Cytomegalovirus infection and graft rejection in renal transplantation

BACKGROUND: Cytomegalovirus (CMV) infection and CMV disease have been associated with acute and chronic graft rejection. The introduction of the sensitive CMV antigenemia pp65 assay for detection of CMV infection allowed us to study the time course of CMV infection and acute rejection and the long-term outcome in renal transplant recipients with and without a CMV risk constellation. METHODS: Prospective single center study including 48 renal transplant recipients at risk for CMV infection (donor and/or recipient CMV seropositive) and a control group of 36 CMV seronegative recipients of CMV seronegative kidney donors. Evidence of CMV infection was monitored by the CMV antigenemia pp65 assay every 1 to 2 weeks and compared with the occurrence of acute rejection in the posttransplant period and graft function at 5 years. RESULTS: CMV infection developed in 83% (40/48) of patients of the CMV risk group within 4 months posttransplant. A total of 18 of patients experienced an acute rejection episode (control group 16/36; P=0.65). In 12/18 CMV infection followed rejection and in three patients antigenemia preceded the diagnosis of rejection. In three patients CMV antigenemia remained negative. Five-year follow up: Patient survival (44/48 vs. 31/36; P=0.48), graft survival (38/48 vs. 27/36; P=0.79), number of patients with at least one acute rejection episode: CMV risk group: 42.1%, control group 51% (P=0.46), serum creatinine: CMV risk group:130 +/- 66 micromol/iter, control group: 126 +/- 37 micromol/ liter (P=0.56), proteinuria: CMV risk group: 0.02 +/- 0.02 g/mmol creatinine, control group: 0.02 +/- 0.02 g/mmol creatinine (P=1.0). CONCLUSION: CMV infection within 4 months posttransplant, as defined by a positive antigenemia assay was not found to be a risk factor for acute graft rejection or chronic graft dysfunction at 5 years.     

"Old-for-old" cadaveric renal transplantation: surgical findings, perioperative complications and outcome

OBJECTIVE: To evaluate the surgical findings and outcome of locally allocated, blood-group-compatible but HLA-unmatched cadaveric kidneys in first renal transplantation of donor/recipient pairs aged 65 years and above (Eurotransplant Senior Program=ESP). METHODS: 26 patients of the study group (donor age 70.4 +/- 3.6/recipient age 67.7 +/- 2.8) were compared to 30 controls aged 60 and above (mean recipient age 62.6 +/- 2.3/mean donor age 43.8 +/- 15.3). For controls kidney allocation included HLA matching. RESULTS: Cold ischemic time (ESP vs. controls 501 vs. 883 min; p<0.05) and mean number of HLA mismatches (4.2 +/- 1.36 vs. 1.6 +/- 1.62; p<0.05) differed significantly. Delayed graft function was lower in the study group (12% vs. 43%; p<0.05), rejection episodes in the ESP group were numerous but did not differ significantly from the controls (46% vs. 30%; p=0.21). More intraoperative complications and a higher incidence of donor organ arteriosclerosis (p<0.05) were seen in the ESP group. Three-year graft survival uncensored and censored for death with functioning graft did not differ, even though mean creatinine and creatinine clearance differed significantly beginning at month three. Three-year patient survival (55% vs. 81%) differed in favour of the control group, even though the difference was not significant due to small number of patients. CONCLUSION: "Old-for-old" kidney transplantation with local allocation yields graft survival rates comparable to HLA-matched young grafts and is a good approach to extend the donor and recipient pool. Careful patient selection is advised.     

Frequency and severity of acute rejection in live- versus cadaveric-donor renal transplants

BACKGROUND: Live donors are an increasingly important source of kidneys for transplantation in Australia. The aim of this study was to compare the rate and severity of rejection between patients receiving kidney transplants from live versus cadaveric donors. METHODS: A retrospective analysis was undertaken of all patients receiving live-donor (n=109) and cadaveric-donor (n=389) renal transplants at our institution between April 1, 1994, and March 31, 2000. Follow-up was completed on all patients until graft loss, death, or May 31, 2001. RESULTS: The baseline characteristics of the live-donor and cadaveric groups were similar, except for recipient age (mean+/-SD, 36.3+/-15.6 vs. 44.5+/-14.4 years, respectively; P<0.001); donor age (46.1+/-11.3 vs. 36.1+/-16.4 years, P<0.001); pretransplant dialysis duration (1.36+/-2.1 vs. 3.4+/-4.4 years, P<0.001); and the proportions of patients receiving first allografts (95% vs. 88%, respectively; P<0.05), antibody induction (8% vs. 20%, P<0.01), and mycophenolate mofetil (MMF) (60% vs. 37%, P<0.001). Acute rejection was observed in 48 (44%) live-donor and 108 (28%) cadaveric transplants (P=0.001). Cadaveric donor type was independently predictive of less acute rejection both on logistic regression (adjusted odds ratio [AOR], 0.47; 95% confidence interval [CI], 0.30-0.73; P=0.001) and multivariate Cox proportional hazards model analysis (hazard ratio, 0.49; 95% CI, 0.34-0.69; P<0.001). Patients receiving cadaveric-donor transplants were also significantly less likely to receive antibody therapy for rejection (univariate, 18% vs. 9%; P=0.006; multivariate AOR, 0.45; 95% CI, -0.25-0.82; P<0.01), independent of recipient age, gender, race, transplant number, human leukocyte antigen mismatch, sensitization, induction therapy, delayed graft function, MMF use, tacrolimus or cyclosporine A use, sirolimus-everolimus use, year of transplant, donor age, or dialysis duration. However, donor type did not independently influence graft survival, immunologic graft survival, or patient survival. CONCLUSIONS: Live-donor kidney transplant recipients had a higher rate and severity of rejection and a shorter rejection-free period than cadaveric renal transplant recipients. Further consideration of the reasons for this difference and the use of alternative immunosuppressive strategies for live-donor transplants are recommended.     

Erythropoietin treatment in the sixth posttransplant month as a prognostic factor for renal allograft survival

The purpose of this work was to assess the prognostic value of the need for erythropoietin (EPO) treatment at 6 months after transplantation. We retrospectively reviewed the outcomes of 143 consecutive cadaveric kidney transplants performed between January 2000 and April 2004, functioning at 6 months postransplantation. Patients were divided into two groups: group EPO6m (n = 24) received EPO treatment in the sixth month, and a control group (n = 119) did not receive EPO. Renal function deterioration (RFD) was considered to be a sustained decrease in creatinine clearance (CrCl) greater than 20% between the sixth month postransplant and the last visit. Mean follow-up was 38 +/- 16 months. The mean ages of the donor (57 +/- 9 vs 49 +/- 12 years; P = .001) and the recipient (59 +/- 12 vs 47 +/- 17 years; P = .000) were greater in the EPO6m group. Delayed graft function (83% vs 48%; P = .001) was more frequent in the EPO6m group. At 6 months after transplantation the EPO6m group showed lower hemoglobin (11.52 +/- 1.71 vs 13.32 +/- 1.69 g/dL; P = .000), higher serum creatinine (2.31 +/- 0.72 vs 1.65 +/- 0.53 mg/dL; P = .000), lower CrCl (33.53 +/- 10.83 vs 53.6 +/- 17.58 mL/min; P = .000), and similar proteinuria. RFD was more common in the EPO6m group (38% vs 10%; P = .026), with a different pattern of evolution of CrCl (-0.098 +/- 0.176 vs +0.093 +/- 0.396 mL/min/mo, P = .000). Multivariate analysis demonstrated that treatment with EPO at 6 months was the only predictor of RFD (RR 4.46; 1.58 to 12.58; P = .005). The need for EPO at 6 months postransplant was a good predictor of later renal allograft deterioration, more sensitive than serum creatinine or proteinuria.     

Multivariate analysis of factors affecting patient and graft survival after renal transplant

AIM: To evaluate factors affecting patient and kidney survival after renal transplant. PATIENT AND METHODS: Among 361 patients undergoing renal transplant: 52% (n = 189) were simultaneous with pancreas transplant (SPKT group) and 48% (n = 172), a kidney transplant alone (KT group). Out of 361 patients, 75% (n = 270) were diabetics. The patients were 220 (61%) men and 141 (39%) women of mean age 41 +/- 9 years. The mean time of dialysis was 42 +/- 21 months (range 0 to 126), and the mean duration of diabetes 24 +/- 7 years (range 5 to 51). A Cox regression analysis was done. RESULTS: The multivariate analysis revealed that in the final model diabetes and donor age were significant predictors of kidney graft survival; moreover, diabetes and recipient age were predictors of patient survival. Overall patient survival was significantly greater among nondiabetic patients (P = .002) or in diabetic patients who received SPKT, when compared with diabetics in whom only the kidney was transplanted (P = .001). CONCLUSIONS: Diabetes and donor age were independent prognostic factors affecting kidney graft survival after renal transplant, and recipient age and diabetes were prognostic factors affecting patient survival. Combined pancreas and kidney transplantation should be offered to patients with end-stage diabetic nephropathy.     

Deceased donor renal transplantation--does side matter?

BACKGROUND: The aim of the present study was to determine whether the deceased donor kidney side (left or right kidney) was predictive of subsequent kidney transplant outcomes. METHODS: A retrospective analysis was undertaken of the left-right deceased donor kidney pairs transplanted into recipients with end-stage renal failure in Queensland between 1 April 1994 and 31 March 2004. RESULTS: A total of 201 left-right deceased donor kidney pairs were transplanted into 402 patients. The baseline characteristics of the recipients in the two groups were comparable, except that the patients receiving right kidneys had lower body mass indices and shorter cold ischaemic times. No differences were seen between the left and right kidney recipient groups with respect to operative duration (3.02 +/- 0.67 vs 3.12 +/- 0.72 h, P = 0.16), warm ischaemic time (0.62 +/- 0.18 vs 0.65 +/- 0.21, P = 0.09), delayed graft function (4 vs 6%, respectively, P = 0.26) or a composite vascular, haemorrhagic, ureteric and infective post-operative complication end-point (22 vs 22%, P = 0.90). Estimated glomerular filtration rates were almost identical at 1 month (52.7 +/- 39.6 vs 51.0 +/- 24.0 ml/min/1.73 m(2), P = 0.34) and remained comparable thereafter. Respective death-censored graft survival rates for left and right kidney recipients were 100 and 100% at 1 year, 99.4 and 96.4% at 3 years and 96.3 and 95.5% at 5 years, respectively (P = 0.67). CONCLUSIONS: Although left and right deceased donor kidneys present different operative challenges, the present results suggest that the probability of early post-operative complications, delayed graft function, impaired early and medium-term renal allograft function or death-censored graft failure is comparable between left and right kidney recipients.     

Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients.

BACKGROUND: Chronic transplant dysfunction is characterized by a gradual decline in renal function with slowly rising serum creatinine. The underlying mechanism is thought to include inflammation and atherosclerosis. C-reactive protein (CRP) is a well-established marker of both inflammation and atherosclerosis. In this prospective study, we investigated whether CRP could be of use as a clinical marker for early identification of renal transplant recipients at increased risk of deterioration of graft function. METHODS: In this prospective study, all participating patients (n = 606) visited the out-patient clinic at least once a year, and serum creatinine was assessed at every visit. Subjects with a follow-up of <1 year (n = 31) were excluded from analysis. RESULTS: A total of 575 patients participated at a median (interquartile range) time of 5.9 (2.6-11.3) years post-transplantation. Median time of follow-up was 3.0 (2.4-3.4) years. Changes in serum creatinine during follow-up were -0.45 (-4.83-4.76) micromol/l/year in 172 subjects with CRP <1.0 mg/l, 1.04 (-3.36-6.12) micromol/l/year in 184 subjects with CRP 1.0-3.0 mg/l and 2.34 (-3.33-9.07) micromol/l/year in 219 subjects with CRP >3.0 mg/l (P < 0.05 for comparison of the three groups). Proteinuria (P = 0.003), CMV IgG titre (P = 0.01), donor age (P = 0.01), CRP concentration (P = 0.02), recipient age (P = 0.02) and recipient gender (P = 0.047) were independently associated with change in serum creatinine during follow-up in a multivariate analysis. CONCLUSIONS: Elevated levels of CRP independently predict accelerated deterioration of graft function in renal transplant recipients >1 year post-transplantation. Further prospective studies are required to investigate whether early intervention can prevent deterioration of graft function in subjects with elevated levels of CRP.     

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology

BACKGROUND: Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS: The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS: The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION: RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.     

Doppler ultrasonographic indices after renal transplantation as renal function predictors

OBJECTIVES: Doppler ultrasonography is mostly used for assessment of both graft and native kidney vascular status. In this study, correlation between Doppler sonographic indices and transplanted kidney function was evaluated. METHODS: In our retrospective study, we reviewed data on 273 renal transplanted (RTx) patients. The Doppler ultrasonographic evaluation included resistive index (RI), pulsatility index (PI) in interlobar arteries as well as stenosis (TRAS) or thrombosis of renal arteries and veins. Serum creatinine (Cr) and cyclosporine levels (CsA) were measured just prior to sonography. RESULTS: The mean age of 154 male and 119 female patients was 36.67 +/- 13.13 years. Both RI and PI showed significant linear correlations with serum Cr (P = .033 and P = .002, respectively). Also, direct linear correlations existed between patient age and RI and PI values (P = .004; r = +.174 and P = .003; r = +.183 respectively). The prevalence of TRAS was 11.35%. Among patients with TRAS or thrombosis the mean Cr level (2.08 +/- 1.7 mg/dL) was significantly higher than that among patients without TRAS or thrombosis (1.48 +/- 0.97 mg/dL; P = .004). Despite this finding, RI and PI were significantly lower among patients with TRAS or thrombosis than those with a patent renovascular tributary (0.59 +/- 0.15 vs 0.65 +/- 0.11; P = .029 vs 1.02 +/- 0.40 vs 1.18 +/- 0.46; P = .049). CONCLUSIONS: Both RI and PI were two valuable Doppler ultrasonographic markers to evaluate renal allograft function and related vascular complications.     

Early proteinuria is a strong indicator of donor renal lesions, ischemia-reperfusion injury and immunological aggression

BACKGROUND: Early proteinuria is associated with reduced long-term graft survival. However, the determinants and mechanisms of proteinuria early after transplantation have not been identified. METHODS: Parameters associated with proteinuria within the first 3 months following transplantation were retrospectively assessed among 484 renal transplant recipients. RESULTS: Proteinuria was more abundant in patients with a history of two or more rejection episodes (0.42 +/- 0.68 vs 0.18 +/- 0.39 g/d; P = .02). Proteinuria was greater when donor age was 60 or more (OR: 4.43; P = .003), when recipient death was due to cardiovascular causes (OR: 1.98; P = .002), or when cold (OR: 1.77; P = .006) or warm (1.21; P = .09) ischemia times were prolonged. CONCLUSIONS: Proteinuria early after transplantation was related to pretransplant renal lesions, ischemia-reperfusion, and immunologic injuries.     

Renal artery resistance index, thyroid hormones, and thyroid volume in the early kidney transplants recipients

BACKGROUND: Thyroid hormones could affect renal function, and, on the other hand, renal dysfunction may affect thyroid function. Disturbances of concentrations of thyroid hormones are often associated with thyroid gland enlargement. The aim of the study was to assess the function and morphology of the thyroid (volume and hormones concentration) and kidney function after transplantation (creatinine concentration and resistance index [RI] of transplant artery). MATERIAL AND METHODS: The group included 13 females, 19 males; aged 19-69 years, mean 44.75 +/- 14.8 years after transplantation with stable graft function. Thyroid volume, renal artery RI, creatinine concentration, and concentrations of T3, rT3, FT3, FT4, and TSH were estimated the day before surgery, and at 1, 3, 6, and 10 days after transplantation. RESULTS: The statistical analysis revealed a negative correlation between delta RI (difference between RI at 3 and 6 days after transplantation) and serum creatinine concentration, 10 days after transplantation (r = -0.63; P < 0.01). We also observed a negative correlation between creatinine serum concentration at 10 days after transplantation and delta thyroid volume (Delta Vol; r = - 0.48; p < .05), a positive correlation between delta FT4 (Delta FT4) serum concentration, and delta creatinine (Delta Crea; r = 0.73; P < .001). CONCLUSIONS: The dynamics of RI changes in the transplant kidney artery between 3 and 6 days after transplantation may predict graft function. Together with improved kidney function at 10 days after transplantation, we observed a regression of goiter.     

Histological factors of 1-h biopsy influencing the delayed renal function and outcome in cadaveric renal allografts

The morphological characteristics of a kidney biopsy specimen taken 1 h after reperfusion of blood into the graft (1-h biopsy) during a cadaveric transplant operation were studied. The aim of the 1-h biopsy is to evaluate the pre-transplant risk factors for the delayed graft function, assess the renal function of the graft, and predict long-term graft survival. The total number of 1-h biopsies was 113, consisting of 86 male and 27 female donors. The mean age of the donors is 39.5 +/- 17.3 yr. Arteriosclerosis (AS) and tubulo-interstitial injury (TI) were both estimated using a semi-quantitative scale. AS score was graded into four categories, according to the severity of the thickening of interlobular artery: 0: none, 1: mild, 2: moderate and 3: severe. No biopsy revealed severe AS of grade 3. The TI score was graded from 0 to 5, according to the morphological injury: 0: none, 1-2 non-specific tubulo-interstitial injury (NSTI), and 3-5 compatible with acute tubular necrosis (ATN) in terms of pathological diagnosis. The mean ages of donors showing as AS of score 0, 1, and 2 were 30.6 +/- 14.6, 49.7 +/- 13.5, and 56.9 +/- 6.30, respectively. The mean donor age of the AS 1 group and AS 2 group was significantly lower than for the AS 0 group. The lowest serum creatinine values after operation (best Cr) of recipients with AS scores of 0, 1, and 2 were 1.31 +/- 0.45, 1.60 +/- 0.70, and 1.84 +/- 0.71 mg/dL, respectively; the best Cr of AS scores of 1 and 2 was significantly higher than in the AS score 0 group. The mean creatinine level at the final point of the AS 0 group was significantly lower than in the combined AS 1 and AS 2 group (serum creatinine 1.44 +/- 1.03 vs 1.87 +/- 1.53 mg/dL: p < 0.01). The duration of severe hypotension less than 50 mmHg or 80 mmHg was significantly shorter in the NSTI group than in the ATN group (less than 50 mmHg was 29.7 +/- 124 vs 72.5 +/- 174, less than 80 mmHg 105 +/- 234 vs 193 +/- 261 min: p < 0.01). The post-operative (po) day expressing diuresis in excess of 1000 mL of urine per d was 8.28 +/- 17.5 and 13.7 +/- 23.3 (p < 0.01) in the NSTI and ATN group, respectively. The po-d of the last hemodialysis and the po-d showing serum creatinine less than 2.0 mg/dL in NSTI and ATN group was 7.74 +/- 17.4 and 13.3 +/- 23.2 (p < 0.01), and 25.0 +/- 30.5 and 38.0 +/- 35.2 (p < 0.01), respectively. We concluded that 1-h renal biopsy is useful for assessing the outcome of renal allograft. AS of a donor kidney is one of the most important risk factors for both short and long-term outcome of the graft. The TI score was useful to predict the outcome of delayed graft function.     

Improving results of renal transplantation with the use of elderly donors: the Budapest experience

The use of elderly donors has become a necessity with the increasing demand for deceased donor organs resulting in transplant centers worldwide expanding their donor criteria. We, therefore, thought it appropriate to review our experience using elderly (>60 years) brain-dead donors for kidney transplantation. We investigated the influence of donor parameters on early graft function and survival. A retrospective comparative analysis of three periods was performed: 1994 to 1998 (P1) n = 40; 1999 to 2000 (P2) n = 28; and 2001 to 2002 (P3) with n = 31 donors. Mean donor age in each period was 63.4 +/- 3.3, 64.5 +/- 3.4, and 63.8 +/- 2.7 years; mean diuresis was 473 +/- 450, 307 +/- 316, and 276 +/- 185 mL/hour; and the need for vasopressors during donor management was 81%, 85%, and 70% respectively. The number of kidney recipients was 59, 30, and 37, mean age was 49 +/- 13, 53 +/- 11 and 54 +/- 8 years, the recipient ratio of patients >60 years was 17%, 33%, and 27% respectively, and no differences among the groups in the HLA mismatch. Primary nonfunction occurred in 8.5%, 0%, and 2.8%; acute rejection ratio at 1 year was 35%, 36%, and 32%, the mean serum creatinine at 12 months was 183.7 +/- 66.0, 157.8 +/- 41.2 and 160.7 +/- 46.5 mumol/L. The 1-year graft survival was 71.2%, 91.0% and 92.0% and the 1-year patient survival 88.2%, 96.6%, and 97.2%, respectively, for periods 1, 2, and 3. There has been a considerable improvement in the 1-year graft and patient survivals. With careful donor and recipient evaluation, individualized immunosuppression, and age matching the results of renal transplantation from elderly deceased donors can be comparable to the results of the "optimal" deceased donor kidney transplantation.     

Double renal transplants from marginal donors: 2-year results

PURPOSE: Marginal cadaveric renal transplant donors represent a potential source for expansion of the donor pool but these kidneys have generally demonstrated significantly poorer survival compared to those from conventional donors. A strategy to provide sufficient renal mass for adequate nephron dosing and subsequent improved survival is the use of both kidneys for a single recipient. We present our 2-year experience with double renal transplants from marginal donors. MATERIALS AND METHODS: During an 8-year period 28 patients received double renal transplants (group 1) and 31 received a single transplant (group 2) from marginal donors. Donors were older than 55 years, or had diabetes mellitus, hypertension, greater than 15% glomerulosclerosis on biopsy, increasing creatinine or intrinsic renal parenchymal disease. RESULTS: Both groups were of similar age and the number of rejection episodes per year was similar but followup time differed (22.4+/-14.6 months for group 1 versus 43.7+/-20.5 for group 2). Male-to-female ratio, cold ischemia time, terminal creatinine and pre-transplant biopsy rates were similar for donors in both groups. Average donor age was younger in group 1 (48.9+/-15.8 versus 57.5+/-8.2 years, p = 0.01), and incidence of intrinsic renal disease and increasing donor creatinine was greater (12 versus 2, p = 0.002 and 4 versus 0, p = 0.04, respectively). Incidence of primary nonfunction (1 group 1 versus 5 group 2 patients) and delayed graft function (6 versus 7) was similar. The 1 and 2-year graft survival rates of 96% and 96%, respectively, for group 1 were significantly higher than those for group 2 (77% and 73%, p = 0.02). CONCLUSIONS: Our experience to date with double kidney transplants from marginal donors demonstrates acceptable 1 and 2-year survival rates significantly superior to the outcome using only 1 marginal kidney. This finding has important implications in the decision to use marginal donors in regard to cost-effectiveness and patient survival compared to the alternative of continued hemodialysis until an ideal donor organ becomes available.     

Post-transplant renal function in the first year predicts long-term kidney transplant survival

BACKGROUND: Improvements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival. METHODS: The influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia time, HLA mismatching, delayed graft function and transplant year), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection, clinical acute rejection and post-transplant renal function in the first year) on graft survival were analyzed for 105,742 adult renal transplants between 1988 and 1998. Renal function in the first year was expressed as serum creatinine at six months and one year and delta creatinine (change in serum creatinine between 6 months and 1 year). Graft half-life was used to measure long-term survival. RESULTS: During this 11-year period, the one-year serum creatinine values for cadaver recipients steadily improved, from 1.82 +/- 0.82 mg/dL in 1988 to 1.67 +/- 0.82 mg/dL in 1998 (P < 0.001), as did the graft half-life. There was a progressive decline in graft half-life for each incremental increase of six month, one year and Delta creatinine for living and cadaver donor transplants as well for cadaver transplants with donor age > and < or =50 years. The Relative Hazard (RH) for graft failure was 1.63 (1.61, 1.65; P < 0.0001) with each increment of 1.0 mg/dL of serum creatinine at one year post-transplant and it increased to 2.26 (2.2, 2.31; P < 0.0001) when the Delta creatinine was 0.5 mg/dL. The RH reduction for graft failure was substantially lower for the years 1993, 1996, 1997 and 1998 when post-transplant renal function was not included in the model (P < 0.05). However, the RH reduction per year was not different when post-transplant creatinine was included in the model, 1.01 (0.94 to 1.05; P = 0.89). CONCLUSION: In conclusion, one-year creatinine and Delta creatinine values predict long-term renal graft survival. Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation.     

Outcome of kidney transplantation from high-risk donors is determined by both structure and function

METHOD: Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both). RESULTS: Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). CONCLUSION: Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.     

Risk factors that can influence kidney transplant outcome

The survival and function of a kidney transplant are influenced by numerous immunological and nonimmunological factors. The aim of this study was to evaluate the role of a number of cadaveric donor parameters on transplanted kidney function, and in particular on the occurrence of delayed graft function (DGF) since DGF is one of the most important factors in long-term organ survival. This study looked at 143 patients who underwent kidney transplant of whom 32 displayed DGF. The creatinine levels in organ recipients, which were evaluated during a follow-up that ranged between 6 months and 4 years, were significantly higher among recipients who developed DGF after transplant (1.8 +/- 0.7 vs 1.4 +/- 0.4; P = .02). The following donor parameters were taken into consideration: history of diabetes and hypertension; creatinine levels; inotropie therapy; problems relating to hemodynamics (hypotension and/or cardiac arrest); and cold ischemia time. We observed that a donor history of hypertension (46.8% DGF vs 23.27% no DGF; P = .01) and high levels of donor creatinine prior to organ removal (1.9 +/- 1.2 mg/dL DGF vs 1.2 +/- 0.9 mg/dL no DGF; P = .007) were significant risk factors for DGF among kidney recipients. No significant differences were found for others factors between recipients with versus without DGF.     

Risk factors for reaching renal endpoints in the assessment of Lescol in renal transplantation (ALERT) trial

BACKGROUND: The aim of the study was to identity risk factors for long-term renal transplant function and development of chronic allograft nephropathy (CAN) in renal transplant recipients included in the Assessment of Lescol in Renal Transplantation (ALERT) trial. METHODS: The ALERT trial was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 and 80 mg/day, in renal transplant recipients who were randomized to receive fluvastatin (Lescol) (n = 1,050) or placebo (n = 1,052) over 5 to 6 years of follow-up. Renal endpoints including graft loss or doubling of serum creatinine or death were analyzed by univariate and multivariate regression analysis in the placebo group. RESULTS: There were 137 graft losses (13.5%) in the placebo group, mainly caused by CAN (82%). Univariate risk factors for graft loss or doubling of serum creatinine were as follows: serum creatinine, proteinuria, hypertension, pulse pressure, time since transplantation, donor age, human leukocyte antigen-DR mismatches, treatment for rejection, low high-density lipoprotein cholesterol, and smoking. Multivariate analysis revealed independent risk factors for graft loss as follows: serum creatinine (relative risk [RR], 3.12 per 100-microM increase), proteinuria (RR, 1.64 per 1-g/24 hr increase), and pulse pressure (RR, 1.12 per 10 mm Hg), whereas age was a protective factor. With patient death in the composite endpoint, diabetes mellitus, smoking, age, and number of transplantations were also risk factors. CONCLUSIONS: Independent risk factors for graft loss or doubling of serum creatinine or patient death are mainly related to renal transplant function, proteinuria, and blood pressure, which emphasizes the importance of renoprotective treatment regimens in this population.     

The development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys

Several reports in animals, and sporadic case reports in humans, have suggested that kidneys with decreased nephron mass may be more susceptible to the development of focal-segmental glomerosclerosis. This prompted a reexamination of our previously reported group of pediatric donor-adult recipient renal transplant combinations. Data were analyzed from 31 adult recipients who had received renal transplants from cadaver pediatric donors (less than 6 years) with graft function for greater than 6 months and no evidence of chronic rejection. These were compared with a control group transplanted during the same period with adult donor kidneys. Immunosuppression consisted of azathioprine/prednisone or quadruple therapy in 16 and 15 patients respectively. End-stage renal disease (ESRD) was secondary to chronic glomerulonephritis (n = 9), diabetes mellitus (n = 6), polycystic kidney disease (n = 5), and miscellaneous causes (n = 11). Twenty patients had radiographic documentation of renal hypertrophy posttransplant. All patients had serial 24-hr urinalysis for protein and creatinine after transplantation during periods of stable renal function. Ten patients had renal biopsies performed at a mean time from transplant to biopsy of 10.4 +/- 1.6 months. Seven recipients had biopsies that revealed glomerulosclerosis at 13 +/- 6 months posttransplant. Protein excretion and serum creatinine in these patients were significantly higher than in control patients (1.6 +/- 0.37 vs. 0.49 +/- 0.15 g/24 hr and 1.96 +/- 0.11 vs. 1.64 +/- 0.09 mg%; P less than 0.03 and P less than 0.01, respectively). Only 3 of 25 control adult donor recipients developed proteinuria greater than 0.8 g/24 hr within 2 years of transplantation vs. 15/31 pediatric donor recipients. No correlations with the etiology of ESRD, age (greater than or less than 40 years), weight, sex, diabetes, hypertension, or the number of acute rejection episodes could be found. Our data suggest that adult recipients of pediatric donor renal transplants may be at greater risk for the development of glomerulosclerosis than those recipients receiving adult donor kidneys.     

Early postoperative spectral Doppler parameters of renal transplants: the effect of donor and recipient factors

Background

The objective of this study was to explore the donor and recipient factors related to the spectral Doppler parameters of the transplant kidney in the early posttransplantation period.

Methods

This retrospective study included 76 patients who underwent renal transplantation assessed using Doppler ultrasonography (US) on the first postoperative day. We compared spectral Doppler parameters (peak systolic velocity [PSV] and resistive index [RI]) of the segmental artery of the transplant kidney according to the type of renal transplant, level of serum creatinine (SCr) of donor prior to organ donation, and donor/recipient age.

Results

RI was significantly higher in deceased-donor kidney transplantation (DDKT) as compared with living-donor kidney transplantation (LDKT; 0.73 ± 0.10 vs 0.66 ± 0.11; P = .007). In the DDKT recipients, multivariate analysis showed donor SCr was the only factor affecting PSV (P = .023), whereas recipient age was the only factor affecting RI (P = .035). In the LDKT recipients, multivariate analysis showed recipient age was the only factor affecting both PSV (P = .009) and RI (P = .018).

Conclusion

Spectral Doppler parameters in the early posttransplantation period are related to the type of renal transplant, donor renal function, and recipient age. These factors should be taken into consideration when interpreting the results of spectral Doppler US.