Velosa, Jorge A.

Three multicenter studies have shown that the addition of mycophenolate mofetil (MMF) to an immunosuppressive regime consisting of cyclosporin A (CSA) and prednisone (PRED) decreases the incidence of acute rejection episodes when compared with azathioprine (AZA) or placebo (1–3). In those patients receiving 3 g/d of MMF, the highest dose used in the studies, there was a trend towards an increased incidence of cytomegaloviral sepsis (CMV). We postulated therefore that MMF may represent an independent risk factor for the development of CMV infection in patients receiving renal allografts and MMF at our institution. Having altered the triple drug regime from CSA, AZA (2‐2.5 mg/kg/d) and PRED to CSA. MMF (2 g/d) and PRED in July 1995, we elected to study all patients undergoing kidney transplantation for the 33‐month period January 1994‐September 1996, by undertaking a case control analysis to determine independent risk factors for the development of CMV infection, as defined by CMV viremia or tissue‐invasive CMV. Three CMV disease‐free control patients were matched to each case, these patients having been randomly selected from the entire pool of patients in the observation period. There were 31 CMV case patients and 102 control patients. Univariate analysis indicated that gender, a concomitant pancreas transplant, acute rejection and CMV seropositivity in the donor were risk factors. However, multivariate analysis indicated that only acute rejection and donor CMV seropositivity were independently linked (p<0.05) to CMV disease in this sample. Specifically, the odds ratio (OR) for CMV disease between MMF and AZA was 1.0 (95% confidence interval (CI): 0.46‐2.18). Therefore, in this case control study we find no evidence that MMF at a dose of 2 g/d is an independent risk factor for primary CMV viremia or tissue invasion in renal allograft recipients.

AbstractBackgroundIgA Nephropathy (IgA N) is one of the most common glomerulopathies and may lead to renal failure in 10–20% of cases. After renal transplantation, IgA N has a strong tendency to recur in the graft. Initially considered a benign condition, graft losses from recurrent IgA N have been reported over the last 20 yr, casting doubt on the initial premise. Since large single‐center studies of the fate of renal allografts in IgA N are rare and the Mayo Clinic transplant experience for IgA N is extensive (dating back to 1970), a review of these issues appeared worthwhile.MethodsA retrospective study was done of all renal transplant patients who had had biopsy‐proven IgA N as underlying disorder. We extracted data on the underlying disease, history leading to renal transplantation, factors affecting transplant outcome, and on the course after transplantation with special attention to rejection activity and recurrence of the primary disease. Standard statistical methods were employed.Results53 renal allografts were transplanted to 51 biopsy‐proven IgA N patients: 12 were cadaveric (CAD) grafts, 3 HLA‐mismatched living related donor (LRD) kidneys, 29 one haplotype‐matched LRD and 9 HLA‐identical LRD organs. Five‐year actuarial graft survival was 100% in HLA‐ identical LRD, 88% in one haplotype‐matched LRD, and 74% in CAD grafts. All three HLA‐mismatched LRD kidneys were functioning up to 1.6 yr (longest follow‐up). Only one patient died after acute rejection of the CAD graft. There were 3 early graft losses from acute rejection and 4 late losses. IgA N recurred in 26% of allografts and led to significant loss of graft function in 10 of the 14 patients (71%) over a long period of observation. Three of four late graft losses were in patients with recurrent IgA N. Recurrence was not related to the type of graft, i.e. CAD vs. LRD, nor to the extent of HLA‐matching in LRD transplantation.ConclusionRenal transplantation in patients with IgA N has excellent patient and graft survival. There is a high rate of recurrence of the primary glomerulopathy in the renal allograft, and this event is by no means inconsequential. Loss of renal function and even graft loss occur over prolonged periods of time. There is no disadvantage getting a well matched LRD in regard to incidence of recurrent IgA N. Thus, we encourage LRD transplantation in IgA N.

We examined the value of thallium‐201 myocardial perfusion scintigraphy in noninvasive assessment of cardiac risk in 36 insulin‐dependent (type 1) diabetic patients being evaluated for pancreas or combined pancreas/kidney transplantation. An extensive cardiovascular evaluation including electrocardiogram was performed in all patients, and most patients were also evaluated by two‐dimensional and Doppler echocardiography. Exercise thallium studies were performed in 31 patients. Five patients were unable to exercise and underwent dipyridamole‐thallium study. The thallium images were abnormal in 12 patients, 10 of whom underwent coronary arteriography. Significant coronary artery disease was found in 7 of these patients. Nineteen patients underwent pancreatic (3 patients) or pancreato‐renal (16) transplantation without any occurrence of cardiac death or nonfatal myocardial infarction peri‐operatively or on follow‐up ranging from 7 months to 21 months. In contrast, 3 cardiac events occurred in 12 patients not approved for transplantation, each of whom had an abnormal thallium study exhibiting significant ischemia. Resting left ventricular global and regional function was not helpful in determining perioperative risk. Thus, thallium‐201 myocardial perfusion scintigraphy may be useful in identifying diabetic patients at low risk for pancreas transplantation and may obviate the need for routine coronary angiography in these patients.

Abstract A lymphocyte surface glycoprotein designated urinary acidic antigen (UA) has been isolated from normal urine by a combination of preparative isoelectric focusing and ammonium sulfate precipitation. It has an m.w. of 14,000 to 17,500 daltons, and is approximately 60% carbohydrate and 40% amino acid in content. The protein exhibited the following physical properties: S20,omega = 1.24; v = 0.693 ml/g; E1%1 cm, 278 nm = 2.08; and pI-2.5. It appears to be unrelated to beta 2-microglobulin, protein HC, urinary proteose, microglobulin, or any previously described normal urine or human serum protein.

Abstract A protein component present in normal human urine has been found on the surface of epidermal cells and lymphocytes. This protein, called urinary acidic antigen (UA), can not be detected in concentrated fractions of normal human serum by double immunodiffusion, suggesting that it is quickly cleared from the circulation. It is readily detected, however, in sera of patients with renal failure. Although it can be eliminated from the cell surface by repeated washings with PBS, it was shown to cap with anti-UA-specific antiserum. Anti-UA suppresses PWM-induced proliferation, but not the lymphocyte response to PHA, Con A, or allogeneic cells. Thus UA appears to have a specific relationship to the pokeweed response. Whether it is a structural component of the PWM receptor is uncertain.

OBJECTIVES— To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management.RESEARCH DESIGN AND METHODS— We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence.RESULTS— Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (&lt;10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P = 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted.CONCLUSIONS— Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs.

OBJECTIVE: To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity RESEARCH DESIGN AND METHODS: We used Computer-Assisted Sensory Examination IV; characterized the QST results of the foot of each patient in three diabetic cohorts (approximately 1,500 patients) as hyperesthetic (&lt; or = 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles), or hypoesthetic (&gt; or = 97.5th percentile); and tested associations with symptoms, impairments, and test abnormalities. RESULTS: Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS: 1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas panmodality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds (and also of attributes of nerve conduction and a measure of autonomic dysfunction) from low-normal (2.5th-50th percentiles) to high-normal (50th-97.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.