet and observed with sera from patients, with clinically / histologically typical constellation of AIH but without the previously known typical autoantibodies. The aim of this study was to define this new reaction patterns and to review their specificity for AIH. Methods and results: Sera from 11 patients with anti-LP/SLA positive AIH III and from 27 patients with clinically / histologically highly suspected AIH (n = 27) and 58 patients with AIH type I were tested in a Western blot against the 100 000g supernatant from rat liver. Sera from 6 patients with primary biliary cirrhosis, and 35 blood donors served as a control group. In sera of AIH-III patients were observed in addition to antibodies against the LP / SLA-associated 52kDa determinant, antibodies against 66, 60, 48 and 35 kDa proteins. Further purification on sucrose gradient centrifugation led an accumulation of the 66, 48 and 35 kDa proteins in a 1.14-gradient fraction, which was used for further investigations. 45% of the sera of AIH type III patients and 81% of the sera of patients with suspected AIH reacted with the 66 kDa band. Additionally to that we found in these patients frequently responses at 48kDa (45% or 37%) and 35 kDa (55% or 37%). Patients with AIH type I had antibodies against the 66 kDa protein in 9% and against the 35 kDa protein in 3% of cases. Healthy controls were negative. In the group of the six PBC patients two (33%) had antibodies against the 66 and / or 48 or 35 kDa determinant. In these two patients was clinically suspected an overlap syndrome with AIH. To characterize these antigens better, the corresponding protein bands from SDS gels cut out and subjected to mass spectrometric analysis. Furthermore, the 66 kDa protein was isolated by immunoprecipitation and also analysed with mass spectrometry. But this research led to so far to no meaningful results. Conclusion: This study shows that in patients with AIH type III further antibodies that react with proteins at 66, 48 and 35 kDa exist. The same antibodies were also seen in patients with a high suspicion of AIH, but with negative previously known autoantibodies. Therefore the described reactions could bee 'new' marker antibodies, which allow the definition of a new subgroup of patients with AIH. This could be helping to improve the serological diagnosis of AIH. The identification of these proteins on a molecular level is still pending

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

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

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.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).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.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

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