T C Knauss

Cleveland State University, Cleveland, Ohio, United States

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Publications (32)103.89 Total impact

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    ABSTRACT: We previously reported excellent short-term outcomes in African American kidney transplant patients receiving tacrolimus/sirolimus and withdrawn from corticosteroid therapy three months after transplantation. We now report the long-term outcomes of patients subjected to this protocol. In all, 47 African American kidney transplant recipients were enrolled in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids, without antibody induction therapy. Eligible patients were withdrawn from prednisone between three and five months posttransplant, and followed for acute rejection and changes in renal function. Outcomes (group 1, n=32) were compared to those of patients deemed not to be candidates for steroid withdrawal (group 2, n=15). After a mean follow-up of 48.5 months, 13 of 32 patients (41%) in group 1 developed acute rejection; only 13 patients (41%) remain steroid-free. Nine of 13 rejection episodes were associated with noncompliance. Graft loss occurred in 8 of 32 patients (25%) in group 1 and in 5 of 15 patients (33%) in group 2 (P=NS). Serum creatinine rose from 1.4+/-0.41 to 2.45+/-1.7 mg/dL in group 1 (P=0.004) and from 2.1+/-0.45 to 2.62+/-1.2 mg/dL (P=NS) in group 2. Among 13 patients in group 1 who remain steroid-free, creatinine concentration has risen from 1.28+/-.0.37 prior to steroid withdrawal to 1.64+0.54 at last follow-up (P=0.027). Late noncompliance and/or rejection in African Americans withdrawn from steroids have a negative impact on long-term graft function and survival. Steroid withdrawal may be associated with long-term deterioration of renal function, even in the absence of overt acute rejection.
    No preview · Article · Mar 2007 · Transplantation
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    ABSTRACT: There is limited data on the potential nephrotoxicity of sirolimus (SRL) and tacrolimus (TAC) in combination. We reviewed the course of 97 kidney transplant patients treated with SRL and reduced-dose TAC. Conversion from SRL to mycophenolate mofetil (MMF) was prescribed in a minority (n = 19) for various nonrenal side effects. We compared outcomes of converted patients to those remaining on TAC/SRL (n = 78). TAC levels were increased in converters (P = 0.009). Rejection rates were similar between groups over 18 months (21% vs. 16%, p = ns). Serum creatinine (Cr) and MDRD glomerular filtration rate (GFR) were similar between groups at nadir and six-months, but at 18 months the percent change from six-month Cr was +17% in non-converters vs. -10% in converters (P = 0.004 for the difference). The difference in GFR between groups at 18 months was also significant (P = 0.01). By multivariate analysis, only conversion to MMF was associated with a greater percent change in Cr from 6 to 18 months (P = 0.015). Conversion to MMF also correlated with higher GFR at 18 months independent of rejection, delayed graft function, and ethnicity. Conversion from TAC/SRL to TAC/MMF led to improved renal function despite increased TAC exposure after conversion.
    No preview · Article · May 2006 · Transplantation
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    ABSTRACT: Anemia and erythrocytosis (PTE) are common after kidney transplantation. We sought to determine the influence of sirolimus compared to mycophenolate mofetil (MMF) on post-transplant erythropoiesis. A total of 214 patients with recent kidney or kidney–pancreas transplants were treated with either sirolimus-based (n = 87) or MMF-based (n = 127) therapy. At 12 months, the prevalence of anemia was 31% with MMF and 57% with sirolimus (p < 0.001). Linear regression was used to examine the independent influence of sirolimus on hemoglobin at 12 months, controlling for multiple factors including gender and renal function. Sirolimus remained a significant correlate of lower hemoglobin in all patients (slope =−1.060, 95% CI: −1.76 to −0.362, p = 0.003), and in patients without PTE (slope =−0.671, 95% CI: −1.32 to −0.028, p = 0.041). PTE, defined as a persistent hematocrit above 51%, occurred in 19% with MMF and 7% with sirolimus (p = 0.013). PTE was examined using logistic regression analysis. Sirolimus use correlated negatively with PTE (odds ratio with sirolimus = 0.33, 95% CI: 0.12 to 0.89, p = 0.028). Our results indicate that, compared to treatment with MMF, treatment of kidney or kidney–pancreas recipients with sirolimus is associated with a higher prevalence of anemia, lower hemoglobin levels and lower incidence of PTE.
    Full-text · Article · Jan 2005 · American Journal of Transplantation
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    ABSTRACT: Withdrawal of corticosteroids from the immunosuppressive regimens of kidney transplant recipients has been associated with an increased risk of acute and chronic allograft rejection. Previous studies indicate that the risk of rejection is particularly high in African Americans. We prospectively enrolled 44 African American kidney transplant recipients to participate in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids. No patient received antibody induction therapy. Prednisone was withdrawn from eligible patients free of acute rejection beginning as early as 3 months posttransplant, and followed for a minimum of 9 months posttransplant. Patients were followed for acute rejection and for changes in blood pressure, body weight, and serum creatinine concentrations before and after withdrawal of steroids. Thirty of 44 patients (68%) were weaned off of prednisone. Follow-up after withdrawal of prednisone ranged from 3 to 26 months (mean, 14.3+/-7.7 months). Two of 30 patients (6.7%) developed acute rejection. At last follow-up, 27 of 30 patients (90%) remain steroid-free. Steroid withdrawal was associated with significant reductions in blood pressure. Use of sirolimus and tacrolimus, without the use of induction antibody therapy, allows withdrawal of prednisone as early as 3 months posttransplant with low rates of subsequent acute rejection in African American kidney transplant recipients. Withdrawal of prednisone was associated with lower blood pressures and the need for fewer antihypertensive medications.
    No preview · Article · Oct 2003 · Transplantation

  • No preview · Article · Oct 2003 · Transplantation Reviews
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    ABSTRACT: Mycophenolate mofetil (MMF) and sirolimus impair wound healing. We compared sirolimus vs. MMF to determine the relative impact on surgical complications and wound healing in adult kidney transplant recipients. This retrospective, single center study of 235 adult kidney transplants performed between 1 January 2000 and 31 January 2002 identified 158 adult, kidney-only recipients treated with tacrolimus and prednisone, from which two groups were defined: group 1 (n = 84) received MMF, group 2 (n = 74) received sirolimus. The incidence of fluid collections, wound problems, dehiscence, and urine leak were compared. A multivariate stepwise logistical regression analysis was performed to identify risk factors. The overall incidence of complications was 21.5%, with rates significantly lower in group 1 (2.4%) vs. group 2 (43.2%, p < 0.0001). Regression analysis showed only sirolimus (p < 0.001) and hypo-albuminemia (p = 0.006) to independently correlate with complication occurrence. In subanalyses, lymphoceles correlated only with sirolimus (p = 0.003), while other wound problems also correlated with higher body mass index (p = 0.067). The use of sirolimus, tacrolimus and prednisone was associated with a greater incidence of lymphoceles, non-lymphocele perinephric fluid collections and other consequences of poor wound healing, as compared to contemporary patients treated with MMF, tacrolimus and prednisone.
    Full-text · Article · Sep 2003 · American Journal of Transplantation
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    ABSTRACT: African American kidney transplant recipients generally exhibit poor long-term graft survival compared with other ethnic groups. The combination of sirolimus, tacrolimus, and corticosteroids has proven to be effective in reducing rejection episodes in high-risk organ and islet cell transplant recipients but has not yet been tested in a large number of African American patients. The outcomes of 56 African American adult, primary kidney transplant recipients treated with corticosteroids, sirolimus, and tacrolimus targeted to relatively low trough blood levels were compared with those of a concurrent group of 65 white patients treated with steroids, mycophenolate mofetil, and tacrolimus targeted to relatively high blood levels. Induction antibody therapy was not routinely used in either group. The incidence of acute rejection in the first 3 posttransplantation months was 7.1% in African Americans and 16.9% in whites (P=NS). Actuarial 2-year patient, graft, and rejection-free graft survival rates were equivalent in the two groups. Posttransplantation diabetes mellitus occurred in 36% of the African American patients, despite similar doses of corticosteroids and lower trough levels of tacrolimus, compared with 15% of white patients (P=0.024). The combination of corticosteroids, sirolimus, and relatively low doses of tacrolimus results in acute rejection, graft survival, and patient survival rates equivalent to those achieved in white patients receiving steroids, mycophenolate mofetil, and relatively high doses of tacrolimus, even without the routine use of induction antibody therapy. Posttransplantation diabetes mellitus remains a problem for African Americans receiving this combination of immunosuppressants, despite relatively low tacrolimus blood levels.
    No preview · Article · Aug 2002 · Transplantation
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    ABSTRACT: Recent reports suggest that hypertension may be less common after simultaneous pancreas-kidney transplantation than after kidney transplantation alone. However, the mechanisms for this beneficial effect have not been delineated. We hypothesize that lower blood pressures may result from chronic volume depletion in patients with bladder-drained pancreatic allografts. We compared the incidence and severity of hypertension 12 months after transplantation in 79 bladder-drained pancreas-kidney recipients and 46 diabetic kidney-only recipients. These two groups were compared with a smaller group of enterically drained pancreas-kidney recipients. Blood pressure was also compared before and after surgical conversion from bladder to enteric drainage in 10 patients. Hypertension was significantly less common and less severe after pancreas-kidney transplantation than after kidney transplantation alone, but the benefit of the pancreas transplant was evident only in bladder-drained patients. Logistic regression analysis of the bladder-drained pancreas-kidney patients confirmed the independent impact of the pancreatic allograft on the presence of hypertension, indicated an independent association with serum creatinine concentration and donor age, but suggested no correlation with recipient age, race, or number of rejection episodes. A comparison of blood pressures before and after pancreatic conversion from bladder to enteric drainage indicated no significant change in the prevalence or severity of hypertension. We conclude that the beneficial effect of a pancreas transplant on the prevalence and severity of hypertension after simultaneous pancreas-kidney transplantation is limited to bladder-drained patients. Although it is possible that the effect is mediated by chronic volume depletion, the observation that blood pressure does not increase after conversion from bladder to enteric drainage suggests that other factors may be involved.
    Preview · Article · Sep 2000 · Transplantation

  • No preview · Article · Apr 1999 · Transplantation
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    ABSTRACT: The high success rate of HLA-identical sibling transplants and our previous experience with steroid-free immunosuppressive regimens and cyclosporine withdrawal prompted us to evaluate the safety and efficacy of monotherapy with azathioprine in 12 HLA-identical kidney transplant recipients with a serum creatinine concentration less than 176.8 mumol/L, a 1-way stimulatory index less than 2.0 in a post-transplant mixed lymphocyte culture, and a demonstrated tolerance of a minimum azathioprine dose of 1.0 mg/kg per day without leukopenia. Eleven of 12 patients were successfully converted to azathioprine monotherapy without a significant change in serum creatinine concentration for as long as 76 months. Benefits of steroid and cyclosporine withdrawal included a significant reduction in mean systolic and diastolic blood pressure, number of blood pressure medications, total serum cholesterol, and glycohemoglobin in diabetic subjects. Our results suggest that azathioprine monotherapy is safe and effective in a select group of HLA-identical sibling transplants, but these benefits must be carefully balanced against an associated risk of precipitating acute allograft rejection.
    No preview · Article · Apr 1999 · Journal of transplant coordination: official publication of the North American Transplant Coordinators Organization (NATCO)
  • M S Simonson · W H Herman · T C Knauss · JA Schulak · D E Hricik

    No preview · Article · Feb 1999 · Transplantation Proceedings
  • D E Hricik · A Dixit · T C Knauss · V Donley · M R Bartucci · J A Schulak
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    ABSTRACT: In an effort to minimize nephrotoxicity resulting from greater exposure to cyclosporine after Sandimmune to Neoral conversion, we compared two conversion regimens using different dosing ratios. Serial serum creatinine concentrations and trough cyclosporine levels were measured in 26 patients converted from Sandimmune to Neoral using a 1:0.8 dosing ratio (Group 1) and compared to those of 26 patients converted using a 1:1 dosing ratio (Group 2). The percentage change in peak serum creatinine concentration after conversion was greater in Group 2. However, at last follow-up, the dose reductions in each group were comparable. Following conversion, patients in Group 1 required fewer dose adjustments and follow-up blood tests. Compared to conversion using a 1:1 dosing ratio, conversion from Sandimmune to Neoral using a 1:0.8 ratio results in comparable dose reductions and less short-term nephrotoxicity, while requiring less frequent laboratory monitoring.
    No preview · Article · Jan 1999 · Clinical Transplantation
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    ABSTRACT: Chronic renal allograft rejection is characterized histologically by transplantation-associated arteriosclerosis and glomerulosclerosis (Tx-AA and Tx-AGS). Recent studies in animal models implicate the mitogenic and pressor actions of endothelin-1 (ET-1) in Tx-AA. In humans, however, a link between elevated ET-1 secretion and Tx-AA or Tx-AGS remains unclear. In this study we analyzed expression of ET-1 in the vasculature of renal transplant patients with chronic or acute rejection and in normal controls. Renal vascular and glomerular ET-1 was assessed by immunohistochemistry in 12 patients with clinically and histologically defined chronic rejection, in 11 patients with acute rejection, and in 5 normal kidneys. ET-1 staining was also correlated with various clinical parameters and with a morphometric index of neointima formation. ET-1 secretion was measured by ELISA in cultured human vascular cell types treated with T cell- and macrophage-associated cytokines. We found that renal allografts with chronic rejection and Tx-AA expressed 6.1-fold more ET-1 in the vasculature relative to allografts with acute rejection or to normal kidneys (P < 0.01). In Tx-AA, ET-1 was detected predominantly in the neointima, which contained mostly endothelial cells and smooth muscle cells. A strong positive correlation (r = 0.82, P < 0.01) was observed between vascular ET-1 peptide expression and hypertension in patients with chronic rejection. We also showed that macrophage-associated cytokines, but not T cell-associated cytokines, stimulated ET-1 secretion in human endothelial cells, vascular smooth muscle and mesangial cells. These results demonstrate that elevated ET-1 in the neointima is associated with Tx-AA and chronic rejection. In addition, these results point to an important role for endothelial dysfunction in chronic renal allograft rejection.
    Preview · Article · Sep 1998 · Kidney International

  • No preview · Article · May 1998 · Transplantation

  • No preview · Article · May 1998 · Transplantation
  • F Z Ghandour · T C Knauss · D E Hricik
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    ABSTRACT: Successful pregnancies are now common in female organ transplant recipients. Despite high rates of success, pregnancy in an organ transplant recipient should be managed as a high-risk condition with emphasis on prevention and prompt treatment of rejection episodes. The number of immunosuppressive drugs and drug combinations has increased in recent years. Data accrued by a national registry indicate that pregnancy is generally successful in patients maintained on some combination of cyclosporine, azathioprine, and steroids. Relatively little information is available regarding the safety of some of the newer immunosuppressive agents in pregnancy. Until additional information is collected, transplant physicians and obstetricians must balance the efficacy of immunosuppressants in preventing allograft rejection in the mother against possible adverse drug reactions in both the mother and fetus.
    No preview · Article · Mar 1998 · Advances in Renal Replacement Therapy
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    ABSTRACT: Previous studies comparing renal function in diabetic subjects receiving either a kidney or kidney-pancreas transplant generally have indicated no differences; however, these studies have been limited by inclusion of either a small number of patients or selected patients followed for relatively short periods of time. To compare long-term renal function and factors affecting renal function in type I diabetic patients receiving either kidney or kidney-pancreas transplants, the slopes of regression lines generated by plotting the reciprocal of serum creatinine (1/Cr) versus time were measured in 109 consecutive patients followed for at least 12 and up to 102 months after transplantation. Multivariate analyses included linear regression using the slope of 1/Cr versus time as the dependent variable and logistic regression using a positive or negative slope as the dependent variable. Significant differences between kidney-pancreas (n=64) and kidney recipients (n=45) included a smaller proportion of African-Americans, lower rates of HLA matching, lower levels of panel-reactive antibodies, shorter cold ischemia times, a lower incidence of delayed graft function, and a higher incidence of acute renal allograft rejection episodes in the kidney-pancreas group. Trough cyclosporine blood levels were significantly higher in the kidney-pancreas group for the first 12 posttransplant months. The slopes of 1/Cr versus time were negative in each group with a trend toward a more negative slope in the kidney-pancreas group. Multivariate analyses indicated that a concomitant pancreas allograft did not influence long-term renal function. The total number of renal rejection episodes was the best independent predictor of a negative slope of 1/Cr versus time. However, use of OKT3 for the treatment of rejection within the first 3 months of transplantation exerted a surprisingly beneficial effect on long-term renal function, a phenomenon that was most apparent in the kidney-alone group. The frequency and timing of acute rejection episodes are more important than the influence of a simultaneously transplanted pancreatic allograft in determining long-term function of the transplanted kidney. A concerning trend toward late deterioration of renal function in kidney-pancreas recipients suggests that the benefits of sustained euglycemia, shorter cold ischemia times, lower rates of sensitization, and early use of OKT3 ultimately may be outweighed by the negative effects of more frequent renal rejection episodes.
    No preview · Article · Dec 1997 · Transplantation
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    ABSTRACT: The ratio of urine protein/urine creatinine in spot urine specimens was measured to determine the influence of steroid withdrawal and other clinical variables on urinary protein excretion in 135 primary renal transplant recipients, including 73 patients in whom steroid withdrawal was never attempted and 62 patients in whom steroid withdrawal was attempted at various times following transplantation. Both univariate and multivariate analyses showed that steroid withdrawal per se did not directly influence proteinuria. However, patients who renewed steroid therapy because of acute allograft rejection following attempted steroid withdrawal exhibited significantly more proteinuria than was encountered either in patients who remained steroid-free or in those for whom steroid withdrawal was never attempted. This study suggests that steroid withdrawal itself does not lead to proteinuria, however, acute rejection following steroid withdrawal clearly accelerates urinary protein excretion that may be the harbinger of chronic allograft rejection.
    No preview · Article · Nov 1997 · Clinical Transplantation
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    ABSTRACT: Conversion of stable renal transplant patients from Sandimmune to Neoral may pose a risk of short-term nephrotoxicity. Serial serum creatinine concentrations were measured in 141 kidney and simultaneous kidney-pancreas transplant recipients converted from Sandimmune to Neoral on a 1:1 dosing basis and followed for up to 11 months. Following conversion, cyclosporine dose was reduced in 74% of patients with a mean dose reduction of 22.6% for the entire cohort. Serum creatinine concentrations transiently increased to more than 30% above baseline in 48% of patients and remained more than 30% above baseline in 16% of patients. Multivariate analyses suggested that acute rejection, maintenance steroid therapy, young age, Sandimmune dose prior to conversion, and an increment in trough cyclosporine levels after conversion were positive predictors of renal insufficiency following conversion. Lower doses of Neoral should be considered at the time of conversion to minimize nephrotoxicity.
    No preview · Article · Jul 1997 · Journal of transplant coordination: official publication of the North American Transplant Coordinators Organization (NATCO)
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    ABSTRACT: To assess the efficacy and safety of fluvastatin in hypercholesterolemic, cyclosporine-treated, renal transplant recipients, and to determine whether concomitant steroid therapy in such patients alters the lipid-lowering effects of fluvastatin. An open-label, prospective, parallel study was performed in 20 cyclosporine-treated renal transplant recipients with hypercholesterolemia defined by a low-density lipoprotein (LDL) concentration greater than 160 mg/dL or a total cholesterol/high-density lipoprotein (HDL) concentration ratio greater than 5.0. Lipid profiles were measured before and 1 month after treatment with fluvastatin 20 mg/d. Lipid profiles in a group of patients receiving concomitant therapy with prednisone (n = 12) were compared with those of patients who had not received steroids for at least 6 months (n = 8). The Renal Transplant Clinic at University Hospitals of Cleveland. The main outcome measures were serum concentrations of total cholesterol, LDL, HDL, and triglycerides. Treatment failure was defined by LDL concentrations persistently above 160 mg/dL after 1 month of fluvastatin therapy. Safety was assessed clinically and by serial measurements of liver enzymes and creatine phosphokinase. LDL concentrations decreased significantly in both the steroid-treated and steroid-free groups after 1 month of fluvastatin therapy. There was no significant change in HDL concentrations or serum triglycerides in either group. Treatment failure was more common in patients receiving steroids (4/12 patients) than in steroid-free patients (1/8 patients). After 1 month of therapy, LDL cholesterol was significantly lower in the steroid-free group (126 +/- 18 mg/dL) than in the steroid-treated group (147 +/- 23 mg/dL) (p < 0.05). There was no clinical or laboratory evidence of myonecrosis in either group. Low dosages of fluvastatin appear to be safe in cyclosporine-treated renal transplant recipients. Steroid-free patients exhibit a response to fluvastatin that is qualitatively similar to that of steroid-treated patients, consisting of a significant decrease in LDL concentrations and no change in HDL or serum triglyceride concentrations.
    No preview · Article · Dec 1996 · Annals of Pharmacotherapy

Publication Stats

919 Citations
103.89 Total Impact Points


  • 1996-2003
    • Cleveland State University
      Cleveland, Ohio, United States
  • 1990-2003
    • Case Western Reserve University
      • School of Medicine
      Cleveland, Ohio, United States
  • 1997-1999
    • Case Western Reserve University School of Medicine
      • Department of Medicine
      Cleveland, Ohio, United States
  • 1991
    • University of Texas at San Antonio
      San Antonio, Texas, United States