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.

Poor early graft function impairs long-term outcome in living donor kidney transplantation.

BACKGROUND: Poor early graft function (EGF) after living donor kidney transplantation (LDKT) has been found to decrease rejection-free graft survival rates. However, its influence on long-term graft survival remains inconclusive. METHODS: Data were collected on 472 adult LDKTs performed between July 1996 and February 2010. Poor EGF was defined as the occurrence of delayed or slow graft function. Slow function was defined as serum creatinine above 3.0 mg/dL at postoperative day 5 without dialysis. RESULTS: The incidence of slow and delayed graft function was 9.3 and 4.4%, respectively. Recipient overweight, pretransplant dialysis and warm ischemia were identified as risk factors for the occurrence of poor EGF. The rejection-free survival was worse for poor EGF as compared to immediate graft function with an adjusted hazard ratio (HR) of 6.189 (95% CI 4.075-9.399; p < 0.001). Long-term graft survival was impaired in the poor EGF group with an adjusted HR of 4.206 (95% CI 1.839-9.621; p = 0.001). CONCLUSIONS: Poor EGF occurs in 13.7% of living donor kidney allograft recipients. Both, rejection-free and long-term graft survivals are significantly lower in patients with poor EGF as compared to patients with immediate graft function. These results underline the clinical relevance of poor EGF as phenomenon after LDKT.

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.

Continuation of cinacalcet immediately after renal transplantation: a prospective cohort study.

BACKGROUND: Cinacalcet is used for treating secondary hyperparathyroidism in dialysis patients, but it is currently unknown whether it can safely be continued immediately after renal transplantation. METHODS: We prospectively studied renal transplant recipients with secondary hyperparathyroidism who were receiving cinacalcet before transplantation and continued treatment afterwards (n = 29) at a dose of 30 mg/day. Cinacalcet dose was titrated to serum calcium. Patients were followed for 6 months. Incidence of hypercalcemia, serum calcium and intact PTH (iPTH) were analyzed. Tacrolimus levels, acute rejection rate and renal function were compared with an age and sex matched control group. RESULTS: In 16 patients hypercalcemia was observed after transplantation. Severe hypercalcemia (>= 2.87 mmol/l) (n = 4) and hypocalcemia (n = 2) were infrequent. No difference in acute rejection rate or renal function between the cinacalcet and the control group was found. There also was no clinically relevant influence of cinacalcet on tacrolimus levels. CONCLUSIONS: Our study shows that cinacalcet can safely be continued immediately after renal transplantation. Studies are needed to determine if continuation of cinacalcet is better than early withdrawal. Also, the optimum dose of cinacalcet and the long-term effects of cinacalcet after renal transplantation must be defined.

Increasing Consent and Assent Rate for Organ and Tissue Donation: Communication About Donation-Telephone Advice by Psychologist.

A high percentage of family refusal is found for several outcomes in the Donor Register. Misconceptions and concerns regarding donation impede next of kin from making a well-considered decision. The donation request is the moment in which such concerns should be addressed by the requestor. The Communication about Donation-Telephone Advice by Psychologist (CaD-TAP) is a direct telephone intervention for requestors who are about to request the relatives for donation. The aim of this intervention is to improve requestors' communication skills regarding the donation request and thereby increase the consent rate for organ and/or tissue donation. The intervention started on the April 1, 2014, and lasted until December 31, 2014. To determine the effects, the consent and assent rates were compared between requestors who received the CaD-TAP intervention and those who did not. The requestors who received the CaD-TAP intervention (N = 141) had a significantly (P < .001) higher consent rate (58%) compared with the group who did not receive the intervention (N = 1563, consent rate: 34%). More tissue donor requestors received the intervention (74%) and most interventions took place outside office hours (82%). No significant difference was found in the effect of the intervention with regard to type of donation, time, or day. Furthermore, the intervention increased requestors' self-confidence in requesting for donation (P < .001), and a higher self-confidence indicated a significant association with increased consent rate. The intervention is unanimously experienced as positive and valuable by users. Based on these results the intervention is effective in increasing the consent rate for organ and tissue donation.

Inferior results with basis immunosuppression with sirolimus in kidney transplantation.

BACKGROUND: The introduction of sirolimus has provided the opportunity to develop an immunosuppressive regimen without the nephrotoxic calcineurin inhibitors. METHODS: We conducted a first trial in 30 renal allograft recipients. Ten patients were followed prospectively and received sirolimus, to achieve a target blood level of 10 to 15 ng/ml, induction therapy with one dose of daclizumab, low-dose steroids and mycophenolate mofetil. We compared this group with a historical control group of 20 patients who received our standard treatment consisting of tacrolimus, low-dose steroids, and mycophenolate mofetil. RESULTS: After a mean follow-up of 15 weeks, seven patients developed an acute rejection in the sirolimus group (70%) compared with three patients in the tacrolimus group (15%) (p.<0.01). Because of this unacceptable high rate of acute rejections we conducted a second prospective pilot study in nine patients. These patients received sirolimus in combination with two doses of daclizumab, high-dose steroids and mycophenolate mofetil. No rejections occurred under this immunosuppressive regimen; however, many immunosuppression-related adverse events were seen. CONCLUSION: The present study demonstrates an unacceptably high rate of acute rejections (70%) in patients treated with sirolimus, daclizumab, mycophenolate mofetil and low-dose prednisolone. No rejections but many adverse events were seen when sirolimus was given in combination with high-dose steroids.

[More potential organ donors than actual donations in 52 intensive-care units in the Netherlands, 2001-2004]. / Orgaandonorpotentieel in 52 intensivecareafdelingen in Nederland groter dan het aantal gerealiseerde donatieprocedures, 2001-2004.

OBJECTIVE: To assess the number of potential organ donors and the main reasons why organ donation is not performed. DESIGN: Retrospective. METHOD: The number of potential heart-beating (HB) and non-heart-beating (NHB) donors was assessed by reviewing the medical records of 588o patients who died between 2001 and 2004 in 52 intensive-care units (ICUs) in 30 hospitals. The number of actual donations was also assessed. RESULTS: The potential of HB donors was 2.5 to possibly 6.6% of all ICU deaths and HB donation was performed in 1.9% of all ICU deaths. The potential of NHB donors of category III was at least 4.2% of all ICU deaths and NHB donation was performed in 1.0% of all ICU deaths. The main difficulty in the donation process was objection from family members, which was reported in 45% of all potential HB and NHB donors and in 59% of all donation requests to relatives. Of the potential HB and NHB donors 7.3% were not identified as potential donors. CONCLUSION: These results confirm that organ-donor potential is greater than the number of actual donations. Objection from family members is the main limiting factor.

[Waiting list registration for kidney transplants must improve]. / Wachtlijstregistratie niertransplantatie moet beter.

OBJECTIVE: To investigate how the composition of the waiting list for postmortem kidney transplant has developed, and whether the waiting list reflects actual demand. DESIGN: Retrospective research and cohort study. METHOD: We used data from the period 2000-2014 from the Dutch Transplant Foundation, 'RENINE' and Eurotransplant. This concerned data on postmortem kidney donation, live donor transplants, the waiting list and kidney transplantation. RESULTS: The postmortem kidney transplant waiting list included transplantable (T) and non-transplantable (NT) patients. The number of T-patients declined from 1271 in 2000 to 650 in 2014, and the median waiting time between the start of dialysis and postmortem kidney transplant decreased from 4.1 years in 2006 to 3.1 years in 2014. The total number of patients on the waiting list, however, increased from 2263 in 2000 to 2560 in 2014 and in the same period the number of new patient registrations increased from 772 to 1212. In about 80% of the NT-patients the reason for their NT status was not registered. A cohort analysis showed that NT-patients have a 2-times lower chance of a postmortem kidney transplant and a 2-times higher chance of leaving the waiting list without transplantation or of live-donor transplantation. CONCLUSION: The demand for donor kidneys remains high. The increased number of transplants resulted in a declining waiting list for T-patients while the total waiting list is getting longer. Waiting list registration and maintenance need to be improved, to give better insight into the real demand.

The effect of immunosuppressive drugs on quality of life after renal transplantation.

This prospective, randomized study investigates the effect of two immunosuppressive treatment regimens on quality of life after renal transplantation. At 3 months after transplantation, patients treated with cyclosporine (CsA) and prednisone (Pred) were allocated to either withdrawal of Pred (n = 60) or to conversion of CsA to azathioprine (Aza) (Aza-Pred, n = 60). Quality of life was evaluated just before randomization, and at 6 and 12 months after transplantation using the Sickness Impact Profile (SIP), the Affect Balance Scale (ABS), the Center for Epidemiological Studies Depression Scale (CES-D), measures of satisfaction with several domains of life experience, and a population-specific physical symptoms questionnaire. In both groups, the overall SIP score as well as the scores on its physical and psychosocial dimensions improved continuously after transplantation, reaching levels that are comparable to those found in the general population. The occurrence of acute or chronic rejection had a significantly negative effect on SIP and CES-D scores. Intention-to-treat analysis showed no differences between groups for scores on SIP, ABS, CES-D, and satisfaction measures. Exclusion of 41 patients who did not strictly adhere to their originally designated therapy showed a tendency for better psychosocial SIP scores in CsA patients (P = 0.05), which mainly resulted from a difference on the category of social interaction (P = 0.01). This difference occurred despite a similar rejection rate and worse renal function in CsA-treated patients. Shortly after steroid withdrawal, a high proportion of CsA patients complained of stiff or painful muscles (CsA: 74%, Aza-Pred: 36%; P = 0.002). Our data indicate that if successfully completed, CsA monotherapy from 3 months after transplantation may lead to a higher degree of psychosocial well-being as compared with conversion from CsA-Pred to Aza-Pred. It seems likely that this advantage is related to the withdrawal of Pred.

Randomized, prospective trial of cyclosporine monotherapy versus azathioprine-prednisone from three months after renal transplantation.

Cyclosporine (CsA) and prednisone (Pred) are the mostly used drugs for immunosuppression after renal transplantation, but both drugs have marked side effects. Either replacement of CsA by azathioprine (Aza) or withdrawal of prednisone (Pred) resulting in CsA monotherapy can be employed to circumvent the adverse effects in the long run. Both treatment regimens were compared to this prospective randomized trial in patients who were treated with CsA and Pred during the first 3 months after renal transplantation (CsA: n=64, Aza-Pred: n=63, median duration of follow-up: 3.9 years). Estimated graft survival rates at 5 years after transplantation (in patients with a functioning graft at 3 months) were 78% in the CsA group and 87% in the Aza-Pred group. The incidence of a rejection within 3 months after start of steroid withdraw or conversion from CsA to Aza was 30% and 25% respectively (NS). At 2 years after transplantation, serum creatinine levels were lower in the Aza-Pred group (126+/-35 micromol/L) than in the CsA group (180+/-78 micromol/L; P>0.001). There were no differences in blood pressure or incidence of infections between the treatment groups. Treatment-related costs were measured during the first year after transplantation and were lower in the Aza-Pred group (DFL 40,882+/-18,895 vs. DFL 53,484+/-44,828; 1 DFL [Dutch guilder] is about US $0.60; P<0.005). In conclusion, CsA monotherapy and Aza-Pred treatment from 3 months after renal transplantation are comparably effective immunosuppressive treatment regimens, although Aza-Pred therapy results in better graft function. Withdrawal of steroids and replacement of CsA by Aza both carry a substantial risk of rejection. The previously demonstrated cost effectiveness of CsA-containing therapies seems to be limited to the first phase after transplantation. Conversion to Aza-Pred at 3 months after transplantation reduces costs.

Medication compliance after renal transplantation.

Noncompliance is known to be an important cause of late graft failure after renal transplantation. We investigated prospectively the degree of compliance with immunosuppressive and antihypertensive drugs during the first year after renal transplantation by monthly pill counts. In addition, we examined whether noncompliance was related to a number of demographic and clinical variables or to the occurrence of rejections. The study population consisted of 127 patients who were involved in a randomized trial comparing cyclosporine monotherapy with azathioprine-prednisone treatment. Average compliance rates approximated 100%, although considerable variability within and between subjects was observed. Using an arbitrary limit to classify patients as compliers or noncompliers, the following frequencies of noncompliance were observed during the study year: cyclosporine, 23%; azathioprine, 13%; prednisone, 23%; atenolol, 36%; and nifedipine, 32%. Average compliance scores for all immunosuppressive drugs were superior to those of antihypertensive medication (P < 0.001). Except for a better compliance for prednisone in men as compared with women, we found no consistent relationship between compliance on the one hand and several demographic variables, graft function, or quality of life on the other hand. Patients who developed one or more acute rejection episodes showed a higher degree of undercompliance, especially for prednisone, than patients without rejections (P < 0.01). Following the occurrence of a rejection episode, compliance scores improved significantly. Keeping in mind the limitations of the pill count method, we conclude that noncompliance with immunosuppressive drugs is not a huge problem during the first year after renal transplantation. However, it is likely that noncompliance contributes to a certain number of acute rejection episodes.

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.

Antihypertensive effect of beta blockade in renal transplant recipients with or without host kidneys.

Host kidneys may contribute considerably to hypertension after renal transplantation. Their role in sustaining hypertension is more prominent if glomerulonephritis (GN) than if interstitial nephritis (IN) is the original renal disease. We compared the antihypertensive effect of beta-blockade in IN (n = 10) and GN (n = 19) hypertensive renal transplant recipients with host kidneys in situ with those who had undergone bilateral nephrectomy (BN, n = 10). Pretreatment blood pressures were comparable in BN, IN, and GN patients, being 165 +/- 6/108 +/- 3, 172 +/- 5/104 +/- 3, and 161 +/- 3/104 +/- 1, mmHg, respectively. Blood pressure did not change on beta-blockade in BN patients, whereas it decreased significantly more (P less than 0.001) in GN than in IN patients, changes of mean arterial pressure being -107 +/- 1.0, -14.9 +/- 1.3, and -6.8 +/- 1.6%, respectively. This failure to respond to beta-blockade in patients without host kidneys may be related to low activity of the renin-angiotensin system or to functional denervation of the grafted kidney. Further investigations of this phenomenon may clarify the mechanism of antihypertensive action of beta-blockade as well as the nature of hypertension after renal transplantation.

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.

HLA-DRW6 and treatment of acute rejection with antithymocyte globulin.

The influence of DRw6-antigen on graft survival was studied in a single-center study in 223 recipients of a cadaveric kidney. Although graft survival in 148 DRw6-negative recipients was not significantly different from that in 75 DRw6-positive recipients, the percentage of patients without a rejection episode in the first three months after grafting was significantly less in the DRw6-negative recipients (p = 0.03). In DRw6-positive patients who had received rabbit antithymocyte globulin (RATG) as the first antirejection treatment, graft survival was significantly better than in prednisone-treated DRw6-positive recipients. In the DRw6-negative patients RATG treatment also gave better results, but these differences were not significant. When RATG-treated patients were excluded from the analysis, the difference in graft survival between DRw6-negative and DRw6-positive patients became apparent (p = 0.03). These findings show that the negative influence of the DRw6 antigen present in the recipients is counterbalanced by the beneficial effect of RATG treatment for first rejection episodes.

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.

Improved patient and graft survival after treatment of acute rejections of cadaveric renal allografts with rabbit antithymocyte globulin.

In a prospective randomized trial, we compared the effectiveness of rabbit antithymocyte globulin (RATG) in the treatment of acute renal allograft rejection with the results of treatment by high oral doses of prednisone. Fifty recipients of cadaveric kidneys were included in each group. In the RATG group, the prednisone dose was not increased and a dose-by-rosette protocol was used to keep T cell levels between 50 and 150/mm. The three-month and one-year graft survival rates in the RATG group were 84% and 78%, and were significantly higher than those in the prednisone group (64% and 50%). A significant difference in patient survival could also be detected. In the RATG group the three-months and one-year patient survival rates were 100% and 98%, and patient survival rates in the prednisone group were 91% and 84%, respectively. The percentage of second rejections was higher in the prednisone group and 70% of these patients showed a good response to subsequent RATG treatment. Renal function after six months was similar in both groups. No serious side effects were encountered in the RATG group. The incidence of infections was the same in both groups. Treatment of acute rejections with RATG is preferable to prednisone treatment. It improves long-term graft and patient survival and is steroid-sparing.