It has been demonstrated that β2-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis, a serious complication leading to bone and joint destruction in long-term hemodialysis patients. However, the molecular pathogenesis of this complication remains unknown. Several lines of evidence suggest that β2-microglobulin plays an active role in the development of dialysis-related amyloidosis. It is unlikely that intact β2-microglobulin per se contributes to the pathogenesis, because no difference in the plasma levels of intact β2-microglobulin has yet been found between hemodialysis patients with and without this complication. Some investigators, therefore, have focused on the modification of this molecule. Recent studies have revealed a new modification of β2-microglobulin in amyloid fibrils: advanced glycation end products (AGES) formed by a nonenzymatic reaction between aldoses and proteins. Further studies have suggested that the interaction of AGE-modified β2-microglobulin with monocyte/macrophage and osteoblast/osteoblast gives a plausible, albeit partial, explanation for the mechanism of bone and joint destruction in dialysis-related amyloidosis. This article focuses on the modification of β2-microglobulin with AGEs, especially on their structure and pathological role in dialysis-related amyloidosis. Furthermore, the implication of renal failure in the pathophysiology of AGES is also discussed.

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We investigated the effect of herbimycin A on the monolayer growth of 4 human renal cell carcinoma (RCC) cell lines and a normal renal tubular cell line (RTC 13) using MTT [3-(4, 5-dimethylthiszo1-2, 5-Biphenyl tetrazolium bromide)] assay. Herbimycin A induced remarkable growth inhibition in each RCC cell line tested, without any morphological changes of the cells. At the concentration of 500 ng/ml, herbimycin A caused more than a 30% growth inhibition in all RCC cells (p < 0.005 vs RTC 13), while less than 7% growth inhibition was observed in RTC 13 at the same herbimycin A concentration. The cell cycle was estimated by analysing DNA (deoxyribonucleic acid) content using a FRCS. A DNA histogram of RCC cells treated at herbimycin A showed a block in the cell cycle at the S and G2M phases. However, little effect by herbimycin A on RTC 13 cells was observed. Our results suggest that protein tyrosine kinases inhibitors, like herbimycin A, may offer a new treatment option for RCC patients.

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We investigated whether acteoside can inhibit mesangial matrix expansion or mesangial cell proliferation in mesangioproliferative anti-Thy 1 nephritis. Untreated control rats were compared to the rats treated with acteoside either during early (day 1 to 8) or late (day 4 to 12) period after the induction of anti-Thy 1 nephritis. The result showed that acteoside and prednisolone treatments (in either early or late period) significantly reduced proteinuria, mesangial matrix expansion (the index of matrix expansion) and mesangial proliferation as determined by the number of proliferating nuclear cell antigen (PCNA)-positive cells. Acteoside also reduced glomerular macrophage infiltration and ICAM-1 expression in glomeruli of anti-Thy 1 nephritic rats. Furthermore, acteoside treatment markedly increased the activities of matrix metaloproteinases (MMP) in glomeruli. These results suggest that acteoside can inhibit mesangial cell proliferation and extracellular matrix overproduction by either inhibiting ICAM-1 expression or increasing activities of MMP.

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Expression of tenascin was studied in normal human adult and fetal kidney specimens, and in renal tissues biopsied from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that tenascin was present weakly in the mesangial area and interstitium, but was absent from the glomerular capillaries. In the fetal kidney, tenascin was detected in the interstitium, but not in the immature glomeruli. In kidney tissues biopsied from patients with various renal diseases, expression of tenascin was associated with increased mesangial expansion and tubulointerstitial changes. In situ hybridization showed that tenascin mRNA was expressed in the renal tissues, but tenascin mRNA and tenascin protein were occasionally dissociated. These findings indicate that expression of tenascin is associated with mesangial expansion and also with tubulointerstitial changes in human glomerulonephritis. Tenascin expression may contribute to repair of injured glomeruli and interstitium.

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The aim of this study was to determine the levels of postprandial plasma remnant-like particlescholesterol (RLP-C) in patients with coronary artery disease (CAD) on chronic maintenance he modialysis (HD). Forty-two patients on chronic maintenance HD with and without CAD were studied. The subjects took a meal within 1 hr before HD then underwent HD for 4 hr with heparin infusion. The plasma level of RLP-C was monitored before and during HD and its biochemical characteristics were analysed. In the CAD group, the RLP-C level was 5.9±3.5 mg/dl before HD and 6.9±4.6 mg/dl after HD. In patients without CAD, RLP-C levels before and after HD were 2.1±0.8 mg/ dl and 2.7±1.2 mg/dl respectively (within the normal range). The RLP-C levels between CAD and non-CAD were highly significant (p<0.001). HPLC analysis of RLP revealed that VLDL remnants were reduced to smaller size, cholesterol rich particles within 1 hr of HD and a marked increase in chylomicron (CM) remnants was observed at the end of HD. These observations suggest that a latent metabolic disorder of chylomicrons and VLDL during HD after a meal can be detected by plasma RLP-C assay. The association between the frequency of latent metabolic lipoprotein disorders and CAD found in HD patients may require appropriate dietary intervention together with drugy therapy for the control of CAD.

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Serum carnitine concentrations are known to decrease in patients on regular hemodialysis and to increase in chronic renal failure. However, there is little information available concerning serum levels of carnitine in different glomerular diseases in patients whose renal functions have not yet deteriorated. In this study, we measured serum carnitine concentrations in 40 pediatric patients with idiopathic nephrotic syndrome, IgA nephropathy, non-IgA glomerulonephritis, focal segmental glomerular sclerosis, and normal controls. The results showed that there were no significant differences in the serumfree and total carnitine concentrations (S-FCC and S-TCC, respectively) between patients with different glomerular diseases and the controls. Of interest was the statistically weak correlations of both S-TCC and S-FCC with BUN in these patients, despite their normal renal functions. The ratio of S-FCC to S-TCC was significantly higher as compared with that of the controls. These findings suggest that serum carnitine concentrations are not affected by the types of glomerular lesions and that serum levels of carnitine depend mostly on the glomerular excretory capacity of urea nitrogens, even when the renal functions have not yet deteriorated. The increase in the ratio of S-FCC to S-TCC may be an early reflection of changes in the serum carnitine profiles of these patients.

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The proband was a 14-year-old girl with hematuria and proteinuria. Many members of her maternal pedigree had hematuria and proteinuria. Her mother, younger brother (age 12 years) and younger sister (age 9 years) had microscopic hematuria and proteinuria with normal renal function. Her mother had nephrotic syndrome during pregnancy and a renal biopsy was performed. Light microscopic findings of the renal biopsy specimen revealed mild mesangial proliferation and irregularity of glomerular basement membrane. The pedigree showed no chronic renal failure and no deafness. The proband had experienced microscopic hematuria and occasionally macroscopic hematuria since 3 years of age. Proteinuria increased steadily and at the age of 14 years, she had nephrotic syndrome and renal dysfunction (creatinine clearance of 57.9ml/min/1.48m²). Renal biopsy was performed and light microscopic findings showed segmental mesangial cell proliferation and numerous interstitial foam cells without significant findings by immunofluorescent study. Electron microscopic examination showed splitting into many layers and thinning of the glomerular basement membrane. She had no complaint of hearing. However, audiological studies detected bilateral low-tone (from 125Hz to 1000Hz) sensorineural hearing difficulty, ranging from 30 to 40dB. High scores on the short increment sensitivity index (SISI) test suggested inner ear hearing difficulty. Audiogram of her brother revealed also low-tone sensorineural hearing loss. Hereditary nephritis with the characteristic lesion of the glomerular basement membrane and sensorineural hearing difficulty has been known as Alport syndrome. Alport syndrome associated with familial low-tone hearing difficulty has not been reported previously.

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