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Tenascin, a large oligomeric glycoprotein, is a recent addition to a list of increasing extracellular matrix proteins. Previous studies have documented the strong expression of tenascin in embryonic kidney and in both normal and abnormal mature glomeruli implicating an important role of this extracellular matrix protein in nephrogenesis and glomerular scarring. Whether tenascin plays any role in interstitial fibrosis, a common final pathway of tubulointerstitial nephritis, is no known; on the other hand, a detailed knowledge of the structural components of interstitial fibrosis is essential for further studies on other fundamental aspects of this biologically and clinically important process. In this study, the expression of tenascin in the renal interstitium was immunohistochemically evaluated in 208 renal specimens during normal kidney (23 cases), acute tubular necrosis (8), acute tubulointerstitial nephritis (8), chronic primary tubulointerstitial nephritis (30), tubulointerstitial nephritis secondary to glomerular diseases of mild (46) and severe (55) degree, ischemic damage (24), and rejection (14). It was found that in normal kidney tenascin expression was limited to the medullary interstitium. In kidney with tubulointerstitial nephritis, tenascin was ubiquitously and constantly expressed in any areas with tubulointerstitial damage regardless of diagnosis, etiology, the cortical vs. medullary location of the lesions, stage of the fibrogenetic process, density of fibroblasts, or severity of interstitial inflammation in the affected areas. Indeed, strong tenascin expression was seen in areas where there was only interstitial edema or inflammation as judged by routine light microscopic preparations. In summary, this study systematically documents tenascin as a novel extracellular matrix protein selectively expressed in the medullary interstitium in normal kidney, and ubiquitously present in areas with interstitial fibrosis.

Sickle cell disease is known to cause glomerulopathy, including focal segmental glomerulosclerosis (FSGS). Patients who have sickle cell glomerulopathy with FSGS are thought to have a poorer prognosis than patients who have sickle cell glomerulopathy without this lesion. The former patients are more likely to have persistent proteinuria and eventually develop end-stage renal disease. We present a boy with sickle cell glomerulopathy and FSGS who is younger than patients with similar findings reported previously. The histopathology of his renal lesions is remarkable for segmental ultrastructural changes in the glomerular basement membranes and endothelial cells. We speculate that these changes are precursory to the pathogenesis of glomerular sclerosis in patients with sickle cell disease.

Dose-limiting nephrotoxicity has hampered the clinical usefulness of amphotericin-B (AmpB). Recently, vascular decongestants, such as pentoxifylline, have shown benefit in reducing drug-associated renal damage of AmpB in rats. The present study investigated a dose-dependent protection of a structurally similar methylxanthine, HWA-448, in the candidiasis rat model given a single dose of AmpB. Forty-eight hours after inoculation with Candida albicans, each rat was treated with 0.8 mg/kg of AmpB or sterile water; animals were further randomized to receive 0.5, 1, 5, or 10 mg/kg i.v. of HWA-448 or saline given every 12 h for 3 doses. Kidney fungal counts, morphology, and renal function were compared between treatment groups upon completion of the study. Rats administered AmpB with HWA-448 had markedly improved renal function compared with those given AmpB alone; these effects were independent of the administered dose of HWA-448. The antifungal effect of AmpB was not impaired with concomitant HWA-448. Marked accumulation of granulomas and organisms was found in all rat groups. In summary, coadministration of low doses of HWA-448 attenuated the dose-limiting nephrotoxicity without impairing the antifungal effect of AmpB.

A patient with membranous glomerulonephritis (MGN) presented with recurrent disease after renal transplantation. The disease on the original and the transplanted kidney was characterized by diffuse subepithelial electron-dense deposits on the glomerular basement membranes. Including this case, 23 cases of MGN have been reported in renal transplants, of which 8 are 'recurrent' and 15 are 'de novo'. This incidence of 'de novo' MGN makes it the most common type of 'de novo' glomerulonephritis in renal transplants. Survey of clinical and morphological features of the cases of both the 'de novo' and the 'recurrent' disease failed to identify a specific cause of the MGN. Hypothetically, immunosuppression in transplanted patients may lower the antibody response to levels that favor the development of membranous glomerulonephritis.

We describe the early lesion of focal segmental glomerulosclerosis (FSGS) as it appeared in 2 cases of recurrent FSGS with early transplant nephrectomies (approximately 2 months) due to uncontrollable nephrotic syndrome. A quantitative evaluation showed that these lesions were present more often in the glomeruli of the juxtamedullary cortex. Epithelial cell proliferation and detachment and foam cells were seen frequently and were considered the hallmarks of the early lesion of FSGS. Hyaline deposits are secondary late phenomena. We suggest that the glomerular foam cells in FSGS are mesangial in origin.

We present a case of granulomatous interstitial nephritis and renal failure after a jejunoileal bypass for obesity. Improvement of the renal function occurred after reversal of the intestinal bypass. The renal biopsy showed an interstitial nephritis, oxalate crystal deposition and several aggregates of multinucleated giant cells related to the crystal material (granulomatous reaction). By ultrastructural and histochemical studies we demonstrated mitochondrial alterations in the tubular epithelial cells, and we suggested the proximal tubule origin of the giant cells. The association of the oxalate crystals with damaged tubules and giant cells suggests that the oxalate crystals are responsible for these alterations. The possibility of an associated immunological process as the cause of the interstitial nephritis cannot be excluded.

The glomerular ultrastructure was retrospectively reviewed from 45 renal transplant biopsies with the clinical and light microscopic diagnosis of acute rejection (25 cases) and chronic rejection (20 cases). Three grades of morphologic alteration were ultrastructurally defined. In acute rejection, capillary lumenal obliteration with endothelial cell hypertrophy and cellular infiltration were interpreted as the local glomerular expression of the endothelial vascular alterations of acute humoral rejection and were correlated with a poor graft survival. Graft nephrectomy was necessary in 9 of 11 patients with grade III glomerulopathy. In chronic rejection, thickened basement membranes and increased amount of mesangial matrix were considered the result of ischemia. The degree of ultrastructural glomerular alterations in chronic rejection did not correlate with graft survival. Urine protein values were consistently elevated, although poorly correlated with the severity of glomerular alterations. Recurrent glomerulonephritis was not documented in any case. We concluded that the glomerular alteration in acute rejection is a component of acute humoral rejection and that the degree of glomerulopathy in acute rejection is a good predictor of the graft survival.