Cardiovascular disease (CVD) is a major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Two decades ago, the common co‐existence of malnutrition and systemic inflammation PD ...patients with atherosclerosis and CVD led to the proposed terminology of ‘malnutrition‐inflammation‐atherosclerosis (MIA) syndrome’. Although the importance of malnutrition is well accepted, frailty represents a more comprehensive assessment of the physical and functional capability of the patient and encompasses the contributions of sarcopenia (a key component of malnutrition), obesity, cardiopulmonary as well as neuropsychiatric impairment. In recent years, it is also increasingly recognized that fluid overload is not only the consequence but also play an important role in the pathogenesis of CVD. Moreover, fluid overload is closely linked with the systemic inflammatory status, presumably by gut oedema, gastrointestinal epithelial barrier dysfunction and leakage of bacterial fragments to the systemic circulation. There are now a wealth of published evidence to show intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on PD, a phenomenon that we propose the term ‘FIFA complex’. In this system, frailty and atherosclerotic disease may be regarded as two patient‐oriented outcomes, while inflammation and fluid overload are two inter‐connected pathogenic processes. However, there remain limited data on how the treatment of one component affect the others. It is also important to define how treatment of fluid overload affect the systemic inflammatory status and to develop effective anti‐inflammatory strategies that could alleviate atherosclerotic disease and frailty.
Summary at a Glance
There are intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on peritoneal dialysis (PD).
We propose the term ‘FIFA complex’, with frailty and atherosclerotic disease as two patient‐oriented outcomes, while inflammation and fluid overload as two inter‐connected pathogenic processes.
Background: Endocan is associated with endothelial dysfunction. In peritoneal dialysis (PD) patients, cardiovascular disease is a common cause of mortality. We examined the relationship between serum ...endocan level and clinical outcome of PD patients. Methods: We recruited 193 new PD patients (118 males, mean age 58.8 ± 11.6 years). Serum endocan levels were determined and stratified into tertile 1 (lowest) to 3 (highest). Nutritional status, arterial pulse wave velocity (PWV) and serum C-reactive protein (CRP) levels were measured. The patients were followed for at least 4 years for clinical outcomes. Results: For the whole cohort, patients with higher serum endocan levels had lower serum albumin and subjective global assessment score, higher carotid-femoral PWV, and higher serum CRP. For patients with suboptimal blood pressure (BP) control, cardiovascular event-free survival was 95.0, 95.5, and 78.5% for tertiles 1, 2, and 3 at 60 months respectively (p = 0.019). Multivariate Cox regression analysis showed that serum endocan level was an independent predictor of cardiovascular event-free survival. No association with cardiovascular event-free survival was found for patients with adequate BP control (95.0, 92.3, and 100% for tertile 1, 2, and 3 at 60 months, respectively, p = 0.6). Conclusions: Higher serum endocan level is associated with unfavourable nutritional, arterial and inflammatory conditions in PD patients. In patients with suboptimal BP control, higher serum endocan is also associated with worse cardiovascular outcome.
Peritoneal dialysis-related peritonitis remains a significant complication and an important cause of technique failure. Based on current International Society for Peritoneal Dialysis guidelines, ...diagnosis of peritonitis is made when two of the three following criteria are met: 1) clinical features consistent with peritonitis; 2) dialysis effluent white blood cell count of >100 cells/μL; 3) positive effluent culture. However, early and accurate diagnosis can still be faulty, and emphasis has been placed on improving the timeliness and accuracy of diagnosis to facilitate early effective treatment. There have been advances in the novel diagnostic tests such as point-of-care molecular tests, genetics sequencing, mass spectrometry, and machine learning algorithm with immune fingerprinting. This article will discuss the latest evidence and updates of these tests in the management of peritoneal dialysis-related peritonitis.
Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping ...presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still's disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing.
A 42 years old man was admitted with suspected adult-onset Still's disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still's disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml).
Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.
Background:
Peritoneal dialysis (PD)-related peritonitis caused by non-tuberculous mycobacteria (NTM) are difficult to diagnose, is associated with significant morbidity and mortality, and clinical ...course remains unclear. We determined the prevalence and clinical course of peritonitis caused by these organisms through our kidney registry over 20-year period.
Method:
We reviewed all patients with NTM peritonitis identified in our tertiary centre between July 2000 and July 2020. The demographic characteristics, microbiological and clinical outcomes were examined.
Result:
Among 27 patients identified, 20 patients presented with abdominal pain and all had cloudy peritoneal fluid. Twenty-one cases had concomitant exit site infection and 14 cases had prior antibiotic use. The majority of the cases are caused by Mycobacterium chelonae (37%) and Mycobacterium fortuitum (29.7%), with most being resistant to fluoroquinolones (59.3%) and cefoxitin (73.1%). They are all sensitive to amikacin otherwise. None of the cases achieve primary response at day 10 and 20 cases resulted in Tenckhoff catheter removal. Only two of them were able to resume PD. Eight patients died in our cohort. The presence of exit site infection, the use of prior antibiotics and topical disinfectants did not associate with a poorer outcome.
Conclusion:
NTM peritonitis remains difficult to treat and often with a delay in diagnosis. Refractory peritonitis with negative culture and a poor response to standard antibiotics should raise a possibility of NTM infection and prompt catheter removal and an expert with experience treating NTM infections should be consulted.
Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for ...lupus nephritis.
We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions.
The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = -0.423,
= 0.018) and ANRIL levels (r = -0.483,
= 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = -0.383,
= 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (
= 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = -0.321,
= 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (
= 0.003) and minimal change nephropathy (
= 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706,
= 0.01).
We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis.
Controversies in Living Kidney Donation Fung, Winston Wing-Shing; Chapman, Jeremy; Nangaku, Masaomi ...
Seminars in nephrology,
July 2022, 2022-07-00, Letnik:
42, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The most precious gift that can be given is, arguably, a living organ to a person in need of replacement because of failure of that organ. Kidney transplantation remains the best modality of renal ...replacement therapy and there is an ever-increasing demand for organ donation. The inability of cadaveric organ donation to meet the needs of the increasing numbers of patients on global waiting lists highlights the important needs for alternate sources for kidneys such as those from living kidney donation. However, living donor kidney transplantation has been a focus of intense debate, with ethical concerns and controversies emanating from operating on an individual who does not need, and is put at a small but quantifiable risk from, the surgical intervention. Furthermore, health care systems across the world also are funded with different levels of national and individual affordability, leading to health inequalities for the sick and risks of exploitation for the poor, especially through commercialization of transplantation. This article highlights some of these contemporary ethical concerns and controversies in living organ donation.
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