Carpal tunnel syndrome and peripheral polyneuropathy in patients with end stage kidney disease.

This study was designed to identify the causes of the development of carpal tunnel syndrome (CTS) associated with end stage kidney disease (ESKD). A total of 112 patients with ESKD, 64 on hemodialysis (HD) and 48 on peritoneal dialysis (PD), were enrolled. The duration of ESKD and dialysis, the site of the arteriovenous (A-V) fistula for HD, laboratory data such as blood urea nitrogen, creatinine, and beta-2-microglobulin were determined. Clinical evaluation of CTS and electrophysiological studies for the diagnosis of CTS and peripheral neuropathy were performed. The electrophysiological studies showed that the frequency of CTS was not different in the HD and PD groups (P = 0.823) and the frequency of CTS was not different in the limb with the A-V fistula compared to the contralateral limb (P = 0.816). The frequency of HD and PD were not related to beta-2-microglobulin levels, an indicator of amyloidosis. The frequency of CTS did not increase as the severity of the peripheral neuropathy and the duration of ESKD and dialysis increased (P = 0.307). The results of this study do not support that microglobulin induced amyloidosis or placement of an A-V fistula are associated with an increase in CTS.

Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury.

BACKGROUND: Recent studies provided evidence of the potential role of CD11c(+) F4/80(+) dendritic subset in mediating injury and repair. The purpose of this study was to examine the role of kidney CD11c(+) F4/80(+) dendritic subset in the recovery phase of ischaemia/reperfusion injury (IRI). METHODS: Following ischaemia/reperfusion (I/R), liposome clodronate or phosphate buffered saline (PBS) was administered, and on day 7 biochemical and histologic kidney damage was assessed. Activation and depletion of CD11c(+) F4/80(+) dendritic subset were confirmed by flow cytometry. Isolation of kidney CD11c(+) cells on days 1 and 7 with in vitro culture for measuring cytokines was performed to define functional characteristics of these cells, and adoptive transfer of CD11c(+) cells was also done. RESULTS: Following kidney IRI, the percentage of CD11c(+) F4/80(+) kidney dendritic cell subset that co-expresses maturation marker increased. Liposome clodronate injection after I/R resulted in preferential depletion of CD11c(+) F4/80(+) kidney dendritic subset, and depletion of these cells was associated with persistent kidney injury, more apoptosis, inflammation and impaired tubular cell proliferation. CD11c(+) F4/80(+) cell depletion was also associated with higher tissue levels of pro-inflammatory cytokines and lower level of IL-10, indicating the persistence of inflammatory milieu. Isolated kidney CD11c(+) cells on day 7 showed different phenotype with increased production of IL-10 compared with those on day 1. Adoptive transfer of CD11c(+) cells partially reversed impaired tissue recovery. CONCLUSION: Our results suggest that kidney CD11c(+) F4/80(+) dendritic subset might contribute to the recovery process by dynamic phenotypic change from pro-inflammatory to anti-inflammatory with modulation of immune response.

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury.

BACKGROUND: Ischaemia/reperfusion is a major cause of acute kidney injury and can result in poor long-term graft function. Although most of the patients with acute kidney injury recover their renal function, significant portion of patients suffer from progressive deterioration of renal function. A persistent inflammatory response might be associated with long-term changes following acute ischaemia/reperfusion. Macrophages are known to infiltrate into tubulointersitium in animal models of chronic kidney disease. However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. We aimed to investigate the role of macrophages on the development of tubulointerstitial fibrosis and functional impairment following acute ischaemia/reperfusion injury by depleting macrophages with liposome clodronate. METHODS: Male Sprague-Dawley rats underwent right nephrectomy and clamping of left renal vascular pedicle or sham operation. Liposome clodronate or phosphate buffered saline was administered for 8 weeks. Biochemical and histological renal damage and gene expression of various cytokines were assessed at 4 and 8 weeks after ischaemia/reperfusion. RESULTS: Ischaemic/reperfusion injury resulted in persistent inflammation and tubulointerstital fibrosis with decreased creatinine clearance and increased urinary albumin excretion at 4 and 8 weeks. Macrophage depletion attenuated those changes. This beneficial effect was accompanied with a decrease in gene expression of inflammatory and profibrotic cytokines. CONCLUSIONS: These results suggest that macrophages play an important role in mediating persistent inflammation and fibrosis after ischaemia/reperfusion leading to a development of chronic kidney disease. Strategies targeting macrophage infiltration or activation can be useful in the prevention of development of chronic kidney disease following ischaemic injury.

Heat preconditioning attenuates renal injury in ischemic ARF in rats: role of heat-shock protein 70 on NF-kappaB-mediated inflammation and on tubular cell injury.

Although heat preconditioning has been known to be protective in various types of injury, the precise molecular mechanism for this is unclear. Recent observations that indicate that previous heat shock has an anti-inflammatory, antiapoptotic effect led to this investigation of the in vivo effect of heat preconditioning on NF-kappaB activation and inflammation and also on tubular cell injury in ischemic acute renal failure (ARF). Heat preconditioning provided marked functional protection and also reduced histologic evidence of tubular necrosis. Ischemia/reperfusion-induced NF-kappaB activation was suppressed by heat preconditioning with a subsequent decrease in monocyte chemoattractant protein-1 expression and inflammatory cell infiltration. Heat preconditioning also suppressed the accumulation of phosphorylated inhibitory kappaBalpha (IkappaBalpha) with a resultant depletion of cytoplasmic IkappaBalpha, indicating that heat preconditioning blocked the activation of the IkappaB kinase complex. Tubular cell apoptosis, determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, also was decreased by heat preconditioning, and this was accompanied by decreased caspase 3 activation. Among several heat-shock proteins (HSP), HSP-70 was induced primarily by heat preconditioning. Inhibition of HSP-70 by quercetin almost completely reversed the functional protection that was provided by heat preconditioning. These data provide evidence that HSP-70 affords protection via inhibition of NF-kappaB-mediated inflammation and also inhibition of the cell death pathway in ischemic ARF. Further elucidation of the cytoprotective mechanism of stress proteins could facilitate new target or drug development in the treatment of ARF.

A case of multiple organ failure due to heat stoke following a warm bath.

Heat stroke is a potentially fatal disorder that's caused by an extreme elevation in body temperature. We report here an unusual case of multiple organ failure that was caused by classical, nonexertional heat stroke due to taking a warm bath at home. A 68 year old diabetic man was hospitalized for loss of consciousness. He was presumed to have been in a warm bath for 3 hrs and his body temperature was 41degrees C. Despite cooling and supportive care, he developed acute renal failure, disseminated intravascular coagulation (DIC) and fulminant liver failure. Continuous venovenous hemofiltration was started on day 3 because of the progressive oligouria and severe metabolic acidosis. On day 15, septic ascites was developed and Acinetobacter baumanii and Enterococcus faecium were isolated on the blood cultures. In spite of the best supportive care, the hepatic failure and DIC combined with septic peritonitis progressed; the patient succumbed on day 25.