M. de Oña

Nationwide and Long-Term Survey of Primary Glomerulonephritis in Japan as Observed in 1,850 Biopsied Cases

Primary chronic glomerulonephritis is the most common cause of end-stage renal failure in Japan. The incidence in dialysis patients in Japan is about four times higher than in the United States for reason which are unclear. We conducted a nationwide survey on the natural history and treatment of primary glomerulonephritis under a program project from the Ministry of Health and Welfare of Japan entitled ‘Progressive Chronic Renal Disease’. We analyzed patient characteristics, disease onset, clinical data, and histological findings in 1,850 patients with primary glomerulonephritis from 53 institutions in 1985 who underwent renal biopsy at least 5 years ago, and the follow-up study was carried out 8 years after registration. The incidence of diffuse-mesangial proliferative glomerulonephritis is 41.9%, that of minor glomerular abnormalities 17.5%, and that of focal-mesangial proliferative glomerulonephritis 13.0%. Of 1,045 biopsy specimens that were examined by immunofluorescence microscopy, 47.4% showed IgA nephropathy. Half of all cases with primary chronic glomerulonephritis were asymptomatic and were detected on routine health examination. The survival rates at 20 years from the apparent onset or earliest known renal abnormality are: focal glomerular sclerosis 49%, membranoproliferative glomerulonephritis 58%, diffuse-mesangial proliferative glomerulonephritis 66%, focal-proliferative glomerulonephritis 81%, membranous nephropathy 82%, minor glomerular abnormalities 94%, and IgA nephropathy 61%. In conclusion, a high incidence of IgA nephropathy and a better renal survival of membranous nephropathy are the features of primary chronic glomerulonephritis in Japan. This high incidence of IgA nephropathy together with its poor prognosis is probably the reason for the increased incidence of primary chronic glomerulonephritis in dialysis patients in Japan. In addition, the importance of routine health examination including urinalysis is demonstrated.

Association between human herpesvirus type 6 and type 7, and cytomegalovirus disease in heart transplant recipients.

CYTOMEGALOVIRUS (CMV) is an important opportunistic infection after heart transplant. The new human herpesvirus, types 6 and 7 (HHV6, HHV7) are two lymphotropic herpesviruses, which, like CMV, have the potential to be pathogenic in immunocompromized individuals. Recent studies suggest that both viruses can cause clinical illness after transplantation. These viruses may be a risk factor for CMV disease in posttransplant patients, possibly through a direct interaction or through a general immunomodulatory effect. However, the pathogenic potential and the clinical features have not been defined. To evaluate the reactivation of HHV6 and HHV7 after heart transplantation and their implication in the cytomegalovirus disease (CMVD), 42 unselected heart transplant patients were studied.

Cytomegalovirus Preemptive Therapy with Ganciclovir in Renal Transplant Patients Treated with OKT3

In an attempt to decrease the prevalence and severity of cytomegalovirus (CMV) disease, preemptive therapy with ganciclovir was administered to all renal transplant patients treated with OKT3 between February 1993 and December 1994 (26 patients). The results were compared with those of a historical group treated with OKT3 but not with ganciclovir (29 patients). Both groups were similar in age, sex, number of previous transplants, number of rejections, serological status of donor and recipient and OKT3 dose. Ganciclovir was administered during the period of treatment with OKT3. Only 2 (7.7%) treated patients developed CMV disease versus 11 (37.9%) of the control group (p = 0.01). In the control group the intensity of the disease was severe in 7 (63.6%) cases, whereas in the treated patients it was always of slight intensity (p = 0.01). In conclusion, preemptive therapy with ganciclovir during treatment with OKT3 decreases the prevalence and severity of CMV disease.

Disseminated Herpes simplex Virus Infection in a Renal Transplant Patient as Possible Cause of Repeated Urinary Extravasations

Disseminated herpes simplex virus type 2 (HSV-2) infections are infrequent in patients receiving organ transplants, but usually have a poor outcome. We describe the case of a renal transplant patient who developed a disseminated HSV-2 infection with repeated urinary extravasations. The diagnosis was carried out using a multiplex polymerase chain reaction nested assay and it suggested HSV-2 as a possible cause of repeated urinary fistulas.

Control of Cytomegalovirus Disease in Renal Transplant Patients Treated with Prednisone, Azathioprine and Cyclosporine Using Intensive Monitoring and Decreased Immunosuppression

Background: The aim of this trial was to study the effectiveness of intensive monitoring, together with an early decrease in immunosuppression, in reducing the prevalence of CMV disease in renal transplant recipients treated with prednisone, azathioprine and cyclosporine. Methods: From 1/95 to 11/97 a prospective, longitudinal study was conducted among 146 consecutive, unselected, renal transplant patients in our unit. Only 96 patients whose immunosuppressive regimens consisted of prednisone, azathioprine and cyclosporine and whose follow-up period was greater than 4 months were included in the study. Preemptive therapy was administered to 27 high-risk patients. CMV antigenemia (CMV-AG) and other virological tests were performed weekly for the first 4 posttransplant months. The immunosuppression was decreased when the first positive CMV-AG was detected. Azathioprine was completely withdrawn when the CMV-AG count was greater than 10 cells per 105 PBLs. The cyclosporine dose was gradually decreased in the next 4 weeks, but it was not withdrawn in any patient. The prednisone dose was modified according to the immunosuppressive protocol. Results: 53% (51/96) of the patients had positive CMV-AG on at least one occasion. The dose of azathioprine was decreased after CMV-AG detection in 41/51 (80.4%) patients and it was completely withdrawn in 23 of these (45%). The mean decrease in the dose of azathioprine was 73 ± 31 (25–175) mg, a mean percentage decrease of 76 ± 27% (25–100%). The dose of cyclosporine was progressively decreased during the 4 weeks after detection of the first CMV-AG (mean cyclosporine levels: 210 ± 66, 196 ± 54 and 164 ± 36 ng/ml at the time of first CMV-AG detection, 2 and 4 weeks respectively, p < 0.0001, repeated measures analysis of variance). None of the 45 patients without CMV-AG and only 2 of 51 (3.9%) patients with CMV-AG developed symptomatic CMV disease (2% of the total). CMV disease was of moderate intensity in both patients. Only 3/51 (5.8%) patients developed acute rejection after the first CMV-AG detection in the 4 posttransplant months. Conclusion: The results of this study suggest that intensive monitoring and an early reduction of immunosuppression, together with preemptive therapy in high-risk patients, is effective in diminishing the prevalence and severity of CMV disease.