Rituximab in the treatment of primary FSGS: time for its use in routine clinical practice?

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome and whilst advances have been made in the pathophysiology, diagnostics and management of other podocytopathies, primary FSGS remains the most elusive. It has been assumed for a long time that a circulatory permeability factor exists that mediates podocyte injury, and the potential for autoantibody-mediated disease therefore raises the question as to whether patients may benefit from targeted B-cell therapy with rituximab. The prospective case series of seven patients by Roccatello et al. adds to the limited but growing evidence suggesting that B-cell depletion therapy can be safe and effective in the treatment of primary FSGS. In this editorial we explore the available evidence that suggests how and in whom rituximab may play a role in the management of primary FSGS, as well as the limitations and other potential future treatments. Further research and randomized controlled trials are needed to include larger numbers of patients, feature genetic screening and incorporate data on B-cell kinetics as a potential guide for dosing and frequency of rituximab.

Frailty assessment as part of transplant listing: yes, no or maybe?

Frailty, characterized by a decreased physiological reserve and an increased vulnerability to stressors, is common among kidney transplant (KT) candidates and recipients. In this review, we present and summarize the key arguments for and against the assessment of frailty as part of KT evaluation. The key arguments for including frailty were: (i) sheer prevalence and far-reaching consequences of frailty on KT, and (ii) the ability to conduct a more holistic and objective evaluation of candidates, removing the inaccuracy associated with 'eye-ball' assessments of transplant fitness. The key argument against were: (i) lack of agreement on the definition of frailty and which tools should be used in renal populations, (ii) a lack of clarity on how, by whom and how often frailty assessments should be performed, and (iii) a poor understanding of how acute stressors affect frailty. However, it is the overwhelming opinion that the time has come for frailty assessments to be incorporated into KT listing. Although ongoing areas of uncertainty exist and further evidence development is needed, the well-established impact of frailty on clinical and experiential outcomes, the invaluable information obtained from frailty assessments, and the potential for intervention outweigh these limitations. Proactive and early identification of frailty allows for individualized and improved risk assessment, communication and optimization of candidates.

The hypokalaemia that came from the cold.

While electrolyte disorders are common in nephrologists' clinical practice, hypothermia is a condition that nephrologists rarely encounter. Hypothermia can induce several pathophysiological effects on the human body, including hypokalaemia, which is reversible with rewarming. Despite growing evidence from animal research and human studies, the underlying mechanisms of hypothermia-induced hypokalaemia remain unclear. Boubes and colleagues recently presented a case series of hypokalaemia during hypothermia and rewarming, proposing a novel hypothesis for the underlying mechanisms. In this editorial, we review the current knowledge about hypothermia and associated electrolyte changes with insights into the effects of hypothermia on renal physiology.

Wearables in Nephrology: Fanciful Gadgetry or Prêt-à-Porter?

Telemedicine and digitalised healthcare have recently seen exponential growth, led, in part, by increasing efforts to improve patient flexibility and autonomy, as well as drivers from financial austerity and concerns over climate change. Nephrology is no exception, and daily innovations are underway to provide digitalised alternatives to current models of healthcare provision. Wearable technology already exists commercially, and advances in nanotechnology and miniaturisation mean interest is also garnering clinically. Here, we outline the current existing wearable technology pertaining to the diagnosis and monitoring of patients with a spectrum of kidney disease, give an overview of wearable dialysis technology, and explore wearables that do not yet exist but would be of great interest. Finally, we discuss challenges and potential pitfalls with utilising wearable technology and the factors associated with successful implementation.

COVID - 19 in two dialysis centers situated in two neighbouring states of the Western Balkans.

BACKGROUND: Bosnia and Herzegovina (BiH) and Serbia are countries in the Western Balkans that share parts of their social and political legacy from the former Yugoslavia, such as their health care system and the fact that they are not members of European Union. There are very scarce data on COVID - 19 pandemic from this region when compared to other parts of the world and even less is known about its impact on the provision of renal care or differences between countries in the Western Balkans. MATERIALS AND METHODS: This observational prospective study was conducted in two regional renal centres in BiH and Serbia, during the COVID - 19 pandemic. We obtained demographic and epidemiological data, clinical course and outcomes of dialysis and transplant patients with COVID - 19 in both units. Data were collected a via questionnaire for two consecutive time periods: February - June 2020 with a total number of 767 dialysis and transplant patients in the two centres, and July - December 2020 with a total number of 749 studied patients, corresponding to two of the largest waves of the pandemic in our region. Departmental policies and infection control measures in both units were also recorded and compared. RESULTS: For a period of 11 months, from February to December 2020, 82 patients on in-centre haemodialysis (ICHD), 11 peritoneal dialysis patients and 25 transplant patients who tested positive for COVID-19. In the first study period, the incidence of COVID - 19 positive in Tuzla was 1.3% among ICHD patients, and there were no positive peritoneal dialysis patients, or any transplant patients who tested positive. The incidence of COVID-19 was significantly higher in both centres in the second time period, which corresponds to the incidence in general population. Total deaths of COVID-19 positive patients was 0% in Tuzla and 45.5% in Nis during first, and 16.7% in Tuzla and 23.4% in Nis during the second period. There were notable differences in the national and local/departmental approach to the pandemic between the two centres. CONCLUSION: There was poor survival overall when compared to other regions of Europe. We suggest that this reflects the lack of preparedness of both of our medical systems for such situations. In addition, we describe important differences in outcome between the two centres. We emphasize the importance of preventative measures and infection control and highlight the importance of preparedness.

Have we missed AINything? Acute interstitial nephritis in SARS-CoV-2 infection and vaccination.

Acute interstitial nephritis (AIN), defined by the presence of interstitial inflammation accompanied by tubulitis, is an often overlooked cause of acute kidney injury (AKI). It is now well established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide variety of kidney injuries, most commonly acute tubular injury and collapsing glomerulopathy. In comparison, AIN is rarely documented in association with SARS-CoV-2 both anecdotally and in larger series of autopsy or biopsy studies. In this issue of the Journal, León-Román describe five cases of AIN in patients with a history of coronavirus disease 2019 (COVID-19) and highlight AIN as a possibly under-reported or ignored facet of renal disease associated with SARS-CoV-2. They describe three scenarios in which AIN can be seen: (i) SARS-CoV-2 infection after diagnosis of AIN, (ii) AIN followed by SARS-CoV-2 infection in the same admission and (iii) Severe SARS-CoV-2 and AIN possibly associated with SARS-CoV-2 itself. Overall, AIN remains rare in SARS-CoV-2 and causality is difficult to ascertain. Interestingly, AIN is not only seen in association with the disease itself but also with SARS-CoV-2 vaccination. This scenario is equally rare and causality is no less difficult to prove. A history of preceding SARS-CoV-2 infection and vaccination should be actively sought when patients present with otherwise unexplained AIN.

Concurrent presentation of IgG4-related tubulointerstitial nephritis and ANCA MPO crescentic glomerulonephritis.

Concurrent IgG4-related tubulointerstitial nephritis and anti-neutrophil cytoplasmic antibodies (ANCA) myeloperoxidase (MPO) crescentic glomerulonephritis is an uncommon scenario, and the link between the two conditions, if any, is incompletely understood. We report the case of a 58-year-old woman who presented with a 2-month history of malaise and joint pain and was found to have acute kidney injury and hemato-proteinuria. Initial immunological tests revealed positive anti-neutrophil cytoplasmic antibodies with a peri-nuclear pattern (pANCA). An enzyme-linked immunoassay (ELISA) for anti-MPO antibodies was also positive, leading to a tentative diagnosis of ANCA-associated small vessel vasculitis with renal involvement. Steroid treatment was commenced, and an urgent kidney biopsy was performed. This showed crescentic glomerulonephritis, but also demonstrated concurrent tubulointerstitial nephritis with a dominance of IgG4-producing plasma cells. Serum IgG4 levels were also elevated. The patient was initially treated with intravenous cyclophosphamide and steroids and then switched to rituximab. When last seen, she was well after 1 dose of rituximab, with kidney function, inflammatory parameters, and serum IgG4 levels returning to normal levels. The concurrent presentation of ANCA-associated vasculitis and IgG4 renal disease is rare with only few cases reported in the literature. More work is needed to understand pathophysiology, outcomes, and management options for this complex scenario.

Remote digital urinalysis with smartphone technology as part of remote management of glomerular disease during the SARS-CoV-2 virus pandemic: single-centre experience in 25 patients.

Background: The COVID-19 pandemic has necessitated the provision of healthcare through remote and increasingly digitalized means. The management of glomerular pathology, for which urinalysis is crucial, has been notably affected. Here we describe our single-centre experience of using remote digital urinalysis in the management of patients with glomerular disease during the COVID-19 pandemic. Method: All patients with native kidney glomerular disease who consented to participate in digital smartphone urinalysis monitoring between March 2020 and July 2021 were included. Electronic health records were contemporaneously reviewed for outcome data. Patient feedback was obtained through the testing portal. Results: Twenty-five patients utilized the digital urinalysis application. A total of 105 digital urinalysis tests were performed for a wide variety of indications. Four patients experienced a relapse (detected remotely) and two patients underwent three successful pregnancies. The majority of patients were managed virtually (60%) or virtually and face to face (F2F) combined (32%). The average number of clinic reviews and urine tests performed during the pandemic either virtually and/or F2F was comparable to levels pre-pandemic and the ratio of reviews to urinalysis (R:U) was stable (pre-pandemic 1:0.9 versus during the pandemic 1:0.8). Patients seen exclusively F2F with supplementary home monitoring had the highest R:U ratio at 1:2.1. A total of 95% of users provided feedback, all positive. Conclusion: Remote urinalysis proved a safe and convenient tool to facilitate decision-making where traditional urinalysis was difficult, impractical or impossible. Our approach allowed us to continue care in this vulnerable group of patients despite a lack of access to traditional urinalysis.