Influence of Pre-renal Transplant Secondary Hyperparathyroidism on Later Evolution After Transplantation.

Persistence of secondary hyperparathyroidism (SHPT) is common after renal transplantation. Good diagnosis and treatment are important to avoid complications. The objective of our work was to perform a retrospective analysis of the evolution of SHPT after renal transplantation. We selected patients who had received a kidney transplant at our hospital between 2000 and 2014. The biochemical variables of chronic kidney disease-metabolic bone disorders (CKD-MBD) were collected at pretransplantation and at 3, 6, 12, and 24 months post-transplantation. Treatments related to SHPT were also analyzed. Five hundred forty-three renal transplants were included. The average preoperative parathyroid hormone (PTH) was 241.14 pg/mL, 115.7 pg/mL at 3 months, and at 12 and 24 months postoperatively, PTH levels stabilized to 112 pg/mL. Treatment related to SHPT was present in 27.3% of patients during the preoperative period, 40.4% at 3 months postoperatively, 24.2% at 12 months postoperatively, and 23.2% at 24 months postoperatively. There was a significant association between requiring some type of treatment preoperatively and the rest of the postoperative periods (P < .005). The sample was later divided into 3 groups based on preoperative PTH (1: <150 pg/mL, n = 223 [41.1%]; 2: 150-300 pg/mL, n = 173 [31.9%]; 3: >300 pg/mL, n = 147 [27.1%]) and their evolutions were compared. Higher levels of postoperative PTH in group pre-PTH 3 were observed. Group 3 also presented with greater need for treatment in the postoperative periods, with significant association (P < .05). A regression analysis was performed and found that postoperative PTH were dependent on preoperative PTH adjusted by glomerular filtration. In conclusion, parameters related to CKD-MBD (mainly PTH) after kidney transplant, dependent on preoperative levels and glomerular filtration. Patients with a greater grade of SHPT presented with higher levels of postoperative PTH despite receiving more intensive treatment.

Cancer incidence and survival in kidney transplant patients.

Immunosuppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer (NMSC) and malignancies, including posttransplant lymphoproliferative disorder (PTLD) and solid organ cancer. This study sought to investigate the incidence of malignancies and the clinical characteristics and risk factors of the renal transplant patients with solid organ tumors and NMSC. We included 1017 patients who received a kidney transplant in our hospital from 1979 to 2007. Results were contrasted with a cohort of patients from the same center without malignancies. The mean follow-up of patients in our series was 10 years. The mean age at presentation of the malignancy was 61 +/- 5 years. The malignancy and NMSC incidences were 6% and 5%, respectively. Patients with malignancy had a longer posttransplant time and greater recipient and donor age. In the multivariate analysis, independent risk factors for developing NMSC were: male sex (hazard ratio [HR] 3.1, P = .004); greater patient age (HR 1.09, P < .001), longer posttransplant time (HR 1.2, P = .004) and tacrolimus treatment (HR 4.4, P = .001). Risk factors associated with developing any malignancy were: patient age (HR 1.06, P < .001), number of grafts (HR 3.2, P = .019), tacrolimus treatment (HR 2.5, P = .035), and time posttransplantation (HR 1.2, P = .011). The mean times to development of an NMSC, solid organ malignancy, on PTLD were 7.5, 6.1, or 3.9 years, respectively. The mean survival time from the diagnosis of any malignancy was 9.6 months (95% confidence interval, 0.12-30) for solid organ malignancies and 1 month (95% confidence interval, 0.24-1.87) for PTLD.

24-Hour Proteinuria Versus Spot Protein-Creatinine Ratio for Kidney Transplant Management in Clinical Practice.

BACKGROUND: 24-hour proteinuria (24h-P) has been the most widespread test for clinical follow-up of proteinuria after kidney transplantation (KT), but urine collection is often not properly collected. Spot protein-creatinine ratio (P/Cr) has become the alternative to 24h-P for proteinuria evaluation in many KT units. However, its reliability, equivalence to 24h-P, and prognostic value regarding allograft outcome remain unknown. Therefore, the aim of this study was to evaluate the correlation and agreement between both methods for assessing proteinuria and to analyze which of them is a better predictor of graft survival. METHODS: We collected proteinuria measurements from KT patients in our center. 24h-P was adjusted for body surface area. Pearson correlation test and the Bland-Altman method were used to analyze correlation and agreement. Survival analysis was performed with the use of the Kaplan-Meier method and multivariate Cox proportional hazard model. RESULTS: A total of 8,549 urine samples were analyzed from 472 patients in whom 24h-P and P/Cr were simultaneously measured. A significant correlation was observed between 24h-P and P/Cr (r = .76; P < .001); however, the agreement between methods showed that P/Cr overestimated proteinuria compared with 24h-P, particularly when the latter was >1 g/24 h. The Cox regression multivariate model showed an increased risk of graft loss associated with proteinuria when assessed by either 24h-P (hazard ratio [HR] 6.53, 95% confidence interval [CI] 2.49-17.1) or P/Cr (HR 3.34, 95% CI 1.04-10.7). CONCLUSIONS: P/Cr is an method interchangeable with 24h-P for detecting proteinuria after KT. When proteinuria increases, the P/Cr overestimates 24h-P, even though it also has a significant and similar prognostic value for predicting graft survival.

Prevalence and Survival of Cancer After Pancreas-Kidney Transplantation.

BACKGROUND: Malignancy is an important cause of mortality in solid organ transplantation. There have been few studies of de novo solid organ malignancy (NSOM) after pancreas-kidney transplantation (PKT). The aim of this study was analyze the prevalence of NSOM and transplant outcomes. METHODS: We studied the development of NSOM after PKT in our center from May 1990 to February 2017. We analyzed demographic characteristics, prevalence of cancer, and survival after cancer diagnosis. We excluded nonmelanoma skin cancer and patients with history of malignancy before transplantation. RESULTS: We included 194 patients who received 206 PKTs (184 simultaneous PKTs and 22 pancreas after kidney transplants) with triple immunosuppressive therapy and basiliximab in more than 95%. The mean age at transplantation was 39 ± 7 years and 74% were male patients. Twelve patients developed malignancies (6.1%). Median time from transplant to NSOM was 6.6 (interquartile range [IQR] 0.2-11.7) years. The malignancies were 2 cecal appendix tumors, 2 hematologic tumors, 2 breast tumors, 1 melanoma, 1 native kidney tumor, 1 brain tumor, 1 bladder tumor, 1 prostate tumor, and 1 leiomyosarcoma. Thirty-five of the 194 patients of the whole cohort died throughout the follow-up, 4 of whom died after NSOM diagnosis (11.4%). Patient and grafts survivals were lower in recipients with tumor compared with recipients without tumor, but the difference was not statistically significant: renal graft survival was 80% vs 90% at 10 years (P = .86); and pancreatic graft survival was 45% vs 70% at 10 years (P = .15), respectively. The mean patient survival time from the diagnosis of cancer was 36.6 (IQR 18-54) months. Patient survival after NSOM diagnosis was 90% at 1 year and 50% at 5 years. CONCLUSION: The prevalence of NSOM in our PKT recipients is low, despite the scarce series of published data for comparison. Also hematologic tumors rate is very low, possibly influenced by age and type of induction.

Donor-Specific Antibodies After Starting Hemodialysis in Nonrenal Solid Organ Transplant Recipients: Role of TH17.

BACKGROUND: Nonrenal transplantation could cause a progressive deterioration in renal function until need dialysis. It is important to know if these patients increased their risk to develop de novo donor-specific anti-HLA antibody (DSA) after starting hemodialysis (HD) and if so, try to find the mechanism. MATERIAL AND METHODS: In this double-phase study, we first analyzed the incidence of development DSA in nonrenal transplant recipients after starting HD by a retrospective study. Secondly, a prospective study was designed to analyze the pharmacokinetics of immunosuppressive drugs and the cytokine profile of these patients. RESULTS: Of 179 pancreas transplant recipients, 16 needed to start HD, and 62.5% of these patients developed de novo DSA after starting HD, with 80% of them class I DSA. In the second phase of the study, the plasma levels of the immunosuppressive drugs as measured by a limited sampling strategy of 3 sample time points (C0, C2, and C4) were stable. The cytokine profile showed that there was an increase in Th1 cytokine (interferon gamma of 0.045 ng/mL) and also in Th17 cytokines (transforming growth factor ß >10 ng/mL). CONCLUSION: Our data suggest that the development of DSA after starting HD in nonrenal transplant recipients could be mediated by Th17 immune response mechanisms.

Short-Term Outcome of Untreated Versus Treated Asymptomatic Bacteriuria in Renal Transplant Patients.

BACKGROUND: Infection of the urinary tract (UTI) is the most common form of bacterial infection in renal transplant patients, but its management is still controversial. We compared symptomatic and asymptomatic bacteriuria, treated or untreated, during two different months (summer or winter). METHODS: This longitudinal, prospective study involved routine urine cultures collected during September 2014 or March 2015. Demographic, clinical, and microbiological characteristics from the patients with positive urine cultures were described. The main outcomes were the need of hospitalization, the bacterial clearance, and the selection of the resistant pathogen. RESULTS: From the 538 urine cultures collected, only 61 were positive urine cultures. Twenty were untreated asymptomatic bacteriuria (AB), 28 were treated AB, and 13 were treated symptomatic bacteriuria. The more prevalent micro-organisms were E coli (27%), K pneumoniae (11%), and E faecalis (7%). There were no differences in the demographic, clinical, and microbiological characteristics depending on the month when the urine cultures were collected. Only 10 patients required hospitalization during follow-up, and all of them belonged to the treated group. Bacterial clearance after the treatment occurred in 20 patients of the 41 treated (48.9%) and spontaneously in 14 of the 20 patients untreated (70%). Of the treated patients, 47.6% developed a new resistance to another antibiotic. CONCLUSIONS: Only 7.6% of the routine urine cultures on renal transplant were positive. Untreated AB did not require hospitalization, and 70% had spontaneous bacterial clearance.

Development of Donor-Specific Anti-HLA Antibodies After Restarting Hemodialysis Due to Graft Failure.

BACKGROUND: Incidents of renal replacement therapy (RRT) from renal transplants are on the rise. Some authors have associated the development of donor-specific anti-HLA antibodies (DSA) with the end of immunosuppression treatment (IS) and/or the performing of a transplantectomy. The objective of this study was to analyze the characteristics of transplant patients having high immunological risk who restarted RRT and the subsequent development of DSA. METHODS: We selected incidents on RRT carried out between 1980 and 2012 in our center: 146 cases; they presented non-DSA cytotoxic antibodies prior to returning to RRT. Survival time for the graft was 77.2 months; the average follow-up period for DSA development was 131.9 months. DSA in 76 cases (52.1%). Of 146 grafts, 72 underwent transplantectomy and 41 presented DSA after returning to RRT. In 17 of these cases (41.5%), the development of DSA occurred prior to the transplantectomy. Fifty-one cases of DSA were registered at the date of completion of the IS treatment, and 40 appeared after discontinuation (median 36 weeks) and 11 with previous appearance. IS was completed, with a median of 13 weeks after the return to RRT. RESULTS: No association was found between DSA development and order of graft, transplantectomy, or premature loss of the graft (≤15 months) after the return to RRT. There were significant differences between the number of HLA incompatibilities of the donor and the development of DSA. CONCLUSIONS: The development of DSA in high-immunological risk patients after restarting RRT is not related to transplantectomy.

Impact of Asystolic Donations in Kidney Transplant Activity From Cadaveric Donors in Andalusia.

BACKGROUND: Kidneys from donors after brain death (DBD) cannot meet the demand for renal transplants in Andalusia. METHODS: We analyzed the impact of using non-heart-beating donors (NHBD) in Andalusia from the start of this program to the present. RESULTS: From 2010 to 2014, brain-death kidney donations remained at a standstill (1,635 in total) although NHBD increased from 2.4% to 16% annually, to 5% of the total (n = 164: 83 type II Maastricht [NHBD-T2] and 81 type III Maastricht [NHBD-T3]). The donors were more frequently men (T2 80.5% and T3 76.5% vs DBD 58.2%; P < .001). NHBD were younger (48.9 ± 10.8 y vs DBD 53.3 ± 16 y; P < .001); 11.6% of NHBD were >60 and 0% >70 years old, versus 39.4% and 15.2% of DBD, respectively; this is mostly explained by NHBD-T2 (48.9 ± 10.8 y vs DBD 53.3 ± 16 y). NHBD were used much less frequently than DBD in recipients over the age of 65 years or for retransplanted or hyperimmunized patients and never on priority recipients (children and combined transplant patients). Blood groups differed significantly among different donor types (A, O, B, AB): NHBD-T2 65.1%, 27.7%, 7.2%, and 0%, respectively; NHBD-T3 45.7%, 45.7%, 8.6%, and 0%; and DBD 46.5%, 39.4%, 10.2 %, and 3.9% (P = .01). The immediate output of the graft also differed in the proportion of primary nonfunction and delayed graft function: NHBD-T2 9.8% and 70.7%, respectively; NHBD-T3 5.0% and 65.0%; and DBD 5.9% and 28.7%. CONCLUSIONS: The development of an NHBD program allows us to maintain and even increase transplants in our region. The impact on transplant access for O group recipients without priority will depend on the type of NHBD (low proportion of O group in NHBD-T2).

Tyrosine-phosphatase and glutamate-decarboxylase antibodies after simultaneous pancreas kidney transplantation: do they have an impact on pancreas graft survival?

INTRODUCTION: The pathogenesis of type 1 diabetes mellitus (T1DM) is associated with auto-antibodies. These auto-antibodies contribute to pancreatic ß-cell destruction. Tyrosine-phosphatases (IA-2) and glutamic acid decarboxylase (GAD65) are the most frequently used by clinicians. When T1DM patients develops advanced chronic kidney disease, simultaneous pancreas-kidney (SPK) transplantation becomes the best option. However, pancreatic graft survival is limited. The role of the auto-antibodies on pancreas graft survival remains controversial. OBJECTIVE: The aim of this study was to assess pancreas graft survival according to the presence of GAD65 and IA-2 auto-antibodies after SPK transplantation. METHODS: We analyzed all SPK transplantations performed in our hospital since January 1990 to December 2013 with at least 30 days of pancreas graft survival. We collected demographic and clinical variables from donors and recipients. Graft failure was defined as complete insulin independence after transplantation. Pancreatic graft survival was analyzed using the Kaplan-Meier method. RESULTS: Overall, 152 SPK transplantations were performed during the period. One hundred sixteen were accessed for de novo post-transplantation auto-antibodies. Also, 17.8% (n = 27) were positive for anti-GAD65, 13.8% (n = 20) for IA-2, 3.9% (n = 6) were positive for both, and the rest were negative for any auto-antibody (n = 63). Kaplan-Meier survival curves estimated a worst pancreas graft survival for patients with positive IA-2 antibodies versus those patients with negative auto-antibodies and GAD65+auto-antibodies (P = .003 and .022, respectively, by log-rank). Mean pancreas graft survival rates at first and fifth year were 72% and 64%, respectively, for those patients with positive IA-2. CONCLUSIONS: IA-2 antibodies after SPK transplantation are associated with long-term graft lost compared with the rest of the groups. Monitoring of these auto-antibodies after SPK may help to identify patients with a higher risk of graft failure.

Long-term survival of simultaneous pancreas-kidney transplantation: influence of early posttransplantation complications.

BACKGROUND: Complications that develop in the early posttransplantation period after simultaneous pancreas-kidney transplantation (SPKT) can contribute to poor long-term survival of grafts and patients. PATIENTS AND METHODS: We studied 86 SPKTs that were performed between 2000 and 2010 in our hospital, analyzing all complications in the early posttransplantation period and their impact on long-term survival in patients and grafts. RESULTS: The mean age of the patients was 38.77 ± 7.13 years (79.1% male). Of the 86 SPKT patients, 22.1% were on peritoneal dialysis (PD) before transplantation, 68.6% were on hemodialysis (HD), and 9.3% had not received any substitutive renal therapy. The immunosuppressive regimens consisted of induction with basiliximab followed by tacrolimus, mycophenolate mofetil, and steroid therapy. More than 75% of patients experienced an infection in the early posttransplantation period: bacteremia (37.2%), central catheter infection (7%), wound infection (4.7%), urinary tract (14%) and positive abdominal drain culture (45.3%). Approximately one third (31.4%) of patients underwent a reoperation, primarily due to bleeding (21.95%) or infection (19.51%). One fifth of patients (19.8%) experienced an acute rejection episode. The 3-year survival of the pancreas was lower among PD patients (82%) compared with patients who did not undergo dialysis before SPKT (100%). The 5-year survival rate of both grafts was lower among patients who underwent a reoperation than those who did not: pancreas survival rates, were 70% versus 93%, respectively (P = .015) and kidney graft survival rates were 75% versus 96%, respectively (P = .0017). Five-year patient survival rates were also lower among reoperated patients than those who were not (85% vs 97%, respectively), although the difference was not significant (P = .27). CONCLUSIONS: Complications in the early posttransplantation period after SPKT were frequent, increasing morbidity and inpatient stay. One third of our patients underwent a reoperation, which had a negative impact on graft survival.

Impact of recurrent glomerulonephritis on renal graft survival.

BACKGROUND: Glomerular disease causes graft loss in the intermediate and long term, especially recurrent primary renal disease, negatively impacting graft survival. Thus, it must be considered a differential diagnosis in the evaluation of chronic graft dysfunction. METHODS: The objectives of our study were to compare the impacts of primary glomerular disease on graft survival and association with interstitial fibrosis/tubular atrophy (IFTA) or transplant glomerulopathy. We examined the influence of the relapse of glomerulonephritis (GN) on renal graft survival in a retrospective study of 1057 patients undergoing renal transplantations between March 1981 and October 2009. Among this group, 128 patients were diagnosed with pretransplant GN by renal biopsy. We examined graft survival on recurrence compared with IFTA and transplant glomerulopathy using Kaplan-Meier analysis. RESULTS: We analyzed a cohort of 128 patients who were diagnosed with pretransplant GN by renal biopsy, including 28.9% (37) of whom were males. The mean age was 42.04 ± 13.82 years. The most frequent type was immunoglobulin A GN (IgAGN; 31.3%), followed by membranoproliferative GN (MPGN; 28.9%), rapidly progressive GN (RPGN; 16.4%), focal-segmental GN (FSGN; 13.3%), membranous GN (9.4%), and minimal change GN; (0.8%). Among the 16 cases (12.5%) of GN recurrence; MPGN was associated most frequently (n = 10, 28.9%), followed by FSGN (n = 4, 23.5%), RPGN (n = 1, 4.8%), and IgAGN (n = 1, 2.5%). We noted that 11.8% of subjects to be positive for hepatitis C virus; while 3.9% were hepatitis B virus(HBV)-positive. We observed no differences in hepatic serology between patients who experienced recurrence (HBV 6.3% vs hepatitis C virus [HCV] 18.8%) compared with IFTA (HBV 3.1% vs HCV 9.4%). Fifty-one patients (39.8%) were biopsied after transplantation due to impaired renal function: there were recurrences of GN in 12.5% (n = 16), IFTA in 25% (n = 32), and transplant glomerulopathy in 2.3% (n = 3) cases. The average graft survival in our cohort was 8.36 ± 0.59 years. The median patient survival among those who experienced a recurrence was 8.36 ± 1.79 years; 7.19 ± 1.01 years in IFTA patients; and 3.31 ± 0.91 years in patients with transplant glomerulopathy (log-rank P = .06). Upon multivariate analysis, recurrence of GN was not an independent predictor of renal loss. CONCLUSIONS: MPGN was the type of GN that recurred most frequently followed by FSGN. No differences in graft survival were noted between long-term recurrence of GN and other causes of chronic graft dysfunction. The recurrence of primary disease did not worsen the renal graft prognosis versus other causes of chronic graft dysfunction.

Recurrent membranoproliferative glomerulonephritis after second renal graft treated with plasmapheresis and rituximab.

We present a case of a 45-year-old man who suffered from idiopatic membranoproliferative glomerulonephritis (MPGN) in the native kidney that relapsed after his first and second renal grafts. The patient was diagnosed in 1990 with lobular MPGN type I, receiving his first renal graft in 1996. In 2001, a biopsy showed recurrence of MPGN type I (rMPGN). He underwent a second renal graft in 2008. In January 2010, he experienced increased proteinuria and creatinine. Upon electron microscopy of a renal graft biopsy we diagnosed a new rMPGN. At the time of the biopsy, complement levels were normal, although C3 and C4 decreased further. We administered 12 plasmapheresis (PP) sessions and four doses of rituximab. Due to persistent renal impairment, we performed a new biopsy 3 months later, showing less severity of the acute lessions. He received a new cycle of treatment (PP+rituximab). One year later, his renal function was stable with a creatinine ranging between 2 and 2.5 mg/dL and a protein/creatinine ratio less than 1 mg/mg. We concluded that the treatment stopped the disease progression.