Immunological tolerance in human transplantation. The possible existence of a maternal effect.

We analyzed data from 93 patients who received a kidney graft from their parents; 55 were transplanted with a kidney from their mothers (Mat.) and thirty-eight from their fathers (Pat.) The Pat. group has shown a better graft and patient survival as well as long-term renal function when compared with the Mat. group. This pattern was more evident with time. Long-term graft function assessed by creatinine levels also showed differences between the groups, favoring the Pat. group. The results are interesting since recent reports have claimed a tolerance developed by the individual to noninherited HLA antigens of their mother.

Renal transplantation and schistosomiasis mansoni.

Eleven patients with schistosomiasis mansoni received a renal transplant. In 5 patients, the schistosomiasis was asymptomatic and had been diagnosed by routine examinations and had no relationship to nephropathy. In 4 patients, the nephropathy was suggestive of being of schistosomal origin. Three of them had symptomatic hepatosplenic schistosomiasis, and histologic studies of original kidneys disclosed chronic glomerulonephritis in 2 and membranous glomerulonephritis in 1 patient. These histologic pictures do not establish definitively the schistosomal origin of nephropathy. The other patient had membranoproliferative glomerulonephritis that recurred in the allograft, but he had intestinal schistosomiasis. This form of the disease is not considered by all as capable of inducing nephropathy. Two patients had the hallmarks of schistosomal nephropathy: hepatosplenic form and membranoproliferative glomerulonephritis. The 1st patient developed nephrotic syndrome 3 years after the transplantation, and an allograft biopsy disclosed membranoproliferative glomerulonephritis. The other patient had an uneventful outcome with good renal function and no proteinuria. An allograft biopsy performed 14 months after the transplant disclosed slight mesangial proliferation with IgM++ and C3++ in the mesangium.

Histological outcome of acute cellular rejection in kidney transplantation after treatment with methylprednisolone.

BACKGROUND: Several studies comparing the response of acute cellular rejection (ACR) episodes to different corticosteroid regimens have been conducted. However, in most of them, the histological evaluation of the infiltrate and its correlation with clinical response was not studied. The clinical and histological outcomes of 37 episodes of ACR treated with methylprednisolone (MP) were studied, with the aim to determine how long the infiltrate takes to be cleared after therapy. METHODS: A total of 37 patients with biopsy-proven ACR were treated with 8 or 16 mg of MP/kg/day. Allograft biopsies were repeated at 5 and 10 days after the end of corticotherapy. Clinical and histological outcomes were compared. RESULTS: Six patients were excluded; 15 (48.4%) patients responded to therapy; the mean serum creatinine of these patients reached normal levels in the 2 weeks that followed treatment. Nine patients (60%) of this group had signs of ACR on biopsies done 5 days after corticotherapy, and four (26.7%) maintained them on the 10th day. Among 16 patients with no clinical response, none reached normal serum creatinine levels; 15 (93.7%) had signs of rejection 5 days after treatment and maintained them on the 10th day. Histological signs of ACR disappeared in 73.3% of patients with clinical response 10 days after therapy, but in only 6.3% of patients with no response (P=0.001). CONCLUSIONS: Biopsies performed 5 days after treatment show a high incidence of features of ACR; such features take on average 10 days to disappear in nearly 75% of cases with successful therapy with MP.

The impact of azathioprine on chronic viral hepatitis in renal transplantation: a long-term, single-center, prospective study on azathioprine withdrawal.

BACKGROUND: In transplanted patients, viral hepatitis progresses to chronic liver disease and patient's death after many years of transplantation. Also, it is well known that azathioprine (AZA) is harmful to the liver of these patients. However, it is unclear whether a low dose of AZA still represents a threat to the viral liver disease. METHODS: A total of 79 patients with hepatitis C, B, or both, transplanted between 1973 and 1990, were grouped according to whether they had AZA either withdrawn from the immunosuppressive regimen [group (G) I, n=45] or a dosage reduction only (group II, n=34). The decision to remove or to keep AZA was restricted to the patient's doctor. Patients records were reviewed by April 1997. RESULTS: After an equal time of follow-up, after the AZA changing (64+/-26 vs. 58+/-29 months), patients in GI showed a significant decrease in the serum liver parameters when compared to baseline [alanine aminotransferase (ALT): P=0.001; gamma-glutamyl transferase (gamma-GT): P=0.001 and total bilirubin: P=0.002], whereas in GII only ALT decreased (P=0.04) although gamma-GT and total bilirubin did not. Compared to baseline, serum creatinine (SCr) increased only in GI (P=0.001) but, at last follow-up, did not differ from GII. The intention-to-perform liver biopsies was equal in GI and GII (16 vs. 14) but the hystological findings of severe chronic liver disease (either chronic active hepatitis or cirrhosis) were more frequent in GII (P=0.004). Death with a functioning graft was much more frequent in GII than in GI (P=0.001). Infection and cirrhosis were more common as a cause of death in GII than in GI. CONCLUSIONS: The use AZA is harmful to renal transplantation patients with both chronic hepatitis C and B and, therefore, should be avoided. AZA withdrawal, but not dose adjustments, diminishes the serum liver enzymes and the progression rate of the chronic viral liver disease as well as the rate of death secondary to infection and cirrhosis.

Recurrence of focal segmental glomerulosclerosis associated with Kimura's disease after kidney transplantation.

A 13-year-old Brazilian boy with Kimura's disease (eosinophylic lymphoid granuloma) and nephrotic syndrome is reported. Native kidney biopsy showed focal segmental glomerulosclerosis (FSGS). Treatment with prednisolone resulted in partial remission of proteinuria, and he had a progressive loss in renal function, requiring initiation of chronic dialysis, which he underwent for 46 months. After kidney transplantation, the patient developed proteinuria. A renal biopsy showed recurrence of focal segmental glomerulosclerosis, and subsequently he developed renal insufficiency.

Prospective study of tetanus-induced acute renal dysfunction: role of adrenergic overactivity.

To assess the mechanisms related to tetanus-induced acute renal failure (ARF), 30 patients with tetanus had their renal function prospectively studied and factors possibly related to renal changes were evaluated during four weeks of hospitalization. Fifty percent of these patients had a glomerular filtration rate (GFR) < or = 50 ml/min in the first or second week of hospitalization (Group I) and 50% had a GFR > 50 ml/min throughout the entire hospitalization period (Group II). Age, gender, tetanus incubation time and tetanus onset time, hospitalization time, use of nephrotoxic drugs, need for mechanical ventilation with intermittent positive pressure, and presence of systemic infection were similar in both groups. None of the patients presented with oliguria. Autonomic nervous system (ANS) overactivity, characterized by intense variations in systolic and diastolic blood pressure, by increased heart rate and elevated urinary metanephrine excretion, was higher in Group I compared with Group II. Plasma renin activity, serum creatinephosphokinase levels, and myoglobinuria were not significantly different between the two groups. These results strongly suggest that tetanus-induced ARF has a high prevalence, is characterized by early onset, and is probably related to ANS overactivity.

Electric showers as a control measure for Legionella spp. in a renal transplant unit in São Paulo, Brazil. Legionellosis Study Team.

After an outbreak of legionnaires' disease Legionella pneumophila serogroup 1 in a renal transplant unit in São Paulo, Brazil, periodic hyperchlorination and flushing of pipes were instituted as control measures. These were only partially effective as every two to five months water cultures turned positive or new cases of the disease occurred. In November 1993 the hot water was disconnected from the unit and small, plastic electric showers were installed in each bathroom. Over a period of 12 months water from showers and taps was cultured for Legionella spp. every two weeks. On only one occasion was a water culture positive for L. pneumophila from a sink tap. No water sample obtained from showers was positive during the study period. No cases of legionnaires' disease occurred. We considered the use of electric showers an inexpensive and effective method of controlling the problem of Legionella spp. in the water system of our renal transplant unit.

An outbreak of nosocomial Legionnaires' disease in a renal transplant unit in São Paulo, Brazil. Legionellosis Study Team.

From June 1989 to March 1990 there were eight cases of Legionnaires' disease caused by Legionella pneumophila serogroup 1 in a renal transplant unit. There were seven cases of pneumonia and one case of pleural effusion. A study was conducted to identify the source of the outbreak. Legionella anisa was cultured from tap water. Twenty-seven staff members of the unit were serologically tested and antibody titres were positive in two. The probable source of infection was the potable water system. Control measures were hyperchlorination and heating of the water, after which there were no further cases during 5 months' follow up. We believe this is the first reported Legionnaires' disease outbreak in Latin America.

Acute glomerulonephritis: three episodes demonstrated by light and electron microscopy, and immunofluorescence studies--a case report.

The patient, a white boy, had 3 episodes of recurrent acute glomerulonephritis at 7, 12 and 17 years of age. The episodes were preceded by impetigo and there was a good clinical and laboratorial recovery after all of them. Renal biopsies were performed during the acute episodes, and the light, immunofluorescence and electron microscopy studies showed only lesions typical of acute glomerulonephritis. Four months after the third episode another renal biopsy demonstrated only lesions compatible with the subsiding stages of acute glomerulonephritis.

Stored blood--an effective immunosuppressive method for transplantation of kidneys from unrelated donors. An 11-year follow-up.

Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P < 0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that transfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft.

Glycosuria in glomerular diseases: histopathology and clinical correlations.

There are doubts about the presence of glycosuria and the progress of glomerular disease. Some reports suggest that glycosuria could be an index of a more severe tubulointerstitial lesion. We investigated the presence of glycosuria in 60 patients with primary glomerular diseases: 17 patients (28%) had glycosuria and 43 patients (72%) were glycosuria free. The two groups were similar in age, arterial pressure and sex. Serum creatinine was higher in patients with glycosuria (2.0 +/- 1.7 vs 1.3 +/- 0.9 mg/dl, P < 0.05). The protein excretion rate was 7.5 +/- 3.7 vs 5.3 +/- 4.2 g/day (P > 0.05) in patients with and without glycosuria, respectively, while serum albumin was lower in patients with glycosuria (1.7 +/- 0.6 vs 2.7 +/- 1.0 g/dl, P < 0.05). Several histological forms were present in the group with glycosuria, with membraneous glomerulonephritis being the most frequent. Histological evidence of tubular atrophy and interstitial fibrosis prevailed in patients with glycosuria, suggesting a poor prognosis for these patients. We may conclude that the presence of glycosuria in patients with glomerular disease is associated with more pronounced tubular atrophy and interstitial fibrosis and therefore imply a poorer prognosis.

HLA compatibility and graft survival in 502 kidney transplants.

The survival of 502 kidney grafts (458 first-grafts and 44 second-grafts) performed at Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, was analyzed in relation to the degree of HLA compatibility. The actuarial graft survival for first-transplants, at 1 and 5 years, was a follows: a) HLA-identical donor: 90 and 83%; b) one-haplotype identical donor: 68 and 54%; c) unrelated living donor: 61 and 37.5% and d) cadaver donor: 52.5 and 32%. These survival data are similar to those reported by other transplantation groups and confirm the important role of the HLA antigens in the outcome of renal transplantation.

Reducing cross-clamping duration in aortoiliac reconstruction after renal transplantation. A case report.

A fifty-two-year-old male renal transplant patient underwent aortoiliac reconstruction with a bifurcated prosthesis for treatment of hypertension and deteriorating allograft function. A modified technique was used that reduced aortic cross-clamping time to twelve minutes. This simple technique is applicable to most patients, reduces warm ischemia to a minimum, and saves time for a careful aortoiliac reconstruction.

Potassium is not a good solute to estimate residual volume in CAPD.

Residual volume is defined as the volume of dialysate remaining in the peritoneal cavity after complete drainage of fluid. In this study the residual volume was estimated in 9 patients, age 42 +/- 9 years, on continuous ambulatory peritoneal dialysis (CAPD) for 14 +/- 12 months, using two different solutes: dextran 70 and potassium. The residual volume was calculated from the change induced in drain dialysate solute concentration by the known volume and solute concentration of the newly infused dialysis solution. The residual volume estimated with dextran 70 was 195 +/- 105 mL (75-375 mL) and with potassium 411 +/- 108 mL (245-596 mL) (K > D, p < 0.001). The correlation between these two measurements was close to significance (r = 0.654; p = 0.056). In conclusion, potassium overestimates the residual volume, probably because of its rapid diffusion during the infusion time.

Influence of spontaneous contractions of the lymphatic vessels on the lymphatic absorption rate of the peritoneal cavity in CAPD.

The lymphatic vessels have sympathetic innervation. Noradrenaline increases the number of spontaneous contractions of the lymphatic vessels, whereas isoprenaline slows these contractions. The purpose of this study was to analyze the influence of the blockade of spontaneous contractions of the lymphatic vessels on the lymphatic absorption rate (LAR) in 6 patients on continuous ambulatory peritoneal dialysis (CAPD) by using 0.12 mg of isoprenaline added to 2 L of 2.5% dextrose dialysis solution. This dose of isoprenaline has been shown to inhibit bovine mesenteric lymphatic contractions. The LAR was measured by the quantification of the intraperitoneal disappearance of dextran 70 added to this same dialysis solution during a 4-hour dwell. All patients were submitted to a control test without isoprenaline. The LAR was 0.57 +/- 0.19 and 0.65 +/- 0.38 mL/minute (p > 0.05), with and without isoprenaline, respectively. We conclude that spontaneous contractions of the lymphatic vessels do not play an important role in the lymphatic drainage mechanism of the peritoneal cavity. The diaphragmatic contractions seem to be more important, since drugs that interfere with such diaphragmatic mechanisms alter the LAR.

Use of dextran 70 to estimate peritoneal lymphatic absorption rate in CAPD.

Peritoneal lymphatic absorption rate (LAR) in 15 patients on a CAPD program was measured by estimation of the disappearance of dextran 70 from the peritoneal cavity. The LAR was 1.03 +/- 0.45 ml/min. The cumulative lymphatic absorption, cumulative net transcapillary ultrafiltration, calculated net ultrafiltration (CUF) and measured net ultrafiltration (MUF) at 4 h exchange were respectively: 261 +/- 127 ml, 694 +/- 134 ml, 446 +/- 135 ml and 409 +/- 136 ml. Calculated and measured net ultrafiltration didn't differ significantly. An inverse correlation between MUF and LAR and a positive correlation between MUF and the ratio for dialysate glucose concentration at 4 hand dialysate glucose at 0 h (G4/G0) were observed (r = -0.522 and 0.547, respectively, p < 0.05). The multiple correlation coefficient between the MUF and LAR plus G4/G0 was higher (r = 0.617, p < 0.05). Peritonitis and the presence of diabetes didn't interfere with LAR. We have concluded that lymphatic absorption plus peritoneal transfer rate of glucose are important determinants of intraperitoneal volumes and that dextran 70 is a useful marker to measure lymphatic absorption.

Influence of the hydrostatic intraperitoneal pressure and the cardiac function on the lymphatic absorption rate of the peritoneal cavity in CAPD.

The purpose of this study was to determine the influence of hydrostatic intraperitoneal pressure (IPP) and cardiac function (CF) on the lymphatic absorption rate (LAR) in 9 patients on continuous ambulatory peritoneal dialysis (CAPD). The LAR was measured by estimation of the intraperitoneal disappearance of dextran 70 added to 2 L of 2.5% dextrose dialysis solution. The patients remained in the supine position during the 4-hour dwell. The IPP was obtained by measuring a column of dialysate in the peritoneal dialysis line, immediately before the drainage of the peritoneal cavity. The pressure was measured at the level of the umbilical cicatrix with point zero located on the mid axillary line of the patient. IPP was measured at inspiration and expiration, and the average of these two measurements was taken. These patients also underwent an echocardiographic examination. The LAR was 0.46 +/- 0.25 mL/minute, and the IPP was 13.07 +/- 2.61 cm H2O. The IPP correlated positively with the LAR (r = 0.80, p < 0.05). The intraperitoneal volume at the 4-hour dwell correlated inversely with the IPP (r = -0.68, p < 0.05). The left ventricular circumferential shortened fraction was 36 +/- 6% (27%-43%) and did not correlate with the LAR. These data suggest that the LAR is higher in patients with more elevated IPP. In addition, the CF, in the range studied, does not affect the lymphatic absorption rate.

[Subcutaneous phaeohyphomycose due to Exophiala jeanselmir. Report of 3 cases in patients with a kidney transplant]. / Feo-hifomicose subcutânea por Exophiala jeanselmei. Registro de três casos em transplantados renais.

We report three cases of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei (Langeron) McGinnis et Padhye 1977, in kidney transplant patients. Exophiala jeanselmei is a dematious fungus having also ability to rarely procedure eumycetoma (black grains). According to KWON-CHUNG & BENNETT (1992) such fungus is antigenically very heterogeneous, since so far three serotypes have been identified; each serotype including subgroups. Subcutaneous phaeohyphomycosis is becoming more and more frequent in kidney transplant patients submitted to an immunosuppressive treatment. As Exophiala jeanselmei has already been isolated from the environment it becomes difficult to explain the pathogenicity of these cases by a reactivation of quiescent processes. The authors suggest an occasional fungistatic action of cyclosporine A upon Exophiala jeanselmei.

Seasonal variation of blood pressure in maintenance hemodialysis.

CONTEXT: Seasonal variation in arterial blood pressure has been reported in studies with hypertensive and normotensive subjects. However, the influence of seasonal change on blood pressure of hemodialysis patients has not been reported. OBJECTIVE: To investigate the seasonal variation of blood pressure in Brazil, a tropical country, in patients on hemodialysis. DESIGN: Prospective, cohort study. SETTING: Dialysis unit of a tertiary medical center (a teaching hospital of the University of São Paulo School of Medicine, São Paulo). PATIENTS: Sixteen patients with chronic renal failure undergoing hemodialysis. OUTCOMES: Blood pressure, body weight, and ambient temperature were evaluated during 6 hemodialysis sessions carried out on 13 days during the four seasons. RESULTS: The diastolic blood pressure was lower in summer than in fall and winter (95 +/- 8 vs 107 +/- 10 and 101 +/- 10 mmHg, respectively; p < 0.05). The same was observed with mean blood pressure (116 +/- 8 vs 130 +/- 11 and 124 +/- 9 mmHg, respectively; p < 0.01). On the other hand, the ambient temperature was higher in summer than in fall and winter (23.0 +/- 1.6 vs 19.5 +/- 3.0 and 15.8 +/- 1.9 degrees C, respectively; p < 0.01). CONCLUSIONS: We concluded that for patients with chronic renal failure the blood pressure has a seasonal variation with higher pressures in fall and winter than in summer. Thus, further studies are needed to elucidate the impact of this observation on the adjustment of antihypertensive treatment and on morbidity and mortality in maintenance dialysis patients.

Endolymphatic irradiation in preparation for renal transplantation: a 26-year's follow-up.

OBJECTIVE: The aim of the present study was to analyze the long-term evolution of patients submitted to endolymphatic irradiation as a pre-transplant preparation. SETTING: Referral center of university hospital. DESIGN: Case-control study. MAIN OUTCOMES MEASURES: The study was designed to evaluate the incidence of rejection, kidney loss, leukopenia, infection, and graft survival in the group treated (group 1) prior to surgery, compared to a control group (group 2) composed of patients under identical clinical conditions (sex, age, type of donor, immunosuppressive therapy and time of transplant) that did not undergo treatment preparation. PATIENTS: Patients were selected from amongst transplantation candidates on a long-term waiting list, some with a high level of antibodies against panel. The control group was chosen from amongst recently transplanted patients. Patients in the treated group received lipoiodine containing 131I with specific activity ranging between 4 and 6 mCu/ml. RESULTS: A significant difference between the two groups was found with regard to the incidence of rejection crises (21.0% in group 1 and 73.6% in group 2; P = 0.003), and the maintenance dose of azathioprine (smaller in group 1; P < 0.01). As to kidney graft loss due to rejection, a tendency to significance could be identified (10.5% in group 1 and 42.1% in group 2; P = 0.063); however, the difference was not significant between the two groups in terms of reversibility of rejection episodes during the first 60 post-transplant days. CONCLUSIONS: The authors concluded that this method, besides being relatively innocuous (there was no compromising of either the thyroid gland or of gonad function and there was no increase in tumor incidence), has an extended immunosuppressive effect, and can be indicated for cadaveric renal allograft recipients, especially those showing high panel reactivity.