Reactivation of Latent HPV Infections After Renal Transplantation.

Female renal transplant recipients (RTRs) have an increased risk for developing human papillomavirus (HPV)-related (pre)malignant lesions of the genital tract. This study aims to assess the genital prevalence of HPV before and after renal transplantation (RT). In female patients who were counseled for RT at the Radboud University Medical Center Nijmegen, the Netherlands, gynecological examination was performed at first visit, and 1 and 2 years later. HPV self-sampling and questionnaires on sexual behavior were performed every 3 months. In 65 patients who underwent RT, the high-risk human papillomavirus (hrHPV) prevalence as assessed with the highly sensitive SPF10 -LiPA25 test increased significantly from 19% before to 31% after RT (p = 0.045). Based upon the clinically validated Cobas 4800 HPV test, the hrHPV prevalence increased from 10% before to 14% after RT (p = 0.31). During follow-up, no changes in sexual behavior were reported. Thirty-three patients who did not undergo RT showed a hrHPV prevalence of 21% at study entry and of 27% after 12 months with the sensitive test, and a stable prevalence of 16% with the clinically validated test. The results of this study indicate that activation of latent HPV infections may contribute to the increased risk of HPV-related (pre)malignant lesions in female RTRs.

The Course and Predictors of Health-Related Quality of Life in Living Kidney Donors: A Systematic Review and Meta-Analysis.

A better understanding of the course and risk factors for impaired long-term health-related quality of life (HRQoL; ie, physical, psychological, and social-relational functioning) after kidney donation might help clinicians improve the care of live kidney donors. This systematic review and meta-analysis summarizes prospective studies about the course and predictors of HRQoL in living kidney donors. Studies indicate that shortly after donation, donors have lower HRQoL, with minor to moderate changes in psychological and social-relational functioning and major changes in physical functioning. At 3-12 months after donation, HRQoL returned to baseline or was slightly reduced, particularly for fatigue, but scores were still comparable to general population norms. Results were mainly robust across surgery techniques. A limited number of studies examined risk factors for impaired HRQoL, with low psychological functioning before donation as the most consistent predictor. Based on these results, clinicians can inform potential donors that, on average, kidney donors have high long-term HRQoL; however, donors with low psychological functioning at baseline are those most at risk of impaired long-term HRQoL. Future studies should focus on other potentially relevant predictors of postdonation HRQoL, including donor eligibility criteria and donor-recipient relationships, to optimize screening and interventions for donors at risk.

Cervicovaginal HPV infection in female renal transplant recipients: an observational, self-sampling based, cohort study.

Immunosuppressive treatment of organ transplant recipients is associated with an increase in the occurrence of human papillomavirus (HPV) related anogenital (pre)malignancies. This cohort study investigated the genotype-specific prevalence of HPV infections in a large cohort of female renal transplant recipients (RTRs). Participants self-collected a cervicovaginal sample for detection and genotyping of HPV. Besides, they completed a questionnaire regarding sociodemographic variables, medical data and sexual behavior. Anogenital screening was offered to all HPV-positive participants. A total number of 218 female RTRs was included. The prevalence of mucosal HPV infections was 27.1% and 17.4% for high risk HPV in particular. The studied cohort showed a broad range of HPV genotypes and multiple HPV genotypes were found in 27.1% of HPV-positive patients. Seven participants were identified with occult premalignant anogenital lesions. In conclusion, this study shows a high point-prevalence of HPV in female RTRs (age-matched West-European general population: 9-10%) with a shift in the distribution of genotypes as compared with the general population. Moreover, a substantial number of patients with occult premalignancies was identified. The introduction of self-sampling for HPV positivity can help in early detection of (pre)malignant anogenital lesions in this vulnerable population.

Low-pressure pneumoperitoneum during laparoscopic donor nephrectomy to optimize live donors' comfort.

Nowadays, laparoscopic donor nephrectomy (LDN) has become the gold standard to procure live donor kidneys. As the relationship between donor and recipient loosens, it becomes of even greater importance to optimize safety and comfort of the surgical procedure. Low-pressure pneumoperitoneum has been shown to reduce pain scores after laparoscopic cholecystectomy. Live kidney donors may also benefit from the use of low pressure during LDN. To evaluate feasibility and efficacy to reduce post-operative pain, we performed a randomized blinded study. Twenty donors were randomly assigned to standard (14 mmHg) or low (7 mmHg) pressure during LDN. One conversion from low to standard pressure was indicated by protocol due to lack of progression. Intention-to-treat analysis showed that low pressure resulted in a significantly longer skin-to-skin time (149 ± 86 vs. 111 ± 19 min), higher urine output during pneumoperitoneum (23 ± 35 vs. 11 ± 20 mL/h), lower cumulative overall pain score after 72 h (9.4 ± 3.2 vs. 13.5 ± 4.5), lower deep intra-abdominal pain score (11 ± 3.3 vs. 7.5 ± 3.1), and a lower cumulative overall referred pain score (1.8 ± 1.9 vs. 4.2 ± 3). Donor serum creatinine levels, complications, and quality of life dimensions were not significantly different. Our data show that low-pressure pneumoperitoneum during LDN is feasible and may contribute to increase live donors' comfort during the early post-operative phase.

Preservation of kidneys from controlled donors after cardiac death.

BACKGROUND: Donation after cardiac death (DCD) expands the pool of donor kidneys, but is associated with warm ischaemic injury. Two methods are used to preserve kidneys from controlled DCD donors and reduce warm ischaemic injury: in situ preservation using a double-balloon triple-lumen catheter (DBTL) inserted via the femoral artery and direct cannulation of the aorta after rapid laparotomy. The aim of this study was to compare these two techniques. METHODS: This was a retrospective cohort study of 165 controlled DCD procedures in two regions in the Netherlands between 2000 and 2006. RESULTS: There were 102 donors in the DBTL group and 63 in the aortic group. In the aortic group the kidney discard rate was lower (4·8 versus 28·2 per cent; P < 0·001), and the warm (22 versus 27 min; P < 0·001) and the cold (19 versus 24 h; P < 0·001) ischaemia times were shorter than in the DBTL group. Risk factors for discard included preservation with the DBTL catheter (odds ratio (OR) 5·19, 95 per cent confidence interval 1·88 to 14·36; P = 0·001) and increasing donor age (1·05, 1·02 to 1·07; P < 0·001). Warm ischaemia time had a significant effect on graft failure (hazard ratio 1·04, 1·01 to 1·07; P = 0·009), and consequently graft survival was higher in the aortic cannulation group (86·2 per cent versus 76·8 per cent in the DBTL group at 1 year; P = 0·027). CONCLUSION: In this retrospective study, direct aortic cannulation appeared to be a better method to preserve controlled DCD kidneys.

Proteinuria following conversion from azathioprine to sirolimus in renal transplant recipients.

Recent studies have reported a significant increase of proteinuria in kidney transplant recipients who were switched from a calcineurin inhibitor (CI) to sirolimus. This has (partly) been ascribed to the hemodynamic renal effects of CI withdrawal. We have evaluated the evolution of proteinuria in renal transplant recipients who underwent conversion from azathioprine to sirolimus. In a randomized, prospective, multicenter study called RESCUE (Recurrent cutanEous Squamous cell Carcinoma Under RapamunE) the efficacy and safety is investigated of conversion to sirolimus in stable renal transplant recipients with a cutaneus squamous cell carcinoma (SCC). In our center 25 patients have been included in this study of which 13 patients were randomized to continue their current immunosuppressive treatment and 12 to conversion to sirolimus. After a mean follow-up of 360 days mean proteinuria increased from 0.37+/-0.34 to 1.81+/-1.73 g/24 h after conversion to sirolimus (P<0.005). In the control group there was no change in proteinuria. A significant increase of proteinuria was observed in all seven patients with proteinuria before conversion, whereas proteinuria remained absent in all patients without previous proteinuria. Two of the patients with proteinuria were converted from cyclosporine and five were converted from azathioprine to sirolimus. Sirolimus was discontinued in five patients with proteinuria, and in all of them proteinuria declined to baseline values. Our study demonstrates that conversion from azathioprine to sirolimus after kidney transplantation may cause a reversible increase of proteinuria. Sirolimus-induced proteinuria therefore cannot be ascribed to the hemodynamic renal effects of withdrawal of CI.

Acitretin treatment of premalignant and malignant skin disorders in renal transplant recipients: clinical effects of a randomized trial comparing two doses of acitretin.

INTRODUCTION: After renal transplantation, the incidence of premalignant and malignant skin lesions is high. Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas, but treatment is hampered by frequent side effects. No optimal long-term dosing advice is available. METHODS: A total of 26 long-term renal transplant recipients were randomized to 1-year treatment with acitretin, either 0.4 mg/kg/d throughout the whole year or 0.4 mg/kg/d during the first 3 months followed by 0.2 mg/kg/d for the remaining 9 months. At 9 different time points, the number of actinic keratoses and tumors was counted, and erythema and thickness of the lesions, and severity of side effects were scored. Patient's judgment was recorded using visual analog scores. RESULTS: In both groups, the number of actinic keratoses decreased by nearly 50%, but the number of new malignant tumors during the study year was similar to the number of tumors in the year before the study. Thickness of the keratoses decreased significantly in both groups. Acitretin dose had to be reduced in most patients because of the frequent occurrence of mucocutaneous side effects, such as cheilitis, excessive peeling of the skin, and hair disorders. In the 14 patients randomized to continuous treatment with a dose of 0.4 mg/kg/d, this dose could be maintained in 3 of 14 patients only. Temporary interruption of acitretin therapy was necessary in 7 of 26 patients. Patients' contentment about the aspect of their skin increased significantly, with no differences between groups. CONCLUSIONS: Acitretin therapy decreased the number of actinic keratoses in renal transplant recipients at a low maintenance dose of 0.2 mg/kg/d and significantly decreased the degree of thickness of the lesions. However, the incidence of new skin malignancies remained unchanged. Despite the high incidence of mucocutaneous side effects, patient's contentment with the aspect of their skin increased significantly.

Outcome of renal transplantation in patients with pauci-immune small vessel vasculitis or anti-GBM disease.

AIM: Pauci-immune small vessel vasculitis (SVV) and anti-GBM disease are the most common causes of rapidly progressive glomerulonephritis (RPGN) and they frequently lead to end-stage renal disease. For renal replacement therapy, renal transplantation is the preferred treatment option. However, in patients with glomerular diseases, the outcome of renal transplantation can be adversely affected by recurrence of the original disease. The information in the medical literature on the outcome of renal transplantation in patients with RPGN is limited because most data are derived from case studies and from studies involving a small number of patients. METHODS: We studied the outcome of renal transplantation in patients with pauciimmune SVV or anti-GBM disease, transplanted in our center between 1968 and 2000. Patient and graft survival were compared with a matched control group from our hospital. We specifically looked for any evidence of recurrent disease. RESULTS: Included in the study were 43 patients (31 male, 12 female) with a mean age (+/- SD) of 48 +/- 15 years at transplantation. Patients were diagnosed as Wegener's granulomatosis (n = 8), microscopic polyangiitis (n = 7), renal limited vasculitis (n = 18) and anti-GBM disease (n = 10). The average follow-up was 62 +/- 57 months. No graft was lost due to recurrence of the underlying disease. One patient with Wegener's granulomatosis had a relapse with only extrarenal manifestations 5 months after transplantation. Patient and graft survival at 5 years after transplantation were 77% and 60%. Survival rates were not significantly different from a matched control group of renal transplant patients with other underlying diseases, 79% and 56%, respectively. Patients with pauci-immune SVV or anti-GBM disease developed significantly more malignancies than the control group (p = 0.02). CONCLUSIONS: Recurrence of pauci-immune SVV and anti-GBM disease after transplantation is rare. Renal transplantation can be successfully performed in patients with pauciimmune vasculitis or anti-GBM disease. Physicians should be aware of the greater risk of developing malignancies, especially skin cancer.

Addition of isradipine (Lomir) results in a better renal function after kidney transplantation: a double-blind, randomized, placebo-controlled, multi-center study.

BACKGROUND: After successful kidney transplantation patients may suffer from the adverse effects due to the use of calcineurin inhibitors. Calcium channel blockers are effective in the treatment of hypertension and may ameliorate cyclosporine- (CsA) induced impairment of renal function after kidney transplantation. Calcium channel blockers may also modulate the immune-system which may result in reduction of acute rejection episodes. PATIENTS AND METHODS: From June 1995 till 1997 the effect of isradipine (Lomir) on renal function, incidence and severity of delayed graft function (DGF), and acute rejection after kidney transplantation, was studied in 210 renal transplant recipients, who were randomized to receive isradipine (n=98) or placebo (n=112) after renal transplantation in a double-blind fashion. RESULTS: In the isradipine group renal function was significantly better at 3 and 12 months (P=0.002 and P=0.021) compared with the placebo group. DGF was present in both groups: isradipine: (28+6)/98 (35%); placebo: (35+9)/112 (40%), P=0.57. Severity of DGF was comparable in both groups (isradipine: 9.1+/-8.7 vs. placebo: 9.3+/-8.1 days). No statistical difference was found in incidence or severity of biopsy-proven acute rejection [isradipine: (42+6)/98 (49%) versus placebo: (46+9)/112 (49%), P=1.00]. Renal vein thrombosis was observed in eight patients. This proved to be associated with the route of administration of the study medication [6/45 (13%) on i.v. medication versus 2/165 (1%) on oral medication, P<0.001]. CONCLUSIONS: Addition of isradipine results in a better renal function after kidney transplantation, without effect on incidence or severity of DGF or acute rejection.

The impact of recurrent glomerulonephritis on graft survival in recipients of human histocompatibility leucocyte antigen-identical living related donor grafts.

BACKGROUND: Graft loss due to rejection is uncommon after human histocompatibility leukocyte antigen-identical living related donor (LRD) transplantation, resulting in an excellent long-term graft survival. Data on the impact of recurrence of the original disease on graft survival after LRD transplantation are scarce. METHODS: We have studied the influence of recurrent glomerulonephritis in adult recipients of a human histocompatibility leukocyte antigen-identical LRD graft transplanted in our center in the period from 1968 to 1996. To that end, the data of 33 patients with proven or suspected primary glomerulonephritis and 27 patients with nonglomerular diseases were analyzed. RESULTS: The patient survival was similar in both groups at 5, 10, and 20 years. The functional graft survival, i.e., graft survival after censoring for death, was, however, significantly worse for patients with glomerulonephritis as underlying disease (P<0.01). At 5 years graft survival was 100% vs. 88%, at 10 years 100% vs. 70%, and at 20 years 100% vs. 63%, respectively. Thus none of the patients with nonglomerular diseases lost a graft, whereas eight grafts were lost in the group of patients with glomerulonephritis. The main cause of graft loss in this patient group was recurrent glomerulonephritis (n=5), whereas chronic vascular rejection caused graft loss in two patients and occlusion of a transplant artery was the cause in one. A clinically significant proteinuria was detected in six more patients in the glomerulonephritis group: a recurrent glomerulonephritis was diagnosed in four patients and in two patients there was no biopsy. The cumulative incidence of recurrence was as high as 45% at 12 years after transplantation. CONCLUSION: Recipients of a human histocompatibility leukocyte antigen-identical LRD kidney have a good prognosis with respect to graft survival. After censoring for death, recurrent glomerulonephritis is the main cause of graft failure in these patients and the impact of recurrent disease on graft survival will become even more prominent with longer follow-up.

Renal transplantation in patients with dense deposit disease: morphological characteristics of recurrent disease and clinical outcome.

BACKGROUND: Dense deposit disease (DDD) is an uncommon cause of end-stage renal disease (ESRD). As a consequence, information on the outcome of renal transplantation in patients with DDD comes from series with a limited number of patients. METHODS: We present the histological and clinical data of 13 adult patients with DDD, who received their first allograft in our centre in the period between 1983 and 1994. RESULTS: Renal transplant biopsies were performed in 11 patients, at 2.9 months after transplantation (median; range 0.4-13.8 months). The indication for taking the biopsy was in all instances a raised serum creatinine level. Five patients also had a significant proteinuria. In only one patient, light microscopy showed alterations in the capillary walls suggestive of a recurrence of DDD. However, by immunofluorescence or electron microscopy, we found glomerular deposits compatible with a recurrence of DDD in all 11 patients. Three patterns of glomerular C3 deposition were found: globular depositions only in the mesangium; mesangial accumulation with linear deposits in the capillary wall; and prominent linear presence in the capillary wall with only a few mesangial granules. The findings by electron microscopy matched the immunofluorescence results. The linear C3 accumulation in the capillary wall was visible ultrastructurally as electron-dense ribbon-like transformation of the glomerular basement membrane. Mesangial C3 deposits were seen ultrastructurally as local electron-dense deposits in the mesangium. Four patients showed a pronounced glomerular influx of neutrophils, accompanied by crescents in three patients. In these three latter patients, the recurrence of DDD was the only histological lesion. In the other patients, the recurrence was merely a coincidence, the biopsy demonstrating an additional histological lesion (three chronic vascular rejection, two acute rejection, one ischaemic necrosis and two cyclosporin A toxicity). Eight patients with a recurrence of DDD have progressed to ESRD at an average of 14 months (range 0.2-38 months) after transplantation. The recurrence was the sole cause of graft loss in the three patients with crescents. The patients in whom the C3 deposits were confined to the mesangium appeared to have a better prognosis. CONCLUSIONS: The histological recurrence rate of DDD is high. The histological picture is quite diverse, and in most patients abnormalities are only found by immunofluorescence and electron microscopy. Up to one-quarter of the patients with DDD lost their grafts because of a recurrence.

[Kidney transplantation without previous dialysis: limitations, but also possibilities]. / Niertransplantatie zonder voorafgaande dialyse: beperkingen, maar ook mogelijkheden.

Kidney transplantation guarantees a better quality of life than dialysis and is less costly. Transplantation without preceding dialysis is an attractive option. However, transplantation long before end-stage renal failure prolongs the period of exposure to immunosuppressive therapy, thereby increasing the risk of malignancy. Transplantation at one year before dialysis-dependency is expected would seem an acceptable compromise. Unfortunately, this option is purely theoretical because there is a long waiting-list due to the existing donor shortage. Patients are usually put on the waiting-list after dialysis has already been started. Extension of the list with pre-dialysis patients is currently only justifiable in exceptional cases. These limitations do not apply to patients who have received an offer of kidney donation from a living (related or unrelated) donor. In these patients transplantation can be done as soon as the creatinine clearance has reached a level of 10-12 ml per minute. More attention should be paid to this form of transplantation, because it can help to decrease the donor shortage.

Recurrence of type I membranoproliferative glomerulonephritis after renal transplantation: analysis of the incidence, risk factors, and impact on graft survival.

BACKGROUND: The information in the medical literature on the incidence of recurrence of type I membranoproliferative glomerulonephritis (MPGN) after renal transplantation and its impact on graft survival is limited because most data are derived from case reports or from studies involving a small number of patients. METHODS: We analyzed the data from our transplant center. Among 1097 adult patients receiving their first allograft between 1977 and 1994, we identified 32 patients with type I MPGN. RESULTS: A recurrence was detected in 9 of the 27 recipients of a first cadaveric graft (33%). The cumulative incidence reached 48% at 4 years after transplantation when patients with graft failure from other causes were censored. All patients with recurrent MPGN had clinically significant proteinuria (>1 g/24 hr) that was first observed at a median time of 20 months (range, 1.5-42 months) after transplantation. Graft survival was significantly worse in patients with recurrence as compared with patients without recurrence. Mean duration of graft survival after the diagnosis of recurrence was 40 months. We could not detect any clinical characteristics of patients or donors that were associated with recurrent disease. However, an increased risk of recurrence was observed in patients with the HLA haplotype B8DR3. Four patients received an HLA-identical graft from a living related donor. Recurrence occurred in three patients (75%), with ensuing graft loss in two. The only patient with a haploidentical living related graft did not have a recurrence. Five patients with a recurrence in the first graft received a second transplant. Recurrence was observed in four of these patients (80%). CONCLUSIONS: Type I MPGN recurred after renal transplantation in half of the patients. The incidence may be even higher in recipients of an identical living related donor graft and in patients receiving a second transplant after having experienced a recurrence in their first graft. Recurrence of type I MPGN has a detrimental effect on graft survival.

Long-term clinical experience with continuous ambulatory peritoneal dialysis: access-related problems.

Patients with end-stage renal failure can be treated with peritoneal dialysis, which is based on the capacity of the peritoneum to exchange fluid and metabolic products. To achieve this, dialysis fluid has to be instilled in the abdominal cavity through a permanent percutaneous access device. Apart from the advantages of peritoneal dialysis, severe problems are related to the access device. In this study, catheter-related morbidity and mortality are described, as found in the patient population from the University Hospital, Nijmegen, The Netherlands. The overall rates of exit-site infections and peritonitis are respectively 0.80 and 1.36 infection episodes per patient-year. Furthermore, it appeared that exit-site infections and peritonitis are the main reasons for discontinuation of dialysis and removal of the catheter. A correlation between the occurrence of peritonitis and exit-site infections was found. Also, the efficacy of the antibiotic treatment necessary to control these infectious complications is described. It is concluded that the design and the materials used to manufacture the currently used access device are the main reason for the existing morbidity in peritoneal dialysis. Therefore, more efforts should be undertaken to improve the access device, in which the design and the material used are critically considered.

Renal transplant thrombosis in children.

Data concerning 100 consecutive renal transplantations in children were analyzed to determine factors enhancing the risk of renal transplant thrombosis. The incidence of renal transplant thrombosis was high, at 12%. It is concluded that in addition to young age and low body weight of recipient and young age of the donor, also a high preoperative urine production contributes to the occurrence of thrombosis. Children with hypoplastic or dysplastic kidneys are at greater risk for thrombosis. Considering the influence of high urine production of the native kidneys, it may be possible to prevent thrombosis by albumin and ample fluid administration.

Soluble tumor necrosis factor-receptors are not a useful marker of acute allograft rejection: a study in patients with renal or cardiac allografts.

In this study, we investigated soluble tumor necrosis factor receptor (sTNF-R) levels in plasma of patients with either a kidney or cardiac allograft when clinical suspicion of acute rejection was raised. In plasma of patients with acute renal graft rejection, the sTNF-R levels were strongly enhanced (20-150 ng/ml) as compared to plasma of patients with stable renal function. Following successful treatment of the rejection, a gradual decline in sTNF-R levels occurred with improving renal function, and an inverse correlation between creatinine clearance and sTNF-R was found. To determine whether the increase was caused by an accumulation of constitutively released sTNF-R and lack of clearance by the kidney, or whether the immunological process of the rejection caused the enhancement, we measured sTNF-R in patients suffering from acute cardiac graft rejection but with predominantly stable kidney function. Rejection of a cardiac graft did not lead to a significant enhancement of sTNF-R levels. However, treatment with ATG or OKT3 did cause enhanced sTNF-R levels, followed by a decline that reached starting values after 7 days. These results provide evidence that the immune reaction that occurs during rejection of a graft does not per se induce discernible changes in sTNF-R levels, whereas that induced by ATG or OKT3 does. Thus, sTNF-R levels are not reliable marker in transplant recipient monitoring.

The extent of peritubular CD14 staining in renal allografts as an independent immunohistological marker for acute rejection.

Previously, we demonstrated that in acute interstitial rejection, immunohistological staining of renal allograft biopsies with the CD14 mAb WT14, reacting with human monocytes/macrophages, shows a characteristic peritubular increase of positive cells. To test the diagnostic value of this CD14 positivity, we compared, in 154 unselected renal allograft biopsies, the extent of peritubular WT14 staining with (a) the original histological diagnosis, made with knowledge of clinical data, (b) the retrospectively and blindly scored histological diagnosis according to the criteria of the Banff classification, and (c) the eventual clinical diagnosis, which included evaluation of the response to therapy. The extent of peritubular WT14 positivity, blindly scored on cryostat sections of the frozen part of the biopsies, correlated positively with the probability of acute rejection (AR). When using a cutoff of 70% WT14 positivity for the diagnosis of AR, as extracted from a receiver operating characteristic curve, the WT14 diagnosis had a positive predictive value of 91% and a negative predictive value of 56%, compared with the original histological diagnosis. Compared with the Banff diagnosis of AR (grade I-III), these values were 95% and 47%, and compared with the clinical diagnosis, 84% and 63%, respectively. The WT14 diagnosis essentially corrected the original histological diagnosis in 7 cases, and was consistent with the eventual diagnosis in 5 equivocal cases. We conclude that the extent of peritubular CD14 positivity can be used as a marker for AR and can serve as a valuable additional criterion for AR in the histological examination of renal allograft biopsies.

Doppler spectrum analysis to diagnose rejection during posttransplant acute renal failure.

During posttransplant acute renal failure (ARF), the diagnosis of allograft rejection constitutes a major problem. We evaluated the value of Doppler ultrasonography in identifying grafts at risk of rejection during ARF. In 184 recipients of a renal allograft, Doppler examinations were performed on the first and fifth postoperative day. Doppler spectra were quantitatively analyzed with a user-written computer program. Doppler findings were not used in clinical decision making. ARF was defined as a diuresis < 400 ml/24 hr and/or the necessity for dialysis. Doppler spectra obtained on the first day after transplantation showed a resistance index (RI) of 0.59 +/- 0.09 in recipients with immediately functioning cadaveric grafts (n = 123), while living related donor grafts (n = 20) showed a lower RI (0.55 +/- 0.07; P < 0.05). Grafts with ARF (n = 41) showed a considerably higher RI (0.67 +/- 0.13; P < 0.05). When grafts with a duration of ARF < or = 4 days (n = 17) were compared with ARF > 4 days (n = 24), RI was not significantly different (0.63 +/- 0.07 vs. 0.68 +/- 0.15; NS). However, the acceleration time of the systolic deflection of the spectrum waveform (Tmax) was shorter in grafts with ARF > 4 days (86 +/- 47 msec vs. 128 +/- 39 msec; P < 0.05). On the fifth day after transplantation, Doppler spectra in grafts with ARF > 4 days (n = 24) showed a Tmax < 90 msec in 9 patients, 8 of whom experienced rejection during ARF (positive predictive value, 8/9 = 89%). In the 15 patients with Tmax > or = 90 msec, only 2 rejections occurred (negative predictive value, 13/15 = 87%). For the RI (> 0.85), positive predictive value was 4/5 = 80% and negative predictive value (RI < or = 0.85) was 13/19 = 68%. In conclusion, a short acceleration time of the Doppler waveform on the first day after transplantation is associated with a longer duration of ARF. Quantitative analysis of Doppler spectra can be helpful in the identification of patients at risk for rejection and in the timing of allograft biopsy during ARF. Persistently short Tmax values on the fifth day after transplantation perform better in identifying grafts at risk of rejection than high RI values.