[Long-term management of renal transplant recipients]. / L'assistenza a lungo termine del paziente trapiantato di rene.

Transplantation has been demonstrated to improve the quality of life and long-term survival of patients with end-stage renal disease (ESRD) when compared with dialysis. This has resulted in a progressive increase in patients living with a functioning kidney graft as a percentage of the total ESRD population. Renal transplant recipients require complex long-term medical care, which is straining the limited resources of transplant centers. Moreover, due to considerations of geography or individual preference, a large number of patients, once their condition has stabilized, move away from the transplant center to the local nephrology unit. To facilitate and enhance the specialized care of these patients, it is crucial that nephrology units understand and manage the medical problems affecting long-term transplant recipients (e.g., chronic graft dysfunction, toxicity of immunosuppressive therapy, cardiovascular, infectious and neoplastic complications, hematological issues, bone disease, pregnancy and nonadherence to prescriptions). Regular interactive communication between the nephrology unit and the transplant center optimizes the continuity of care. Practice guidelines and the available literature on the subject are revised and critically analyzed in this paper.

Autoreactive lymphocytotoxic IgM antibodies in highly sensitized dialysis patients waiting for a kidney transplant: identification and clinical relevance.

The contribution of different families of lymphocytotoxic antibodies in the serologic reactivity of 45 highly sensitized dialysis patients (HSDP) (panel reactivity antibody value-PRA greater than 80%) was assessed by analyzing patients' sera for the presence of auto- and alloreactive IgM and alloreactive IgG antibodies. A total of 220 sera was screened at different incubation temperatures, before and after treatment with the reducing agent dithiothreitol, against a large variety of cell targets by means of complement dependent cytotoxicity (CDC) and antiglobulin augmented (AHG) CDC assays. The results allowed to subdivide the HSDP under study into four groups: Group 1 consisted of 13 untransplanted patients and 14 patients with a prior failed graft whose PRA values did not change following DTT treatment. Alloreactive IgG antibodies alone, with anti-HLA specificity, were present in the sera of this patient group. Group 2 consisted of 3 untransplanted patients whose sera did not contain any autolymphocytotoxic antibody but appeared completely unreactive to panel lymphocytes following DTT treatment, thus confirming the presence of alloreactive IgM only endowed with antiHLA reactivity. Group 3 consisted of 4 untransplanted and 4 patients with a prior failed graft whose sera were found to contain in addition to autoreactive IgM also alloreactive IgG antibodies. Their PRA values declined after DTT treatment on average from 96.2% to 45% and from 95% to 52.5%, respectively. Group 4 consisted of 6 untransplanted patients whose PRA reactivity to both autologous and panel lymphocytes completely disappeared following DTT treatment, thus indicating that their sera contained exclusively autolymphocytotoxic IgM antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of erythropoiesis in uremic patients on CAPD.

Chronic renal failure anemia noticeably improves only in patients who undergo CAPD treatment. In order to understand why it is so, the behaviour of some hematological parameters and the weekly clearances of creatinine and peak 7c1 were studied in the course of hemodialysis (HD) and CAPD. Our study shows that an improvement in hematological data is obtained in patients undergoing CAPD but not in those undergoing HD: this result is directly correlated with the increase of the peak 7c1 weekly clearance. Since the serum erythropoietin values are not modified, the improvement of the anemia appears to be related to the reduction of the biochemical abnormality of uremia using a better qualitative or quantitative depuration of bone marrow activity inhibitory material by CAPD.

Effects of biofiltration versus hemofiltration in the treatment of chronic uremia.

Biofiltration (BF), a new depurative hemo-diafiltration employing a high efficiency membrane (acrylonitrile and metallylsulphonate of sodium) and reinfusion of 8-9 liters of fluid was tested as an alternative method to hemofiltration (HF). Sixteen uremic patients who showed circulatory instabilities during traditional hemodialysis (HD) were treated with HF (27 liters infused in postdilution), or BF (210 min/session) for 12 months. Low and middle molecular weight metabolites weekly clearances, calcium, phosphorus and bicarbonate serum levels in BF and HF showed no significant differences: in BF the incidence of symptomatic hypotension events and orthostatic changes of mean blood pressure were lower than in HD, but a little higher than in HF. Our results show that BF achieves satisfactory depuration of low and middle molecular weight metabolites in a shorter time than HF and an improvement of autonomic nervous system abnormalities is observed.

Red cell membrane during erythropoietin therapy in hemodialysis and in hemodiafiltration.

This study assessed the effect of recombinant human erythropoietin (r-HuEPO) on red cell membrane behaviour in patients undergoing hemodialysis (HD) and hemodiafiltration (HDF). We studied erythrocyte osmotic fragility (EOF), mechanical fragility (EMF) and deformability (ED) before and after r-HuEPO therapy in patients on conventional dialysis treatment with a cuprophan membrane and in subjects undergoing HDF with a polyacrylonitrile membrane. Non-uremic, non-anemic subjects were enrolled as controls. Red cell membrane defects were more evident in HD than in HDF; r-HuEPO seemed to improve deformability in both groups compared to controls (p less than 0.005) possibly through the great production of red cells during this therapy.

Efficacy of recombinant erythropoietin after subcutaneous or intraperitoneal administration to patients on CAPD.

Recombinant erythropoietin (R-EPO) administered i.v. is effective in correcting anemia in patients on hemodialysis (HD). As subcutaneous (s.c.) or intraperitoneal (i.p.) dosing would be preferable in CAPD patients, we have evaluated its efficacy when given by these routes. Sixteen CAPD patients (mean Hb 7.3 +/- 1.6 g/dl) have been divided into two groups: group A received s.c. self-administered R-EPO (starting dose 92 +/- 35 U/kg/week) two times a week; in group B R-EPO was given i.p. (170 +/- 42 U/kg/week) thrice weekly. The observation period lasted about 12 months. All patients reached a target Hb greater than 10 g/dl. Group A achieved a full response within 9 +/- 2 weeks, group B within 13 +/- 1.7 (p less than 0.005). In group A the starting R-EPO dose was not changed; in group B it was increased to 225 +/- 45 U/kg/week. We observed no differences in the incidence of peritonitis in the two groups. Our findings show that both R-EPO administration routes are safe and efficient in correcting anemia in patients on CAPD. A shorter period of treatment and lower doses of R-EPO seem to be required to achieve the same target Hb level when using the s.c. rather than the i.p. application route.

[Kidney involvement in rheumatoid arthritis]. / Coinvolgimento renale in corso di artrite reumatoide.

Rheumatoid Arthritis (RA) is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively), followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy). Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs) nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept) are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment), followed by minimal change glomerulopathy (3-14%) and p-ANCA positive necrotizing crescentic glomerulonephritis.

Polycythaemia is erythropoietin-independent after renal transplantation.

Serum erythropoietin increased in 55 patients after transplantation. The serum erythropoietin decreased when the haematocrit and haemoglobin reached high levels, indicating recovery of a feed-back control system. Despite the diminution of erythropoietin, six patients demonstrated a state of erythrocytosis while the in vitro cultures of BFU-e revealed high sensitivity to the reduced doses of erythropoietin, using monocyte-free T-lymphocyte-depleted peripheral blood. In polycythaemic transplanted patients it is possible that cellular interactions stimulate an early hyperproliferation of BFR-e with a greater erythropoietin sensitivity and a partial capacity to grow in the absence of erythropoietin.

Gel-filtration on psoriasic and uremic serum and dialysis fluid.

In this search the serum and dialysis fluid of psoriasic patients in comparison with those of normal and uremic subjects have been evaluated by gel-filtration through a Sephadex G-15 column. The results showed a storage of the substances with various molecular weight in these patients. Particular attention was addressed to those with MW less than 1500 because they are not generally present in the normal subjects, decrease in the serum of psoriasic and uremic patients during the dialytic therapy, simultaneously with positive effects on the clinical symptomatology.

KSHV sequences in biopsies and cultured spindle cells of epidemic, iatrogenic and Mediterranean forms of Kaposi's sarcoma.

The pathogenesis of Kaposi's sarcoma (KS) is still unclear, and several factors appear to be involved in the onset of the Kaposi's lesion. Epidemiological studies suggest that a common infective agent may contribute to KS. Sequences which appear to represent a new gammaherpesvirus, currently termed KSHV/HHV8, have recently been identified in KS. To further examine the relationship between this virus and KS, we obtained biopsy samples of KS lesions; these samples, the spindle cells cultured from these lesions and the PBMC of the same patients were tested for the presence of KSHV sequences by PCR. In addition, we tested several "late passage" KS spindle cell lines as well as control samples. The biopsy samples were from lesions of the following forms of KS: one sporadic KS, two epidemic KS and three iatrogenic KS, one of which was in the process of regressing after reduction of immunosuppressive therapy, and two that were at different stages (patch and nodular) from a single patient. The sporadic KS specimen was positive, as were the PBMCs from this patient, and cells grown from this biopsy appeared to contain KSHV viral sequences up to the fifth passage. Both epidemic KS biopsies were positive, but in these cases KSHV sequences were not detected in the cultured cells. The biopsy from the regressing iatrogenic KS lesion was negative, as were the cells cultured from this lesion. However, the PBMCs of this patient were weakly positive for KSHV at the time of biopsy, and PBMCs collected from this patient one month later were completely negative. The samples of both the patch and the nodular KS lesions obtained from another immunosuppressed patient showed amplifiable sequences of KSHV, but both the PBMCs of this patient and primary KS cell cultures from these biopsies were negative. Of the late-passage KS lines tested, only one, IST AIDS KS 12, was positive for KSHV. This line is derived from an early angiomatous-macula lesion. Taken together, these data suggest that an active KSHV infection is associated with KS and that elimination of KSHV from the lesion precedes regression of the lesion, strongly correlating KSHV with KS. In addition, early KS lesions may have a higher KSHV burden, or contain cells more susceptible to KSHV infection, further linking KSHV to KS.