Paul Sweny

Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus.

74 patients receiving cadaver kidney grafts were investigated prospectively for cytomegalovirus (CMV) infection. Among seropositive recipients CMV infection, especially symptomatic and disseminated infection, occurred significantly more frequently when kidneys came from seropositive than from seronegative donors. Since seropositive recipients can become infected with donor virus, the excess is probably accounted for by reinfection. This conclusion was supported by restriction enzyme typing of virus isolates from recipient pairs receiving kidneys from the same donor; proven reinfection with donor strain virus was significantly commoner than proven reactivation of recipient virus. Furthermore, symptoms occurred only in the proven reinfection group. Although the proportion of reinfections that caused symptoms was less than that seen in primary infections, prior natural infection with CMV clearly does not prevent symptomatic reinfection in seropositive recipients, a point which has profound implications for future vaccination strategies in renal allograft recipients and choice of donors.

Prolonged action of a chimeric interleukin-2 receptor (CD25) monoclonal antibody used in cadaveric renal transplantation

A high affinity chimeric CD25 mAb (chRFT5: SDZ CHI 621) blocking interleukin-2 binding to the interleukin-2 receptor alpha-chain was evaluated in a phase I/II study in human renal cadaveric transplantation. The chRFT5 was well tolerated with no immediate adverse effects during 6 spaced infusions (from before transplantation to day 24) in 24 patients escalating from 2.5- to 25-mg dosages. The chRFT5 had a long terminal half-life with a mean of 13.1 days. There was good correlation between the detection of chRFT5 in the serum by radioimmunoassay, the coating and suppression of CD25 on T cells, and antibody activity in patient serum samples. The chRFT5 activity persisted in vivo for up to 120 days. No antibody response to the chRFT5 was detected in any of the patients, even though two patients who required treatment with antithymocyte globulin or OKT3 developed xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There was a 33% incidence of rejection and the first rejection episode always occurred during chRFT5 therapy. Patients who did not reject during therapy did not reject during the first year following transplantation. Equal numbers of patients received dual and triple immunosuppressive therapy together with chRFT5. Posttransplant lymphoproliferative disorder developed in 2 patients, both on triple therapy, at 9 months after transplantation. The disorder did not develop in any patient receiving dual therapy, and no further cases have been observed to a minimum of 2 years follow-up. No other viral, fungal, or bacterial infectious complications were prevalent in patients treated with chRFT5.

LONG-TERM T-CELL-MEDIATED IMMUNITY TO EPSTEIN-BARR VIRUS IN RENAL-ALLOGRAFT RECIPIENTS RECEIVING CYCLOSPORIN A

Peripheral-blood mononuclear cells from renal-allograft patients receiving cyclosporin A (CSA) were tested for their ability to produce T cells cytotoxic for EB-virus-infected B-cell targets in culture and compared with those from healthy seropositive subjects. Whereas in the control cultures the proliferating foci of EB-virus-transformed B cells regressed after 2 weeks, no such regression was seen in cultures from CSA-treated patients. These results indicate that patients receiving CSA cannot mount a cytotoxic response to EB-virus-infected B cells in vitro. It is suggested that suppression of memory-T-cell proliferation contributes to the high incidence of lymphomas in CSA-treated renal-allograft recipients.

Hyperlipidaemia in untreated nephrotic syndrome, increased production or decreased removal?

The relative importance of increased lipoprotein synthesis and decreased lipoprotein catabolism is examined in 13 patients with untreated nephrotic syndrome by the use of intravenous fat tolerance tests analysed in relation to other parameters of lipid metabolism. Increased lipoprotein synthesis in nephrotic patients was indicated by the fact that at a given fractional clearance rate of Intralipid (K2), nephrotic patients had higher serum TG concentrations than did control subjects. A defect in lipoprotein catabolism was also suggested by the frequent finding of intermediate density lipoproteins on electrophoresis and the marginally low (p = 0.05) mean K2 in nephrotic patients. A highly significant (p less than 0.001) positive correlation between HDL-cholesterol concentrations and postheparin fractional clearance rates (K2) of Intralipid led to the speculation that in the severe nephrotic state (albumin less than 20 g/l) the loss of high density lipoproteins may contribute to the hyperlipidaemia.

Nephrotoxicity of ionic and non-ionic contrast material in digital vascular imaging and selective renal arteriography.

We assessed the nephrotoxicity of ionic and non-ionic radiocontrast material (CM) in two groups of patients in a prospective study. One group of 25 potential live kidney donors was studied following conventional renal angiography, carried out as part of the routine pre-operative assessment. The other group of 49 renal transplant patients with varying degrees of renal impairment was studied following digital vascular imaging carried out for investigation of hypertension. Plasma creatine, urinary N-acetyl-D-glucosaminidase (NAG), urinary microglobulin (B2M) and urinary protein excretion were measured before and after the imaging procedure. There were no significant changes in these parameters following digital vascular imaging, but there were increases in plasma creatinine (p less than 0.005) and urinary NAG creatinine ratio (p less than 0.002) in the conventional angiography group following the procedure. Substantial proteinuria developed in 35% of patients following conventional angiography. The differences in nephrotoxicity of radiocontrast agents during the two procedures could not be accounted for by the dose of material used, but probably reflect the effect of differences in the route of administration on the maximal concentration of the material reaching the kidney. Non-ionic radiocontrast material proved less toxic than ionic and may be preferable in conventional angiography.

Guidelines for kidney transplantation in patients with HIV disease

1.0 Key recommendations 2.0 Audit standards 3.0 Background 4.0 Indications for transplantation 4.1 HIV-specific inclusion criteria 4.2 Other inclusion criteria 4.3 Exclusions 4.4 HIV-disease-specific exclusions 5.0 Cadaveric versus live-donor graft 6.0 Pre-transplant assessment and vaccination 7.0 Immunosuppressant protocols 7.1 Treatment of acute rejections 8.0 Monitoring of allograft function 9.0 Psychological support 10.0 References Appendix Specimen consent form

THREE YEARS' EXPERIENCE OF CONTINUOUS AMBULATORY PERITONEAL DIALYSIS

Patients on continuous ambulatory peritoneal dialysis (CAPD) were studied for three years. 29 of them who had been on CAPD for six months or more were compared with patients on intermittent peritoneal dialysis (IPD) and on haemodialysis (HD). CAPD patients had significantly higher levels of HDL-cholesterol than HD patients. Urea, potassium, phosphate, and urate levels were significantly lower, and haemoglobin levels significantly higher, than in the IPD and HD groups. 43 CAPD patients studied had a peritonitis rate of 2.22 episodes per patient-year. CAPD offers an alternative form of dialysis to those unsuitable for HD, but until peritonitis rates can be reduced CAPD cannot rival HD as a long-term treatment.

Phenytoin-induced pseudolymphoma. A report of a case and review of the literature.

Summary We report a patient with phenytoin‐induced pseudolymphoma mimicking cutaneous T‐cell lymphoma (CTCL). Despite withdrawal of phenytoin, there was persistence of the cutaneous eruption and lymphadenopathy. Southern blot analysis of immunoglobulin and T‐cell receptor genes was therefore used to assess whether there was a clonal lymphoid expansion. However, no rearrangement of the beta T‐cell receptor gene or immunoglobulin heavy‐chain gene was detected in tissue DNA from skin and lymph nodes. One year later the patient became asymptomatic, although he is still at risk of developing a true malignant lymphoma in the future, a condition known as pseudo‐pseudolymphoma. It is suggested that genotypic studies may help in the initial diagnosis and the subsequent management of such patients.

Effect of Pamidronate on Bone Loss After Kidney Transplantation: A Randomized Trial

BACKGROUNDnKidney transplantation is associated with an increased risk of bone fracture and rapid loss of bone mineral density after kidney transplantation.nnnSTUDY DESIGNnRandomized controlled trial.nnnSETTING & PARTICIPANTSnPatients were randomly assigned to treatment (n = 46) or control (no treatment; n = 47) groups. Patients were stratified according to parathyroid hormone level and sex. Those with parathyroid hormone level less than 150 pg/mL were excluded.nnnINTERVENTIONnThe treatment and control groups received pamidronate, 1 mg/kg, perioperatively and then at 1, 4, 8, and 12 months or no treatment, respectively. All received calcium (500 mg) and vitamin D (400 units) daily. Immunosuppression was cyclosporine and prednisolone, with no difference in dosing between the 2 groups.nnnOUTCOMES & MEASUREMENTSnBone mineral density was evaluated by means of dual-energy x-ray absorptiometry of the lumbar spine and hip at baseline and 3, 6, 12, and 24 months, with the primary end point at 1 year of percentage of change in bone mineral density from baseline. Clinical fractures were recorded and also evaluated by means of spinal radiographs at baseline and 1 and 2 years.nnnRESULTSnPamidronate protected bone mineral density at the lumbar spine; bone mineral density increased by 2.1% in the treatment group and decreased by 5.7% in the control group at 12 months (P = 0.001). Protection was also seen in Wards area of the hip (P = 0.002) and the total hip (P = 0.004). There was no difference in femoral neck bone mineral density loss between the 2 groups. Fracture rates in the treatment and control groups were 3.3% and 6.4% per annum, respectively.nnnLIMITATIONSnThis study was not powered to detect differences in fracture rates.nnnCONCLUSIONnPamidronate protects against posttransplantation bone loss at the lumbar spine and Wards area of the hip.

Can urinary thyroid hormone loss cause hypothyroidism

Four patients presented with nephrotic syndrome associated with hypothyroidism; none had thyroid antibodies. Hypothyroidism resolved on remission of nephrotic syndrome in two patients; thyroxine (T4) replacement was ineffective during periods of gross proteinuria in another, and the fourth had had normal thyroid function a year before presentation. Urinary T4 excretion was measured in ten further patients with proteinuria. It was detectable in the urine in five, who had significantly lower serum free T4 (8.5 [95% confidence interval 5.8-11.2] vs 13.9 [11.1-16.7] pmol/l; p less than 0.01) and free triiodothyronine (3.1 [2.2-4.0] vs 4.9 [3.8-6.0] pmol/l; p less than 0.01) concentrations than the five patients without detectable urinary T4.