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Summary Background A discrepancy between sex-specific treatment of kidney failure by dialysis (higher in men) and the prevalence of chronic kidney disease in the general population (higher in women) has been reported internationally, but the prevalence by sex has not been described for Austria. Sex disparity among nephrology outpatients has not been studied. Methods We employed two formulae (2009 CKD-EPI suppressing the race factor, and race-free 2021 CKD-EPI) to estimate the sex distribution of CKD in Austrian primary care, based on creatinine measurements recorded in a medical sample of 39,800 patients from general practitioners’ offices (1989–2008). Further, we collected information from all clinic appointments scheduled at nephrology departments of 6 Austrian hospitals (Wien, Linz, Wels, St. Pölten, Villach, Innsbruck) during 2019 and calculated visit frequencies by sex. Results Using the 2009 CKD-EPI formula, the prevalence of CKD in stages G3–G5 (estimated glomerular filtration rate 2) was 16.4% among women and 8.5% among men aged > 18 years who had attended general practitioners’ offices in Austria between 1989 and 2008 and had at least one creatinine measurement performed. Using the 2021 CKD-EPI formula, the respective CKD prevalence was 12.3% among women and 6.1% among men. In 2019, 45% of all outpatients at 6 participating nephrology departments were women. The median of nephrology clinic visits in 2019 was two (per year) for both sexes. Conclusion CKD is more prevalent among Austrian women than men. Men are more prevalent in nephrology outpatient services. Research into causes of this sex disparity is urgently needed.

The Coronavirus Disease 2019 (COVID-19) pandemic revealed that our understanding of infectious complications and strategies to mitigate severe infections in patients with glomerular diseases is limited. Beyond COVID-19, there are several infections which specifically impact care of patients receiving immunosuppressive measures. This review will provide an overview of six different infectious complications frequently encountered in patients with glomerular diseases, and will focus on recent achievements in terms of vaccine developments and understanding of the use of specific antimicrobial prophylaxis. These include influenza virus, Streptococcus pneumoniae, reactivation of a chronic or past infection with hepatitis B virus (HBV) in cases receiving B-cell depletion, reactivation of cytomegalovirus (CMV), and cases of Pneumocystis jirovecii pneumonia (PJP) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Varicella zoster virus (VZV) infections are particularly frequent in patients with systemic lupus erythematosus (SLE) and an inactivated vaccine is available to be used as alternative to the attenuated vaccine in patients receiving immunosuppressants. As with COVID-19 vaccines, vaccine responses are generally impaired in older patients, and after recent administration of B-cell depleting agents, high doses of mycophenolate mofetil and other immunosuppressants. Strategies to curb infectious complications are manifold and will be outlined in this review.

The differential diagnosis of hyponatraemia is notoriously wide. However, only a minority is acute, ie develops in less than 48 hours. We describe an unusual cause of water intoxication due to toothache. A 30-year-old man with no medical history of note presented in an acute confusional state. Laboratory results disclosed profound hyponatraemia. Urinary indices were consistent with overdrinking, but in the absence of a reliable history, other aetiologies had to be excluded. This case highlights the benefit of a structured approach in the assessment of electrolyte disturbances.

Was ist neu? Wie effektiv sind die zugelassenen Impfstoffe bei Nierenerkrankungen und Immunsupprimierten? Zahlreiche Beobachtungsstudien legen nahe, dass vor allem eine systemische Immunsuppression eine geringe oder fehlende Antikörperbildung bedingt. Auch Patienten mit fortgeschrittener chronischer Nierenerkrankung, insbesondere mit Dialysepflichtigkeit, ohne Einnahme systemischer Immunsuppressiva haben ein reduziertes humorales Ansprechen. Ich habe eine COVID-19-Erkrankung durchgemacht. Ist für mich eine COVID-19-Impfung sinnvoll? Nach durchgemachter COVID-19-Erkrankung scheint auch für Nierenkranke eine Boosterung mit einem mRNA-Impfstoff sinnvoll zu sein. Kann ich trotz laufender Immunsuppression geimpft werden? Für Patienten unter Immunsuppression ist das Ansprechen auf Impfstoffe reduziert. Dennoch sollten sie geimpft werden. Eine Anti-CD20-Therapie beeinträchtigt die humorale Immunantwort erheblich. Besteht die Möglichkeit einer Abstoßungsreaktion meines Transplantats bzw. eines Rezidivs der Grunderkrankung? Im Zuge der globalen Impfanstrengungen erscheinen nun einzelne Berichte über Erstmanifestationen, Schübe oder Krankheitsrezidive über das Spektrum autoimmuner Nierenerkrankungen, die in zeitlichem Zusammenhang mit der Impfung stehen. Da die meisten Rezidive/Abstoßungen behandelbar sind, der Verlauf einer COVID-19-Erkrankung aber oftmals schwer bzw. tödlich ist, überwiegt der Nutzen die Risiken. Habe ich eine dauerhafte Protektion nach erfolgter COVID-19-Impfung? Im Vergleich zur altersentsprechenden gesunden Population weist die nephrologische Patientengruppe nach Impfung deutlich niedrigere Titer auf, welche auch rascher abnehmen (vor allem Evidenz für Transplantierte und Dialyse). Eine frühzeitige Auffrischung sollte auch aufgrund der besorgniserregenden Virusvarianten und der reduzierten Wirksamkeit der Impfstoffe erwogen werden. Nach der ersten Impfserie haben sich keine/kaum Antikörper nachweisen lassen. Gibt es Strategien, die Impfantwort zu verbessern? Viele Länder empfehlen eine 3. Impfdosis für vulnerable Populationen, v. a. auch wegen der reduzierten Antwort nach 2 Dosen bzw. auch des Risikos eines schweren Verlaufs einer COVID-19-Erkrankung. Der Einsatz einer Drittimpfung muss aber im Rahmen prospektiver klinischer Studien überprüft werden.

HOW EFFECTIVE ARE THE APPROVED VACCINES IN KIDNEY DISEASES AND THOSE RECEIVING IMMUNOSUPPRESSION?: Several observational studies indicated that immunosuppression is associated with a weakened or absent humoral response. Patients with chronic kidney diseases or undergoing maintenance dialysis without immunosuppression have a reduced humoral response to COVID-19 vaccines. I HAD COVID-19. SHOULD I GET VACCINATED?: It is recommended to receive a booster after SARS-CoV-2 infection with a mRNA vaccine. IS A COVID-19 VACCINATION DESPITE ONGOING IMMUNOSUPPRESSION POSSIBLE?: Patients receiving immunosuppression have a reduced humoral response, and this is especially observed when anti-CD20 therapy is used. IS THERE A POSSIBILITY THAT THE VACCINE PROVOKES REJECTION OF MY TRANSPLANTED KIDNEY OR RELAPSE OF MY GLOMERULAR DISEASE?: Several reports were published in the last months highlighting new-onset diseases, recurrences and relapses of different glomerular diseases, which occurred after the receipt of the first or second vaccine dose. As a clear association of vaccines and induction of autoimmunity still needs to be established, most of these diseases are treatable, and COVID-19 in patients under immunosuppression is often fatal, there is a clear net benefit of vaccination. DO I HAVE A PERMANENT PROTECTION AFTER VACCINATION?: The antibody titers and likely the cellular immune response is significantly reduced in patients with kidney diseases, and titers are reducing at a fast pace under ongoing immunosuppression. A booster dose should be considered, especially taking into consideration the evolvement of virus variants and their impact on vaccine efficacy. AFTER THE FIRST SERIES OF VACCINATION, NO OR ONLY A MARGINAL AMOUNT OF ANTIBODIES WERE DETECTABLE. ARE THERE STRATEGIES TO IMPROVE VACCINE RESPONSE?: Many countries recommend the application of a third dose for vulnerable patient cohorts, especially because of a weakened response and their risk to develop a severe disease course of COVID-19. Prospective clinical trials are ongoing to test the ideal strategy to improve vaccine response in these cohorts.WIE EFFEKTIV SIND DIE ZUGELASSENEN IMPFSTOFFE BEI NIERENERKRANKUNGEN UND IMMUNSUPPRIMIERTEN? : Zahlreiche Beobachtungsstudien legen nahe, dass vor allem eine systemische Immunsuppression eine geringe oder fehlende Antikörperbildung bedingt. Auch Patienten mit fortgeschrittener chronischer Nierenerkrankung, insbesondere mit Dialysepflichtigkeit, ohne Einnahme systemischer Immunsuppressiva haben ein reduziertes humorales Ansprechen. ICH HABE EINE COVID-19-ERKRANKUNG DURCHGEMACHT. IST FüR MICH EINE COVID-19-IMPFUNG SINNVOLL?: Nach durchgemachter COVID-19-Erkrankung scheint auch für Nierenkranke eine Boosterung mit einem mRNA-Impfstoff sinnvoll zu sein. KANN ICH TROTZ LAUFENDER IMMUNSUPPRESSION GEIMPFT WERDEN?: Für Patienten unter Immunsuppression ist das Ansprechen auf Impfstoffe reduziert. Dennoch sollten sie geimpft werden. Eine Anti-CD20-Therapie beeinträchtigt die humorale Immunantwort erheblich. BESTEHT DIE MöGLICHKEIT EINER ABSTOßUNGSREAKTION MEINES TRANSPLANTATS BZW. EINES REZIDIVS DER GRUNDERKRANKUNG?: Im Zuge der globalen Impfanstrengungen erscheinen nun einzelne Berichte über Erstmanifestationen, Schübe oder Krankheitsrezidive über das Spektrum autoimmuner Nierenerkrankungen, die in zeitlichem Zusammenhang mit der Impfung stehen. Da die meisten Rezidive/Abstoßungen behandelbar sind, der Verlauf einer COVID-19-Erkrankung aber oftmals schwer bzw. tödlich ist, überwiegt der Nutzen die Risiken. HABE ICH EINE DAUERHAFTE PROTEKTION NACH ERFOLGTER COVID-19-IMPFUNG?: Im Vergleich zur altersentsprechenden gesunden Population weist die nephrologische Patientengruppe nach Impfung deutlich niedrigere Titer auf, welche auch rascher abnehmen (vor allem Evidenz für Transplantierte und Dialyse). Eine frühzeitige Auffrischung sollte auch aufgrund der besorgniserregenden Virusvarianten und der reduzierten Wirksamkeit der Impfstoffe erwogen werden. NACH DER ERSTEN IMPFSERIE HABEN SICH KEINE/KAUM ANTIKöRPER NACHWEISEN LASSEN. GIBT ES STRATEGIEN, DIE IMPFANTWORT ZU VERBESSERN?: Viele Länder empfehlen eine 3. Impfdosis für vulnerable Populationen, v. a. auch wegen der reduzierten Antwort nach 2 Dosen bzw. auch des Risikos eines schweren Verlaufs einer COVID-19-Erkrankung. Der Einsatz einer Drittimpfung muss aber im Rahmen prospektiver klinischer Studien überprüft werden.

Patients with kidney diseases should be prioritized for COVID-19 vaccination and the available data suggest that replication-defective viral-vectored vaccines and mRNA vaccines are safe to use. As vaccine responses are likely to be lower in patients with kidney diseases than in the general population, highly potent vaccines should be preferred.

Anti-glomerular basement membrane (GBM) disease (Goodpasture disease) often presents with severe kidney failure and pulmonary hemorrhage. Anti-GBM antibodies are pathogenic, and other autoantibodies such as laminin-521 have been identified recently, potentially indicating a subset with a more severe disease phenotype and poor prognosis. Around 30%-40% of patients are also anti-neutrophil cytoplasmatic antibody (ANCA)-positive and this subset combines features of anti-GBM disease and ANCA-associated vasculitis, with particular impact on long-term treatment. A combination of therapeutic plasma exchange (or immunoadsorption), cyclophosphamide, and glucocorticoids is considered standard of care management, but despite early initiation, patients with poor prognostic factors often remain dialysis dependent. Imlifidase (IdeS), capable to cleave IgG within hours, has been tested in a phase II trial. Among 15 patients, 10 with poor prognosis at baseline (eGFR

The coronavirus disease 2019 (COVID-19) pandemic poses important challenges to the care of patients with immune-mediated kidney diseases and to kidney transplant recipients. Here, we discuss the management of immunosuppression for these patients during the pandemic and suggest potential approaches that could be considered in the absence of validated strategies.

ZusammenfassungANCA-assoziierte Vaskulitiden sind seltene Kleingefäßvaskulitiden, wobei die jährliche Inzidenz in etwa bei 20 pro 1 000 000 Einwohner liegt. Eine Nierenbeteiligung kommt bei über 50% der betroffenen Patienten vor und geht mit Morbidität und Mortalität einher. Ein Screening auf Nierenbeteiligung sollte zum Zeitpunkt der Erstdiagnose und periodisch im Verlauf stattfinden. Eine Nierenbiopsie hat nicht nur einen diagnostischen Nutzen, sondern ist essentiell zur Prognoseabschätzung. Verschiedene histologische Kriterien sind in den letzten Jahren entwickelt worden, welche in den klinischen Alltag Einzug finden werden. Neben glomerulären Veränderungen scheinen für die Langzeitprognose auch tubulointerstitielle Veränderungen von Interesse zu sein. Die Therapie der ANCA-assoziierten Vaskulitis, sowohl in der Induktions- als auch in Erhaltungstherapie, wurde durch Rituximab verändert. Strategien zur Glucocorticoidreduktion bzw. -elimination wurden entwickelt, welche die Nebenwirkungen von Steroiden minimieren sollen. Da eine eingeschränkte Nierenfunktion das kardiovaskuläre Risiko von Patienten mit ANCA-assoziierter Vaskulitis deutlich erhöht, muss auf eine adäquate Kontrolle dieser Faktoren geachtet werden. Zudem haben Patienten während aktiver Phasen der Erkrankung ein hohes thromboembolisches Risiko und bei dementsprechenden Beschwerden sollte frühzeitig ein Screening stattfinden. Zusammengefasst hat das zunehmende wissenschaftliche Interesse auf dem Gebiet der Vaskulitiden dazu geführt, dass die Diagnostik und Therapie über das letzte Jahrzehnt deutlich optimiert wurde. Weitere Studien werden in der Zukunft „maßgeschneiderte“ therapeutische Behandlungen erlauben.

Purpose of Review There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. Recent Findings Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Summary Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a “personalized medicine.”

Although nephrologists are responsible for the long-term care of dialysis patients, physicians from all disciplines will potentially be involved in the management of patients with kidney failure, including patients on peritoneal dialysis, the major home-based form of kidney-replacement therapy. This review aims to fill knowledge gaps of non-experts in peritoneal dialysis and to highlight key management aspects of in-hospital care of patients on peritoneal dialysis, with a focus on acute scenarios to facilitate prompt decision-making. The clinical pearls provided should enable non-nephrologists to avoid common pitfalls in the initial assessment of peritoneal dialysis-related complications and guide their decision regarding when to refer their patients to a specialist, resulting in improved multidisciplinary patient care.

Background: Factor H-related-5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement and follow-up data.Results: 120 patients with a histologically-proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger-sequencing, and selected mutants were studied as recombinant proteins in ELISA and SPR.Eight relevant CFHR5 variations in 14 patients (11.7%) were observed, 5 of them identified as pathogenic for C3G. The FHR-5G278S and FHR-5R356H mutations altered the interaction of FHR-5 with C3b, when compared to the FHR-5WT. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period, furthermore, it showed clear association with signs of hypocomplementemia and clinically meaningful clusters.Conclusions: Our observations support the hypothesis that FHR-5 protein and its genetic alterations play a role in the pathogenesis of IC-MPGN/C3G.

The term refeeding syndrome (RFS) refers to the metabolic perturbations and its attendant complications in subjects who are refed after fasting. The syndrome is characterized by profound shifts of electrolytes and fluids. Its consequences are widespread and sometimes fatal. Patients with malignancies are especially vulnerable due to the presence of multiple comorbidities. We report the course of four patients with malignant or hematological disorders who developed RFS while being treated for their underlying illness. All physicians caring for susceptible patients should be cognizant of the risks of refeeding and treat RFS appropriately to reduce patient morbidity as well as mortality.

Background A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. Methods A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. Results High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2—which is not reliable because of the small number of cases—strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3–4 had worse renal survival than patients in Clusters 1–2. Conclusions Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.

Background Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. Results One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. Conclusions In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10–15% of IC-MPGN/C3G patients.

Background: Hereditary renal hypouricemia (RHUC) is a genetically heterogenous disorder characterized by defective uric acid (UA) reabsorption resulting in hypouricemia and increased fractional excretion of UA; acute kidney injury (AKI) and nephrolithiasis are recognized complications. Type 1 (RHUC1) is caused by mutations in the SLC22A12 gene, whereas RHUC2 is caused by mutations in the SLC2A9 gene. Patient ethnicity is diverse but only few Caucasian families with an SLC2A9 mutation have been reported. Methods: The current report describes the clinical history, biochemical and molecular genetics findings of a native Austrian family with RHUC2. The propositus presented with 2 episodes of exercise-induced AKI and exhibited profound hypouricemia. Mutational screening of the SLC22A12 and SLC2A9 genes was performed. Results: The molecular analyses revealed the homozygous c.512G>A transition that leads to the p.Arg171His missense substitution in SLC2A9, confirming the diagnosis of RHUC2. Segregation study of the causal mutation revealed that the mother and elder sister were heterozygous carriers, whereas the younger sister was found to be homozygous. Conclusion: We report the identification of a novel mutation in SLC2A9 as the cause of RHUC2 in a native Austrian family. We show that glucose transporter 9 mutations cause severe hypouricemia in homozygous individuals and confirm the high risk of AKI in male individuals harbouring these mutations. In our literature review, we provide an overview of the putative underlying pathophysiology, potential renal complications, findings on kidney biopsy as well as potential long-time renal sequelae.

Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations.

The administration of iodinated contrast medium (CM) has immediate negative impact on multiple levels of the nephron, including vasoconstriction, an increase in apoptotic pathways and oxidative stress. Therefore, contrast-induced acute kidney injury (CI-AKI) remains an important cause of sudden impairment of renal function. Far from being just a transient phenomenon, CI-AKI has consistently been shown to be associated with adverse outcomes. The phenomenon of chronic kidney disease (CKD) following AKI might explain why this entity portends a poor prognosis in the long run. While it is generally acknowledged that in individuals with normal renal function, the risk of CI-AKI is negligible, pre-existing renal disease is its greatest independent risk factor. Although several recent publications have challenged the dogma of CI-AKI as a stand-alone disease entity, these trials, despite careful propensity matching, are hampered by their retrospective nature. In this article, we concede that there is always a trade-off and that administration of CM may be justified if its diagnostic value is believed to outweigh its associated risks. However, we reason that despite considerable progress in the field, the risk of CI-AKI is still high in the modern era and that CM-based imaging should be employed with great restraint in patients with CKD.

Rituximab (RTX), a chimeric, monoclonal anti-CD20 antibody, is increasingly used in immune-mediated renal diseases. While licensed in the induction treatment of ANCA-associated vasculitis, it represents one of the most commonly prescribed off-label drugs. Much of the information regarding its safety has been drawn from experience in hematology and rheumatology. Ample evidence illustrates the safety of RTX, however, rare but serious adverse events have emerged that include progressive multifocal leucoencephalopathy and hepatitis B reactivation. Moderate to severe hypogammaglobulinemia and late-onset neutropenia following RTX therapy confer an increased infectious risk and factors predicting these side effects (i.e. a genetic basis) need to be identified. Nephrologists initiating RTX need to bear in mind that long-term risks and optimal dosing for many renal indications remain unclear. Special considerations must be given when RTX is used in women of childbearing age. We summarize practical aspects concerning the use of RTX. This review will provide nephrologists with information to guide their use of RTX alerting them to safety risks and the need for patient counselling.

Leptospirosis is a ubiquitous and potentially fatal zoonosis with protean manifestations. Human infection commonly occurs through contact with contaminated water or soil. In developed countries, leisure or household activities are increasingly associated with the disease. Within few months, we encountered five unrelated and autochthonous cases of severe leptospirosis, three of them requiring interim dialysis. In this case series, we present their clinical course. Furthermore, we provide an overview on the spectrum of organ involvement, with an emphasis on kidney injury, and comment on pitfalls in establishing the diagnosis. The considerable variance in presentation-with admissions both to internal and neurological units-emphasises the high index of suspicion required to arrive at the right diagnosis, particularly in countries of perceived low risk such as Austria.

In this paper, we present two women with hypokalaemic rhabdomyolysis in the context of increased diuretic intake and gastroenteritis, respectively. While their clinical manifestations and laboratory results were strikingly similar, two different underlying disorders were subsequently unveiled. The first patient was diagnosed with Conn syndrome, and adrenalectomy led to significant improvement of hypertension and sustained normokalaemia. The diagnosis in the second patient was Gitelman syndrome. Electrolyte supplements improved long-term lassitude and the frequency of muscle cramps declined significantly. These case vignettes illustrate the importance of establishing the underlying cause of hypokalaemia.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNALeu(UUR). Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney.

We read with interest the case report by Witczak et al .1 The authors describe a young woman who presented with headache, neck stiffness and confusion and was eventually found to have primary adrenal insufficiency. The authors speculate that the patient’s neurological manifestation was a consequence of the underlying adrenal failure, although they acknowledge that there is no reported association of the patient's initial presentation with adrenal crisis. We wonder whether a better recognized entity was considered by the authors, which could easily account for the patient's …

For the treatment of acute ischemic stroke (AIS), IV recominant tissue plasminogen activator (rtPA) has proven efficacy n eligible patients, but carries an increased risk of intracereral hemorrhage [1]. Preexisting anticoagulation, including the irect thrombin inhibitor dabigatran, usually contraindicates the se of rtPA. This notwithstanding, several single cases of IV tPA treatment in patients with AIS under dabigatran have een reported, with mixed results [2]. Endovascular therapy has merged as a potential, yet still experimental, alternative treatment ption for a number of clinical scenarios with contraindications o IV rtPA [3]. We report successful rescue thrombectomy in two patients who uffered AIS under treatment with dabigatran for atrial fibrillation AF).

A 46-year-old lean man presented with rapidly progressing shortness of breath at rest, chest discomfort, lower limb oedema, and general fatigue over the past 3 weeks. Medical history included hearing loss, proteinuria due to focal segmental glomerular sclerosis and visual impairment due to changes in the retinal pigment epithelium and macular dystrophy ( Panels A–C ). The patient had impaired glucose tolerance. Family history showed diabetes and deafness in maternal relatives. On admission, blood pressure was 100/60 mmHg, heart rate was 118 beats …

The acronym MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) belies the true scope of one of the most prevalent mitochondriopathies in adults. While the original description focused on neuromuscular symptoms, we now recognize this syndrome as genetically well defined but phenotypically profoundly heterogeneous, as exemplified by our experience. Here we report the case of a man who initially presented in 1986. In hindsight, his was a classic manifestation of MELAS, but the illness was ascribed to an ill-defined viral encephalitis. Over the years, diabetes and hearing impairment developed and his functional status deteriorated progressively. It took the quarter of a century to arrive at the correct diagnosis. It is worthwhile to keep an open mind when dealing with chronically ill patients with a seemingly clear-cut diagnosis.

The interesting article by Vikrant and colleagues1 prompts us to contribute our recent experience. Herein we report a case in which profound hypothyroidism was the trigger for severe rhabdomyolysis...

To the Editor The development of an acute ischemic stroke (AIS) despite anticoagulant therapy has been called an ‘anticoagulation failure’ (1). In their case report, Tabata et al. (2) reviewed the literature pertaining to the use of intravenous thrombolysis in patients on the new oral anticoagulant (NOAC), dabigatran, presenting with AIS. Their article illustrates the challenges that clinicians face in trying to treat patients in situations where there are no evidence-based recommendations. Given the rapidly growing popularity of the direct oral anticoagulants, stroke neurologists are likely to be confronted with scenarios of this sort more frequently in the near future. All in all, the available case reports about thrombolysis in stroke patients on dabigatran paint a mixed picture, and indicate that there is still a significant risk of bleeding. In a recent review, Epple and Steiner expertly discussed the practical issues inherent to this therapeutic dilemma (1). The authors advised caution and concluded that “it is unlikely that patients on NOAC who experience an AIS would be suitable for thrombolysis, unless they have missed their NOAC dose for the last 24-48 hours”. For this reason, we would like to point to a different treatment option. We and others (3, 4) have shown that neurointerventional recanalization might constitute a promising treatment alternative in centers with high neuroradiological expertise. An endovascular approach using mechanical clot extraction devices does not expose patients to thrombolytic agents. Hence, a lower risk of intracranial hemorrhage is conceivable. All three cases reported so far showed a good clinical outcome. An asymptomatic intimal tear with transient extravasation of contrast medium was deemed likely in the first patient, and represents the only complication reported. As rightly commented by Hankey (5), such a “simple solution” remains unproven in terms of whether it is a safe and effective alternative to thrombolysis. Nevertheless, physicians occasionally face complex clinical situations and patient subgroups for which information derived from controlled clinical trials cannot be applied. We believe that case reports like those by Moey et al. and our group could form the basis of future observational studies. In our opinion, endovascular revascularization might emerge as a valuable treatment option for AIS patients on treatment with dabigatran, and possibly other novel oral anticoagulants.