The mechanism of glomerular infiltration of monocytes remains unknown in diabetic nephropathy. We examined the effect of a high glucose concentration on monocyte chemotactic peptide 1 (MCP-1) expression in human mesangial cells (MCs) by using enzyme-linked immunosorbent assay and reverse transcription coupled with polymerase chain reaction (PCR). More than a 50% increase in the MCP-1 protein production was observed in MCs cultured in high-glucose medium (450 mg/dl) as compared to normal glucose (100 mg/dl; 1,496 ± 75 vs. 966 ± 15 pg/ml after 24 h, 1,910 ± 93 vs. 1,250 ± 55 pg/ml after 48 h). Semiquantitative PCR showed that phorbol myristate acetate (100 nM) increased the ratio of PCR products for MCP-1 to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase on densitometric results at 24 h by 2.7-fold, which was prevented by calphostin C (200 nM) pretreatment. High glucose increased the ratio by 3-fold as compared to normal glucose at 24 h (0.72 ± 0.11 vs. 0.24 ± 0.01). This was also suppressed by calphostin C pretreatment. These findings demonstrate that high glucose can directly increase MCP-1 expression in MCs, which may contribute to monocyte infiltration in diabetic nephropathy, and this is regulated by protein kinase C.

To investigate the changes of renal type IV collagen turnover in diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one-step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 698 diabetic patients and 191 healthy adults. Among the patients, 264 had urinary albumin levels of less than 29 mg/g.creatine (Cr) (Stage I: normoalbuminuric stage), 169 had microalbuminuria from 30 to 299 mg/g.Cr (Stage II: microalbuminuric stage), 84 patients had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of less than 1.1 mg/dl (Stage IIIA: macroalbuminuric stage without renal dysfunction), 97 had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of more than 1.2 mg/dl (Stage IIIB: macroalbuminuric stage with renal dysfunction), and 84 had renal failure (Stage IV). The levels of urinary type IV collagen in Stages II, IIIA, IIIB, and IV were significantly higher than those in Stage I (P < 0.0001). The level of urinary type IV collagen in Stage I (5.00 +/- 0.23 microg/g.Cr; mean +/- SE) was also higher than that in normal adults (3.44 +/- 0.11 microg/g.Cr; mean +/- SE). These levels increased gradually due to progression of the clinical stage of diabetic nephropathy. It appears that the levels of urinary type IV collagen can be a useful marker for detecting renal injuries in diabetes according to our Asian multicenter trials.

Hypertension, poor glycemic control and albuminuria are well known risk factors for diabetic nephropathy, but these factors do not explain all of the inter-individual variabilities in the rate of progression to kidney failure. Recent evidence showed that genetic predisposition affected the hyperglycemia-induced nephrotoxicity in patients with type 2 diabetes mellitus (DM). We reviewed the present state of knowledge concerning the relationship between genetics and diabetic nephropathy in type 2 DM. However, the results are inconclusive and the genetic determinants of diabetic nephropathy are not fully understood. In addition, genetic background of nephropathy in type 2 DM was thought to be more complex than in type 1 DM. Recent studies suggested that the inflammation would be an essential component of type 2 DM and its complications. We postulated that increased systemic and/or intrarenal inflammation in high glucose milieu is important in the pathogenesis of nephropathy in patients with type 2 DM. To investigate the impact of inflammation on diabetic nephropathy, we studied several polymorphisms in genes encoding inflammatory cytokine and chemokine in patients with type 2 DM. Among them, -511 C/T in interleukin-1beta (IL-1beta), tandem repeat in IL-1 receptor antagonist (IL-1Ra), -308 G/A in tumour necrosis factor-alpha (TNF-alpha) were significantly associated with an increased risk of kidney failure. In addition, some of them were remarkably different from those previously reported in the NCBI or literature based on the western population. Our results suggest that inflammation could play a pathogenic role in diabetic nephropathy in type 2 DM. A better understanding of genetic factors predisposing to diabetic nephropathy would not only help to identify diabetic patients at risk, but also be helpful to unveil the pathogenesis of DN.

The pathogenic role of the hepatitis B virus (HBV) infection for glomerulonephritis (GN) is not clear. The frequency of HBsAg has been studied in sera of 732 consecutive patients who have glomerular diseases by using radioimmunoassay. The frequency of HBs antigenemia was 11.9%, which was not different from that in the general population of South Korea. Of the 87 HBsAg seropositive patients with GN, 29 cases with membranoproliferative GN (MPGN) and eighteen with membranous nephropathy (MN) were diagnosed as having HBV-associated nephropathy. Eighty-seven and one-half percent of the adults with MPGN and 80% of the children with MN were HBsAg carries. The morphologic findings and laboratory data in cases with HBV-associated MPGN and MN did not differ significantly from those observed in patients with MPGN and MN without circulating HBsAg. Yet mesangial deposits were more frequently noted in patients with HBV-associated MN when compared to others with idiopathic MN. Glomerular deposits of HBsAg were not detected using indirect immunofluorescence technique. Even though HBsAg was not demonstrable within the glomeruli, HBV infection seems to play an important role in the pathogenesis of MPGN in Korean adults and MN in children.

Cryptococcus albidus, a non-neoformans species of the genus Cryptococcus, is generally regarded as a rare cause of disease. There have been only 14 previously reported cases in which this organism has been isolated as a pathogen, none of which occurred in a renal transplant recipient. A 23-year-old renal transplant recipient taking medication consisting of cyclosporine and prednisolone was admitted with a 10-day history of dry cough, fever and progressive dyspnea. The next day, his respiratory status deteriorated dramatically, and he developed acute respiratory distress syndrome (ARDS) and fulminant septic shock. On the eighth hospital day, tender macules on both his shins coalesced to form erythematous patches. Cryptococcus albidus was isolated by skin biopsy and tissue culture. We report here the first case of disseminated cryptococcosis caused by C. albidus in a renal transplant recipient who had been successfully treated with fluconazole monotherapy.