Maria Teresa Tenorio

Long-term functional evolution after an acute kidney injury: a 10-year study

BACKGROUND Data on long-term effects of acute kidney injury (AKI) on renal function (RF) are scarce and factors implicated in the functional outcome are not established. Our aim was to investigate these aspects. METHODS At hospital discharge and annually for 10 years, we retrospectively reviewed RF of 187 patients surviving AKI. Glomerular filtration rates estimated with MDRD equation (eGFR) and KDOQI stages were used to evaluate RF. Only 34.8% of patients had pre-existing renal dysfunction (KDOQI-3). Variables determining long-term RF were collected during AKI and at discharge and analysed with a regression model. RESULTS At discharge no patient necessitated dialysis, but eGFR was lower than baseline (47.5 +/- 23.3 ml/min/ 1.73 m(2) versus 75.8 +/- 25.4 ml/min/1.73 m(2)); 38.4% of survivors had recovered basal RF: 26% of those with previous normal RF and 61% of those in KDOQI-3, respectively. At 1 year, eGFR increased to 61.9 +/- 24.4 ml/min/1.73 m(2) and remained stable later. During an 8-year median follow-up (P25:2; P75:10), 31% improved RF, 50% remained stable and 19% deteriorated. In total only 46% (n = 82) definitively recovered RF. Finally, at the end of the study period 61.6% presented some degree of renal dysfunction: 40% of those with previous normal RF developed moderate-severe renal dysfunction and 37% KDOQI-3 progressed into more severe renal failure. Only two patients needed dialysis. Regression model identified age, co-morbidities, discharge eGFR and follow-up time as independent predictors of long-term RF. CONCLUSIONS AKI carries implication for long-term RF even in patients without pre-existing renal dysfunction. Ageing, co-morbidities and RF at discharge are determinants of the long-term functional outcome.

Influence of immunosuppression on the prevalence of cancer after kidney transplantation.

The prevalence of cancer in renal transplant patients is greater than in the general population. It is influenced by demographic and ethnic characteristics. We performed a retrospective study of 793 patients who received 872 kidney transplants at our center during 23 years. The age at transplantation was 41.4+/-14.0 years, the follow up 75.4+/-69.4 months. The cohorts include 203 patients treated with azathioprine-prednisone; 510, cyclosporine-based therapy; and 159, tacrolimus-based therapy. There were 95 patients (10.9%) who developed at least one neoplasm with 9 having more than one type of tumor. The incidence was of 17.3 cases per 1000 patients-years. Forty-four (46.3%) had skin cancer, 8 (8.4%) Kaposi sarcoma and 43 (45.3%) a non-skin cancer. Seven of eight patients with Kaposi sarcoma were on CsA therapy. The risk of developing a neoplasm at 5, 10, and 15 years was 8%, 17%, and 30% respectively. In a multivariate analysis, the risk factors associated with neoplastic diseases were older age (OR=1.061; 95% CI 1.039-1.084; P=.000), male sex (OR=2.658; 95% CI 1.536-4.599; P=.000), length of follow-up (OR=1.121; 95% CI 1.073-1.172; P =.000), and immunosuppression with CsA (OR=4.448; 95% CI 1.334-14.764; P=.015). Cancer was the cause of death in 26 patients, the fourth most common cause after cardiovascular disease, infection, and liver failure. We conclude that malignancies are an important cause of morbidity and mortality among transplant patients. Special attention must be devoted to older male patients with a long-term follow up to develop preventive and surveillance strategies.

Predicting Acute Renal Failure after Cardiac Surgery: External Validation of Two New Clinical Scores

BACKGROUND AND OBJECTIVES Different scores to predict acute kidney injury after cardiac surgery have been developed recently. The purpose of this study was to validate externally two clinical scores developed at Cleveland and Toronto. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective analysis was conducted of a prospectively maintained database of all cardiac surgeries performed during a 5-yr period (2002 to 2006) at a University Hospital in Madrid, Spain. Acute kidney injury was defined as the need for renal replacement therapy. For evaluation of the performance of both models, discrimination and calibration were measured. RESULTS Frequency of acute kidney injury after cardiac surgery was 3.7% in the cohort used to validate the Cleveland score and 3.8% in the cohort used to validate the Toronto score. Discrimination of both models was excellent, with values for the areas under the receiving operator characteristics curves of 0.86 (95% confidence interval 0.81 to 0.9) and 0.82 (95% confidence interval 0.76 to 0.87), respectively. Calibration was poor, with underestimation of the risk for acute kidney injury except for patients within the very-low-risk category. The performance of both models clearly improved after recalibration. CONCLUSIONS Both models were found to be very useful to discriminate between patients who will and will not develop acute kidney injury after cardiac surgery; however, before using the scores to estimate risk probabilities at a specific center, recalibration may be needed.

Cytomegalovirus infection after renal transplantation: selective prophylaxis and treatment

We have reviewed our experience in selective cytomegalovirus (CMV) infection prophylaxis and treatment in our renal transplant population. Between 1996 and 2001, 263 cadaveric renal transplant recipients had at least 6 months follow up. Immunosuppression was based on cyclosporine Neoral (n=108) or tacrolimus (n=155). CMV infection prophylaxis (oral acyclovir or gancyclovir at half usual doses) was only prescribed in recipients receiving a CMV positive ve kidney and in recipients treated with OKT3. CMV infection was diagnosed by a positive pp65 antigenemia upon appearance of CMV-related symptoms, leading to specific treatment (IV ganciclovir) only if symptoms were intense or there was visceral involvement. Thus, no preemptive treatment or programmed or periodic antigenemia was performed in any case. Nineteen episodes of symptomatic CMV infection were diagnosed (prevalence 7.2%). The frequency was similar for all immunosuppressive regimens. Only 9 of 19 (47%) of patients were given IV ganciclovir; the others were not treated. All patients survived without apparent complications, relapses, or recurrences. No oral gancyclovir was delivered after IV treatment. Our CMV prophylaxis protocol was limited to high-risk patients, using lower gancyclovir dosages than those usually advocated. It does not include programmed or scheduled search for CMV antigenemia in asymptomatic renal transplant patients. Despite these factors, our CMV infection rate and severity were similar to those reported with more aggressive protocols, with extended prophylaxis, preemptive therapy, or intense surveillance.

Acute kidney injury as a risk factor for chronic kidney diseases in disadvantaged populations

Acute kidney injury (AKI) is considered to be a potential cause for developing chronic kidney disease (CKD); on the other hand, CKD predisposes to AKI. The lack of adequate epidemiological data makes it difficult to determine if AKI induces CKD in less developed countries. The etiology of AKI in rich populations, in whom sophisticated surgery, interventional radiology and oncology treatments are usually the cause of AKI, is very different from that of disadvantaged populations, where the origin of AKI is associated with endemic infections, obstetric problems, poisons, toxins and natural disasters. Any conclusions extrapolated from these two settings should be treated with caution. Moreover, people living in disadvantaged conditions are usually much younger than those in rich areas and this age factor could facilitate total recovery of renal function after AKI if treatment based on an adequate supply of water, rehydration and anti-infectious measures were provided. In the small segment of the population of less developed countries having an income per capita similar to that observed in the developed countries, the long-term outcome of AKI should also be expected to be similar. New data coming from two single centers analyzing only the long-term outcome of acute tubular necrosis (ATN) patients, with a normal or near normal renal function prior to the AKI episode, coincide in reporting a requirement for chronic dialysis among the surviving patients of 2%. If these data are confirmed, the importance of AKI as cause of CKD should be reconsidered, both in developed and less developed countries.

Treatment of Secondary Hyperparathyroidism in Hemodialyzed Patients with High-Dose Calcium Carbonate without Vitamin D3 Supplements

Background: Vitamin D compounds are usually indicated for the treatment of secondary hyperparathyroidism in dialysis patients. The possibility to induce a reversal of hyperparathyroidism with calcium supplementation alone is controversial. The present study was conducted to assess if oral calcium carbonate may constitute a therapeutic option for the control of hyperparathyroidism in patients with high PTH concentrations at the beginning of the treatment with chronic hemodialysis. Methods: Thirty-one patients with end-stage renal failure with an intact PTH concentration above 250 pg/ml at the beginning of chronic hemodialysis therapy were treated with high doses of calcium carbonate; no patient received either aluminium-containing binders or vitamin D compounds. To minimize hypercalcemia, a calcium dialysate concentration of 2.5 mEq/l was used in all patients. The goal of the study was to reduce the intact PTH concentration to 250 pg/ml with oral calcium carbonate supplements alone. Results: Throughout the first year on hemodialysis treatment, the intact PTH concentration decreased from 538 ± 256 to 251 ± 218 pg/ml (p < 0.001). By the end of the study, the therapeutic objective was achieved in 22 patients (71%) (‘responder’ group). The remaining 9 patients were classified as the ‘treatment failure’ group. The basal intact PTH concentration was not different between both groups (508 ± 235 vs. 612 ± 303 pg/ml, respectively, p = n.s.), but 5 ‘treatment failure’ patients admitted to take a dose of calcium carbonate lower than that prescribed. There were 40 episodes of hyperphosphatemia (11% of all measurements) in 7 of 31 patients, 5 of them belonged to the noncompliance ‘treatment failure’ patients. Only 15 episodes (4% of all measurements) of transient hypercalcemia (range 11.1 – 11.9 mg/dl) were detected in 8 patients. Conclusions: Secondary hyperparathyroidism in hemodialysis patients can often be reverted by oral calcium carbonate alone. But a good adherence to treatment is absolutely necessary.

Comparison of C0 and C2 cyclosporine monitoring in long-term renal transplant recipients

Recent data show that monitoring cyclosporine A (CsA) concentrations with 2-hour postdose levels (C2) correlates with the incidence of rejection and graft outcome in de novo renal transplant patients. The purpose of the present work was to evaluate the advantage of C2 monitoring after the first year of kidney transplantation. We studied 161 patients, 96 on CsA-prednisone and 65 on triple therapy (Aza or MMF) who had been transplanted for a mean of 103+/-44 months. Mean serum creatinine (SCr) was 1.65+/-0.69 mg/dL, mean C0 was 174+/-44, and C2 was 667+/-194 ng/mL. Patients were classified according to C2 values: >850 (n=29), between 850 and 450 (n=109), and <450 (n=23) ng/mL. Patients with C2 <450 ng/mL displayed higher SCr values (1.97+/-0.99; 1.59+/-0.51; 1.52+/-0.4 mg/dL; P<.001), received lower CsA doses (172+/-54; 207+/-54; 227+/-56 mg/d, P<.01), showed lower C0 levels (155+/-48; 172+/-41; 199+/-45 ng/mL; P< .001), and included more patients on triple therapy (54.5%; 44%; 17.2%; P<.05). We found weak correlations between C0 and C2 (r=0.37), between C2 and CsA dose (r=0.36), and between C0 and SCr (r=-0.37). Among 117 patients followed up for 1 year with several C0 and C2 measurements, the coefficient of variation of C0 was 17% and of C2 was 21%. Graft functional deterioration occurred in 16 patients independent of the differences among the C2 groups, but 7 recipients (43.7%) had C0 <150 ng/mL and C2/C0 >5. We conclude that C2 in monitoring stable patients needs further evaluation.

A low incidence of new-onset insulin-dependent diabetes mellitus using tacrolimus in kidney recipients in Europe.

Employing tacrolimus (Tac) for routine immunosuppression in renal transplantation (RT), produced an incidence of new-onset, insulin-treated, diabetes mellitus (newDM) as high as 20%. More recently, several large multicenter kidney studies using Tac as the primary immunosuppressant have been reported in Europe. Between 1997 and 2001, we performed 155 RTs using Tac (0.2 mg/k/per day, targeting whole blood trough levels <15 ng/mL) with a rapid steroid taper. The acute rejection rate was 13%, and 89% of grafts are still functioning. Only 5 Tac-treated patients not previously requiring insulin needed insulin therapy for > or =30 days (3.2%). Eight separate studies employing Tac in at least one arm (N=2728) have been reported between 1997 and 2002. Tac was combined with azathioprine or MMF, and/or steroids. The incidence of new DM at study end ranged from 2.3% to 8.3%. The only trial with >6% incidence was the first one, using an initial dose of 0.3 mg/kg per day. The most recent studies utilized an initial dose of 0.2 mg/kg per day, targeting whole blood trough levels of <15 ng/mL and a steroid taper, with newDM at <6%. On the basis of these data, we confirm in that the use of Tac as a first-line immunosuppressant in renal transplant patients affords protection against acute rejection with a low level of newDM. The tendency to employ lower oral doses of Tac, lower blood target levels, and a reduced steroid dose appear to minimize glucose disturbances in RT.

One-center comparison between primary immunosuppression based on neoral cyclosporine and tacrolimus for renal transplantation.

TACROLIMUS is a well-established basic immunosuppressive drug in renal transplantation (RT), but the efficacy and safety comparisons with the new formulation of microemulsified cyclosporine, Neoral, come only from a multicenter study. In the only published 3-month multicenter trial, tacrolimus triple therapy with azathioprine and steroids was associated with less acute rejection episodes (in number and severity) than was triple therapy with Neoral. However, these large multicenter international trials are frequently quite heterogeneous and include too short follow-up. Consequently, they may not reliably reflect the impact of new immunosuppressive regimens on routine clinical practice. We have reviewed the 5-year experience in our unit with RT treated with Neoral or tacrolimus.

Analysis of Renal Function in the Immediate Postoperative Period After Partial Liver Transplantation

Although renal dysfunction is common after liver transplantation, postoperative renal function after split liver transplantation (SLT) has not been well studied. Renal function immediately after surgery was analyzed retrospectively in 16 patients that received a SLT (SLT group). The results were compared with corresponding data from 31 matched patients that received a full‐size liver transplant (FSLT group) during the same period. Serum creatinine (SCr) was measured before surgery, and, after transplantation, daily during the first week and at days 14, 21, and 28. Renal dysfunction (RD) was defined as the requirement for renal replacement therapy (RRT) or a 100% increase in SCr if the basal value had been <1.0 mg/dL or a 50% increase in SCr if the basal value had been >1.0 mg/dL. SCr had to be at least 1.5 mg/dL for a diagnosis of RD to be considered. The classification of RD was: mild, SCr 1.5‐2.4 mg/dL; moderate, SCr 2.5‐4.0 mg/dL; or severe, SCr >4.0 mg/dL (the requirement for RRT). Both donor and recipient age and cold ischemia time were lower in the SLT group than in the FSLT group (P < 0.05). Length of surgery was longer in the SLT group (P < 0.05). There were no significant differences between groups with respect to Model for End‐Stage Liver Disease scores, the need for transfusions, the length of admission to the intensive care unit (ICU), survival rate, individual severity index, or sepsis‐related organ failure assessment scores at the time of diagnosing RD. Immunosuppression regimens were similar in both groups. RD developed in 82% of SLT patients, but in only 58% of FSLT patients (P = not significant [NS]). Among SLT patients, RD (23.0% mild, 15.5% moderate, and 61.5% severe) was more severe (P = 0.007) than in FSLT patients (63.1% mild, 15.8% moderate, and 24.1% severe). The requirement for RRT in the SLT group (43.7%) was significantly greater (P < 0.05) than that in the FSLT group (12.9%). This finding may be due to the different incidence of sepsis in the 2 groups (SLT 37.5% vs. FSLT 9.7%; P < 0.05). In conclusion, although the number of patients studied was small, our data suggest a higher incidence of RD and a greater requirement for RRT in patients that receive a split liver graft than in those that receive a full size liver graft. Liver Transpl 12:1371‐1380, 2006.