Immunosuppression in renal transplantation: viral diseases and chronic allograft nephropathy.

Chronic allograft dysfunction after renal transplantation can be ascribed to different causes, among which are viral infections. The aim of this work was to show the various ways by which different kinds of viruses affect transplant structure and function. Polyoma virus is an example of viruses directly affecting the kidney because of a specific tropism to the uroepitelial cells. Cytomegalovirus (CMV) has been chosen both because of the frequency of this infection and because CMV (as other viruses) can produce transplant vascular sclerosis. Finally, we describe hepatitis C virus (HCV) because of its capacity to induce renal lesions independently from chronic allograft nephropathy. Indeed HCV is likely to determine immunologically mediated nephritis in the transplanted kidney as well in the native one.

Nodular macroglossia with combined light chain and beta-2 microglobulin deposition in a long-term dialysis patient.

We describe a case in which nodular macroglossia, a very rare type of tongue involvement, was associated with the co-deposition of lambda light chain and beta-2 microglobulin fibrils in the tongue. The combined presence of two different amyloid fibrils did not lead to a more unfavourable clinical outcome. We believe that both these features often remain underdiagnosed and are in fact more frequent than reported. A careful clinical examination of the tongue together with serum immunofixation should be routine in all patients with dialysis-related amyloidosis in order to investigate the prevalence and type of tongue involvement and to rule out other types of amyloidosis. In all cases of suspected mixed amyloidosis, immunohistochemical characterization of fibrils should be carried out by electron microscopy.

Role of ageing, chronic renal failure and dialysis in the calcification of mitral annulus.

Mitral annulus calcification, a common lesion of the elderly (over age 60 years), has been detected with increased frequency and at younger ages in patients with uraemia. To date a pathogenic role for dialysis and secondary hyperparathyroidism has been suggested only on the basis of older dialytic age and increased serum iPTH observed in the affected individuals. Because this is a potentially dangerous lesion we deemed it useful to evaluate more completely the respective roles of possible pathogenetic factors in uraemic individuals. Evaluation included echocardiography, ECG, limb radiography, and serum assays. A total of 225 dialysis (HD) patients, 67 chronic renal failure (CRF) patients on conservative treatment and 67 normal subjects were studied. Mitral annulus calcification was detected in 87 of 225 (38.6%) HD patients, 11 of 67 (16.4%) CRF and six of 67 (8.9%) normals. In HD, patients with calcification were older and on longer-term renal replacement therapy compared to those without calcification. They also had greater values of iPTH, BGP, AP, and Rx score of secondary hyperparathyroidism. Mitral annulus calcification was associated more frequently (chi 2 = 14.8; P < 0.0001) with rhythm and cardiac conduction defects, but not with ectopic calcifications. Multiple stepwise regression analysis, with mitral annulus calcification score as dependent variable, selected dialysis duration, age, and iPTH (rm = 0.368) as the most predictive parameters, with the first two carrying most of the information. The stratification of patients according with these two parameters showed a progressive increase in the frequency of calcification both with HD duration and age.(ABSTRACT TRUNCATED AT 250 WORDS)

Progression of uremic hyperparathyroidism involves allelic loss on chromosome 11.

In occasional cases of secondary hyperparathyroidism, long term stimulation of the parathyroid glands leads from compensatory to autonomous hyperfunction, and thus, hypercalcemia develops. This clinical entity, named tertiary hyperparathyroidism, is possibly due to the formation of an adenoma in one of the hyperplastic glands. Previous studies have shown that parathyroid adenomas may arise with allelic loss on chromosome 11. We tested for allelic loss at several loci on chromosome 11 in 12 enlarged parathyroid glands from 6 uremic patients and found loss of heterozygosity in 2 of the glands from 2 different patients with higher serum calcium levels (11.3 +/- 0.29 vs. 9.8 +/- 0.28 mg/dL; P < 0.004) and, therefore, ascribable to the so-called tertiary hyperparathyroidism. The 2 glands with allelic loss were significantly greater in mass than those without loss (3.42 +/- 0.37 vs. 1.60 +/- 0.54 g; P < 0.001). These data offer new evidence that autonomous parathyroid proliferation in uremic patients can develop through overgrowth by a monoclonal tumor, presumably with inactivation of a tumor suppressor gene(s) on chromosome 11.