Diabetes mellitus after kidney transplantation: role of the impaired fasting glucose in the outcome of kidney transplantation.

INTRODUCTION: Most patients suffering from chronic renal insufficiency show impaired carbohydrate metabolism. Our goals were to analyze the accumulated incidence of impaired fasting glucose (IFG) and post-transplant diabetes mellitus (PTDM) after kidney transplantation in our hospital, to assess their impacts on the survival of the graft and of the patient, and to discover the major risk factors for the development of PTDM. MATERIALS AND METHODS: We examined alterations in carbohydrate metabolism in 920 adult patients after they received kidney transplantation. Patients were followed for a minimum period of 5 yr. RESULTS: One year after transplantation, 12.8% of the patients had developed PTDM, and 10.3% showed an IFG level. The IFG had a negative and statistically significant influence on graft and patient survival. Host and donor age, weight, hepatitis C virus infection, and acute rejection were found to be significant risk factors. DISCUSSION: Our study found a high incidence of PTDM, as described in previous studies, but with an emphasis on a greater role played by IFG, not only in its incidence, but also as a prognostic factor for the outcome of graft and patient survival. Identifying patients at risk of developing PTDM is important in offering them early and appropriate treatment.

Renal donor implication in the origin of BK infection: analysis of genomic viral subtypes.

UNLABELLED: BK virus (BKV) reactivation in immunocompromised kidney transplant patients can produce a tubulointerstitial nephropathy (BKVN). Molecular tools that test for DNA-BKV provide early detection and assist in management, but some aspects of the pathogenesis of this infection, such as donor causality, remain unclear. MATERIALS AND METHODS: Between November 2004 and January 2006, 55 Spanish kidney donors were studied for BK infection. A quantitative PCR assay was performed on urine and serum to detect BKV. To determine the origin of the viral infection, a transcription control region of the BK polymorphism sequence was designed to identify the viral subtype. RESULTS: Fifteen of 55 (27%) donors were BK-PCR positive: 13 in urine and 2 in serum and urine. Moreover, monitoring of recipient pairs detected BK-PCR positivity in 14 of 73 recipients. We studied eight BK-PCR positive recipients (corresponding to four pairs) and their respective donors. The same viral genome was observed in the four pairs, namely, the A250-1-a, WW-like, AS, and JL genotypes. Interestingly, one of the four pairs showed the donor and the two recipients to display exactly the same JL genotype. CONCLUSION: On the basis of our preliminary results analyzing the molecular fingerprints of donor and recipient pairs, we have presented new data implicating the donor, in at least some cases, as the source of BK infection.

Donor-derived Strongyloides stercoralis hyperinfection syndrome after simultaneous kidney/pancreas transplantation.

Most cases of strongyloidiasis associated with solid organ transplantation have been due to the reactivation of a latent infection in the recipient as a result of the immunosuppressive therapy; however, donor-derived infections are becoming increasingly frequent. The case of a patient who nearly died of a Strongyloides stercoralis hyperinfection after receiving simultaneous kidney/pancreas transplants is described herein. No specific parasitological tests were performed pre-transplantation, despite the fact that both the recipient and the donor originated from endemic areas. Serological analysis of the donor's serum performed retrospectively revealed the origin of the infection, which if it had been done beforehand would have prevented the serious complications. Current practice guidelines need to be updated to incorporate immunological and molecular techniques for the rapid screening of Strongyloides prior to transplantation, and empirical treatment with ivermectin should be applied systematically when there is the slightest risk of infection in the donor or recipient.

Polymerase chain reaction detection of BK virus and monitoring of BK nephropathy in renal transplant recipients at the University Hospital La Fe.

INTRODUCTION: Reactivation of BK infection occurs in immunocompromised hosts causing tubulointerstitial nephropathy (BKVN). Approximately 5% of kidney transplant recipients (KTR) develop BKVN, special half of whom lose their grafts. However, BKVN morphologic diagnosis on a renal biopsy is complicated, because the cytopathic changes can sometimes mimic rejection. Thus, BKV DNA-polymerase chain reaction (PCR) assay on serum, urine, and renal tissue is useful for early detection and monitoring of BKV. MATERIALS AND METHODS: We performed routine monthly urine cytologies looking for decoy cells as a marker of virus replication. Then, we performed a qualitative PCR on urine and serum in all recipients (independently of positive or negative cytology). We amplified 3 BK viral genome regions, LT (early transcription region) and VP1 (late transcription region) seeking a more accurate virus detection, and the TCR (control transcription region) region to perform a polymorphism sequence analysis to identify the BK genomic variant. Finally, the BKVN diagnosis was confirmed using renal biopsy. RESULTS: At present, 132 patients have been monitored. Thirteen of 40 (33%) were PCR-urine-positive cases (5 LT+/VP1- and 8 LT+/VP1+), and 10 of 132 (7.5%) were PCR-serum-positive cases (7 LT+/VP1- and 3 LT+/VP1+). When we compared PCR-urine and cytology results, 11 of 40 (27.5%) patients showed a positive cytology, 6 of whom were PCR- urine-positive (1 LT+/VP1- and 5 LT+/VP1+); whereas, 29 patients showed a negative cytology, 7 of whom were PCR-urine-positive(3 LT+/VP1- and 4 LT+/VP1+). Thus, comparison of PCR- urine and cytology results revealed false-positive and false-negative cases. Finally, TCR sequence analysis was performed in 9 patients to identify the BK genomic variants. CONCLUSION: Testing for BKV DNA in urine and serum is a noninvasive early detection assay and monitoring tool.

[Cytomegalovirus viral load and antigenemia in the monitorization of prophylactic treatment with valganciclovir in renal transplant recipients]. / Carga viral y antigenemia de citomegalovirus en la monitorización de la profilaxis con valganciclovir en pacientes con trasplante renal.

Cytomegalovirus (CMV) disease is one of the most relevant infectious complications in solid organ transplant, and we must perform an appropriate prophylactic intervention. The goal of this study was to evaluate the effectiveness of prophylactic treatment with valganciclovir in renal transplant recipients in the first three months post transplantation by shell vial urine culture assay, and by measuring antigenemia (pp65) and CMV viral load, the latter by PCR. The population of the study included 100 renal transplant recipients. We analyzed the results of 36 patients recruited between November 2003 and July 2004 who were receiving a prophylactic oral treatment with valganciclovir, and who had finished the follow-up period of 90 days. The three tests mentioned above were performed on days 7, 15, 30, 45, 60, 75 and 90. No positive antigenemia was detected, the virus was cultured in a urine specimen and, in one patient, three measurements of viral load in serum were positive. Preliminary results of the study suggest that universal chemoprophylaxis with valganciclovir is effective for the prevention of CMV infection in renal transplant recipients and that, although all three tests used were useful, the measurement of CMV viral load seems to be the most appropriate method for monitoring these patients.

Mycobacterial infection in a series of 1261 renal transplant recipients.

OBJECTIVE: To describe the incidence and clinical characteristics of mycobacterial infection in renal transplant recipients. METHODS: We retrospectively analyzed the cases of mycobacterial infection in a series of 1261 renal transplants carried out in our Unit of Renal Transplantation from 1980 to 2000. Demographic parameters and clinical antecedents such as age, cause of end-stage renal disease, time of follow-up of the graft, previous renal function and type of immunosuppression were considered. Moreover, the clinical onset, diagnostic tools, treatment policy and evolution were studied. The pathogenesis of the different types of mycobacteria isolated was also analyzed. Diagnosis was made with the Ziehl-Neelsen staining method. Culture was performed by the conventional Löwenstein-Jensen method and the Bactec-460 radiometric method. RESULTS: We found mycobacterial infection in 27 patients (2.1%), due to Mycobacterium tuberculosis in 20 cases, M. kansasii in five patients, and M. fortuitum in two patients. The mean elapsed time from the renal transplant was 20.5 months; the infection appeared in 18 patients during the first eight months after transplantation. The clinical onset was pulmonary infection in 17 cases (12 M. tuberculosis and five M. kansasii); five had urinary symptoms (three M. tuberculosis and two M. fortuitum); three cases of M. tuberculosis infection had abdominal symptoms; another one began with a perineal tuberculous abscess; the rest of the patients were asymptomatic. The types of specimen on which microbiological identification was carried out were, in decreasing order: sputum and/or bronchial washing/pleural aspiration, urine, feces, gastric and peritoneal fluids, bone marrow and blood. The first-line drug isoniazid had the highest resistance index in the susceptibility test. Clinical dissemination was observed in eight patients, four of whom died. Another three patients had a significant impairment in renal function, and in one of these patients an allograft nephrectomy was necessary due to a severe septic syndrome. CONCLUSIONS: Mycobacterial infection, mainly by M. tuberculosis, has an important impact on kidney transplant recipients, particularly during the first year after surgery. Diagnosis often presents some difficulties, and a delay in treatment represents a determinant factor for the evolution, with a risk of death or permanent damage in renal function. Therefore, early diagnosis is mandatory. When the Mantoux reaction is positive, antituberculous prophylaxis seems advisable.

Immunoprophylaxis with Simulect (basiliximab) in kidney transplantation: results from routine clinical practice at 18 kidney transplant units.

OBJECTIVE: The objective of this study is to assess a Simulect (basiliximab) regimen in routine clinical practice in the Spanish kidney transplantation units to evaluate efficacy and safety. METHODS: In this prospective, observational study, data on demographics, parameters of efficacy, and safety in patients who under with kidney transplantation treated with Simulect (basiliximab) were collected through an on-line collection system. RESULTS: One hundred sixty three patients at 18 kidney transplant units included 12 months follow-up. The patient mean age was 52 years (DS 13,67) including 96 (58.90%) men and 67 (41.10%) women. Cold ischemia time was 19 hours (DS 6,79). Only 2 patients presented with PRA >50%. For prophylactic immunosuppression, 67.13% of patients received triple therapy with CNI (cyclosporine 49.65% or tacrolimus 17.48%), MMF (66.43%) or AZA (10.49%), and steroids. Incidence of acute rejection (AR) at 12 months was 12.27% (1.84% steroid-resistant). In subgroup analysis, AR was 13.5% in nondiabetics and 4.5% in diabetics, including 3 steroid-resistant episodes (1.84%) in nondiabetics and none in diabetics. In relation to donor age, AR was incidence 10.3% in patients with kidneys from donors aged 50 years or younger and 10.6% when donors were older than 50 years, including 1 (1.73%) and 2 (1.93%) steroid-resistant episodes, respectively. The graft and patient survival rates at 12 months were 90% and 98%, respectively. CONCLUSIONS: Simulect (basiliximab) used in routine clinical practice provided good prophylaxis against acute rejection in several kidney transplant patient populations, similar to that observed in randomized clinical studies with excellent tolerability and safety.

[Prostatism in patients with chronic renal failure and in renal transplant recipients. Comparative study]. / Prostatismo en pacientes con fracaso renal crónico y trasplantados renales. Estudio comparativo.

Though hypogonadism is part of the clinical picture of chronic renal failure, its etiology remains unknown. Because of the consequences it may have on the prostate gland, it was decided to conduct a prospective evaluation on its influence on prostatic signs and symptoms and glandular growth in a group of patients with chronic renal failure undergoing dialysis and a second group with renal transplantation. To this end, the presence of symptoms was assessed in 78 subjects over 50 years of age: 22 healthy controls (group C) (28.2%), 28 in haemodialysis (Group HD) (35.0%) and 28 with renal transplantation (Group RT) (35.9%). All subjects were aged between 53 and 80 years (mean 58.29 +/- 5.45). Determination of degree of prostatism was done by the International Prostate Symptoms Score (IPSS-S and L), flowmetry, ultrasound postmictional residue, transrectal ultrasound with 3 prostatic diameters (cross-sectional, antero-posterior and longitudinal), prostate weight and plasma levels of PSA, testosterone, FSH, LH, PRL and oestradiol. In 26 of 28 patients in the HD group IPSS-L, flowmetry and post-mictional residue was not assessed as they had no spontaneous miction. There were significant differences in IPSS between C and RT (p = 0.003), Qmax between C and RT (p = 0.009), post-mictional residue between C and RT (p = 0.045), cross-sectional diameter between C and HD (p = 0.036), prostate weight between C and HD (p = 0.001), and between HD and RT (p = 0.001), PSA between C and RT (p = 0.026), FSH between C and HD (p = 0.005), LH between HD and RT (p = 0.020), PRL between HD and RT (p = 0.023), Oestradiol between C and HD (p = 0.032). We conclude that hypogonadism is a factor which, in patients with chronic renal failure and renal transplantation, contributes to prevent prostate growth thus minimizing the symptoms of prostatism.

[Post-transplantation renal rupture]. / Rotura renal postransplante.

INTRODUCTION: Renal allograft rupture in the transplanted patient represents a usually early postoperatory complication threatening graft and patient survival. Urgent management is often required. MATERIAL AND METHODS: Renal transplanted patients which had rupture of the renal allograft have been reviewed retrospectively. Between February 1980 and June 1996 a total of 868 renal transplants were performed, and 21 (2.41%) suffered from allograft rupture. Diagnosis was based mainly on the symptoms, blood analysis to test hematocrit value, and ultrasounds. RESULTS: Men age of the patients was 34 years old (21-49), 15 (71.4%) males and 6 (28.6%) females. Evolution was as follow: 4 patients underwent extracapsular nephrectomy due to non-functioning kidney; in 16 patients the graft could be preserved using different methods of renal corsetage (lyophilized human dura was applied in 8 cases, fascia lata in one, fascia lata and lyophilized human dura in 3 cases, and polyglycolic acid mesh in other 4 patients); and finally one patient was managed conservatively. There was no intra and post-operatory mortality. Four patients died lately of other causes not related to renal transplantation. Other 4 patients underwent chronic rejection and fail of the renal function. Two of these four patients have already received their second graft. A total of 13 patients have a good renal function (61.9%). CONCLUSIONS: Early diagnosis of the renal allograft rupture must be the main objective in order to initiate as soon as possible therapeutic measures that firstly should be aimed to preserve the graft (medically or surgically). Nephrectomy must be reserved for renal allograft rupture secondary to venous thrombosis and other situations threatening life.

[Renal transplantation in patients with enterocystoplasty]. / Trasplante renal en pacientes con enterocistoplastia.

OBJECTIVES: To asses the impact of augmentation enterocystoplasty on the success of cadaveric renal transplantation in patients with dysfunctional bladders. PATIENTS AND METHODS: Between 1980 and 2001, 3 men and a woman with severe dysfunctional lower urinary tract underwent a total of 4 cadaveric renal transplantations. The etiologies of the bladder dysfunction were bladder contraction secondary to urinary tuberculosis in all cases. In 3 patients were performed an enterocystoplasty with ileocecal segment and one with ileon. RESULTS: The overall allograft survival was 58.7 months. Two patients have functioning grafts 27 and 74 months after transplant, 1 has died due to an intestinal disease and other had chronic rejection after follow-up of 98 months. Technical complications occurred in 3 patients. All patients remain continent without catheterization after the transplantation. CONCLUSIONS: Enterocystoplasty is a safe and effective method of restoring lower urinary tract function in the patient with end stage renal disease and a small non compliant bladder.

Validation on the simplified medication adherence questionnaire (SMAQ) in renal transplant patients on tacrolimus.

BACKGROUND: Non-adherence to immunosuppressive medication is associated with graft loss and death. The simplified medication adherence questionnaire (SMAQ) is a short and reliable instrument for assessing adherence to medication. OBJECTIVE: Validation of a version of the SMAQ instrument adapted for use in transplant patients in a sample of kidney graft recipients. METHODS: Observational, longitudinal prospective study in 150 renal transplant patients on tacrolimus, over 18 years old, who had received a graft at least one year before. Basic sociodemographic and clinical data were recorded; patients completed the SMAQ twice (administered by doctor/nurse) and self-administered the Morisky-Green scale. The analysis database included 144 patients that met selection criteria and that provided the required data. Descriptive characteristics for all recorded parameters and psychometric characteristics of the questionnaire (reliability and validity) were studied. RESULTS: Mean age in the sample was 50.63 (12.44) years, 60.42% were men. Some 20.14% of patients had sub-target tacrolimus levels (<5 ng/ml), and unjustified variations in immunosuppressive drug levels were reported for 13.48%. Regarding SMAQ results, 39.01%/41.84% of patients were non-adherent (doctor/nurse administration); 22.38% according to the Morisky-Green scale. Interobserver agreement (kappa) was 0.821 (P<.001). The Cramer's-V statistic for convergent validity was 0.516 (P<.001). SMAQ scores were associated with unjustified variations in tacrolimus levels. In the prediction of tacrolimus levels (target vs subtarget), SMAQ compared to Morisky-Green provided a better classification of patients, with greater sensitivity and lower specificity. CONCLUSION: The questionnaire provides good levels of validity and interobserver agreement. An enhanced sensitivity is advantageous to better detect non-adherent patients for a better follow-up.

Influence of pharmacogenetic polymorphisms in routine immunosuppression therapy after renal transplantation.

Pharmacogenetics is the study of the cause of various individual responses to the same pharmacologic therapy. Genetic alterations in a single nucleotide in the genes responsible for transport and metabolism of an immunosuppression drug may modify patient response. Although pharmacogenetics is of interest, its clinical relevance remains to be demonstrated. The objective of the present study was to evaluate the effect of single-nucleotide polymorphisms (SNPs) in renal transplant recipients and their donors relative to blood concentrations of tacrolimus in the first 2 weeks posttransplantation. Seventy-one blood samples each from renal transplant recipients and their donors were analyzed using a genetic analysis system (MassARRAY; Sequenom, Inc, San Diego, California) in an attempt to characterize the more relevant SNPs of the ABCB1 and CYP3A5 genes for correlation with recipient trough concentrations of drug. Two-way analysis of variance and Bonferroni post hoc tests were used. In agreement with theoretical predictions, the wild-type genotype in ABCB1 SNPs (CC) tended to stabilize drug concentrations within the therapeutic range, whereas the T variant induced a mean increase in blood concentrations of more than 60%. These findings are in agreement with statistical tests that compared mean concentrations in various recipient-donor populations and found significant differences between them (P<.001) in CC vs TT, and P<.01 in CT vs TT). Donor genotype did not seem to be relevant. However, further studies are required to achieve more robust conclusions.

Importance of technical aspects in the beginnings of a pancreas transplantation program.

Pancreas and kidney transplantation is the treatment of choice for patients with type 1 diabetes mellitus and terminal renal insufficiency. Herein we have presented a series of 35 patients transplanted between 2002 and 2009 including periods before and after 2007 divided based on introduction of some technical aspects. In the first phase (learning period) we have noted complications related to pancreatic surgery with a morbidity among 12 of 18 patients (66.6%). In the second period (stabilization period), complications appeared in 6 out of 17 patients (35.2%; P < .028). The reoperation rate was 83.3% in the learning period and 23.5% in the stabilization period (P < .03). Seven transplantectomies were performed in the first period (P < .004). Five patients died, all of them in the learning group (P < .019). Changes in the technical aspects of the procedure were responsible for improved outcomes obtained among pancreas and kidney transplantations.

Tacrolimus combined with two different dosages of sirolimus in kidney transplantation: results of a multicenter study.

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.

[Lithiasis of the transplanted kidney: therapeutical potential]. / Litiasis en el riñón trasplantado: posibilidades terapéuticas.

OBJECTIVES: The formation of calculus in the transplanted kidney is an uncommon complication. Metabolic derangements, infectious or obstructive processes, factors related with the surgical technique and the presence of ureteral catheters have been implicated in its etiopathogenesis. The therapeutic possibilities have changed in the last decade. The different factors related with stone formation in the transplanted kidney, the indications and treatment utilized in each case are analyzed. METHODS: We analyzed the cases of lithiasis following renal transplantation in our series of 800 renal transplants. The metabolic anomalies and other associated lithogenic factors in 5 cases that required treatment are described. RESULTS: All 5 patients were treated by ESWL. Complete resolution of the lithiasis was achieved in 4 cases whose kidney graft is currently stone free with preserved renal function, except one patient with hyperuricemia and hyperuricosuria who is again on hemodialysis for chronic rejection. In the fifth case fragmentation of the caliceal stone was not achieved after 4 sessions of ESWL. Subsequem ultrasound control evaluations have disclosed no changes in stone size or location. CONCLUSIONS: In our view, the approach to renal lithiasis in the transplanted kidney is similar to that of patients with solitary kidney, although stone size for treatment by ESWL should be limited to 2 cms. If stone size is between 1 and 2 cms, placement of a double-J catheter prior to ESWL is recommended, whenever possible. For stones larger than 2 cms, percutaneous nephrolithotomy is more effective and has less complications. Surgery is reserved for those patients in whom these techniques are unamenable or have failed.

Nocardial infection in immunosuppressed kidney transplant recipients.

OBJECTIVE: Nocardiosis is a very rare, opportunistic infection caused by microorganisms of the genus Nocardia, and is associated with significant morbidity and mortality in kidney transplant patients receiving immunosuppressive therapy. MATERIAL AND METHODS: Since 1980, our Renal Transplant Unit has carried out 1239 kidney transplants, and five cases of Nocardia infection have occurred during this time. In this retrospective study, special consideration is given to clinical manifestations, treatment response (efficacy and side-effects) and the evolution of both the patient and the graft. Microbiological factors studied included biochemical profiles and antimicrobial sensitivity. RESULTS: Nocardiosis was observed in five men with a mean age of 49.2 years who had received immunosuppressive therapy (generally cyclosporin/azathioprine and prednisone) for a mean of 47.8 months (range 1-148 months). Four of the patients had good previous renal function. The clinical presentation of nocardiosis was as follows: pleuropulmonary pattern of infection, n = 3; subcutaneous abscess, n = 1; and fulminant multi-organ disseminated nocardiosis, n = 1. In all cases, direct observation using modified Ziehl-Neelsen staining proved positive, and in vitro culture revealed good sensitivity to trimethoprim-sulfamethoxazole and variable sensitivity to the other groups of antibiotics. Nocardia brasiliensis was isolated in two cases, and Nocardia asteroides in three. Two patients died, one due to multiple organ involvement and the other due to acute respiratory failure associated with severe hepatopathy caused by hepatitis C virus. The remaining cases improved. CONCLUSION: A low incidence of nocardiosis following kidney transplantation was observed. Fatal cases occurred in patients with bacteremia and serious comorbid medical conditions, in whom early diagnosis and specific treatment was required.