Leukocyte toll-like receptor expression in end-stage kidney disease.

BACKGROUND: End-stage renal disease (ESRD) is simultaneously associated with inflammation, impaired immunity and increased susceptibility to microbial infections. Innate immune cells, monocytes and polymorphonuclear leukocytes (PMN) recognize pathogens via toll-like receptors (TLR) triggering phagocytosis, cellular activation and secretion of inflammatory cytokines. Data on expression and function of TLRs in ESRD are limited. METHODS: Blood samples from 21 stable ESRD patients and 21 normal controls were processed for TLR2, TLR4, TLR7 and TLR 9 expression on monocytes and PMN by flow cytometry. TLR activity was examined by determining the response to TLR4 and TLR2 ligands. RESULTS: The ESRD group exhibited significant upregulation of TLR2 and TLR4 (but not TLR7 or TLR 9) expressions on monocytes and of TLR4 on PMN. This was coupled with heightened cytokine production in response to TLR4 activation with lipopolysaccharide. However, the response to TLR2 stimulation with peptidoglycan was unchanged in the ESRD group. CONCLUSIONS: Monocyte TLR2 and TLR4 and neutrophil TLR4 expressions and TLR4 activity are increased hemodialysis patients, representing another dimension of ESRD-associated inflammation.

Proteinuria in patients with arterial/arteriolar nephrosclerosis.

UNLABELLED: Controversy exists regarding the level of proteinuria in patients with nephrosclerosis. MATERIAL AND METHODS: We retrospectively examined the clinical parameters of 67 patients with the histologic diagnosis of nephrosclerosis defined as arteriolar hyalinization and/or arterial intimal fibrosis in the absence of other findings in an adequate renal biopsy. Biopsies were performed for clinical indications and were submitted to Cedars-Sinai Pathology Department from January 1994 to March 1999. RESULTS: The mean age and blood pressure (+/- SD) was 60 +/- 17 years, and 139 +/- 19/80 +/- 12 mmHg. Mean serum creatinine was 2.3 +/- 1.3 mg/dl and 24-hour urinary protein excretion was 0.94 +/- 0.73 g, 66% had < or = 1 g/day, 25% had > 1 but < or = 2 g/day, 6% had > 2 g but < 3 g/day and 1 patient had nephrotic range proteinuria. Twelve patients had no history of hypertension. They had a mean blood pressure of 121 +/- 8/76 +/- 8. Their mean serum creatinine was 1.5 +/- 0.6 mg/dl and their mean 24-hour urinary protein excretion was 0.78 +/- 0.43 g. CONCLUSIONS: Our data do not confirm that of Innes et al. [1993] who reported proteinuria > 1.5 g/day in 40% and nephrotic syndrome in 22% of patients with nephrosclerosis; systemic hypertension may not be a prerequisite for the development of nephrosclerosis.

Continuous arteriovenous hemodiafiltration in postoperative and traumatic renal failure.

Management of acute renal failure (ARF) in surgical patients has relied on supportive measures including hemodialysis and peritoneal dialysis. An alternative technique currently available is continuous arteriovenous hemodiafiltration (CAVH-D). Records of 44 surgical patients with ARF who were treated with CAVH-D in our surgical intensive care unit from 1989 to 1992 were reviewed. Thirty-five patients underwent emergency operations, and 4 patients underwent elective operations. Thirty-three patients were hemodynamically unstable immediately prior to the institution of CAVH-D, making hemodialysis a contraindication. A total of 565 CAVH-D days with an average of 13 days per patient were evaluated. Seventeen patients survived, with recovery of renal function in 13 patients. Vascular access was obtained via 227 percutaneous femoral catheters and 4 Scribner shunts. Seven vascular complications occurred, including arteriovenous fistula, pseudoaneurysm, limb ischemia, femoral artery hemorrhage, and femoral vein thrombosis. Based on these data, we conclude that CAVH-D is a safe and effective alternative in surgical patients with ARF.

Hepatobiliary pathology in hemodialysis patients: an autopsy study of 78 cases.

Necropsy findings of hepatobiliary system from 78 patients with end-stage renal disease maintained on hemodialysis are reported. Ninety percent of the patients exhibited some abnormalities. Multiple abnormalities often coexisted in each patient. Hepatomegaly was found in 50% of the patients and could be attributed to a discernible cause in all but two of the affected patients who had isolated hepatomegaly. Hepatic congestion was also prevalent and was complicated by fibrosis, cardiac cirrhosis, and centrilobular necrosis and hemorrhage in some patients. This was associated with chronic fluid overload, hypertension, and/or cardiovascular disease in the affected patients indicating the importance of adequate control of these factors. Mild periportal hepatic fibrosis, fatty metamorphosis, triaditis, hemosiderosis, and cystic changes were also seen with some frequency--the latter were associated with polycystic kidney disease and were complicated by massive intracystic hemorrhage and abscess formation, each in one patient. Chronic active hepatitis was found in three patients and was associated with chronic HBs antigenemia in one patient and presumed non-A, non-B infection in two. Nearly 22% of the patients showed either cholelithiasis at autopsy or before cholecystectomy due to complications. Significant negative findings included lack of acute viral hepatitis, silicone hepatosis, and recently described focal anoxic lesions associated with erythrocyte sludging. In conclusion, the present study has demonstrated the spectrum of hepatobiliary pathology in a large group of patients with end-stage renal disease maintained on hemodialysis.

Cardiovascular pathology in dialysis patients with spinal cord injury.

Necropsy findings were examined in 20 male patients with end-stage renal disease associated with longstanding spinal cord injury and treated with maintenance hemodialysis. All patients exhibited cardiovascular abnormalities. Fibrinous pericarditis was found in 50% of the patients. Left and right ventricular hypertrophy was present in 45% and 20% of the cases, respectively. The respective incidences of left and right ventricular dilatation were 40% and 30%. Cardiac amyloidosis was noted in 25% of the cases, whereas myocardial fibrosis was found in 45% of the patients. Valvular abnormalities were limited to one case of aortic stenosis and two cases of mitral ring dilatation. No evidence of infective endocarditis was observed despite the high incidence of infections in this population. Whereas 45% of the patients exhibited some degree of coronary arteriosclerosis, none exhibited evidence of acute myocardial infarction and only one showed pathologic changes consistent with old myocardial infarction. Aortic atherosclerosis was noted in the majority of patients.

Clinicopathological characteristics of dialysis patients with spinal cord injury.

Forty-three spinal cord injured patients with endstage renal disease (ESRD) maintained on hemodialysis were studied. The most prevalent renal lesions consisted of chronic pyelonephritis and amyloidosis while the main renal functional features included nephrotic range proteinuria, high urine output and relatively low serum creatinine for the degree of renal insufficiency. Normocytic, normochromic anemia with low reticulocyte response, low serum iron and iron binding capacity and high transfusion requirement and serum ferritin were noted. Various cardiovascular, pulmonary and gastrointestinal abnormalities were found with considerable frequencies. The incidence of amyloidosis was much higher than that reported previously. This is thought to be due to continued progression of amyloidosis occasioned by longer survival in the present series.