Course of glomerular filtration rate after renal transplantation and the influence of hypertension.
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A gradual decline in the glomerular filtration rate (GFR) is a general problem in patients after renal transplantation that may be due to several factors.The glomerular filtration rate (GFR) was estimated using the corrected Schwartz formula in 16 pediatric renal transplant recipients over a period of 5 years post-transplant. Several potential risk factors for graft outcome were analyzed. The mean age of the patients (8 female, 8 male) at the time of transplantation was 11.1 years (range: 2.7-17.3). All patients received a cadaveric renal graft for the first time. Immunosuppression consisted of cyclosporine in combination with steroids in all children treated; 3 patients received azathioprine in addition. Blood pressure (BP) was monitored regularly and its extent was expressed by an antihypertensive treatment (AHT) score.At the end of the first post-transplant year the mean GFR was 88 +/- 24 ml/min/1.73 m2. During the following 4 years the GFR declined to 68 +/- 29 ml/min/1.73 m2 representing an overall GFR loss of 20 ml/min/1.73 m2 (23%). With regard to the GFR loss, 2 groups could be distinguished. The first group of 7 patients showed a significant GFR decrease from 89 +/- 26 to 49 +/- 27 ml/min/1.73 m2 (p = 0.0025), whereas the second group of 9 patients had a relatively constant GFR during the 5 years (87 +/- 26 and 83 +/- 24 ml/min/1.73 m2). In each group, two acute rejections were observed in the first post-transplant year. Blood pressure, expressed by an AHT score, increased in Group 1 moresso than in Group 2 during the 5 years.During the course of a 5-year period post-transplant the GFR declined significantly in 7 of 16 patients. One of the factors responsible for GFR loss is probably the increase in blood pressure.Keywords:
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Nephrology
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All conventional immunosuppressive tree drugs-protocols are based on Cyclosporine; consisting of low doses of Cyclosporine (CsA), Azathioprine (AZA) or Mycophenolate Mofetil (MMF) and Prednisolone, AZA has been used in clinical transplantation for more than 30 years and was the first immunosuppres-sive agent to achieve widespread use in organ transplantation. MMF was introduced in clinical practice in 1995 after several clinical trials proved that it was more efficient than AZA for prevention of acute rejection episodes. Our aim was to evaluate influence of AZA and MMF on renal graft function in early post-transplant stage. Study recruited 74 patients who underwent kidney transplantation in University Clinical Centre Tuzla. All patients received CsA and corticosteroid-based immunosuppression, as a part of triple immunosuppressive regiment, 40 patients received AZA and 34 MMF. In order to assess renal graft function, following parameters were evaluated: glomerular filtration rate GFR (ml/min) creatinine clearance (CrCl) (ml/min), 24 h urine output (ml/day), and from the serum potassium, sodium, urea and creatinine (mmol/dm3). Significantly higher average values of 24 hour urine output were recorded during first seven postoperative days in patients receiving MMF compared to those treated with AZA. Serum creatinine values showed statistically significant decrease, starting with the second postoperative day, in MMF vs. AZA group (168,7±70,5 vs. 119,9±42,6; p<0,0007). GFR was significantly higher in MMF compared to the AZA group of patients. On the first post-transplant day CrCl was higher in AZA group (24,3±10 vs. 17,5±7,3; p=0,01), next six days situation is reversed CrCl is significantly higher in the MMF group (43,7±15 vs. 53, 4±22, 8 p=0,006). MMF vs. AZA therapy was associated with protective effect against worsening of renal function in first seven post-transplant days.
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A gradual decline in the glomerular filtration rate (GFR) is a general problem in patients after renal transplantation that may be due to several factors.The glomerular filtration rate (GFR) was estimated using the corrected Schwartz formula in 16 pediatric renal transplant recipients over a period of 5 years post-transplant. Several potential risk factors for graft outcome were analyzed. The mean age of the patients (8 female, 8 male) at the time of transplantation was 11.1 years (range: 2.7-17.3). All patients received a cadaveric renal graft for the first time. Immunosuppression consisted of cyclosporine in combination with steroids in all children treated; 3 patients received azathioprine in addition. Blood pressure (BP) was monitored regularly and its extent was expressed by an antihypertensive treatment (AHT) score.At the end of the first post-transplant year the mean GFR was 88 +/- 24 ml/min/1.73 m2. During the following 4 years the GFR declined to 68 +/- 29 ml/min/1.73 m2 representing an overall GFR loss of 20 ml/min/1.73 m2 (23%). With regard to the GFR loss, 2 groups could be distinguished. The first group of 7 patients showed a significant GFR decrease from 89 +/- 26 to 49 +/- 27 ml/min/1.73 m2 (p = 0.0025), whereas the second group of 9 patients had a relatively constant GFR during the 5 years (87 +/- 26 and 83 +/- 24 ml/min/1.73 m2). In each group, two acute rejections were observed in the first post-transplant year. Blood pressure, expressed by an AHT score, increased in Group 1 moresso than in Group 2 during the 5 years.During the course of a 5-year period post-transplant the GFR declined significantly in 7 of 16 patients. One of the factors responsible for GFR loss is probably the increase in blood pressure.
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Nephrology
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Versluis, D. J.; WENTING, G. J.; DERKX, F. H. M.; SCHALEKAMP, M. A. D. H.; JEEKEL, J.; WEIMAR, W. Author Information
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Everolimus
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To assess the effect of cyclosporine therapy on the rate of renal function recovery after renal transplantation, patients with no clinical evidence of rejection and who were treated with either cyclosporine or azathioprine in addition to steroid therapy were studied (n = 74). Of the patients with immediate renal function (n = 57), those receiving organs from living, related donors had a faster recovery rate of glomerular filtration than patients with cadaveric grafts (azathioprine, 15 +/- 2 versus 7 +/- 1 mL/min/day, P = 0.0001; cyclosporine, 14 +/- 3 versus 6 +/- 1 mL/min/day, P = 0.001). Recipients of cadaveric grafts with delayed renal function (n = 17) had a decreased recovery rate of allograft function when treated with cyclosporine as compared to those treated with azathioprine (4 +/- 2 versus 6 +/- 1 mL/min/day, respectively; P = 0.026). Patients on azathioprine achieved better renal function (P = 0.01) than those on cyclosporine (recipients of organs from living, related donors, 59 +/- 5 versus 52 +/- 3 mL/min; recipients of cadaveric grafts, 52 +/- 5 versus 40 +/- 2 mL/min). Thus, even in this early period, cadaveric-graft recipients treated with cyclosporine demonstrate an apparent reduction in creatinine clearance when compared to patients treated with azathioprine.
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This study was designed to gain initial experience with rapamycin in thoracic organ transplant recipients with severely compromised kidney function, i.e. to see whether and how kidney function will improve with a rapamycin-based immunosuppressive protocol.Twelve heart transplant patients were included into the study (serum creatinine > 2.5 mg/dL), with an average time after transplantation of more than 4 years. The calcineurin inhibitor (cyclosporine A = 9, tacrolimus = 3) was reduced by 50 %, and rapamycin added to reach a target level of 8 - 12 ng/dL. Azathioprine was halted, corticosteroid treatment remained unchanged.After implementing the rapamycin-based immunosuppression kidney function improved in all patients within one week. Serum creatinine dropped from 3.1 +/- 0.6 mg/dL to 2.7 +/- 0.5 mg/dL ( p = 0.0004), creatinine clearance increased from 30.4 +/- 11 mL/min to 40.8 +/- 10.5 mL/min ( p = 0.003). This improvement continued until 3 months after the conversion ( p = 0.032). Thereafter, no statistically significant changes were noted up to 6 months posttransplant ( p = 0.41). Serum cyclosporine levels dropped from 180 +/- 40 ng/mL to 132 +/- 46 ng/mL on average ( p = 0.002). Side-effects occurred in 4 patients and were all related to a rapamycin level exceeding 12 ng/mL.We conclude that transplant patients with impaired kidney function will have an immediate benefit from partially replacing calcineurin inhibitors by rapamycin.
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The kidney volume after transplantation was compared in two groups, one treated by conventional immunosuppression and the other receiving small amounts of ciclosporin (CsA) together with azathioprine and steroid (the so-called triple therapy). Fourteen pairs of donors and recipients were investigated in each group. The kidney volume was measured, using computed tomography (CT scan), before and after transplantation in the donors and after transplantation in the recipients during the allograft rejection-free period. The graft volume at 2-3 months after transplantation was smaller (215.9 +/- 30.9 ml, mean +/- SD) in patients who received small amounts of ciclosporin A (CsA) together with azathioprine and steroid than that (270.9 +/- 75.0 ml) in those treated by conventional immunosuppression. The remaining kidney in the donor after transplantation underwent a similar increase in volume in the conventional and triple therapy groups. It is suggested that even a small amount of CsA can significantly limit the compensatory renal growth.
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Mycophenolate
Trough level
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Renal growth and function were studied in a sixteen year old recipient of a renal transplant from a 16 month old cadaveric donor. Within one month, as measured by sequential inulin and creatinine clearances, glomerular filtration rate was 40 ml/min, which was more than 6 times the estimated pretransplant clearance. Ultrasound of the transplanted kidney revealed longitudinal growth from 7 cm at transplant to 11.5 cm by 8 weeks post-transplant. Radionuclide renal scintiphotography confirmed rapid functional and dimensional growth. There was no evidence of rejection, obstruction, or other complications during the time the allograft rapidly increased in size. Thus this case demonstrates a remarkable capacity of the human kidney to hypertrophy rapidly.
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