Abstract. Experimental renal scarring indicates that tissue transglutaminase (tTg) may be associated with the accumulation of extracellular matrix (ECM), both indirectly via TGF-␤1 activation and directly by the formation of ⑀(␥-glutamyl) lysine dipeptide bonds within the ECM. The latter potentially accelerates deposition and confers the ECM with resistance to proteolytic digestion. Studied were 136 human renal biopsy samples from a range of chronic renal diseases (CRD) to determine changes in tTg and ⑀(␥-glutamyl) lysine crosslinking. Immunofluorescence for insoluble tTg showed a 14-fold increase in the kidneys of CRD patients (5.3 Ϯ 0.5 versus 76 Ϯ 54 mV/cm 2 ), which was shown to be active by a similar 11-fold increase in the ⑀(␥-glutamyl) lysine crosslink (1.8 Ϯ 0.2 versus 19.3 Ϯ 14.2 mV/cm 2 ). Correlations were obtained with renal function for tTg and crosslink. In situ hybridization for tTg mRNA showed that tubular epithelial cells were the major source of tTg; however, both mesangial and interstitial cells also contributed to elevated levels in CRD. This mRNA pattern was consistent with immunohistochemistry for soluble tTg. Changes in renal tTg and its product, the ⑀(␥-glutamyl) lysine crosslink, occur in progressive renal scarring in humans independently of the original etiology and in a similar manner to experimental models. tTg may therefore play a role in the pathogenesis of renal scarring and fibrosis in patients with CRD and can therefore be considered a potential therapeutic target.

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MCs as an infiltrating hematopoietic cell and its growth factor (SCF) seem to be up-regulated in glomerulonephritis, and may play a role in the development of renal fibrosis.

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From January 1986 through December 1991, a total of 221 patients with alcoholic liver disease received liver transplantation. In 147 of these cases, complete pretransplant histopathologic, demographic, and laboratory data (minimum of CBC, AST, ALT, total bilirubin, albumin, and prothrombin time) were available for review. Forty-five (30%) of the 147 recipients had alcoholic hepatitis plus cirrhosis (AH), whereas 70% had cirrhosis (CIRR) alone. Age and sex were similar in the subgroups, but the patients with CIRR had a greater AST/ALT ratio, longer protime, and lower platelet count (all p < 0.01). Coexistent hepatitis B (4.7%) or hepatitis C (4.1%) was similar in both groups. Current survival is 80% for patients with AH and 84% for those with CIRR (NS). Overall, survivors were younger (43.4 +/- 1.7 years) than nonsurvivors (53.6 +/- 3.2) (p < 0.01), an age influence that was significant in the CIRR group (p < 0.01) but not in the AH group. Inexplicably, the AST/ALT ratio was greater in AH survivors (1.5 +/- 0.2) than it was in nonsurvivors (0.4 +/- 0.1) (p < 0.01). In patients with CIRR, the platelet count was greater in survivors (252 +/- 29 vs. 86 +/- 11 x 10(9) cells/liter). The data support the clinical impression that patients with chronic decompensated cirrhosis referred for liver transplantation had more severe complications of their liver disease than did those with AH. Survival in both subgroups was similar, but overall the survivors are nearly a decade younger than the nonsurvivors.(ABSTRACT TRUNCATED AT 250 WORDS)