Anti-neutrophil cytoplasmic antibodies:Current diagnostic and pathophysiological potential

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by rapid deterioration of renal function occurring within days or weeks together with signs of glomerulonephritis, that is, proteinuria and hematuria with cellular casts. The syndrome is, in many cases, histopathologically manifested as fibrinoid necrosis of the capillary wall with extracapillary proliferation and crescent formation [1]. This so-called necrotizing crescentic glomerulonephritis (NCGN) is seen in 5 to 15% of renal biopsies in most series [1–3]. Although it is infrequent, the importance of the condition is illustrated by the fact that most cases of NCGN, if left untreated, develop renal failure within days or weeks [1]. Based on immunohistopathology NCGN can be subdivided into three distinct categories. The first one, occurring in 2 to 20% of the cases and characterized by linear staining of the glomerular capillary wall for immunoglobulin and complement, has classically been described as anti-glomerular basement membrane (GBM) disease. It is associated with autoantibodies to structural antigens of the GBM, in particular to the first globular noncollagen domain of collagen type IV [4]. The antibodies are considered of pathogenetic significance. The second category, comprising 15 to 50% of cases, is characterized by granular deposits of immunoglobulin and complement suggesting that immune complexes are pathogenetically involved. This type occurs in conjunction with systemic autoimmune diseases such as lupus erythematosus, in cases of post-infectious glomerulonephritis, IgA nephropathy or Henoch-Schönlein purpura, or as an idiopathic variety. The third group of NCGN, occurring in 40 to 80%, demonstrates only a few or no immune deposits and is designated as pauci-immune NCGN [1–3, 5, 6]. Pauci-immune NCGN occurs as part of Wegener's granulomatosis (WG) or related conditions, or without systemic vasculitis (idiopathic NCGN). The pathophysiology of this pauci-immune type of NCGN has not been elucidated. Within the last decade, however, it has been recognized that the condition is associated with autoantibodies to cytoplasmic components of neutrophils (anti-neutrophil cytoplasmic antibodies or ANCA).ANCA were first described in 1982 by Davies et al in a few patients with segmental necrotizing glomerulonephritis [7]. Only in 1985 did it become apparent that ANCA are a sensitive and specific marker for Wegener's granulomatosis (WG) [8]. Later on, ANCA were described in patients with microscopic polyarteritis [9]. Falk and Jennette, in 1988, showed that ANCA are also associated with the idiopathic form of pauci-immune NCGN [10]. These data have now been confirmed by many groups and support the view that ANCA-associated glomerulonephritis and vasculitis is, indeed, a distinct disease category. A number of studies, in addition, have suggested that ANCA are involved in the pathophysiology of the aforementioned disorders. As ANCA, however, have recently also been detected in a wide range of inflammatory and infectious conditions, a critical reappraisal of the diagnostic significance of ANCA-testing seems justified.In this review we will evaluate the current state of ANCA-testing as well as elaborate on the pathophysiological role of the autoantibodies in necrotizing glomerulonephritis and vasculitis. Data presented recently at the Fifth International Workshop on ANCA, held in Cambridge, United Kingdom, will be included [11]. As such, it adds to previous reviews on ANCA that were published following the Second [12], Third [13], and Fourth [14] Workshops on ANCA

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Adequacy of peritoneal dialysis and the importance of preserving residual renal function

The well-being and survival of dialysis patients not only depend on the removal of waste products and excess fluid, but also on the prevention of cardiovascular complications by maintaining normovolaemia and adequate blood pressure and avoidance of ectopic calcification. Also, the maintenance of nutritional status and adequate removal of middle molecules are amongst the most important issues in long-term renal replacement therapy. In this review, attention is given to optimal peritoneal small solute clearance and Kt/V and to the evidence concerning the role of residual renal function. In addition, factors that can influence this residual function are also discusse

The influence of bicarbonate supplementation on plasma levels of branched-chain amino acids in haemodialysis patients with metabolic acidosis.

Department of Internal Medicine, University Hospital Maastricht, The Netherlands. BACKGROUND: It has been hypothesized that correction of metabolic acidosis might improve the nutritional state of acidotic haemodialysis (HD) patients partly because of a reduced oxidation of branched-chain amino acids (BCAA). AIM: We investigated whether bicarbonate (Bic) supplementation in acidotic HD patients results in increased plasma levels of BCAA. METHODS: In a longitudinal study (run-in period, 2 months; study period, 6 months), the effect of Bic supplementation on plasma levels of BCAA was studied in 12 acidotic HD patients (7 men, 5 women, mean age 54 +/- 18 years) with a predialysis bicarbonate (Bic) concentration smaller or equal to 22 mmol/l. Bic was supplemented by increasing Bic concentration of the dialysate and by oral Bic supplementation. RESULTS: Predialysis Bic increased significantly during the study period (18.7 +/- 2.7 vs. 23.1 +/- 11.5 mmol/l). There was no change in nutritional parameters. However, plasma levels of the BCAA valine, leucine, and isoleucine increased significantly. CONCLUSIONS: In haemodialysis patients with metabolic acidosis, Bic supplementation over a 6-months period resulted in an increase in plasma levels of BCAA. Further study is needed to elucidate the mechanisms behind, and the clinical importance of the observed changes in plasma BCAA levels

The effect of sodium profiling and feedback technologies on plasma conductivity and ionic mass balance: a study in hypotension-prone dialysis patients.

Item does not contain fulltextBACKGROUND: Sodium profiling improves haemodynamic tolerance in haemodialysis (HD) patients but may also influence sodium homeostasis. Changes in blood volume and plasma conductivity (PC) during HD can be modelled by feedback technology, but their effects on sodium homeostasis are not widely studied. METHODS: This randomized crossover study compared PC and ionic mass balance (IMB) as surrogate markers of sodium balance between standard HD [dialysate conductivity (DC) 14.0 mS/cm], sodium profiling (DC 15.0-->14.0 mS/cm), blood volume (BV)-controlled and PC-controlled feedback (target: post-HD PC: 14.0 mS/cm) in 10 HD patients with frequent hypotension. RESULTS: 440 treatments were studied. Pre-dialytic PC was significantly higher during SP (14.4+/-0.2 mS/cm) compared to standard HD (14.2+/-0.3 mS/cm), and was not different between the other manoeuvres: PC-controlled (14.1+/-0.3 mS/cm), and BV-controlled feedback (14.2+/-0.2 mS/cm). Except for the first treatment, during which IMB was lower during the sodium profile, IMB did not differ significantly between the various manoeuvres and was strongly dependent upon ultrafiltration volume and the difference between pre-dialytic PC and DC. Symptomatic hypotensive episodes occurred least frequently during BV-controlled feedback (8%) compared to the other manoeuvres (standard HD, 16%; sodium profile, 14%; PC-controlled feedback, 17%), but differences were not significant. Inter-dialytic weight gain and pre-dialytic systolic blood pressure did not differ. CONCLUSIONS: Pre-dialytic PC increased during the sodium profile, and did not differ between BV- or PC-controlled feedback compared to standard HD. Thus, it appears that both BV- and PC-controlled feedback can be safely prescribed without substantial salt- and water-loading, at least in the short term. Analysis of IMB is useful to assess differences in sodium balance between single treatment sessions but appears of less value in a steady-state situation

Fluid status in CAPD patients is related to peritoneal transport and residual renal function: evidence from a longitudinal study

Both peritoneal transport characteristics as well as residual renal function are related to outcome in patients treated with continuous ambulatory peritoneal dialysis (CAPD). It has been suggested that part of this relationship might be explained by an effect of both parameters on the fluid state in CAPD patients or by the relationship between inflammation and peritoneal transport. In the present study, the relationship between fluid state [extracellular water (ECW) (sodium bromide); total body water (TBW) (deuterium oxide)] with peritoneal transport characteristics (2.27% glucose dialysate/plasma creatinine [D/P (creat)] ratio), residual renal function (residual glomerular filtration rate [rGFR] by urine collection) and C-reactive protein (CRP) was assessed in 37 CAPD patients in a cross-sectional and longitudinal design, with 25 patients completing the study. In the cross-sectional part ECW, corrected for height (ECW:height), was inversely related to rGFR (r=-0.40, P=0.016), whereas during the longitudinal part, D/P[creat] was related to the change in ECW (r=0.40, P=0.05). Neither D/P[creat] nor rGFR were related to CRP, whereas a significant relationship was observed between ECW:height and CRP (r=0.58, P=0.0001). Patients were dichotomized according to rGFR ( <2 or >2 ml/min). Despite a higher daily peritoneal glucose prescription (216.3+/-60.0 vs 156.5+/-53.0 g/24 h; P=0.004) and peritoneal ultrafiltration volume (1856+/-644 vs 658+/-781 ml/24 h, respectively; P=0.0001), the patients with a rGFR <2 ml/min showed a higher ECW:height compared with the group with rGFR >2 ml/min (12.5+/-3.8 vs 9.2+/-2.2 l/m, respectively; P=0.003). Results for TBW were comparable. Fluid state was significantly related to peritoneal transport characteristics and rGFR. The larger ECW:height in CAPD patients with a negligible rGFR existed despite a higher peritoneal ultrafiltration volume and higher peritoneal glucose prescription. These findings raise doubts as to whether fluid state in CAPD patients with a diminished rGFR can be adequately controlled on standard glucose solutions without an additional sodium and fluid restriction. The preliminary finding of a relationship between CRP and fluid state might suggest a relationship between overhydration and inflammatio