Chronic kidney disease in renal transplant recipients

The aim of the present study was to investigate the utility in renal transplant patients of the guidelines for the diagnosis and classification of chronic kidney disease (CKD) based on the estimated glomerular filtration rate (GFR) elaborated by the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation. PATIENTS AND METHODS: Four hundred forty-seven cadaveric kidney transplants performed between 1980 and 1994 with graft function at 12 months were included in the study. The GFR was calculated according to the MDRD equation. RESULTS: The mean GFR at 12 months was 54.5 +/- 20.3 mL/min/1.73 m(2): 23 patients (5.1%) had a GFR > or =90 mL/min/1.73 m(2); 136 patients (30.6%), 60-89; 246 (54.7%), 30-59; 35 patients (7.8%), 15-29; and 7 patients (1.6%), GFR <15. Similar distribution of CKD stages was observed at 5 and 10 years. Unadjusted graft survival at 10 years was better among patients with a higher GFR at 12 months: 87% in patients with GFR >90 mL/min/1.73 m(2); 83% of GFR 60-89 mL/min/1.73 m(2); 63%, GFR 30-59 mL/min/1.73 m(2); and 23%, GFR <30 mL/min/1.73 m(2) (P < .001). The association between GFR and graft survival persisted when adjusted by the age and gender of the recipients and donors, time on dialysis, body mass index, immunosuppression, delayed graft function, rejection, and HLA mismatches. The prevalence of complications, such as anemia, hypertension, dyslipidemias, and number of drugs increased as GFR declined. CONCLUSIONS: More than 60% of recipients presented chronic kidney disease. GFR was a predictive factor for graft survival at 10 years. The classification of renal transplant patients by CKD stages may help to identify patients with increased risk of graft loss and also to design strategies to improve outcomes.     

Assessment of Changes in Kidney Allograft Function Using Creatinine-Based Estimates of Glomerular Filtration Rate

These analyses assessed whether creatinine based estimates of glomerular filtration rate (eGFR) accurately represent (1) graft function at different times post-transplant and (2) changes in function over time. These analyses compared iothalamate GFR to eGFR in 684 kidney allograft recipients. Changes in graft function over time (GFR slope) were measured in 360 of 459 recipients (78%) who were followed for at least 3 years. Ninety-five percent of the patients were Caucasians and 72% received kidneys from living donors. All eGFR calculations correlated significantly with GFR at all time points. However, eGFR were less precise and less accurate during the first-year post-transplant than thereafter. The average rate of GFR change (slope) was -2.93 +/- 11.3%/year (-1.06 +/- 5.3 mL/min/1.73 m(2)/year). Fifty-four percent of patients had stable or positive GFR slopes. The GFR and eGFR slopes were highly correlated. However, eGFR slope, particularly when calculated by MDRD, significantly underestimated the number of patients with declining graft function. For example, 165 out of 360 patients (46%) lost GFR faster than -1 mL/min/1.73 m(2)/year. eMDRD identified only 83 of these patients (50%) while the eMayo formula identified 134 (81%). In conclusion, eGFR correlate with GFR but they have relatively low precision and accuracy particularly early post-transplant. eGFR slopes underestimate graft functional loss although some formulas are significantly better than others for this calculation.     

Donor Kidney Volume and Outcomes Following Live Donor Kidney Transplantation

Pre-donation kidney volume and function may be crucial factors in determining graft outcomes in kidney transplant recipients. We measured living donor kidney volumes by 3D helical computed tomography scanning and glomerular filtration rate (GFR) by (125)I-iothalamate clearances in 119 donors, and correlated these values with graft function and incidence of acute rejection at 2 years post-transplantation. Kidney volume strongly correlated with GFR (Pearson r= 0.71, p < 0.001). Body size and male gender were independent correlates of larger kidney volumes, and body size and age were predictors of kidney function. The effects of transplanted kidney volume on graft outcome were studied in 104 donor-recipient pairs. A transplanted kidney volume greater than 120 cc/1.73 m(2) was independently associated with better estimated GFR at 2 years post-transplant when compared to recipients of lower transplanted kidney volumes (64 +/- 19 vs. 48 +/- 14 mL/min/1.73 m(2), p < 0.001). Moreover, recipients of lower volumes had a higher incidence of acute cellular rejection (16% vs. 3.7%, p = 0.046). In conclusion, kidney volume strongly correlates with function in living kidney donors and is an independent determinant of post-transplant graft outcome. The findings suggest that (1) transplantation of larger kidneys confers an outcome advantage and (2) larger kidneys should be preferred when selecting from otherwise similar living donors.     

The older living kidney donor: Part of the solution to the organ shortage

BACKGROUND: Strategies to increase kidney transplantation are urgently needed. METHODS: We studied all (n = 73,073) first kidney-only transplant recipients in the United States between 1995 and 2003 to determine the incidence and outcomes of living donor transplantation as a function of donor age. Because 90% of living donors were <55 years, we defined older living donors as > or =55 years. Factors associated with transplantation from older living donors and the association of living donor age with allograft function and survival were determined. RESULTS: Recipients of older age, female gender, white race, and preemptive transplants had higher odds of older living donor transplantation. Older living donor transplantation was more likely from spousal donors rather than blood relatives, and more likely when a husband was the donor. The glomerular filtration rate (GFR) one year after transplantation decreased with increasing donor age (P < 0.001). Graft survival from living donors > or =55 years was 85% and 76% at three and five years (compared to 89% and 82% with living donors <55 years, and 82% and 73% with deceased donors <55 years). In a multivariate model, the risk of graft loss with living donors 55-64 years was similar to that with deceased donors <55 years, while recipients from living donors 65-69 years (HR = 1.3, 95% CI: 1.1-1.7) and >70 years (HR = 1.7, 95% CI: 1.1-2.6) had a higher relative risk of graft loss. CONCLUSIONS: Outcomes are excellent with living donors <65 years. Expanded use of older living donors may help meet the demand for transplantation.     

Graft function 5-7 years after renal transplantation in early childhood

BACKGROUND: Low recipient age is still a risk factor for graft failure after kidney transplantation (Tx). Detailed prospective reports on long-term graft function in small children after renal Tx are still lacking. METHODS: Forty-nine kidney allograft recipients who received transplants before the age of 5 years were followed prospectively. The most common disease was congenital nephrotic syndrome of the Finnish type. Twenty patients were recipients of living related donors (LRD), and 29 were cadaveric kidney (CAD) recipients. All patients received triple immunosuppression. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), sodium, urate, and potassium handling, and concentrating capacity were studied for up to 7 years after Tx. RESULTS: Patient survival 7 years after Tx was 100% for LRD and 96% for CAD recipients. Graft survival was 94% for LRD and 79% for CAD recipients (P=NS) and 89% and 83% for children >2 years and <2 years of age at Tx, respectively (P=NS). Five years after Tx, GFR was 70 vs. 64 and ERPF was 380 vs. 310 ml/min/1.73 m2 for LRD and CAD recipients, respectively (P=NS). Mean absolute GFR remained stable. GFR was lower in children who received transplants at <2 years than in children who received transplants at >2 years of age, 54 vs. 75 ml/min/1.73 m2 (P=0.02). Sodium handling remained intact, but hyperuricemia was seen in 43-67%; 17-33% showed abnormal handling of potassium; and most patients had a subnormal concentrating capacity. CONCLUSIONS: Excellent long-term graft survival and good graft function can be achieved with triple immunosuppression, even in young CAD kidney recipients.     

Expanded criteria donors for kidney transplantation: quality control and results

Although the number of kidneys from expanded criteria deceased donors (ECDs) is growing in most transplant centers, the limits for acceptance of these kidneys and the safety standards have still not been fully established. We evaluated 342 kidney transplants performed between January 1999 and December 2004. In 77 (22.5%) of these, the kidneys were from ECDs, that is, donors age >60 years and with one of the following characteristics: hypertension, death due to cerebrovascular accident (CVA) or glomerular filtration rate (GFR) <70 mL/min. The results of the ECD transplants were compared with 265 transplants during the same period from standard donors (SDs), that is, donors age <60 years and GFR > 70 mL/min. All the ECD kidneys underwent biopsy and were accepted for transplantation only if the score was <7. The ECDs (66.5 +/- 4.3 years) in comparison with the SDs (48.0 +/- 16.0 years) had a greater frequency of death due to CVA (94.8% vs 49.8%) and a lower GFR (80.4 +/- 25.0 vs 111 +/- 41.6 mL/min; P < .05). Of the ECDs, 97.4% had a history of hypertension versus 24.3% of the SDs. Kidney biopsies were performed in 116 SD kidneys because the donor age was >55 years or there was a history of hypertension. The median score for the kidney biopsies of the ECD kidneys was 3 versus 2 for the SD kidneys. Graft survival was not significantly different until the fifth year. The GFR at 12 months was significantly different (SDs, 58.0 +/- 22.7 vs ECDs, 48.9 +/- 16.5 mL/min; P < .05). Although the GFR in the ECD kidneys was lower than that of the SD kidneys, it could still be adequate for recipients older than 50 years of age. Accordingly, the acceptance criteria for ECD kidneys based mainly on the kidney biopsy score and donor GFR benefit the recipients.     

Higher Renal Allograft Function in Deceased-Donor Kidney Transplantation Rather Than in Living-Related Kidney Transplantation

Objectives

To compare the clinical outcome of kidney transplantation from living-related and deceased donors.

Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients

The clinical profile of belatacept in kidney transplant recipients was evaluated to determine if earlier results in the BENEFIT study were sustained at 3 years. BENEFIT is a randomized 3 year, phase III study in adults receiving a kidney transplant from a living or standard criteria deceased donor. Patients were randomized to a more (MI) or less intensive (LI) regimen of belatacept, or cyclosporine. 471/666 patients completed ≥3 years of therapy. A total of 92% (MI), 92% (LI), and 89% (cyclosporine) of patients survived with a functioning graft. The mean calculated GFR (cGFR) was ～21 mL/min/1.73 m(2) higher in the belatacept groups versus cyclosporine at year 3. From month 3 to month 36, the mean cGFR increased in the belatacept groups by +1.0 mL/min/1.73 m(2) /year (MI) and +1.2 mL/min/1.73 m(2) /year (LI) versus a decline of -2.0 mL/min/1.73 m(2) /year (cyclosporine). One cyclosporine-treated patient experienced acute rejection between year 2 and year 3. There were no new safety signals and no new posttransplant lymphoproliferative disorder (PTLD) cases after month 18. Belatacept-treated patients maintained a high rate of patient and graft survival that was comparable to cyclosporine-treated patients, despite an early increased occurrence of acute rejection and PTLD.     

Steroid pretreatment of organ donors does not impact on early rejection and long‐term kidney allograft survival: Results from a multicenter randomized,controlled trial

Steroid pretreatment of deceased donors reduces inflammation in allografts and is recommended by organ procurement guidelines. The impact on long‐term graft outcome, however, remains elusive. In this multicenter randomized controlled trial, 306 deceased donors providing organs for 455 renal transplant recipients were randomized to 1000 mg of methylprednisolone or placebo prior to organ procurement (ISRCTN78828338). The incidence of biopsy‐confirmed rejection (Banff>1) at 3 months was 23 (10%) in the steroid group and 26 (12%) in the placebo group (P = .468). Five‐year functional graft survival was 84% and 82% for the steroid group and placebo group, respectively (P‐value = .941). The hazard ratio of functional graft loss was 0.90 (95% confidence interval 0.57‐1.42, P = .638) for steroid vs placebo in a multivariate Cox model. We did not observe effect modification by any of the predictors of graft survival and treatment modality. A robust sandwich estimate was used to account for paired grafts of some donors. The mean estimated GFR at 5 years was 47 mL/min per 1.73 m² in the steroid group and 48 mL/min per 1.73 m² in the placebo group (P = .756). We conclude that steroid pretreatment does not impact on long‐term graft survival. In a donor population with higher risk of delayed graft function, however, repetitive and higher doses of steroid treatment may result in different findings.     

Course of glomerular filtration rate after renal transplantation and the influence of hypertension.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Estimated and Measured Donor Creatinine Clearance are Poor Predictors of Long-Term Renal Graft Function and Survival

The objective of this study was to evaluate estimated and measured donor renal function in predicting graft function long-term and to identify donor criteria associated with nonacceptable graft prognosis. In 200 consecutive cadaver donors creatinine clearance was measured at explantation and estimated using the Cockcroft formula on admission serum creatinine. Graft function was evaluated in recipients (n = 387) by 24-h creatinine clearance regularly during 3 years after transplantation. Measured creatinine clearance correlated to some extent with long-term graft function, while Cockcroft estimation was slightly superior and similar to using donor age only. Kidneys from donors with intra-operative creatinine clearance < or = 55 mL/min (median 50 mL/min) produced acceptable recipient graft function of 48 mL/min at 3 years and 76% 3-year graft survival. Donor age > or =60 years resulted in clearance at 3 years of 29 mL/min and 78% 3-year graft survival; adding the criteria of admission Cockcroft < or =60 mL/min, graft function at 3 years (28 mL/min) and 3-year graft survival (76%) were similar. In conclusion, creatinine-based estimates of the functional capacity of the donor kidney, calculated or intra-operatively measured, do little to improve the ability of donor age alone to predict long-term allograft function after renal transplantation, and nonacceptable donors are not discriminated.     

Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival

BACKGROUND: The use of older donors for cadaveric renal transplantation (CRT) remains controversial because older donors are associated with decreased graft survival, yet offer the opportunity for donor pool expansion. We investigated the impact of two age-related donor factors, hypertension and calculated creatinine clearance (C(Cr)), as predictors of graft outcome in recipients of CRTs from donors > or =55 years of age. METHODS: We reviewed 33,595 recipients of CRTs reported to UNOS since 4/1/94, of which 4,732 were from donors aged > or =55 years. Outcome measures were graft survival, serum creatinine, and incidence of delayed graft function with 3 years of follow-up. We first analyzed the effect of hypertension on outcome from donors > or =55 years: 2679 donors had no hypertension, 1058 had hypertension < or =10 years, and 557 had hypertension > 10 years. Next, the effect of donor C(Cr) as a risk predictor was investigated. Based on this analysis, recipients of older donors were grouped into two cohorts for comparison: 2570 donors with C(Cr)<80 ml/min and 2162 donors with C(Cr) > or =80 ml/min. RESULTS: Actuarial graft survival from donors aged <55 years was 88.0, 83.4, and 78.5% at 1, 2, and 3 years, vs. 80.6, 73.5, and 65.3% from donors > or =55 years (P<0.0001). When stratified by hypertension, older donors hypertensive > 10 years had survivals of 77, 66, and 57% vs. 81, 73, and 65% from donors without hypertension (P<0.017) and 80, 74, and 66% from donors hypertensive <10 years (P<0.017). When stratified by C(Cr), older donors with C(Cr) <80 ml/min had survivals of 77, 69, and 62% vs. 83, 76, and 66% from donors with C(Cr) > or =80 (P<0.0001). Finally, older donors with both hypertension > 10 years and C(Cr) <80 ml/min had survivals of 77, 61, and 53%. CONCLUSIONS: Long-standing hypertension and low calculated creatinine clearance are risk factors for decreased graft survival of CRTs from older donors. When both factors are present, graft survival is significantly decreased.     

Superior Long-Term Results of Simultaneous Pancreas–Kidney Transplantation from Pediatric Donors

The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation has prompted the use of cadaveric organs from pediatric donors. The long-term outcome and its impact on overall long-term survival are unknown. A total of 680 recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation from pediatric and adult donors between July 1986 and September 2001 were analyzed and compared. Ten-year kidney and pancreas graft survival for SPK transplantation from donors aged <18 years (n = 142) were 80% and 72%, respectively, compared to 61% pancreas and kidney graft survival from donors > or =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post-transplant, blood glucose, HbA1c and creatinine clearance were significantly better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and 65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1 +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002, respectively). Causes of graft failure for kidney and pancreas transplants were similar between the two groups. No statistically significant difference was observed in patient survival between recipients from pediatric donors compared to adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric donors were stratified according to age (3-11 years and 12-17 years) and compared, no difference in kidney or pancreas graft survival was observed (kidney 76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively). Pediatric donors represent a valuable source of organs, providing excellent short- and long-term outcomes. Wide utilization of pediatric organs will substantially increase the donor pool.     

Why do preemptive kidney transplant recipients have an allograft survival advantage?

BACKGROUND: Preemptive kidney transplantation is associated with an allograft survival advantage and is promoted in part because of this association. The basis for the allograft survival advantage in preemptive recipients is unclear. Possibilities include a lead time bias due to the earlier transplantation of patients with preserved native kidney function, less rapid loss of kidney function after transplantation, or the longer patient survival of preemptive recipients. METHODS: We compared the glomerular filtration rate (GFR) six months after transplantation and the subsequent rate of loss of kidney function as defined by the annualized change in GFR (mL/min/1.73 m2/year) in 5,966 preemptive and 34,997 non-preemptive recipients. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Multiple regression was used to determine the independent effect of preemptive transplantation upon the annualized change in GFR. RESULTS: The mean GFR six months after transplantation was similar among preemptive (49.5+/-15.7 mL/min/1.73 m2) and non-preemptive (49.2+/-14.7 mL/min/1.73 m2) recipients (P=0.37). In multivariate analysis, preemptive recipients had a slower decline in GFR (0.28 mL/min/year/1.73 m2; 95% confidence interval 0.11, 0.46; P=0.002). However, this difference was of modest clinical significance and would not explain the allograft survival advantage of preemptive transplantation. CONCLUSIONS: Neither the preservation of native kidney function nor differences in the rate of loss of kidney function explain the superior allograft survival of preemptive recipients. By exclusion, the allograft survival advantage associated with preemptive transplantation may be due to the longer survival of preemptive recipients.     

De Novo Kidney Transplantation Without Use of Calcineurin Inhibitors Preserves Renal Structure and Function at Two Years

We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure and gene expression. Sixty-one kidney recipients treated with basiliximab mycophenolate mofetil (MMF) and prednisone (P) were randomly assigned to concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Comparing sirolimus/MMF/P to cyclosporine/MMF/P there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dL; p = 0.008), higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 mL/min; p = 0.008), iothalamate GFR (60.6 vs. 49.2 mL/min; p = 0.018) and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p = 0.013). Regression analysis of calculated GFRs from 1 to 36 months yielded a positive slope for sirolimus of 3.36 mL/min/year, and a negative slope for cyclosporine of -1.58 mL/min/year (p = 0.008). Gene expression profiles from kidneys with higher Banff chronic allograft nephropathy (CAN) scores confirmed significant up-regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. At 2 years the sirolimus-treated recipients have better renal function, a diminished prevalence of CAN and down-regulated expression of genes responsible for progression of CAN. All may provide for an alternative natural history with improved graft survival.     

The effect of maintenance immunosuppression medication on the change in kidney allograft function

BACKGROUND: The optimum maintenance immunosuppression regimen for kidney transplant recipients is uncertain. In this study we determined the effect of maintenance immunosuppression medications on the rate of kidney allograft function loss defined by the annualized change in glomerular filtration rate (GFR). METHODS: We studied 40,963 first kidney only transplant recipients between 1987 and 1996 with allograft survival of at least two years in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Patients were classified according to the type of maintenance calcineurin and purine metabolism inhibitor received after transplantation. Multiple linear regression was used to determine the independent effect of maintenance immunosuppression medications on the annualized change in GFR (mL/min/1.73m2/year). RESULTS: Compared to patients who received cyclosporine microemulsion (Neoral), a slower decline in GFR was observed in tacrolimus-treated patients (1.60 mL/min/1.73m2/year, 95% CI 1.22-1.97, P < 0.001) and patients who did not receive calcineurin inhibitors (0.82 mL/min/1.73m2/year, 95% CI 0.08-1.56, P= 0.03). In contrast, compared to compared to patients who received Neoral, a faster decline in GFR was observed in patients who received the original oil-based formulation of cyclosporine (Sandimmune) (-0.16 mL/min/1.73m2/year, 95% CI -0.003 to -0.32, P= 0.04) and patients with unknown calcinuerin inhibitor exposure (-2.11 mL/min/1.73m2/year, 95% CI -2.27 to -1.95, P < 0.001). Compared to patients who received azathioprine, patients who received mycophenolate mofetil (MMF) had a slower decline in GFR (0.61 mL/min/1.73m2/year, 95% CI 0.14-1.08, P= 0.01) and patients with unknown purine metabolism inhibitor exposure had a faster decline in GFR (-0.61 mL/min/1.73m2/year, 95% CI -0.75 to -0.47, P < 0.001.) In a subgroup analysis of patients who received a transplant after 1993, the decline in GFR was slower for tacrolimus compared to neoral treated patients (1.64 mL/min/1.73m2/year, 95% CI 1.15-2.14, P < 0.001) but was not different for MMF compared to azathioprine-treated patients (0.24 mL/min/1.73m2/year, 95% CI -0.38-0.85, P= 0.45). CONCLUSION: Tacrolimus and MMF were the calcineurin inhibitor and purine metabolism inhibitor associated with the most favorable effects on rates of change in allograft function. Because most transplant recipients establish a low baseline level of allograft function, the effect of immunosuppression medication on GFR decline should be considered when selecting a maintenance immunosuppression regimen.     

Can a Transplanted Living Donor Kidney Function Equivalently to its Native Partner?

Early renal functional adaptation was examined in 81 haploidentical donor and recipient pairs, as well as long-term stability of glomerular filtration rate (GFR) in 78 recipients. GFR was determined pre- and 1 month postnephrectomy in donors and 1 month post-transplant and yearly thereafter in recipients. Compensatory increase in filtration (CIF) of transplanted and native kidneys was calculated using donor pretransplant GFR: [CIF= (GFR at 1 month/donor prenephrectomy GFR) x 100]. Annual rates of change in GFR were estimated using within-patient linear regression analysis (slopes). Recipients without rejection (n = 62) and their donors had similar early GFR and CIF. Those with acute rejection (n = 19) had significantly lower GFR and CIF than their donors (61 +/- 16 mL/min/1.73 m2 and 57 +/- 14% vs. 75 +/- 11 and 69 +/- 9; p = 0.01 and p < 0.001). Recipients without cyclosporine (n = 52) had 1 month GFR and CIF of 70 +/- 14 and 67 +/- 14 vs. 72 +/- 11 and 69 +/- 11 for their donors. Those with cyclosporine (n = 29) had 1 month GFR and CIF of 64 +/- 14 and 62 +/- 16 vs. 69 +/- 12 and 67 +/- 11 for their donors (p = 0.15 and 0.16). Comparison of median (25th, 75th) rates of change of GFR with and without acute rejection or cyclosporine did not demonstrate significant effects of either on stability of allograft function, although there was a trend towards greater loss of GFR in cyclosporine-treated patients [-1.1 (-2.5, 0.8) vs. 0.0 (-1.8, 1.2) mL/min/1.73 m2/year, p = 0.47]. We conclude that, in the absence of rejection, the transplanted kidney maintains the same capacity for functional adaptation as its native partner. Therapy with cyclosporine does not significantly inhibit early physiological adaptation of renal transplants.     

Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7 – 16) years in 46 patients [median age 11.8 years (range) 3 – 16.8 years]. The median age of the adult donors was 34.4 (19 – 54) years in 59 patients [median age 12.1 years (range) 7 – 17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of ⁵¹chromium-EDTA and ¹²⁵iodine-hippurate 1 – 48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2 – 3 months after transplantation the GFR in recipients of pediatric grafts was 62±20 ml/min per 1.73 m² compared with 61±21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486±239 versus 362±158 ml/min per 1.73 m². From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279±131 ml/min per 1.73 m² compared with 273±123 ml/min per 1.73 m² in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2 – 3 months after transplant the mean GFR of grafts from pediatric donors increased to 118%±51%, whereas the GFR of adult donor grafts fell to 60%±22% over the same period. After 4 – 6 months the ERPF in pediatric grafts was 96%±55% compared with 50%±22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient. Received December 6 1995; received in revised form March 19 1996; accepted March 22 1996     

The natural history of renal function following orthotopic heart transplant

BACKGROUND: The outcome of solid organ transplantation has dramatically improved after the introduction of the calcineurin inhibitor cyclosporine. With the increasing longevity of heart transplant recipients, the long-term effects of cyclosporine on renal function have become more evident. The natural history of kidney function following orthotopic heart transplant is not well defined and long-term follow up studies are scant. METHODS: We conducted an observational study on patients who received a heart transplant at Saint Louis University Hospital between January 1, 1983 and December 31, 1988. Patients were followed up for 15 yr or until death whichever occurred first. In order to assess the effect of heart transplantation and cyclosporine exposure on long-term renal function we restricted the statistical analysis to patients who survived the first year post-transplantation. RESULTS: A total of 68 patients received orthotopic heart transplants at Saint Louis University Hospital between 1983 and 1988. Forty-eight (71%) patients survived for more than 1 yr. All patients were treated with cyclosporine based triple immunosuppressive regimen, with gradual cyclosporine dose reduction over time. The mean duration of follow-up was 8 yr. The estimated GFR at 5 and 10 yr post-transplant were significantly lower than estimated GFR at baseline and 1 yr post-transplant. There was no significant difference between estimated GFR at 15 yr and estimated GFR at baseline or 1 yr post-transplant. The cumulative incidence of chronic renal failure (GFR < or = 29 mL/min/1.73 m2) at 5, 10 and 15 yr was 4.2, 10.4 and 12.5%, respectively (p < 0.05). The cumulative incidence of severe chronic renal failure (GFR < or = 15 mL/min/1.73 m2) at 5, 10 and 15 yr was 2.1, 8.3 and 8.3%, respectively. The mortality rate was 8, 37, and 52% at 5, 10, and 15 yr, respectively. The 10 and 15 yr survivors had an estimated GFR at 1 yr post-transplant that was significantly higher than the non-survivors. Age, pre-transplantation estimated GFR, pre-transplantation diabetes and pre-transplantation hypertension are risk factors associated with > or = 10 mL/min/1.73 m2 decrement in estimated GFR. CONCLUSION: Heart transplant survivors beyond the first year post-transplant have a significant decrease in renal function and significant mortality observed over time. Age, pre-transplant GFR, pre-transplant diabetes and pre-transplant hypertension are important risk factors for decrement in renal function.     

Kidney Allograft Fibrosis and Atrophy Early After Living Donor Transplantation

Kidney allograft failure is most often caused by chronic allograft nephropathy, a process of interstitial fibrosis (GIF) and tubular atrophy (TA). We assessed the pathology of living donor (LD) grafts compared to deceased donor (DD). Included are 321 recipients (245 LD; 76 DD) with protocol biopsies the first 2 years of transplant. In LD, GIF was present in 7%, 31%, 61% and 71% of grafts at 0, 4, 12 and 24 months. TA progressed in parallel to GIF. Compared to LD, more DD grafts had GIF at time 0 (29%, p = 0.002); thereafter the incidence of GIF was similar. In LD, GIF was associated with lower glomerular filtration rate (GFR)(1 year) (no GIF, 62 +/- 16; GIF, 49 +/- 15 mL/min/m(2) iothalamate clearance, p = 0.001) and reduced graft survival (HR = 2.2, p = 0.009). GIF in LD related to acute rejection (HR = 2.6, p = 0.01), polyoma nephropathy (OR = 4.4, p = 0.02) and lower levels of GFR 3 weeks post-transplant (HR = 0.961; p = 0.03, multivariate). However, GIF also developed in 53% of recipients lacking these covariates. Thus, GIF/TA develops in the majority of LD grafts, it is often mild but is associated with reduced function and survival. GIF frequently develops in the absence of risk factors. Lower GFR post-transplant identify patients at highest risk of GIF.