Hyperparathyroidism after renal transplantation.

Renal transplantation reduced circulating parathyroid hormone in recipients of renal allografts. Nevertheless, biochemical and histological evidence of mild hyperparathyroidism persisted up to eight years after renal transplantation despite good graft function.     

Hypertension after renal transplantation.

The incidence of hypertension (mean diastolic pressure above 90 mm Hg) was evaluated in 85 patients with renal transplants whose follow-up ranged from 3 to 84 months. Bilateral nephrectomy had been performed in 80 recipients. The proportion of hypertensive subjects rose during the first three months, subsequently stabilised around 50-60% for up to five years, and then decreased slightly during the next two years. Over the years hypertension fluctuated so that one-third of the initially hypertensive patients became normotensive, and over one-third of the initially normotensive patients became hypertensive. The main single aetiological factor was renal failure. A significant relation between steroid dosage and blood pressure was found in only a quarter of the hypertensive patients, and in another quarter no cause could be found.     

Restrictive antibiotherapy after renal transplantation.

Forty-two patients were followed up after 44 renal transplantations in an effort to evaluate possible benefits from the following protocol: systematic microbiologic and clinical surveillance, early and aggressive research for the cause of suspected infections, refusal to use prophylactic antibiotherapy, and selection of treatment according to the established cause of the infection. During 18,030 days of follow-up 124 infections were recorded, of which 110 were bacterial, 11 viral and 3 protozoal. Eighty originated in the urinary tract, 17 in skin wounds and 10 in the lower respiratory tract. Septicemia occurred three times, and one death due to infection was recorded. In the treatment of bacterial infections patients received antibiotics for 2486 days. Ampicillin (given for 816 days) and "minor" drugs such as sulfonamides and urinary antiseptics (given for 1036 days) were used 74.5% of the time, whereas gentamicin was used only 2.6% of the time (64 days). Combined antibacterial therapy was needed 1.2% of the time (29 days). A restrictive policy regarding anti-biotherapy seems to be beneficial to renal transplant recipients.     

Comparison of high-dose intravenous methylprednisolone with low-dose oral prednisolone in acute renal allograft rejection in children.

Two corticosteroid regimens were compared in a randomised, prospective study of 48 consecutive acute rejection episodes occurring at least one month after transplantation in 22 children who had received renal allografts. The higher dose schedule (intravenous methylprednisolone 600 mg/m2 daily for three days) was no more effective than the lower (oral prednisolone 3 mg/kg daily for three days) in reversing rejection, being successful in 70% as opposed to 72% of episodes. Few major side effects were seen with either treatment, but unpleasant sensations were reported much more frequently in the group given intravenous methylprednisolone; this regimen was much more disruptive of the patient''s life. Oral prednisolone in the dosage described is as effective as about 10 times that dose of intravenous methylprednisolone; it is much cheaper and is viewed as less unpleasant by patients.     

The role of DRB1 amino acid residue differences on donor-specific antibody production and acute rejection after cadaveric renal transplant.

The correlation between DRB1 amino acid residue matching, post-transplant humoral response and acute rejection (ARj) episodes was analysed in 51 renal transplant donor-recipient pairs in order to determine new criteria for organ assignment based on the alloreactivity of the residue within the peptide binding groove. HLA class I and II compatibility was defined using serological and genomic techniques; a sequence-based typing (SBT) was used for a higher resolution of DRB1 alleles. Humoral response was monitored in the first post-transplant year using triple staining flow cytometric analysis of donor-specific antibodies (Abs). Our data showed that DRB1 residue compatibility was always correlated to the absence of ARj while the presence of one or more aminoacid differences was associated with a similar frequency of ARj. Analysis of the mismatched DRB1 amino acid residue localised in the beta-pleated sheet and the alpha-helix of the DRB 1 molecule revealed that the frequency of beta-pleated sheet residue mismatches (MMs) was higher in the ARj-positive than in the ARj-negative group. A significant increase in the alpha-helix residue MMs was observed in patients with anti-class II Ab production (p = 0.034). Furthermore, analysing in detail DRB 1 MMs at the level of single amino acid residue, we found that the frequency of the mismatches localized in codon 9 and codon 28 in the beta-pleated sheet, as well as in codon 57 in the alpha-helix, was higher in patients who experienced ARj; on the other hand, MMs in codon 58 of the alpha-helix were more frequently associated with anti-class II Ab production. The identification of the residues more involved in alloreactivity onset will make it possible to define the existence of "permissive" or immunogenic" allele combinations which could simplify and increase the chances of a successful transplant.     

Long-term survival after cadaveric renal transplantation.

In a series of 404 consecutive first cadaver kidney transplants performed since 1967 the actuarial five- and 10-year survival of patients were 61% and 47% respectively and of grafts 46% and 36%. In more than four-fifths of the patients surviving these intervals the original cadaveric grafts were functioning at these times, and most of the remainder were sustained by subsequent grafts. Although graft survival has remained static since 1967, patient survival improved. Results for 43 consecutive second cadaver transplants were similar after five years to those of first grafts. These results promote the acceptability of cadaveric transplantation as a long-term treatment for chronic renal failure.     

Renal excretion of fluoride in renal failure and after renal transplantation.

We have compared the renal excretion of fluoride in a variety of patients with chronic renal failure maintained with and without protein restriction before and during regular dialysis treatment and after transplantation. The patients tended to continue to excrete normal dietary loads of fluoride quite well until renal function was seriously reduced. From a regression of function on excretion the mean level of creatinine clearance when a normal dietary load of fluoride 0.0526 plus or minus 0.019 mmol/2 h (1.0 plus or minus 0.36 mg/24h) has a 90% chance of being excreted lies around 16 ml/min, a level when most patients with renal failure will be symptomatic. Acute loading of such patients with additional fluoride in the form of sodium fluoride from 40 mg to 60 mg/day showed a twofold to threefold increase of serum fluoride concentrations, slight increases in urinary fluoride excretion, and heavy tissue absorption, suggesting that prior fluoride loading of the skeleton had not taken place. These effects contrasted with those in one patient with normal renal function and with those in one patient with skeletal saturation due to prolonged loading. After renal transplantation fluoride excretion increased but reached normal levels within three months of satisfactory function, suggesting that fluoride loading in renal failure and during regular dialysis therapy had not been excessive.     

Vascular transplant rejection of rat renal allografts across strong histocompatibility barriers

Sixty-one rat renal allografts were studied by light microscopy and in 18 cases also by immunohistology. Donor and recipient differ at a major histocompatibility locus in the one group (n=37), and by an additional weak histocompatibility antigen in the other (n=24). The mean survival time is 10.4 days and 8.3 days, respectively. A semiquantitative grading of the histologic findings shows that in both groups the rejection is predominantly manifested by lesions of extraglomerular and glomerular vessels, whereas mononuclear cell infiltration appears to be of less significance. The essential findings are necrosis of arteries and arterioles, necrosis of glomerular cells with mesangiolysis, and focal tubular necroses. This morphologic rejection type is interpreted as the result of a mixed humoral and cellular immune response, although the constant participation of circulating antibodies in the vascular damage could not be established. Since the tubular necroses correlate well with the degree of vascular alterations, but not with the mononuclear cell infiltration it would seem reasonable to conclude that these necroses are secondary to ischemia produced by vascular lesions. Finally, there is no significant difference in the degree of rejection between the two donor/recipient groups, and, therefore, there is no morphologic evidence for an increase of the rejection process by additional weak histoincompatibility in the examined strain combinations.     

Recovery of renal function after prolonged dialysis and transplantation.

Out of 250 patients with renal failure, seven (2.8%) treated by regular haemodialysis alone (four) or given cadaveric allografts (three) later showed recovery of function of their own kidneys lasting from one to four years. In the patients receiving haemodialysis alone recovery was easily recognised from their serum creatinine concentrations, but in those with transplants recovery was discovered unexpectedly during radionuclide scanning. These findings suggest that recovery of renal function may be more common than generally recognised, which should be borne in mind when beginning renal replacement treatment and particularly when contemplating bilateral nephrectomy.