Tissue level of advanced glycation end products is an independent determinant of high-sensitivity C-reactive protein levels in haemodialysis patients.

AIM: C-reactive protein (CRP) level predicts future cardiovascular events in patients on haemodialysis (HD). Advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in HD patients. However, which variables including tissue AGE levels are independently associated with CRP remains unknown. Therefore, whether tissue AGE and CRP levels were correlated with atherosclerosis in HD patients was examined. METHODS: Fifty-four HD patients underwent determinations of blood chemistries and tissue AGE. Tissue AGE levels were evaluated by measuring skin autofluorescence. Pulsatility index (PI) in the carotid artery was measured using a Doppler ultrasonography. RESULTS: Univariate analyses showed that age, white blood cells, serum albumin (inversely), alkaline phosphatase (inversely), tartrate-resistant acid phosphatase 5b (TRAP5b) (inversely) and skin AGE levels were significantly correlated with high-sensitivity CRP (hsCRP). Multiple stepwise regression analysis revealed that serum albumin, TRAP5b and skin AGE levels were independent determinants of hsCRP. Further, PI was highest among HD patients with high skin AGE and high hsCRP levels. CONCLUSION: The present study suggests that tissue AGE level is one of the independent determinants of hsCRP in HD patients. Tissue AGE and hsCRP levels may be correlated with each other, which could in concert contribute to the progression of atherosclerosis in these subjects.

Interstitial Foxp3-positive T cells may predict renal survival in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

1. Regulatory T cells (T(reg)) and cytotoxic T cells (CTL) are involved in various immune diseases. However, the prognostic impact of T(reg) and CTL in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) is not well known. Therefore, in the present study, we examined the relationship between expression of forkhead box P3 (Foxp3) and T cell intracytoplasmic antigen (TIA)-1, T(reg) and CTL markers and renal survival in patients with MPO-ANCA-GN. 2. Forty patients with MPO-ANCA-GN and 10 patients with minimal change nephrotic syndrome (MCNS) underwent physical examination, determination of blood chemistry and renal biopsy. Immunohistochemical staining for Foxp3 and TIA-1 was performed on paraffin-embedded renal sections. 3. Although almost all patients received standard immunosuppressive treatment for 6 months, seven MPO-ANCA-GN patients needed maintenance haemodialysis (HD), whereas 33 patients did not (non-HD). Both Foxp3- and TIA-1-positive cells were detected in the interstitium and glomeruli of MPO-ANCA-GN patients, whereas they were rarely detected in patients with MCNS. The total crescent rate was significantly higher in the HD group than in the non-HD group (35.9 +/- 3.5 vs 65.8 +/- 7.4, respectively). In the interstitium, the age-adjusted Foxp3/TIA-1 ratio was significantly higher in the non-HD group than in the HD group (0.016 +/- 0.016 vs 0.004 +/- 0.008, respectively; P < 0.05). The Foxp3/TIA-1 ratio, but not the Foxp3/CD3 ratio, remained significantly higher in the non-HD group than in the HD group even after adjustment for crescent rate. Age- and total crescent rate-adjusted renal survival rates were higher in patients with a Foxp3/TIA-1 ratio > or = 0.06 than in patients with a Foxp3/TIA-1 ratio < 0.06 (P = 0.02). 4. The results of the present study suggest that T(reg) could play a protective role against MPO-ANCA-GN and that a decreased Foxp3/TIA-1 ratio in interstitial areas may predict future renal failure in patients with MPO-ANCA-GN.

[Case of acute kidney injury related to intravenous zoledronic acid in a patient with multiple myeloma].

We report the first case of acute kidney injury related to intravenous zoledronic acid (ZA)in a patient with multiple myeloma in Japan. A 37-year-old male was diagnosed as having multiple myeloma (MM) of the Bence Jones lambda type. He showed a good response to two courses of vincristine, adriamycin and dexamethasone (VAD) therapy, and remarkable reduction was seen in plasma cells in bone marrow from 38.4% to 6.8% and 24-hour urine protein from 18.5 g/dL to 2.8 g/dL. At that time, serum Cr(s-Cr) of 0.7 mg/dL and calcium of 9.3 mg/dL were in the normal range. ZA was administered intravenously at the dose of 4 mg for the first time. Subsequently, he developed a fever of up to 39.4 degrees C and used NSAIDs and cefepime. Four days later, s-Cr increasd rapidly to 7.3 mg/ dL and he received hemodialysis (HD) therapy. Four weeks later, renal biopsy was performed and demonstrated cast nephropathy (CN) and acute tubular necrosis. Seven months later, renal function had improved. ZA may be an identifiable precipitating factor of CN. We recommend that ZA should be used with caution, especially hypovolemia and NSAIDs, in patients with MM and renal insufficiency.

Circulating matrix metalloproteinase-2 is an independent correlate of proteinuria in patients with chronic kidney disease.

BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) has been implicated in chronic kidney disease (CKD) and cardiovascular disease. However, there is no knowledge about the correlations between serum levels of MMP-2, proteinuria and atherosclerosis in patients with CKD. We investigated whether serum MMP-2 levels were associated with proteinuria, intima media thickness (IMT), and the presence of carotid atherosclerotic plaque in CKD patients. METHODS: CKD patients without hemodialysis (n = 99) were enrolled. MMP-2 levels were measured by an ELISA system. IMT and carotid atherosclerotic plaque were evaluated by a high-resolution ultrasonography. RESULTS: Multivariate analyses revealed that low-density lipoprotein (p < 0.001), MMP-2 (p = 0.001) and systolic blood pressure (p = 0.011) were independent correlates of proteinuria. Age- and serum creatinine-adjusted MMP-2 levels were significantly increased (p = 0.001) in proportion to the increasing levels of proteinuria. Further, age (p < 0.001), systolic blood pressure (p = 0.015) and MMP-2 levels (p = 0.042) were independent correlates of IMT. MMP-2 levels were significantly (p < 0.01) higher in patients with atherosclerotic plaque than those without it. CONCLUSIONS: The present study demonstrated that serum levels of MMP-2 were one of the independent correlates of proteinuria and IMT in patients with CKD. Our results suggest that serum MMP-2 levels may be one of the risk factors for renal damage and atherosclerosis in CKD patients.