Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial.

BACKGROUND: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. METHODS: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. RESULTS: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. CONCLUSIONS: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.

The macrophage is the predominant inflammatory cell in renal allograft intimal arteritis.

BACKGROUND: Intimal arteritis defines acute vascular rejection in the Banff 97 schema. The arteritis is generally considered to be lymphocytic, although the cellular infiltrate in tubulitis is composed of both lymphocytes and macrophages. This study aimed to determine the extent of macrophage involvement in renal allograft intimal arteritis. METHODS: We obtained archival biopsy material from 57 biopsies of 34 renal allografts transplanted between March 1999 and February 2002. All biopsies were diagnostic. We examined clinical and histological parameters. Biopsies were graded using the Banff 97 criteria. We identified macrophages and memory T cells using immunohistochemistry for CD68 and CD45RO, respectively. RESULTS: In all, 24 biopsies showed borderline rejection, and 12 biopsies showed grade IA, 13 showed grade IB, and 8 showed grade II or III acute rejection. Both lymphocytes and macrophages were present in the tubulointerstitium in all grades of acute rejection. We identified intimal arteritis in 10 vessels in eight biopsies. The infiltrating cells invariably included CD68-positive cells; however, we saw intimal CD45RO-positive cells in only seven vessels. There were significantly more CD68-positive cells than CD45RO-positive cells (mean, 9.5 vs. 4.4 positive cells per vessel, P< 0.01). CD45RO cells were never the predominant component of the intimal inflammatory infiltrate. CONCLUSIONS: In the intimal arteritis of biopsies graded as Banff II or III acute rejection, the infiltrating cells were predominantly macrophages. T cells were in the minority. This finding challenges the assumption that the mononuclear cells in intimal arteritis are predominantly lymphocytic.

Predictors of chronic allograft nephropathy from protocol biopsies using histological and immunohistochemical techniques.

AIM: Chronic allograft nephropathy is a predictor of poor allograft survival. Protocol and diagnostic biopsies were used to identify markers contributing to its pathogenesis. METHODS: Diagnostic, 3- and 12-month protocol biopsies in renal transplant recipients were examined. Immunohistochemical staining with monoclonal antibodies for memory T cells (CD45RO), macrophages (CD68) and alpha smooth muscle actin was undertaken on protocol biopsies. RESULTS: Protocol biopsies revealed the incidence of chronic allograft nephropathy to be 10.7% (3/28) at 3 and 57.6% (19/33) at 12 months. There was a trend towards a higher serum creatinine in patients with chronic allograft nephropathy compared with those without (0.15 +/- 0.04 vs 0.12 +/- 0.04 mmol/L, P = 0.047). The strongest predictor of chronic allograft nephropathy at 12 months was the presence of arteriolar hyaline change (P = 0.035; odds ratio 1.22, 95% CI 0.036-0.887) whereas a higher CD45RO and CD68 count at 12 months was associated with chronic allograft nephropathy (74.7 +/- 56.9 cells/mm(2) and 22.4 +/- 23.5 cells/mm(2)) compared with patients without it (29.2 +/- 29.2 cells/mm(2) and 8.3 +/- 9.9 cells/mm(2), P = 0.006 and P = 0.03, respectively). The number of smooth muscle actin positive cells correlated significantly with chronic allograft nephropathy at 12 month (107.6 +/- 44 vs 73.9 +/- 20.8 cells/mm(2), P = 0.009). CONCLUSION: The high prevalence of chronic allograft nephropathy in renal transplant recipients is associated with renal dysfunction. Arteriolar hyalinosis was the most significant predictor at 12 months. There was a significantly higher macrophage and T cell infiltrate in stable grafts undergoing chronic allograft nephropathy at 12 months post transplant.