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Biomedical subjects

J A Velosa

Publications and source records attributed to J A Velosa.

At least 19 recordsLinked to original sources
PubMed2006

Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sirolimus and tacrolimus.

Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival, but their use has been implicated in the development of chronic nephrotoxicity. We performed a prospective, randomized trial in kidney transplantation comparing sirolimus-MMF-prednisone to tacrolimus-MMF-prednisone. Eighty-one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled (mean follow-up = 33 months; range 13-47 months). At 1 year, patient survival was similar in the groups (98% with sirolimus, 96% with tacrolimus; p = 0.42) as was graft survival (94% sirolimus vs. 92% tacrolimus, p = 0.95). The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 +/- 19 mL/min vs. 63 +/- 18 mL/min, p = 0.57) or 2 years (61 +/- 17 mL/min vs. 61 +/- 19 mL/min, p = 0.84). At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone.

Adult↗
PubMed2001

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.

Adult↗
PubMed2001

Increased weakness after pancreas and kidney transplantation.

BACKGROUND: Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete. METHODS: In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy. RESULTS: We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness. CONCLUSIONS: We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.

Adolescent↗
PubMed2001

Cyclosporine elimination in the presence of TOR inhibitors: effects on renal function, acute rejection, and safety.

Sirolimus in combination with cyclosporine reduces the incidence of acute rejection in renal transplant recipients when administered in double- or triple-therapy immunosuppressive regimens. Sirolimus administered as primary therapy has a beneficial effect on renal function, and the frequency of rejection episodes is similar to that of primary immunosuppression with cyclosporine. A strategy that may result in a more benign immunologic course with a substantially beneficial effect on renal function is to administer sirolimus and a calcineurin inhibitor early after transplantation, thereby promoting immunologic adaptation, and then to withdraw the calcineurin inhibitor at some point after transplantation to prevent nephrotoxicity. This article examines the results of this approach in recent studies that evaluated the effect of cyclosporine withdrawal on renal function, acute rejection, and safety in patients treated with sirolimus. Two open-label randomized trials of cyclosporine withdrawal were conducted in the United States, Canada, Europe, and Australia. In one of the studies, graft survival, patient survival, and the incidence of acute rejection at 6 months posttransplantation were not statistically significantly different between the patients receiving cyclosporine and the group that had undergone cyclosporine withdrawal. Furthermore, significantly better renal function was observed in the patients who underwent cyclosporine withdrawal compared with patients who continued to receive full-dose cyclosporine. These studies indicate that cyclosporine withdrawal has a beneficial effect on renal function without a significant increase in the incidence of acute rejection episodes.

Acute Disease↗
PubMed2001

Donor scoring system for cadaveric renal transplantation.

We studied early renal function in 241 consecutive patients who received cadaveric renal transplants at two different transplantation centers (group 1, n = 90; group 2, n = 151). Univariate and multivariate analyses of data from group 1 showed a significant correlation between seven donor variables and early renal function after cadaveric renal transplantation. A scoring system was developed from these seven donor variables (cause of death, 0-6 points; history of hypertension, 0-6; final creatinine clearance before procurement, 0-6; age, 0-6; history of diabetes mellitus, 0-3; cold ischemia time, 0-3; and severity of renal artery plaque, 0-3). Data from group 2 were used to validate the donor scoring system and stratify cadaver kidneys on the basis of score: grade A, 0-5 points; grade B, 6-10; grade C, 11-15; and grade D, 16-32. A significant decline in early renal function was observed with increasing donor score and grade of cadaver kidney. In conclusion, a donor scoring system based on information available at the time of procurement can be used to estimate early graft function after cadaveric renal transplantation and may assist in the allocation of marginal organs.

Adolescent↗
PubMed2000

Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy: a study of three cohorts. Nerve growth factor study group.

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 (< or = 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles), or hypoesthetic (> 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.

Adult↗
PubMed2000

Pancreas transplantation for the prevention of diabetic nephropathy.

Diabetic nephropathy is the leading cause of kidney failure in the United States. Poor glycemic control, hypertension, and smoking have been implicated as risk factors for the development and progression of diabetic nephropathy in patients with type 1 diabetes mellitus. Improved medical therapy including angiotensin-converting enzyme inhibitors and tight glycemic control with use of intensive insulin therapy have been shown to reduce the progression of diabetic nephropathy substantially based on albumin excretion rates. Despite these improvements in medical management, many patients still experience progression from early diabetic nephropathy to end-stage renal disease. Successful pancreas transplantation leads to normal glycemic control in patients with type 1 diabetes, but historically it has generally been limited to patients with both kidney failure and diabetes. In this review of the current treatment of diabetic nephropathy, we examine the potential role of preemptive pancreas transplantation in patients with diabetic nephropathy.

Albuminuria↗
PubMed1999

Hantavirus-specific IgG, IgM, and IgA in acute and chronic renal disease versus congenital renal disease in the United States.

In a blinded fashion, 165 serum samples from patients with biopsy-characterized acute and chronic renal diseases (ACRDs), 34 serum samples from patients with congenital renal diseases (CRDs), and 100 serum samples from healthy adults were assayed for immunoglobulin G (IgG), IgM, and IgA antibodies to Hantaan and Puumala viruses by enzyme immunoassay (EIA). Twenty-six percent (44 of 165) of ACRDs, 3% (1 of 34) of CRDs, and none (0 of 100) of the healthy serum samples were positive for hantavirus-specific antibodies (P < 0.001, Fisher's exact test). Thirty of 44 positive serum samples (68%) were from three groups: ie, acute tubulointerstitial nephritis (AIN), 20% (9 of 44); necrotizing glomerulonephritis (NG), 27% (12 of 44); and IgA nephropathy, 20% (9 of 44). The remaining 14 positive samples were from patients with a varied group of renal conditions. IgA antibody levels alone were elevated in 37%, IgG alone in 33%, IgM alone in 17%, and all three isotypes in 13% of the AIN-, NG-, and IgA-positive samples. These data indicate that three renal diseases account for approximately 68% of the hantavirus-positive sera tested and that serological evaluations should include all three isotypes of antibodies.

Acute Kidney Injury↗
PubMed1998

Prolonged anuria complicating primary sclerosing cholangitis: successful outcome following orthotopic liver transplantation.

A 49-year-old man with progressive obstructive jaundice secondary to primary sclerosing cholangitis developed acute, anuric renal failure requiring prolonged hemodialysis. Renal biopsy showed evidence of tubular epithelial toxicity, pigmented casts, interstitial fibrosis, and ischemic glomerular changes. After orthotopic liver transplantation (OLT), there was an immediate return of urine output. The introduction of tacrolimus (FK506) was delayed for 3 weeks after transplantation, during which time a gradual improvement in renal function occurred. Renal function remained stable 1 year later at a level of moderate impairment with good hepatic function.

Acute Kidney Injury↗
PubMed1998

Is cytomegalovirus infection related to mycophenolate mofetil after kidney transplantation? A case-control study.

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.

Adult↗
PubMed1997

Pregnancy after pancreatic-renal transplantation because of diabetes.

In this article, we describe two pregnancies in the same patient after pancreatic-renal transplantation. Severe, labile hypertension necessitated delivery at 35 weeks during the patient's first pregnancy and at 30 weeks (associated with renal graft obstruction) during her second pregnancy. Women with insulin-dependent diabetes mellitus who undergo pancreatic-renal transplantation can have a successful pregnancy if adequate multidisciplinary, specialized medical care is rendered.

Adult↗
PubMed1997

The fate of renal transplants in patients with IgA nephropathy.

BACKGROUND: IgA 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. METHODS: A 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. RESULTS: 53 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 allograft 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. CONCLUSION: Renal 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.

Adolescent↗
PubMed1995

Pretransplantation assessment of the risk of lymphoproliferative disorder.

Posttransplantation lymphoproliferative disorder (PTLD) is an uncommon but often fatal complication of solid organ transplantation that occurs in approximately 3% of patients. To determine the relative importance and relationship of potential risk factors for PTLD before transplantation (i.e., Epstein-Barr virus [EBV] serostatus of the recipient and the cytomegalovirus [CMV] sero-status of the recipient and the potential donor) and the principal risk factor after transplantation (immunosuppression with antilymphocyte antibody), we analyzed the findings for the first 381 consecutive adult nonrenal transplant recipients seen at Mayo Clinic. In the absence of the other risk factors, the incidence rate of PTLD for EBV-seronegative recipients was 24 times higher (95% confidence interval [CI]: 6.2, 89) than that for EBV-seropositive recipients. The additional risk factors of therapy with OKT3 for rejection and CMV seromismatch (i.e., a negative recipient and a positive donor) each further amplified this risk four- to sixfold. Together, all three risk factors acted synergistically to increase the incidence rate of fatal and/or CNS PTLD by a factor of 654 (CI: 368, 1,162) compared with the low incidence rate (.458 cases per 100 person years) when none of these risk factors were present. Pretransplantation determination of recipient EBV and CMV serostatus can identify a subgroup of patients whose risk for severe PTLD may preclude transplantation.

Adult↗
PubMed1994

Percutaneous renal allograft biopsy. A comparison of two needle types and analysis of risk factors.

We retrospectively reviewed all (n = 369) percutaneous renal allograft biopsies performed at our institution between 1987 and 1992, comparing 14-gauge Franklin-Silverman (internal diameter = 2.0 mm, n = 169) and 18-gauge automated (internal diameter = 1.2 mm, n = 200) core biopsy needles. Visualization method, specimen adequacy, and complications were grouped by needle type. Five or more glomeruli were present in 88.9% of specimens obtained with Franklin-Silverman needles and in 82.7% with automated needles. A histologic diagnosis was obtained in 94.1% and 95.5% of Franklin-Silverman and automated biopsies, respectively. A complication was detected in 27 Franklin-Silverman biopsies (16.0%) and in 21 automated biopsies (10.5%) (not significant [NS], P > 0.05). Some procedures had more than one complication. Excluding asymptomatic gross hematuria, incidental hematomas, and incidental arteriovenous fistulas detected by routine ultrasonography, clinically significant complication rates were 6.5% for Franklin-Silverman biopsies and 2.5% for automated biopsies (NS). No allograft losses or patient deaths occurred as a result of allograft biopsy. Subgroup analysis of all biopsies performed with ultrasound marking alone (Franklin-Silverman, n = 119; automated, n = 148) revealed no significant (NS) difference in complication rates (15.1% vs. 10.8%). Additional subgroup analyses of palpation, ultrasound marking, and real-time ultrasonographic visualization techniques within each needle type also revealed no significant difference in the complication rate. Biopsy within 30 days of transplantation and no antihypertensive therapy were the only factors univariately associated (P < 0.05) with an increased complication rate. Multivariate analysis found biopsy within 30 days of transplantation (P = 0.007) was associated with the overall presence of one or more complications of any type. Type of needle (Franklin-Silverman vs. automated) achieved borderline significance (P = 0.047) when time to biopsy was statistically adjusted for; the Franklin-Silverman needle had a higher complication rate.

Adult↗
PubMed1994

Effects of systemic delivery of insulin on plasma lipids and lipoprotein concentrations in pancreas transplant recipients.

OBJECTIVE: To determine whether pancreas transplantation alters lipid and lipoprotein concentrations and whether peripheral hyperinsulinemia is always associated with altered lipid levels. DESIGN: We assessed the lipid profiles of seven pancreas-kidney recipients with insulin-dependent diabetes mellitus, seven kidney recipients without diabetes who received the same immunosuppressive agents, and eight normal subjects. MATERIAL AND METHODS: In the three study groups, fasting and postprandial plasma glucose, insulin, C-peptide, cholesterol, triglyceride, free fatty acid, and apolipoprotein A-I, A-II, C-II, and C-III concentrations were determined. RESULTS: Fasting and postprandial glucose concentrations did not differ between the two transplant groups; however, peripheral insulin concentrations were twice as high (P < 0.05) in the pancreas-kidney recipients as in the kidney recipients both before (102 +/- 15 versus 53 +/- 6 pmol/L) and after (123 +/- 22 versus 61 +/- 6 nmol/L per 6 hours) ingestion of a meal. Preprandial and postprandial insulin levels in both transplant groups also were greater (P < 0.05) than those in normal subjects (35 +/- 6 pmol/L and 40 +/- 7 nmol/L per 6 hours, respectively). Despite significant differences in insulin concentrations, no differences were noted in total cholesterol, high-density or low-density lipoprotein cholesterol, plasma free fatty acids, or apolipoprotein A-I, A-II, C-II, and C-III concentrations among the study groups. Plasma triglyceride concentrations in the two transplant groups were similar (114 +/- 20 versus 142 +/- 18 mg/dL) and were slightly more than those in the normal subjects (80 +/- 7 mg/dL). CONCLUSION: Despite peripheral hyperinsulinemia, pancreas transplantation can result in normal or near-normal lipid and lipoprotein concentrations. Thus, systemic delivery of insulin does not invariably produce an atherogenic lipid profile.

Adult↗
PubMed1993

Prospective study of anti-neutrophil cytoplasmic autoantibody tests in the diagnosis of idiopathic necrotizing-crescentic glomerulonephritis and renal vasculitis.

We prospectively assessed the value of anti-neurtrophil cytoplasmic autoantibodies (ANCA) and nuclear or perinuclear anti-neutrophil autoantibodies measured by indirect immunofluorescence microscopy and antimyeloperoxidase autoantibodies measured by a solid-phase assay in the diagnosis of idiopathic (pauci-immune) necrotizing-crescentic glomerulonephritis (NCGN) and renal vasculitis at our institution. A diagnosis was established on the basis of clinical and renal biopsy findings, and follow-up continued for at least 6 months. ANCA were measured at the conclusion of the study. Of the 111 study patients, 28 had NCGN and renal vasculitis. The immunofluorescence assay had 50% sensitivity and 79% specificity. The combination of the enzyme-linked immunosorbent assay for antimyeloperoxidase autoantibodies and the immunofluorescence assay for cytoplasmic ANCA had 78% sensitivity and 84% specificity. A firm diagnosis was established before the determination of ANCA in 26 of the 28 patients with NCGN and renal vasculitis. The antimyeloperoxidase autoantibody values would have suggested the diagnosis in the other two patients. Of these 28 patients, 5 had negative ANCA results. High antimyeloperoxidase autoantibody values were detected in patients with NCGN and renal vasculitis, whereas lower values were less specific and were detected mainly in patients with anti-glomerular basement membrane antibody disease and lupus glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗