The Clinical Significance of Serum and Urinary Neopterin Levels in Several Renal Diseases

Neopterin is a pyrazino-pyrimidine compound, and is known to be a marker associated with cell-mediated immunity in various diseases. We hypothesized that the levels of serum and urine neopterin would be elevated in renal disease, and would correlate with certain clinical parameters. We evaluated serum and urinary neopterin levels in patients with several renal diseases, including nephrotic syndrome (NS, n=19), chronic renal failure (CRF, n=8), end stage renal disease (ESRD, n=64) and controls (n=22). Serum neopterin was elevated in patients with CRF and ESRD, as compared to controls. Urinary neopterin levels were also found to be elevated in patients with CRF and ESRD, as compared to controls. Serum neopterin levels showed significant positive correlation with age, serum BUN and creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, serum albumin and total iron binding capacity. Urine neopterin levels exhibited positive correlation with age and serum creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, BUN and serum albumin. In conclusion, increased serum and urinary neopterin levels were found in some patients with renal disease and were correlated with certain clinical parameters.

Clinical Significance of Serum and Urinary Neopterin Levels in Some Renal Diseases / 대한신장학회잡지

BACKGROUND: Neopterin is a pyrazino-pyrimidine compound, produced by human monocytes or macrophages primarily upon stimulation with gamma interferon. Neopterin is a marker associated with cell- mediated immunity. The levels of neopterin in body fluids are elevated in allograft rejection, infections, autoimmune diseases, malignancies, cardiac and renal diseases. We hypothesized that the levels of serum and urine neopterin maybe elevated in some renal disease including nephrotic syndrome (NS), chronic renal failure (CRF) and end stage renal disease (ESRD). METHODS: We examnined the serum and urinary neopterin levels in 19 patients with NS underwent renal biopsy, 8 patients with CRF, 64 patients with ESRD undergoing maintenance hemodialysis. Twenty-two healthy controls were enrolled to define the normal range of neopterin levels. Serum and urinary neopterin were measured by radiommunoassay method. We also correlated the levels of serum and urinary neopterin with many clinical parameters such as WBC, hemoglobin, hematocrit, BUN, creatinine, total protein, albumin, triglyceride, iron, total iron binding capacity. RESULTS: The serum neopterin levels elevated in patients with NS (14.1+/-30.9 ng/mL), CRF (28.2+/-19.4 ng/mL) and ESRD (68.6+/-25.5 ng/mL) than control (1.6+/-0.3 ng/mL). Particularly the patients with CRF and ESRD showed statistically significant elevation (p<0.05, p<0.01). The urine neopterin levels elevated in patients with NS (203.2+/-349.6 microgramol/mol creatinine), CRF (319.2+/-107.7 microgramol/mol creatinine) and ESRD (407.9+/-256.9 microgramol/mol creatinine) than control (108.9+/-57.9 microgramol/mol creatinine). Particularly the patients with CRF and ESRD showed statistically significant elevation (p<0.05, p<0.05). The serum neopterin showed significantly positive correlation with serum creatinine levels, inverse correlation with total iron binding capacity and serum triglyceride levels among clinical parameters in all groups (respectively p<0.01). The urine neopterin showed significant inverse correlation with hemoglobin (p< 0.05). CONCIUSION: The serum and urinary neopterin levels elevated in patients with some renal diseases. And also neopterin levels showed clinical correlations with some renal parameters in these patients. We suggest that serum and urinary neopterin levels may be useful marker to predict disease acitivity and prognosis in some renal diseases. They should be confirmed by a prospective study during a long-lasting and in a higher number of patients.

A decrease in glomerular filtration rate with aging: the effect of smoking and obesity / 대한내과학회지

BACKGROUND: The kidney function with aging is the dramatic changes of human organ system. Recent studies have suggested that many risk factors such as smoking and obesity could contribute to the progression of chronic kidney disease, though there is a little evidence in the literature showing this relationship in the general population prospectively. We aimed to identify the change of calculated glomerular filtration rate (GFR) with aging in healthy adults and to evaluate the effect of prior risk factors to the change of GFR after 5 years follow-up. METHODS: This study included 3,928 healthy adults who participated in health screening examinations in 1997 and 2002. Average age was 42 +/- 5 years in 2002 (2,955 males, 973 females). The study population had no diabetes, hypertension, renal disease and other major diseases. The clinical and laboratory monitoring were performed each on 1997 and 2002; 5 years follow-up. In this study population, GFR was calculated using the MDRD (Modification of Diet in Renal Disease) equation: calculated GFR = 186 X Scr(-1.154) X age(-0.203) X (0.742 if female). We evaluated the change of calculated GFR with aging and compared the change of calculated GFR after 5 years follow-up according to smoking and obesity. RESULTS: The decreased GFR in adults was associated with aging. The mean calculated GFR (mean +/- SD) was 82.2 +/- 9.7 mL/min/1.73 m2 at 1997, 76.2 +/- 9.1 mL/min/1.73 m2 at 2002, respectively, so decrease is 6.0 mL/min/1.73 m2/yr (1.2 mL/min/1.73 m2/yr). The change of calculated GFR was more decreased in smoking group (5.2 vs 5.0 mL/min/1.73 m2) and obesity group (6.4 vs 5.7 mL/min/1.73 m2), but not statistically significant(p>0.05). CONCLUSION: Aging is an important factor of decrease in renal function. The mean decrease in calculated GFR was 1.2 mL/min/1.73 m2/yr. We suggest that smoking and obesity had some effects on decrease in renal function. These changes in renal function should be confirmed by a prospective study for a long period and in a large number of subject.

Eosinophilic Peritonitis in a Patient with Continuous Ambulatory Peritoneal Dialysis (CAPD)

Eosinophilic peritonitis is defined as when there are more than 100 eosinophils present per milliliter of peritoneal effluent, of which eosinophils constitute more than 10% of its total WBC count. Most cases occur within the first 4 weeks of peritoneal catheter insertion and they usually have a benign and self-limited course. We report a patient of eosinophilic peritonitis that was successfully resolved without special treatment. An 84-year-old man with end stage renal disease secondary to diabetic nephropathy was admitted for dyspnea and poor oral intake. Allergic history was negative. and physical examination was unremarkable. Complete blood count showed a hemoglobin level of 11.1 g/dL, WBC count was 24, 500/mm3 (neutrophil, 93%; lymphocyte, 5%; monocyte, 2%), platelet count was 216, 000/mm3, serum BUN was 143 mg/dL, Cr was 5.7 mg/dL and albumin was 3.5 g/dL. Creatinine clearance was 5.4 mL/min. Three weeks after peritoneal catheter insertion, he was started on peritoneal dialysis with a 6-hour exchange of 2L 1.5% peritoneal dialysate. After nine days, he developed turbid peritoneal effluents with fever (38.4degrees C), abdominal pain and tenderness. Dialysate WBC count was 180/mm3 (neutrophil, 20%; lymphocyte, 4%; eosinophil, 76% [eosinophil count: 136/mm3]). Cultures of peritoneal fluid showed no growth of aerobic or anaerobic bacteria, or of fungus. Continuous ambulatory peritoneal dialysis (CAPD) was commenced, and he was started on intraperitoneal ceftazidime (1.0 g/day) and cefazolin (1.0 g/day). After two weeksr, the dialysate had cleared up and clinical symptoms were improved. Dialysate WBC count decreased to 8/mm3 and eosinophils were not detected in peritoneal fluid. There was no recurrence of eosinophilic peritonitis on follow-up evaluation, but he died of sepsis and pneumonia fifteen weeks after admission.

The relationship between eosinophilia and serum cytokine concentrations in maintenance hemodialysis patients / 대한내과학회지

BACKGROUND: Eosinophilia in hemodialysis (HD) patients has been associated with allergic reactions to dialyzers and exaggerated activation of complement during HD. Complement activation can lead to cytokine production. The cause of the eosinophilia is controversial and maybe multifactorial. Eosinophilia is stimulated by T lymphocytes and maybe related to the immune dysfunction of uremic patients. The aim of this study is to elucidate the relationship between the eosinophilia and serum cytokine concentrations in maintenance HD patients and to reveal whether the eosinophilia in HD patients reflects HD-associated cytokine production. METHODS: We examined 40 HD patients who were stable for a minimum of 3 months at our hemodialysis unit. We measured eosinophil count and eosinophil percent on peripheral blood smear. Eosinophilia was defined as >or=350 cells/mm3 or >or=5% on smear. The serum concentrations of Interleukin-1beta (IL-1beta), Interleukin-2 (IL-2), Interleukin-5 (IL-5), Interleukin-6 (IL-6) were measured by ELISA before (pre) and after (post) dialysis. RESULTS: Thirteen patients with eosinophilia were compared 27 patients without eosinophilia. In patients with eosinophilia, serum concentrations of IL-1beta and IL-2 were significantly elevated after dialysis than before dialysis (p<0.05). Post-HD IL-6 concentrations also were elevated, but statistically insignificant. IL-5 concentrations were not elevated after dialysis. In patients without eosinophilia, serum concentrations of IL-1beta, IL-2 and IL-6 were significantly elevated after dialysis (p<0.05). IL-5 concentrations were not elevated after dialysis. The eosinophil counts were not correlated to age, gender, underlying disease, serum levels of blood urea nitrogen, creatinine, albumin, CRP and the levels of post dialysis cytokines. CONCLUSION: Independently on eosinophilia in HD, the serum concentrations of cytokines (IL-1beta, IL-2 and IL-6) were elevated after HD. IL-5 concentrations were not elevated after dialysis. But we could not reveal whether the eosinophilia in maintenance HD patients may be a surrogate marker for the reflection of exaggerated cellular cytokine production during HD or not by this study.