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Return to dialysis after renal transplantation. Which would be the best way?

2002; Elsevier BV; Volume: 61; Linguagem: Inglês

10.1046/j.1523-1755.61.s80.15.x

1523-1755

Manuel Arias, R Escallada, Ángel L.M. de Francisco, Emilio Rodrigo, Gema Fernández‐Fresnedo, Ma ÁNgeles Setien, Celestino Piñera, Juan Carlos Ruiz, I Herráez, J.G Cotorruelo,

Neurological Complications and Syndromes

Return to dialysis after renal transplantation. Which would be the best way? The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hispital admissions during the first year after initiation of dialysis were considereably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss. Return to dialysis after renal transplantation. Which would be the best way? The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hispital admissions during the first year after initiation of dialysis were considereably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss. Over the past few years, renal graft survival has considerably improved. In a large U.S. series published last year1.Hariharan S. Jonson C.P. Bresnahan B.A. Improved graft survival after renal transplantation in the United States, 1998 to 1996.N Engl J Med. 2000; 342: 605-613Crossref PubMed Scopus (1626) Google Scholar with almost 100,000 transplants analyzed, an increase in the average graft life of 6 years was observed (and more than 8 years when those cases lost because of death with a functioning kidney were excluded from the study). Similar results have also been observed in Europe, in accordance with the Collaborative Transplant Study data: An increase of over 9 years has been achieved since 1982. In the same way, in our population of renal transplant patients, we have observed an increase in graft survival of over 20% in the first post-transplant year, and almost 40% in the fifth post-transplant year, when the past two decades are considered. Nevertheless, despite this considerable improvement, there is still a continuous loss of renal transplants as of the first year, which has not been completely avoided with the past generation of immunosuppressive drugs. In our series, these losses suppose an average of 4% per year during the first 5 years, and between 1% and 3% thereafter; these figures increase slightly if the patient has suffered an acute rejection episode (AR) (between 2% and 5%). Isolated acute tubular necrosis (ATN) does not appear to influence those losses in the long term but does have a direct influence through its association with AR, at least in our series. This situation, together with the progressive increase in the number of renal transplants, means that the population of transplant patients readmitted to a dialysis program will be progressively greater. In fact, the loss of a functioning renal graft has been, during the past year, the second cause for entry into a dialysis program in our population. Therefore, it is necessary to consider this group of patients as a specific subgroup among the predialysis patients given their specific characteristics and, above all, to answer the key question: When do we have to restart dialysis? There are no clear references in the literature with respect to the optimal moment to return to dialysis for patients with a failing transplant, so the only recommendations available are those made for the initiation of dialysis in the population of chronic renal failure patients in general2.Hakim R.M. Lazarus J.M. Initiation of dialysis.J Am Soc Nephrol. 1995; 6: 1319-1328PubMed Google Scholar. Classically, these recommendations were based on clinical criteria, clinical symptoms compatible with uremia or fluid overload, and on biochemical criteria centered on the renal function, measured by serum creatinine, urea, and creatinine clearance (CCr). Nevertheless, there is currently a greater tendency to include more accurate methods or calculations as the average of urea and CCr as a more exact measure of the real glomerular filtration rate, and to apply the urea kinetic model (weekly Kt/V) as an indirect or orientative measure of the elimination of uremic toxins3.Tattersall J. Greenwood R. Farrington K. Urea kinetics and when to commence dialysis.Am J Nephrol. 1995; 15: 283-289Crossref PubMed Scopus (160) Google Scholar. With regard to the figures that show the need for entry into dialysis, there is controversy; so the U.S. opinion, represented mainly in the DOQI Guidelines (National Kidney Foundation-Dialysis Outcomes Quality Initiative), recommends an early entry: weekly Kt/V equal to or greater than 2 which would approximately represent a CCr of 14 mL/min and an average urea and CCr of 104.NKF-K/DOQI Clinical practice guidelines.Am J Kidney Dis. 1997; 30: S67-S136Google Scholar,5.Obrador G.T. Arora P. Kausz A.T. Level of renal function at initiation of dialysis in the U.S. end-stage renal disease population.Kidney Int. 1999; 56: 2227-2235https://doi.org/10.1046/j.1523-1755.1999.00779.xAbstract Full Text PDF PubMed Scopus (101) Google Scholar. On the other hand, the European criteria are more flexible and, in general, delay the initiation of substitutive treatment somewhat more. As we have already mentioned above, these criteria are those used for patients with primary chronic renal insufficiency, not because of graft failure. So, what happens with the second group? Are those criteria adequate for their return to dialysis? The answer to these questions is the reason for this current study in which we analyze our experience in the following specific aspects: the biochemical situation of the patients with chronic graft nephropathy at the time of their return to dialysis; the comparison with the situation of patients who are starting the substitutive therapy for the first time, and the impact of these factors on morbimortality after the initiation of dialysis. One hundred and ninety-two patients who started substitutive therapy were analyzed. This group includes two subgroups of patients: 70 patients with chronic allograft nephropathy (CAN, group A), and 122 patients initiating substitutive therapy for the first time (group B). The whole group corresponds to all the patients entering dialysis at our institution between January 1995 and December 2000, with clinical and analytical data available for at least 2 years before the initiation of dialysis. Serum chemistry and complete blood cell count were performed in all patients in every evaluation, and the following parameters were specifically analyzed or calculated: Urea, serum creatinine, classical CCr (corrected for body surface area), calculated CCr (Cockcroft-Gault formula), urea clearance, average urea-CCr, and weekly Kt/V of urea. Data collection was carried out on the following time scheme: at the initiation of dialysis, and 1, 3, 6, 9, 12, and 24 months before that moment. The intensity of morbidity and the mortality of the patients was evaluated and correlated with the renal function at the moment of initiation of dialysis. For the analysis of patient morbidity, the number of hospital admissions was computed, as was the total days of hospitalization for all the patients between months 2 and 12 after entering or returning to dialysis. Admissions during the first month and those episodes secondary to vascular access problems (both internal arteriovenous fistula or central venous catheter) were excluded. Mortality rate was analyzed by means of actuarial survival curves (Kaplan-Meier). The evolution of analytical main data on the patients with CAN are summarized in Table 1. It shows that at the start of dialysis all the average values were below the aforementioned DOQI recommendations. Table 2 shows the percentage of patients with values above the theoretically ideal ones. The comparison of those values related to renal function in groups A and B are shown in Table 3. Statistically significant differences con be observed between both groups.Table 1Evolution of the analytical data in the group of patients with chronic nephropathy of the implant-2 years-1 year-9 months-6 months-3 monthsStartUrea mg/dL119129160169211249CCrmL/m34332221159Cur.+CCr/232262117116Weekly Kt/V5.44.23.72.92.01.3Hemoglobin12.112.211.110.89.48.9Abbreviations are: CCr, creatinine clearance; Weekly Kt/V, urea kinetic model. Open table in a new tab Table 2Percentage of patients with chronic allograft nephropathy with analytical values above the theoretically ideal-2 years-1 year-9 months-6 months-3 monthsStart%urea>200058162979CCr <10 mL/m3813154178Cur.+CCr/2 <1081015273989Weekly Kt/V <281519265287Hemoglobin <8004121631Abbreviations are in Table 1. Open table in a new tab Table 3Comparison of the analytical values in patients with chronic allograft nephropathy and with chronic renal insufficiency without transplant (CRI no tx.), at the start or return to dialysisCANCRI no tx.PUrea mg/dL2492140.018CCrmL/m9130.048Cur.+CCr/26100.019Weekly Kt/V1.41.650.01Hemoglobin8.910.20.04 Open table in a new tab Abbreviations are: CCr, creatinine clearance; Weekly Kt/V, urea kinetic model. Abbreviations are in Table 1. With regard to morbidity, Figure 1 shows how the patients in group A with CAN were admitted to the hospital (at least once during the first year after returning to dialysis) in a percentage almost double that of group B (57% vs. 29%). Also, the average number of admissions per patient was significantly higher in group A. With respect to the total number of days of hospitalization in the first year after entering dialysis, patients in group A had an average of 21.1 compared with 10.2 days in the group B (P = 0.012). When the total days of hospitalization of patients in group A was correlated with renal functional parameters, a significant negative statistical correlation could be observed when the average of urea and CCrFigure 2a and the weekly Kt/V Figure 2b were considered.Figure 2Correlation between the total number of days admitted to hospital in the first year after returning to dialysis for implant failure and the average values of urea-creatinine clearance (CCr) (A) and of weekly Kt/V of urea (B).View Large Image Figure ViewerDownload (PPT) Patient survival after return to dialysis (group A) was 73% at 1 year, and 67% at 5 years. Those patients who died had an average of urea-CCr that was lower than those who were alive (5.2 ± 4.8 vs. 8.1 ± 5.5, P = 0.02) and a weekly Kt/V of urea also lower (0.97 ± 0.6 vs. 1.5 ± 0.7, P = 0.02) on their admission to dialysis. The progressive increase in the number of patients who return to dialysis after a failed renal transplant means that it is necessary to consider the clinical conditions of this return, something that has not yet happened, at least as far as a review of the literature shows. Graft failure causes the patient, and sometimes the doctor, a feeling of failure and emotional stress (generally greater than the first time) which may lead to a delay in the return to dialysis, very often not adequately justified by the patient's clinical and analytical situation. This fact, together with the special characteristics of this kind of patient (immunosuppressive therapy, chronic inflammatory state, associated pathologies, and relative resistance to the effect of erythropoietin)6.EDTA-ERA European best practice guidelines for the management of anaemia in patients with chronical renal failure. Guidelines 14–16. Inadequate response to epoetin.Nephrol Dial Transplant. 2000; 15: 43-50Google Scholar, among others, means that the clinical situation could clearly be worse than in those patients who are starting substitutive treatment for the first time. In our series, patients with CAN return to dialysis with a clearly worse analytical profile than that recommended as ideal in the DOQI guidelines4.NKF-K/DOQI Clinical practice guidelines.Am J Kidney Dis. 1997; 30: S67-S136Google Scholar. So, the average urea figure is 20% greater than that recommended, and the percentage of patients with a urea greater than 200 is over 75%. Also, the average urea and CCr are 30-40% lower that those considered ideal for starting dialysis. The analysis of the weekly Kt/V of urea corroborates these results: The patients with graft failure start dialysis with an average value of 1.4, 30% lower than that considered as the minimum for an insufficient elimination of uremic toxins. If we look at the evolution of the analytical values, we can see how this situation would be corrected to a large extent if this group of patients started dialysis approximately 3 months earlier. Also, the comparison with the group of patients who are starting substitutive treatment for the first time clearly shows us that there is a difference in our attitude when deciding the time to start dialysis: All the parameters studied show that it is much earlier when the patient does not come from a failed graft. The hemoglobin also has values well below those recommended, although in this case the cause is not only because of the theoretical delay in returning to dialysis but could be due to a state of relative ferropenia (the patients that are still not under dialysis usually receive less intravenous iron) and the very resistance itself to the action of the erythropoietin6.EDTA-ERA European best practice guidelines for the management of anaemia in patients with chronical renal failure. Guidelines 14–16. Inadequate response to epoetin.Nephrol Dial Transplant. 2000; 15: 43-50Google Scholar. The solution, in accordance with the European Guidelines, is the same as for patients in pre-dialysis for the first time: treatment with EPO when the hemoglobin is lower than 11 g/L, although, generally, in greater doses7.EDTA-ERA European best practice guidelines for the management of anaemia in patients with chronical renal failure. Guideline 9–13. Anemia management.Nephrol Dial Transplant. 2000; 15: 33-42Google Scholar. This late return to dialysis also seems to have a certain negative impact on the morbimortality of this kind of patient: Both the number of admissions (excluding those caused by vascular access problems) and the total days of admission during the first year are significantly greater in patients with graft failure. There is also a significant correlation between the total number of days of hospitalization and the values of the average urea and CCr and the weekly Kt/V of urea, which may indicate a negative impact on the clinical situation of these patients; this will have to be confirmed with wider studies. Another worrisome circumstance is the high mortality observed after the return to dialysis, especially in the first year. This is greater than the general mortality of our patients on substitutive therapy, and one that has also been described recently in very wide series of patients with graft failure once they have returned to dialysis (abstract; Meier-Kriesche, Kaplan, 2001 A Transplant Odyssey, Istanbul, August 2001). As with the morbidity, we have observed that the patients who died had significantly greater figures of average urea and CCr and weekly Kt/V than those in patients who are still alive. The small number of patients, the same as with the morbidity, means that these data are not conclusive and that later studies are needed. In summary, from the analysis of our series of patients with graft failure who returned to dialysis, we can see that this return took place later. It would be very advisable, in order to prevent the possible negative impact on their morbimortality, to begin substitutive therapy earlier or to perform a therapeutic intervention that would increase the renal function to more suitable levels. One possibility would be growing dialysis that would take advantage of the renal function of the graft8.Keshaviah P.R. Emerson T.F. Kolth K.D. Timely initiation of dialysis: A urea kinetic approach.Am J Kidney Dis. 1999; 2: 344-348Abstract Full Text Full Text PDF Scopus (41) Google Scholar, and another would be retransplantation of these patients before the total loss of function. The latter would also have the advantage of being able to use kidneys with a relatively low nephronal mass (very elderly donors, low weight, or with a relatively high percentage of sclerosed glomeruli), in the same way as a double transplant9.Andrés A. Morales J.M. Herrero J.C. Double versus single renal allografts from aged donors.Transplantation. 2000; 69: 2000-2001Crossref Google Scholar. In this situation the emotional stress of a return to dialysis would be avoided, and the immunosuppressive treatment the patient has already taken could be utilized.